Bac e ial nanocellulose as a e sa ile sca old o biomedical applica ions:
Syn hesis, unc ionaliza ion, and u u e p ospec s
Liliana Mel o
a,*
, C´
a ia Al es
a
, Ma a Fe nandes
a
, So ia Rocha
a,b,c
, Behnaz Meh a ani
a
,
Ana Isabel Ribei o
a
, Sa a Aze edo
a,b,c
, Vanessa F. Ca doso
b,c
, ´
Osca Ca alho
b,c
,
Nuno Dou ado
b,c
, An ´
onio J. Salgado
d,e
, And ea Zille
a
, Jo ge Pad ˜
ao
a,*
a
Cen e o Tex ile Science and Technology (2C2T), Depa men o Tex ile Enginee ing, Uni e si y o Minho, Campus o Azu ´
em, 4800-058 Guima ˜
aes, Po ugal
b
Cen e o Mic oElec oMechanical Sys ems (CMEMS), Uni e si y o Minho, Campus Azu ´
em, 4800-058 Guima ˜
aes, Po ugal
c
LABBELS – Associa e Labo a o y, Uni e si y o Minho, 4800-058 Guima ˜
aes, Po ugal
d
Li e and Heal h Sciences Resea ch Ins i u e (ICVS), School o Medicine, Uni e si y o Minho, Campus de Gual a 4710-057 B aga, Po ugal
e
ICVS/3B’s – PT Go e nmen Associa e Labo a o y, 4710-057 B aga Po ugal
ARTICLE INFO
Keywo ds:
Bac e ial nanocellulose
Bioac i e compounds, Cance he apy
Composi es
Implan s
Wound d essings
ABSTRACT
Bac e ial nanocellulose (BNC) consis s o nano ib es o cellulose andomly en angled du ing hei syn hesis by
pa icula bac e ium cells du ing e men a ion. Thus, i may be ega ded as a unique h ee-dimensional o pu e
cellulose ha is consolida ed du ing he gene a ion o he ib es by hei mic obiological ac o ies. The me abolic
syn hesis and pu i ica ion p ocesses a e app oached, unde sco ing i s po en ial as an ideal empla e o he
p oduc ion o biomedical composi e solu ions, based on i s inhe en nano-d i en asse s. Also, BNC p ope ies can
be g ea ly enhanced by he inco po a ion o bioac i e subs ances, which may be ino ganic o o ganic, leading o
he o mula ion o supe io wound d essings and implan s. In wound d essings, he mos ele an agen s
encompass sil e and coppe nanopa icles, cu cumin, and hyalu onic acid. BNC implan s co e se e al o gans
such as blood essels, hea al es, ne e sca olds, co nea, ympanic memb anes, ocal co ds, bone, ca ilage,
den al s uc u es, con as and d ug deli e y agen s. The unc ionaliza ion o BNC wi h i on oxide nanopa icles,
g aphene, algina e, chi osan, silk ib oin, o bone mo phogene ic p o ein 2 human in implan s allows he
enhancemen o mimicking o mechanical p ope ies, cell mig a ion, p oli e a ion, di e en ia ion, and
biocompa ibili y. This highligh s he po en ial o using BNC as a sca old o biomedical applica ions, o e ing a
compelling al e na i e o pe ochemical-based bioma e ials.
1. In oduc ion
Bac e ial nanocellulose (BNC) is a e sa ile polysaccha ide exc e ed
by bac e ia ha has gained in e es in he biomedical ield due o i s
in insic physicochemical p ope ies. This biopolyme p esen s high
pu i y and lexibili y, high wa e e en ion (>90 %), high deg ee o
polyme iza ion (2,000–6,000) and c ys allini y (70–90 %). I s en angled
nano ib ous s uc u e esul s in a e y po ous ma e ial simila o he
ex acellula ma ix (ECM). In addi ion, he BNC hyd ogel possesses
excellen mechanical p ope ies, namely high ensile s eng h and elas ic
modulus [1–3]. Such p ope ies endow BNC wi h a b oad spec um o
possible applica ions in he biomedical ield. Hyd ogels a e some o he
mos p omising bioma e ials because hey a e p one o chemical mod-
i ica ions wi h bioac i e chemicals, genes, and cells, hus opening an
a ay o a a ie y o applica ions in den al ca e, wound d essing, and
con olled d ug deli e y. Tissue enginee ing has conside ably in es ed
in he egene a ion and econs uc ion o damaged issues.
Th ee-dimensional (3D) s uc u al sca olds ha e led o he de elopmen
o unc ional enginee ed issues o mechanical suppo du ing in i o
implan a ion, such as ca ilage, bone, skin, hea al es, ne es, and
endons [4].
A a ie y o ino ganic nanopa icles (NPs) a e used in heal hca e
applica ions: sil e (Ag), gold (Au), coppe (Cu), pla inum (P ), i anium
(Ti), and hei oxide de i a i es. Thei size anges om abou 1 o 100
nm and a y in shape, e.g., nanodisks, nanowi es (Nws), nano ubes, and
nano ods (NRs). These in insic physicochemical p ope ies ema kably
e olu ionize heal hca e, including he apeu ics, op oelec onics, d ug
disco e y, diagnos ic biological p obes, ca alysis, display ins umen s,
* Co esponding au ho s.
E-mail add esses: [email p o ec ed] (L. Mel o), [email p o ec ed] (J. Pad ˜
ao).
Con en s lis s a ailable a ScienceDi ec
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biological senso s, and he de ec ion o en i onmen al oxic me als o
eagen s and medicines. Me al o ba e NPs a e known o po en ially
induce oxici y by di ec ly in e ac ing wi h cells, o h ough he elease
o oxic me al ions, hinde ing hei use in biomedical applica ions. Thus,
biological p ocesses a e aking o e he p oduc ion o NPs, due o i s
sa e and eco- iendlie app oach. These p ocesses include he use o
dis inc biological esou ces such as plan s, bac e ia, ac inomyce es,
ungi and yeas s, i uses, and a wide a ie y o ma ine and eshwa e
algae [5]. Ano he aspec o conside ega ding me al NPs is hei high
su ace ene gy and an de Waals o ces ha acili a e agg ega ion,
hinde ing hei e ec i eness. Agg ega ion may be mi iga ed h ough he
use o a subs a e able o s abilize he NPs [6].
Hyalu onic acid, bone mo phogenic p o ein 2, gela ine, chi osan,
lignin, and polylac ic acid (PLA), a e some examples o biocompa ible
o ganic ille s used in biomedical applica ions. These ille s a e less
likely o cause an immune esponse o o he ad e se eac ions. Howe e ,
simila o ino ganic NPs, hei syn hesis can be bo h labo ious and
haza dous. Added ea u es include imp o ed s eng h, lexibili y, p o-
mo ion o cell g ow h, and an imic obial p ope ies [7–11].
This e iew p o ides a de ailed desc ip ion o he syn hesis o BNC
and i s mechanical p ope ies acco ding o he physical s a e o he
biopolyme . In addi ion, i ocuses on he a ious applica ions o BNC
when unc ionalized o in combina ion wi h ino ganic o o ganic com-
pounds, and i s signi icance in wound d essings, implan s, and cance
he apy.
2. Bac e ial nanocellulose
2.1. Syn hesis
Di e en gene a o e men a ion bac e ia a e ecognized as pos-
sessing he equi ed genes o BNC p oduc ion such as Rhizobium,
Azo obac e , Ag obac e ium, Ae obac e , Salmonella, Esche ichia, among
o he s. Ne e heless, he mos p ominen belong o he Ace obac e aceae
amily, namely: No ace imonas and Komaga aeibac e [12]. The biosyn-
hesis o BNC co esponds o an ex emely complex and highly egula ed
me abolic p ocess ha unde goes se e al s eps and in ol es a se ies o
genes esponsible o he encoding o bo h enzymes and di e en
Fig. 1. Schema ic ep esen a ion o he biosyn he ic pa hway o BNC and o ganiza ion o he a ious subuni s in he bac e ial cellulose syn hase complex. Adap ed
om Re . [14], unde he Licence CC BY 4.0, 2021, Nanjing Medical Uni e si y.
L. Mel o e al.
Applied Ma e ials Today 46 (2025) 102858
2
ca aly ic complexes [13,14]. BNC is p oduced as ib es ha in e wine
wi h each o he . As hei concen a ion inc eases, a 3D ne wo k is
de eloped hus c ea ing a loa ing mac oscopic po ous memb ane. This
s uc u e is o med by he bac e ial cells en apped be ween he p o-
duced cellulosic ibbons, which allows o hese non-mo ile, s ic ly
ae obic bac e ia o g ow a he in e ace o he cul u e medium [12,15].
This p ocess can use mul iple ca bon sou ces o he BNC building blocks
such as glucose, uc ose, and galac ose. The e o e, i is impo an o
no e ha BNC will a y depending no only on he ca bon sou ce used,
bu also on he bac e ial s ain. Di e en ca bon sou ces and di e en
me abolic p o iles will go e n BNC p ope ies such as he mechanical
p ope ies, c ys allini y, and hickness o he p oduced BNC [15,16].
BNC biosyn hesis (Fig. 1) using glucose as he main ca bon sou ce is
he mos common and s aigh o wa d me abolic pa hway. I may be
b oken down in o ou main enzyma ic s eps: (i) phospho yla ion o
glucose in o glucose-6-phospha e ia glucokinase; which is ollowed by
he (ii) p epa a ion o linea glucan chains, meaning he isome iza ion o
glucose-6-phospha e by phosphoglucomu ase in o glucose-1-phospha e;
(iii) u idine diphospha e glucose (UDP-Glc), a di ec p ecu so o cel-
lulose, is syn hesized by UDPG-py ophospho ylase, which ansla es
in o he assembly and c ys alliza ion o glucan chains in o hie a chically
s uc u ed cellulose ibbons; las ly, (i ) UDP-Glc polyme izes in o cel-
lulose by a memb ane p o ein complex called cellulose syn hase, and i
is sec e ed o he ex acellula en i onmen [13,14,17–20]. I should be
unde sco ed ha o BNC syn hesis using disaccha ides, such as suc ose,
lac ose, and mal ose, he ini ial me abolic p ocess is di e en . The di-
saccha ides mus i s be con e ed in o hei espec i e mono-
saccha ides h ough an addi ional hyd olysis s ep and only hen unde go
he cycle e e ed abo e [16,17]. As o he genes in ol ed in his p o-
cess, i is impo an o highligh hose belonging o he BNC syn hase
ope on (bcs), namely bcsA, bcsB, bcsC, and bcsD [12,13,17]. BcsA has a
ca aly ic ole in cellulose p oduc ion and i s ac i i y can be egula ed
h ough he cyclic di-GMP (di-guanosine monophospha e) messenge . I
is embedded in he inne memb ane as eigh ansmemb ane helices and
consis s o wo cy oplasma ic domains: a ca aly ic β-1,4-glycosyl-
ans e ase domain conse ed be ween ansmemb ane helices ou and
i e and a C- e minus con aining a PilZ domain. The binding o cyclic
di-GMP o BcsA occu s in i s PilZ domain and induces a con o ma ional
change ha allows UDP-Glc access o he ca aly ic si e. Once ac i a ed,
his ca aly ic domain p omo es he polyme iza ion o UDP-Glc mono-
me s in o β-1,4-glucan chains [14,17]. BcsB is a la ge pe iplasmic p o-
ein ancho ed o he inne memb ane h ough a single ansmemb ane
helix. This p o ein in e ac s wi h BcsA, being esponsible o he BcsA
s abiliza ion and enabling i s ca aly ic ac i i y. I is assumed ha BcsB
also has an impo an unc ion in he anspo a ion o he syn hesized
glucan chain h ough he pe iplasm in o he ou e memb ane [14,17].
BcsC is a β-ba el ype ou e memb ane po in p o ein. I is sugges ed
ha BcsC leads o he o ma ion o memb ane po es ha allow cellulose
sec e ion in o he ex acellula en i onmen . In pe iplasmic domain o
BcsC he e is a e a icopep ide epe i ion [13,14,17]. BcsD is a pe i-
plasmic p o ein ha assis s in he associa ion and c ys alliza ion p o-
cesses o he glucan chain. Mo eo e , he hie a chical cellulose assembly
p ocess is also la gely con olled by he BcsD-d i en a angemen o
linea e minal complex a ays and hei o ien a ion longi udinal o he
axis o he cell. I also p epa es he glucan chain o sec e ion h ough
BcsC p o ein; howe e , he mechanism o i s unc ion is no ully
desc ibed ye . Ne e heless, i is e iden ha his p o ein is essen ial o
he op imal p oduc ion o BNC [13,14,16,17]. The up egula ion o
ca boxyme hyl cellulase has been sugges ed as an addi ional ac o o
BNC enhanced p oduc ion. This enzyme ca alyses he hyd olysis o
endo-β-1,4-glycosidic bonds o cellulose chains. Howe e , i s ac i i y
has been co ela ed wi h highe p oduc ion o BNC due o i s po en ial as
cellulose e o co ec ion enzyme. This enzyme is exp essed by he
cmcAx gene [14]. O he p o eins wi h a hypo hesized ele an ole in
BNC p oduc ion a e ccpAx p o ein and ß-glucosidase. CcpAx p o ein
possibly assis s BNC p oduc ion du ing he c ys alliza ion phase. I
in e ac s wi h he BcsD subuni and is also able o acili a e
p o ein-p o ein in e ac ions du ing he assembly o he cellulose syn-
hase complex [12,14]. Finally, ß-glucosidase (exp essed by bglxAx
gene), is en isioned o modi y and a ec he deg ee o polyme iza ion o
he newly syn hesized glucan chains. Howe e , he de ails o i s ac ual
ole ha e no been un eiled ye [14,17]. Ini ially, sub- ib ils a e o med,
hen hey c ys allize and o ganize hemsel es o o m ib ils, which in
u n combine o o m cellulose nano- o mic o ib es, consis ing o abou
1,000 indi idual glucan chains [13,14,20].
Thus, BNC consis s o an ul a- hin 3D ne wo k de eloped and s a-
bilized h ough in e - and in amolecula hyd ogen bonds. The high
amoun o hyd ogen bonds endow he ma e ial wi h i s ema kable
wa e -holding capaci y (abou 200 imes i s d y weigh ) [14] and also
he o ma ion o i s hie a chical s uc u e. The nano ib ous s uc u e o
BNC is able o mimic he ib ous a chi ec u e o he ECM (e.g. collagen,
elas in and ib in ib es ha a e componen s o connec i e issues), and
i s esis ance, lexibili y, and po osi y a e impo an in he suppo o
issues ha unde go cons an s ess and de o ma ion like skin, muscle
and ca ilage, and he po osi y and pe meabili y ha allows di usion o
gases o nu ien s [13,14,16–18] [16,19].
The mo phology o BNC can a y depending on he cul u e me hods
used, anging om uni o m memb anes o sphe ical o i egula pelle -
shaped hyd ogels. The e a e wo main ypes o bac e ial cul u e used o
ob ain BNC: s a ic and agi a ed cul u e. Fig. 2 displays some examples o
BNC p oduced om di e en s ains, ob ained om s a ic and agi a ed
cul u es. This dis inc ion in luences no only he sup amolecula s uc-
u e o he ob ained p oduc bu also i s mechanical cha ac e is ics and
physical p ope ies [14]. Due o i s simplici y, s a ic cul u e ep esen s
he mos commonly used echnique o he p oduc ion o BNC as a la
memb ane wi h a homogeneous sup amolecula s uc u e [13,14,18,20,
21]. This app oach allows he use o con aine s o any shape, which in
u n, will dic a e he shape o he memb ane o med [17,18]. In his
echnique, BNC p oducing bac e ium a e incuba ed o 2 o 20 days a
empe a u es be ween 25 and 30 ◦C [13,14]. The mos commonly used
cul u e medium is he Hes in-Sch amm medium, which uses glucose as
he main ca bon sou ce, yeas ex ac as a sou ce o ni ogen and g ow h
ac o s, pep one as a ni ogen sou ce, and ci a e-phospha e bu e o
p e en pH educ ion caused by gluconic acid du ing he bac e ia ae -
obic g ow h [16,21]. I should be no ed ha he a ia ion o any o hese
pa ame e s a ec s he inal p oduc , making he incuba ion ime he
mos c i ical ac o . I is ele an o men ion ha he memb ane is
gene a ed a he ai -liquid in e ace, whe e he e is mo e oxygen
a ailable. As he memb ane p oduced on he medium g ows downwa ds
and en angles he bac e ia, i limi s he oxygen supply, esul ing in
educed oxygena ion and o e all lowe p oduc i i y. Incuba ion ime is
he main ac o ha go e ns he hickness o he BNC memb ane p o-
duced [13,14,16–18,20,22]. Howe e , his o ically, s a ic cul u e is
cha ac e ized as incompa ible wi h indus y. The mos common a gu-
men s a e he high cos s associa ed wi h cul u e medium and he
assu ance o asep ic condi ions in a la ge a ea. An es ablished s a egy o
educe cos s is he use o al e na i e cul u e media based on ag icul u al
and indus ial was es pa icula ly ich in ca bon sou ces, such as suga
cane p ocessing indus ies and ui juice p oduc ion plan s [14]. The
agi a ed o dynamic cul u e comp ises agi a ion o mixing o he cul u e
medium o enhance he dissol ed oxygen and imp o e he a ailabili y o
nu ien s concen a ion, consequen ly inc easing he a e o BNC
biosyn hesis [14,16–18,21]. The shape and size o BNC is go e ned by
he applied o a ional speed. I usually p esen s i sel wi h a sphe ical,
cocoon-shaped, pelle -shaped, o e en i egula clump-shaped
mo phology, he e o e i s applica ions a e gene ally di e en om he
memb anes ob ained h ough s a ic cul u e [13,17,18,22]. Fu he mo e,
BNC om dynamic cul u e possesses highe wa e abso p i i y and
highe suspension iscosi y. The dynamic cul u e inc eases he amoun
o dissol ed oxygen [21,22]. Fu he mo e, in dynamic cul u e, BNC
usually possesses lowe c ys allini y and in e io mechanical p ope ies
such as lowe Young’s modulus, due o he dec eased deg ee o
L. Mel o e al.
Applied Ma e ials Today 46 (2025) 102858
3
polyme iza ion and o ganiza ion o he BNC nano ib es [13,14,16,21].
Bio eac o s a e able o ensu e a sui able con ol o media low and
ae a ion which aids in he p ope g ow h o mic oo ganisms and animal
cells. I is hus expec ed ha hey should be able o o e come hose
p e iously iden i ied disad an ages. Howe e , despi e se e al ypes o
bio eac o s being es ed o he scale-up p oduc ion o BNC, he ideal
au oma ed p ocess o indus ial-scale p oduc ion o his ma e ial has
no ye been achie ed [13,19,20]. The e a e a se ies o bio eac o s ha
ha e been s udied in his p ocess, including he s i ed, ai li , mem-
b ane, and o a ing disc eac o s, as illus a ed in Fig. 3. The mos
appealing p ope y o s i ed- ype bio eac o s o he indus ial p o-
duc ion o BNC is hei high olume ic mass ans e coe icien o he
ans e o oxygen. Howe e , he agi a ion associa ed wi h his ype o
bio eac o can ha m he p oduc i i y o BNC by he same p inciples o
he agi a ed cul u e. In addi ion, his p ocess is ene gy-in ensi e when
compa ed o o he bio eac o s, especially ai li bio eac o s [17,24].
Ai li bio eac o s a e pa icula ly in e es ing due o hei simple design
and acile main enance. Besides, hey ha e p o ed o be an
ene gy-e icien me hod ha in ol es less shea s ess on he memb anes
han he one el in ypical agi a ed me hods. No mally, ai li p oduced
BNC bio eac o is cha ac e ized by ei he a ib ous o pelle shape, wi h
highe wa e -holding capaci y. I s mechanical p ope ies can be al e ed
by changing he numbe o sepa a ing pla es [14,17,18]. Memb ane
eac o s, on he o he hand, o en use oxygen-pe meable silicone
Fig. 2. Op ical images o BNC p oduced by i e s ains o K. xylinus, (a-e) in s a ic condi ion, and ( -j) in agi a ed condi ion. Rep oduced om Re . [23] wi h pe mission,
Copy igh 2018, Spinge Na u e.
Fig. 3. Schema ic ep esen a ion o bac e ial cellulose p oduc ion in (a) s a ic and agi a ed eac o s (b) o a ing disc eac o s (c) silicon memb ane eac o s (d) s i ed
ype eac o s (e) ai li eac o s, hei componen s and shape o BNC p oduced. Rep oduced om Re . [17] wi h pe mission, copy igh 2022, IPO Science.
L. Mel o e al.
Applied Ma e ials Today 46 (2025) 102858
4
memb anes so ha a BNC memb ane can be o med on i s su ace. The
deg ee o oughness o his memb ane di ec ly co ela es wi h he a e o
BNC ha can be p oduced. These bio eac o s a e cha ac e ized by hei
high oxygen pe meabili y and la ge su ace a ea bu hey a e associa ed
wi h high ope a ing cos s and di icul ies in he ha es ing o he BNC
[17,20]. A di e en op ion is he o a ing disc eac o s, which a e
designed so ha hal o he disc’s su ace is in con ac wi h he ai , while
he o he hal is subme ged in he cul u e medium. This pa icula
con igu a ion allows o be e access o he bac e ium a ached o he
disc o oxygen and nu ien s p esen in he eac o , which inc eases he
yield o he p ocess a low o a ion speeds. The p oduc ion a e can be
al e ed by changing ei he he o a ional speed o he discs o he dis-
ance be ween hem. Despi e his, i has been shown ha he yield o
BNC is no ha highe han he one ob ained om s a ic cul u e [17,20,
24]. Al hough all hese bio eac o s o e sligh ly imp o ed yields
compa ed o con en ional s a ic and agi a ed me hods [20]. One
possible explana ion o he absence o highe BNC yields h ough dy-
namic cul u e may be co ela ed o he shea s ess o dynamic cul u es
which is e lec ed by he p esence o a highe concen a ion o nega i e
cellulose p oducing mu an s [13,14,17,20–22].
2.2. Pu i ica ion
Ubiqui ously BNC is embedded wi h bac e ium cells and cul u e
medium con aining seconda y me aboli es [25]. Li ing bac e ium cells
and o he impu i ies ep esen po en ial sa e y haza ds and will impac
he quali y and cha ac e is ics o he BNC ib es. Thus, BNC mus be
submi ed o di e en pu i ica ion s eps. Typical pu i ica ion p ocedu es
a e desc ibed in Table 1 [26]. Pu e BNC displays imp o ed mechanical
s eng h, biocompa ibili y, and enhanced unc ional cha ac e is ics,
such as wa e -holding capaci y. In addi ion, i BNC con ains a low
hickness, i becomes mo e anspa en , becoming mo e adequa e o
op ics and elec onics applica ions [27]. Commonly, he pu i ica ion
p o ocols displayed in Table 1 a e su icien o mee biomedical appli-
ca ions equi emen s, such as physicochemical, cy o oxici y, hemo-
compa ibili y, and biocompa ibili y [28]. Nume ous indus ies a e
explo ing he po en iali ies o BNC, and as his ield o s udy de elops, so
do no el me hods o pu i ica ion and unc ionaliza ion.
As obse able in Table 1, all pu i ica ion me hodologies comp ise he
use o an alkali solu ion (NaOH o KOH). Thus, all pu i ica ion p ocesses
in ol e he me ce iza ion o BNC. Me ce iza ion will simul aneously
deg ade amo phous egions o cellulose and will con e cellulose I
polymo phs o cellulose II. Cellulose II polymo ph con ains one addi-
ional hyd ogen bond pe cellulose monome ; hus, i is a mo e he -
modynamically s able polymo ph. The e o e, pu i ied BNC exhibi s
enhanced p ope ies in compa ison o unpu i ied BNC [38].
2.3. P ope ies o biomedical applica ions
Conside ing he a ious applica ions in biosensing, immuno he apy,
d ug deli e y, issue enginee ing and egene a ion, implan s, and
medical de ices, i is o u mos signi icance ha he ma e ials po en ia e
a a ou able en i onmen o he g ow h and di e en ia ion o cells.
Non- oxici y, biocompa ibili y, mechanical, and physical equi emen s
a e also manda o y when classi ying a bioma e ial as ideal. Na u ally
occu ing polyme s, such as: chi osan, algina e, gela ine, s a ch, cellu-
lose, and silk ib oin (SF), p esen enhanced biocompa ibili y. I is hy-
po hesized ha hei simila i y wi h ECM p e en s immunological
eac ions and inhibi s ch onic in lamma o y esponse. Thei deg ada ion
wi hin he human body may o may no be desi able, depending on he
p oposed applica ion [39,40].
BNC is highly biocompa ible and has been es ed in animals and
humans as long- e m implan s o up o one yea . Fu he mo e, he
li e a u e suppo s his s a emen h ough es s pe o med wi h BNC-
based implan s ha showed no se e e signs o in lamma ion, no o -
ma ion o ib o ic capsule, no did i p esen oxici y acco ding o
gene ic and cellula assays [2]. This p o es ha BNC can be an excellen
ma e ial o wound d essing, ha d and so issue enginee ing (e.g. skin
egene a ion, a i icial du a ma e memb ane, acial ne e egene a ion,
p os he ic he nioplas y, cance diagnosis, d ug deli e y,
issue-enginee ed co nea s oma, and neu oendo ascula applica ions)
[40–42].
Rela ing o i s in i o deg ada ion, ha is, deg ada ion unde
Table 1
Pu i ica ion me hods applied o di e en bac e ia and he ca bon sou ce used
h oughou hei e men a ion.
Bac e ium Ca bon Sou ce Pu i ica ion Me hod Re
Bacillus sp. s ain SEE-
3Glucose
•Dis illed wa e (wash
and boil)
[25]
•0.1 M NaOH (3 h, 80
◦C)
•Dis illed wa e (un il
neu al pH)
Komaga aeibac e
eu opaeus SGP37 Glucose
•Tap wa e (wash)
[29]
•0.5 M NaOH (1 h, boil)
•Dis illed wa e (30
min, boil)
•Dis illed wa e (un il
neu al pH)
S a keya sp. s ain N1B Naph halene
•0.5 % aqueous KOH
solu ion [30]
•Wa e (un il neu al
pH)
Komaga aeibac e sp.
High uc ose co n
sy up (Hung aswee
F50)
•1 o 4 M NaOH
(depending on he
hickness, 10 o 30
imes) [31]
•Dis illed wa e (un il
neu al pH)
Komaga aeibac e
pas eu ianus ATCC
23760
Glucose
•Tap wa e (24 h, wash)
[32]
•0.1 % solu ion o
NaOH (15 min, 70 ◦C)
•Dis illed wa e (un il
neu al pH)
•S e ilized by Gamma
i adia ion (20 kGy)
Komaga aeibac e
hansenii
Glucose, manni ol,
uc ose, suc ose, and
glyce ol
•1 M KOH solu ion (48
h)
[33]•0.5 M HCl ba h (1 h)
•Dis illed wa e (un il
neu al pH)
Komaga aeibac e
suc o e men ans
DSM15973
Glucose, pu e
glyce ol, and c ude
glyce ol (20 %)
•0.1 M NaOH solu ion
(2 h, 80 ◦C) [34]
•Dis illed wa e (un il
neu al pH)
Komaga aeibac e
xylinus
ATCC 23770
Glucose
•0.5 % (w/ ) aqueous
NaOH solu ion (6 h, 80
◦C) [28]
•Deionized wa e (un il
neu al pH)
Komaga aeibac e
suc o e men ans
ATCC 700178
F uc ose
•0.5 M NaOH solu ion
(3 days, solu ion
eplaced wice a day) [35]
•Deionized wa e (un il
neu al pH)
Taonella mepensis Glucose
•Dis illed wa e (12 h,
wa e changed hou ly)
[36]
•1 % NaOH solu ion (1
h, 80 ◦C)
•Dis illed wa e (un il
neu al pH)
Komaga aeibac e
hansenii
ATCC 53582
Glucose
•2 % sodium dodecyl
sulpha e (SDS) solu ion
(magne ic s i e ,
o e nigh )
[37]
•Dis illed wa e (un il
SDS emo al)
•1 M NaOH solu ion (50
pm, 90 min, 60 ◦C)
•Dis illed wa e (un il
neu al pH)
L. Mel o e al.
Applied Ma e ials Today 46 (2025) 102858
5
physiological condi ions, BNC is known o be p incipally deg aded by
cellulase, an enzyme ha is no p oduced by he human body. So, in
p inciple, his is bene icial o long- e m implan s. Bu i also limi s i s
applica ions, o ins ance, o achie e a d ug deli e y sys em, BNC should
be deg aded wi hin a sho pe iod [2,40]. Fac o s a ec ing biodeg a-
da ion a e he mechanical s ess o bodily mo emen s o in lamma o y
cellula esponse, ha con ibu e o changes in c ys allini y and mo-
lecula weigh . In addi ion, se e al o he mechanisms ha con ibu e o
BNC deg ada ion ha e been iden i ied: hyd olysis, enzyma ic deg ada-
ion, oxida ion, and physical deg ada ion. The chemical s uc u e o
BNC is composed o linea glucose uni s, each wi h one p ima y hy-
d oxyl (OH) g oup and wo seconda y OH g oups. These ac ing si es
o m glycosides ha can be chemically a acked by body luids con-
s i uen s o ming oligome s, and consequen ly monome s. Du ing hy-
d olysis, he bioma e ial abso bs he body luids, leading o swelling and
deg ada ion. Enzyma ic deg ada ion occu s due o he p esence o
endogenous hyd olase enzymes p esen in plasma and in e s i ium ha
accele a e he hyd olysis o he glycosidic linkages. Oxida i e deg a-
da ion occu s as a esul o hyd ogen emo al om he polyme chains
by oxidan s p oduced by issues. Physical and chemical scission o bonds
in he polyme chain can be due o swelling and wea ing, which accel-
e a e he damaging o he amo phous egion by en i onmen al s ess
[40].
I desi ed, a bioma e ial can be ailo ed o become biodeg adable
h ough modi ica ion wi h me al NPs o bioac i e molecules [40].
Conside ing he ib ous nanosized 3D ne wo k, high OH con en , and
wa e e en ion capaci y, i is expec ed ha BNC can e ain conside able
concen a ions o d ugs, ei he small (e.g., diclo enac, oc enidine, and
lidocaine) o la ge molecules (polyme ic d ugs, pep ides, o p o eins)
ele an o d ug deli e y. Speci ic applica ions include de mal/-
ansde mal, o al, and den al adminis a ions [2]. A d ug-loaded BNC
o den al he apies was epo ed by Weyell and co-wo ke s [43] and
demons a ed slow pa ial deg adabili y unde physiological condi ions
in he mou h, showing po en ial as an inno a i e wound d essing and
d ug deli e y sys ems. A hyd oly ic deg adable BNC-based hyd ogel
sca old inco po a ing calcium phospha e o bone issue egene a ion
was de eloped by Basu e al. [44].
The mechanical s eng h o BNC is equi alen o syn he ic polyme s,
esul ing om he complex in e laced nano ib es ha de elop in o a
po ous ma ix. The a angemen o BNC mic o ilamen s wi hin he 3D
nano ib illa ne wo k gi es ise o a hin, ex emely luid, and hyd o-
philic s uc u e. In addi ion, he c ucial mechanical s eng h o BNC is
a ibu able o i s linea cellulose chains and high cohesion be ween
mac omolecules [45].
The Young’s modulus and s i ness a e signi ican ly highe in d y
samples compa ed o hyd a ed BNC [46]. D ying a a mosphe ic p es-
su e and empe a u e leads o a highe densi y o cellulose ib ils due o
i s smalle olume ( hickness), e lec ed in less po osi y, mo e homo-
geneous s uc u e, highe quan i y and s onge hyd ogen bonds and
highe c ys allini y, ul ima ely imp o ing s eng h and Young’s
modulus. The eeze-d ying me hod main ains he ca i ies be ween he
laye ed s uc u e leading o lowe c ys allini y and less quan i y and
weake hyd ogen bonds be ween he cellulose molecules, impac ing
Young’s modulus [47]. I on he one hand, he ypical beha iou o
b i le ma e ials was e idenced by o en-d ied BNC, eeze-d ied BNC on
he o he hand, exhibi ed low Young’s modulus and highe elonga ion
be o e ac u e [48]. A summa y o he di e en alues ob ained in he
li e a u e is p esen ed in Table 2.
3. Bioac i e subs ances and an imic obial agen s and hei
applica ions
Bioac i e subs ances p omo e issue g ow h by in e ac ing wi h and
in eg a ing in o damaged issue, hus exhibi ing biological ac i i y. The
inco po a ion o bioac i e molecules wi hin BNC, such as na u al poly-
me s (e.g., p o eins: collagen, silk, gela ine, and ib in; polysaccha ides:
s a ch, chi osan, cellulose, and algina e; polynucleo ides: DNA, RNA)
and ino ganic compounds (e.g., me al NPs: Cu, Ag, Ti, and Au; mine als:
hyd oxyapa i e, calcium phospha e, and silica (Si)) ins il e y desi able
p ope ies o he polyme ic sca old. These may include s uc u al,
egene a i e, and/o an imic obial p ope ies, o ac as cance ea -
men agen s. Some o hese p ope ies can be achie ed h ough he
applica ion o ex e nal s imuli like adia ion and ul asound. In e nal
s imuli include pH, enzymes, and edox [54,55]. Hyalu onic acid is o en
used in ligamen issue enginee ing, os eochond al de ec s, and ascula
g a s. Chi osan applicabili y can be ound in bone o ma ion and
ca ilage issue enginee ing. P o eins like collagen o gela ine a e la gely
used in d ug deli e y and issue enginee ing sca olds, and silk can be
Table 2
Mechanical p ope ies o BNC p oduced unde s a ic mode, acco ding o he physical s a e o he sample.
Sample Size
(cm)
Thickness
(
μ
m)
Load
(kN)
S ain a e (mm min
-
1
)
Young’s modulus
(GPa)
Tensile s eng h
(MPa)
Elonga ion a b eak
(%)
Re
Vacuum d y n.d. n.d. n.d. n.d. 5.13 n.d. n.d. [47]
D y n.d. n.d. n.d. n.d. 13.02 n.d. n.d. [47]
O en d ied 2.0 ×
6.0
22.7 1.0 5.0 5.6±0.76 37.2±3.3 2.20±0.06 [48]
D y (25 ◦C) 1.5 ×10 300–500 n.d. 10 n.d. 17.38±7.23 6.63±1.55 [49]
D y (25 ◦C) -
ehyd a ed
1.5 ×10 300–500 n.d. 10 n.d. 17.40±3.68 11.04±3.68 [49]
D y (40 ◦C) 6.5 ×2 2670±670 10 2–4 0.139±0.022 10.34±3.69 7.94±3.39 [46]
D y (80 ◦C) 1.5 ×10 300–500 n.d. 10 n.d. 12.94±1.80 6.40±1.61 [49]
D y (80 ◦C) -
ehyd a ed
1.5 ×10 300–500 n.d. 10 n.d. 8.49±5.47 11.08±2.75 [49]
Hyd a ed 0.6 ×
3.5
800 0.005 10 0.0056±0.0030 n.d. n.d. [50]
Hyd a ed 0.6 ×
3.5
800 0.005 10 0.0011±0.0004 n.d. n.d. [50]
Hyd a ed 1.0 ×10 300–500 n.d. n.d. 9.14 112.4 0.6 [51]
Hyd a ed 1.5 ×10 300–500 n.d. 10 n.d. 1.18±1.01 12.80±2.17 [49]
Mois (1.82 %) 1.5 ×10 280 n.d. 4.8 1.044 20.76 2.28 [52]
Mois 6.5 ×
2.0
2670±670 10 2–4 0.02638±15.22 4.64±0.32 21.74±6.25 [46]
F eeze d ied 2.0 ×
6.0
34.9 1.0 5.0 0.18±0.06 7.2±1.1 4.92±1.2 [48]
F eeze d ied 6.0 ×
1.0
n.d. n.d. n.d. 2.68±0.73 n.d. n.d. [53]
n.d. – no de ined
L. Mel o e al.
Applied Ma e ials Today 46 (2025) 102858
6
ound in d ug deli e y applica ions. Biopolyme s, o example PLA o
poly-(γ-glu amic acid) (PGA), a e ound in implan and su u e [39]. A
mo e ho ough desc ip ion and examples o he applicabili y o such
bioac i e molecules wi hin he BNC ma ix a e desc ibed below.
3.1. Wound healing and wound d essing
Skin diso de s, including wounds, can p o oundly a ec he well-
being, esul ing in a no iceable dec ease in o e all quali y o li e [56].
Despi e he a ailabili y o se e al he apeu ic s a egies, he ongoing
demand o de eloping and enhancing new wound healing me hods
emains c ucial [57,58]. As pa o he ea men o skin wounds, he
applica ion o wound d essings plays a pi o al ole. These wound
d essings a e designed o os e an op imal healing en i onmen ,
enhance pa ien com o , and o e mechanical p ope ies ha simpli y
hei applica ion o enhanced e icacy [59]. To es ablish an op imal
en i onmen o wound healing, i is equi ed o uphold mois u e
e en ion, imp o e exuda e abso p ion, acili a e oxygen exchange, and
p omo e e-epi helializa ion, minimizing wound exposu e du a ion and
p e en ing in ec ions. These essen ial elemen s con ibu e o an e ec i e
and accele a ed wound healing p ocess [57]. Being a biopolyme
endowed wi h ema kable cha ac e is ics, BNC ul ils he undamen al
equi emen s o p omo ing an excep ional and accele a ed wound
healing p ocess, ei he h ough i s inco po a ion as a skin subs i u e o
di ec applica ion as a wound d essing (see Fig. 4) [60,61].
Ex ensi e e idence indica es ha BNC exhibi s supe io p ope ies o
adi ional gauze-based wound d essings o syn he ic p oduc s, making
i an ou s anding choice o wound healing applica ions [26]. The
biocompa ibili y o BNC is a ibu ed o i s s uc u al simila i y o
collagen, which acili a es bo h epi helializa ion and angiogenesis. This
ema kable p ope y enables i s e ec i e applica ion in ea ing di e se
wound ypes, including ulce s, bu ns, skin g a s, lace a ions, and skin
subs i u es. I s wide- anging e icacy in managing di e se ypes o
wounds u he accen ua es i s p omising p ospec s o applica ions in
wound healing [20,62]. Fu he mo e, high wa e e en ion enhances
mois u e e en ion and con ibu es o minimizing he adhe ence o he
wound d essing o he a ec ed a ea, pa icula ly in bu n cases [63].
Consequen ly, emo ing he wound d essing conside ably educes pain
and discom o , ensu ing pa ien s a mo e com o able and less dis-
essing wound healing expe ience [64]. The ema kable lexibili y o
BNC wound d essings allows o ull adap a ion and co e age o he
a ec ed a ea, making hem a highly e sa ile and op imal choice o
ea ing a ious wound ypes, including ch onic, acu e, and bu ns. This
adap abili y p o ides consis en wound suppo h oughou he healing
p ocess, leading o be e pa ien ou comes and enhanced healing po-
en ial [61]. Due o i s excep ional in insic p ope ies, his biopolyme
has led o he comme cializa ion o a ious wound d essings. These
wound d essings show excep ional e ec i eness, leading o posi i e and
no able ou comes [24]. Table 3 p o ides examples o comme cialized
BNC-based p oduc s speci ically de eloped o wound d essing and
wound healing.
Modi ica ion o BNC wi h ac i e compounds (e.g., an ibio ics, an i-
in lamma o y d ugs, pep ides, p o eins, and ino ganic NPs) acili a es
he healing p ocess by quickly enhancing i , hus minimizing exposu e o
he in lamma o y phase [57,71]. The BNC s uc u e’s abundance o OH
g oups p o ide excep ional capaci y o modi ica ions. This in insic
e sa ili y empowe s he p oduc ion o BNC as a e sa ile ma e ial wi h
po en ial applica ion in se e al biomedical ields, including wound
healing, d ug deli e y, and issue enginee ing [13,72–74].
3.1.1. Ino ganic compounds in wound d essings
The la ge su ace- o- olume a io o ino ganic NPs, oge he wi h
hei hea esis ance and long- e m s abili y, a e in e es ing and e ec i e
cha ac e is ics ha demons a e he apeu ic po en ial agains in-
ec ions. This is especially impo an conside ing he subs an ial in-
c ease in an imic obial esis ance. In ac , mul id ug- esis an pa hogens
a e esponsible o he dea h o 700,000 people yea ly, acco ding o he
Wo ld Heal h O ganiza ion (WHO) [75]. Me al NPs can imp o e he
an ibac e ial p ope ies o wound d essing ma e ials by killing he
bac e ia, he eby con olling he in ec ions and p omo ing wound
healing p ocesses. They can s imula e he cellula and molecula p ocess
o main ain he wound mic oen i onmen such ha he healing p ocess
is acili a ed by inducing an ibac e ial, an imic obial,
an i-in lamma o y, and angiogenic e ec s [76]. Se e al a emp s we e
made o imp o e he an ibac e ial p ope ies o wound d essing ma e-
ials and enhance wound healing by inco po a ing me al NPs such as
AgNPs, CuNPs, zinc oxide (ZnONPs), and magnesium oxide NPs
(MgONPs) [77–81].
E ec i e agains bac e ia, ungi, and i uses, he mechanism o ac-
ion o AgNPs can be based on Ag
+
ion elease ha in e ac s wi h he cell
memb ane o bac e ia leading o cell dea h. In addi ion, hese ions
gene a e eac i e oxygen species (ROS), hus a ge ing he bac e ial cell
en elope causing DNA damage [75]. The shape and size o AgNPs a e
o he ac o s ha in luence hei an ibac e ial e ec i eness. This can be
con olled wi h he syn hesis me hodology, and he applica ion ields
a y [82]. The use o AgNPs in wound d essings is known o p omo e
wound healing due o dec eased in lamma o y esponse. Howe e , he e
is e idence o signi ican ansde mal pene a ion o AgNPs in o
P e en s he en y o mic oo ganisms
Flexible and non-ab asi e s uc u e
P omo ion o oxygen anspo
T apping o ac i e agen s
High wa e con en
Biocompa ible
Biodeg adable
High pu i y
High po osi y
Hypoalle genic
Capabili y o con olled elease o d ugs
Reduced loss o elec oly es and p o eins
P ese es he equi ed wound mois u e le el
So ness
T anspa ency
Cell adhesion
Wa e apou pe meabili y
P omo es issue g anula ion
Con o mi y o he speci ic wound a ea
Easy emo al, educing pain caused on use
Accele a ion o he g anula ion p ocess
P e en s dehyd a ion o he wound
Excellen mechanical p ope ies
Reduced wound adhesion
Abili y o abso b exuda e
Non-ca cinogenic
Easily modi ied
Inju y
BNC
Fig. 4. P ope ies ha classi y BNC as an ideal sca old o wound healing.
L. Mel o e al.
Applied Ma e ials Today 46 (2025) 102858
7
capilla ies du ing he use o su gical d essings. In ac , dose-dependen
his opa hological abno mali ies in he skin ha e been epo ed [83].
Despi e some nega i e iews and ac s o e he use o AgNPs, ilms o
AgNws wi h BNC p epa ed by Wan e al. (2020) we e able o p o ide
biophysical cues ha acili a ed cell p oli e a ion and p og essed he
wound- epai ing p ocess, along wi h he expec ed an ibac e ial e ec
and excellen s e chabili y and lexibili y, as illus a ed in Fig. 5 [84].
Ag, in he o m o nanop isms (AgNP s), we e p epa ed using a
ligh -induced ans o ma ion eac ion wi h ligh -emi ing diodes (LED)
o educe hei inhe en oxici y o mammalian cells. Cell iabili y o he
ilms using human de mal ib oblas s (HDFa) was in he ange o
68.86–124.19 % o di ec cy o oxici y es and 89–118 % o indi ec
cy o oxici y es , indica ing ha he ilms can be conside ed non- oxic.
The composi e also demons a ed good an ibac e ial ac i i y agains
Esche ichia coli, Pseudomonas ae uginosa, En e ococcus aecalis, and
S aphylococcus au eus [85]. Xie and co-wo ke s (2019) used polydop-
amine (PDA) as a educing agen o p oduce AgNPs o educe hei
oxici y and enhance he biological compa ibili y o he BNC composi es.
The chela ion be ween PDA and Ag and he 3D ne wo k o BNC plays a
c ucial ole in he s able elease o Ag
+
ions. The samples showed good
Table 3
Examples o comme cialized BNC-based p oduc s speci ically de eloped o wound d essing and wound healing.
Comme cial name (p oducing
bac e ia)
Company/dis ibu o Ac i e compound P ope ies Wound ype Re
Bio ill® (Ace obac e xylinum) BioFill P odu os Bioe ecnologicos,
Cu i iba, B azil
None Reduced isk o in ec ion
Facili a es he healing p ocess
Pain elie
Wa e apo pe meabili y
Du able
Bu ns
Ab asions
Ulce s
[24,
65]
Biop ocess® (n.d.) BioFill P odu os Bioe ecnologicos,
Cu i iba, B azil
None Accele a ion o he healing
p ocess
Bu ns
Ab asions
Ulce s
[66]
De ma ill
TM
(Ace obac e
xylinum)
Cellulose Solu ions l d, Geo gia, USA None Pain elie
Accele a ion o he healing
p ocess
Bu ns
Ab asions
Lace a ions
Ulce s
[65]
Nanoskin® (Komaga aeibac e
xylinum)
Inno a ec None Non- oxic
Biocompa ible
Hypoalle genic
Main enance o a humid
en i onmen
Facili a es oxygen exchange
P omo es g anula ion and
epi ilisa ion
Ulce s
Skin cance s
Ampu a ions
[57,
67]
Memb acel® (Komaga aeibac e
xylinum)
Vuelo Pha ma, Cu i iba, B azil None Rapid skin egene a ion
Main enance o wound mois u e
Pain elie
Facili a es oxygen exchange
Ulce s
Bu ns
Lace a ions
[57]
CelMa ®
(n.d.)
Bowil Bio ech Sp., Władysławowo,
Poland
None Hypoalle genic
Non- oxic
P omo es cell egene a ion
P o ec s agains en y o mic o-
o ganisms
Bu n wounds [57]
EpiP o ec ®2117 (n.d.) S2Medical AB, Link¨
oping, Sweden None Pe meable o wa e apou and
ai
Impe meable o liquids
Bac e ial ba ie
Facili a es e apo a ion o
exuda e
Bu n wounds [68]
Bionex ® (Komaga aeibac e
xylinum)
Bionex P odu os Bio ecnol´
ogicos,
Cu i iba, PR B azil
None Pain elie
Reduced isk o in ec ion
Facili a es he healing p ocess
Ulce s
Bu ns
Lace a ions
[69]
P ima Cell
TM
(n.d.) Xylos Co po a ion, US None Pain elie
Facili a es he healing p ocess
Ulce s [65]
Nanode m
TM
(n.d.) Axcelon Biopolyme s Co po a ion,
On a io, Canada
None P e en s in ec ions
Pain elie
Reduces bac e ial p oli e a ion
Minimises hyd oelec oly ic loss
In ec ed wounds [57]
Nanode m
TM
Ag (n.d.) Axcelon Biopolyme s Co po a ion,
Mon eal, Canada
Ag Con olled elease o Ag
Sus ained an imic obial ac i i y
Flexible
Economical
In ec ed wounds [26,
57]
Sup aso b X® (n.d.) Lohmann & Rausche In e na ional,
Neuwied, Ge many
Polyhexame hylene biguanide
(PHMB)
Main enance o wound mois u e
High exuda e abso p ion
Com o able
Reduced isk o in ec ion
An imic obial ac i i y
Ulce s Bu ns
Pos -su gical
wounds
Skin g a s
Ab asions
Lace a ions
[26]
Xcell® (n.d.) Xylos Co po a ion, US PHMB Pain elie
Accele a es he g anula ion
p ocess
An imic obial ac i i y
Main enance o wound mois u e
Ulce s [70]
n.d. – no de ined
L. Mel o e al.
Applied Ma e ials Today 46 (2025) 102858
8
cy ocompa ibili y agains no mal human de mal ib oblas s, demon-
s a ing ha PDA suppo ed cell g ow h and eased he s able elease o
Ag
+
[86]. The educing p ope ies o he ca echol g oups o PDA we e
simila ly explo ed by Jiji e al. (2020). Cell iabili y was es ed using
NIH/3T3 cells and ound ha he BNC/PDA/AgNPs composi e showed
cell iabili y, a non- oxic na u e, and imp o ed cell p oli e a ion. A
syne gis ic e ec o AgNPs and PDA has assis ed in p omo ing ib oblas
p oli e a ion, g anula ion issue o ma ion, angiogenesis, and
e-epi helializa ion. AgNPs elimina e he in ec ion om pa hogens and
lead o an e ec i e healing p ocess. The an imic obial ac i i y
Fig. 5. (a) Digi al images showing he obus ness and excellen s e chabili y and lexibili y o he BNC/AgNws d essings, (b) wa e apou pe meabili y (WVP), (c)
wa e up ake, (d) wa e e en ion a e, o BNC/AgNws d essings, (e) Scanning Elec on Mic oscopy (SEM) images o bac e ia on BNC/Ag d essings (scale ba s: 1
μ
m),
( ) elease p o iles o Ag
+
om BNC/AgNws d essings (*p <0.05, n =4, NS means insigni ican , p >0.05), (g) wound healing a e (WHR) a e in i o animal
expe imen (h) iabili y o NIH/3T3 cells cul u ed on BNC/AgNws d essings. Adap ed om Re . [84] wi h pe mission, Copy igh 2020, Else ie .
L. Mel o e al.
Applied Ma e ials Today 46 (2025) 102858
9
(72.4±3.1 %) on human ke a inocy es (HaCaT). Thus, his composi e
p esen s p omising a ibu es o po en ial applica ion in diabe ic o
bu n wound d essings due o i s ul a iole (UV) p o ec ion,
non-cy o oxici y, anspa ency, and an i ungal ac i i y [141]. Table 5
summa izes examples o BNC unc ionalized wi h o ganic compounds
o applica ion in d essings and wound healing.
3.1.3. Combina ion o o ganic and ino ganic compounds in wound
d essings
Combining o ganic and ino ganic compounds holds impo an po-
en ial o p oducing nanocomposi es o wound healing. Thi d-deg ee
bu ns can be ea ed by applying a bioadhesi e nanocomposi e
composed o BNC, PDA, and AgNPs. BNC se es as an excep ional ECM
and a sca old o in si u inco po a ion o AgNPs. Applying PDA coa ing
acili a es he educ ion o sil e ni a e, leading o he o ma ion o
AgNPs. Mo eo e , he dis inc i e adhesi e p ope ies o PDA and i s
su ace unc ionaliza ion capabili ies con ibu e o i s in iguing and
e sa ile ole in wound d essing ma e ials [87]. Ch onic wounds a e
di icul o ea due o he ele a ed numbe o mic oo ganisms, and o
he signi ican inc ease in an ibio ic esis ance. Ag is a b oad-spec um
na u al an imic obial ha has a ac ed a en ion in wound manage-
men . The inco po a ion o AgNPs on o BNC showed conside able e i-
cacy agains he wound-in ec ing pa hogenic mic obes like S. au eus, P.
ae uginosa, and Candida au is, acco ding o a wo k p esen ed by Gup a
and co-wo ke s (2020). In a de elopmen o hei p e ious wo k [127],
he complex cu cumin:hyd oxyp opyl-β-cyclodex in was in his case
used as educing agen o AgNO
3
o p epa e AgNPs. The loading o bo h
AgNPs and cu cumin p o ed o be cy ocompa ible demons a ing po-
en ial o be used in wound d essing applica ions [142].
Simila ly, Zhao e al. (2022) ha e p oduced ilms using BNC, AgNPs,
PDA, and chi osan o imp o e he an ibac e ial ac ion and p o ec
wounds om in ec ions caused by bac e ia. A syne gis ic e ec was
obse ed wi h imp o ed an ibac e ial ac ion agains S. au eus and
P. ae uginosa. The ensile s eng h o he ilm inc eased due o inc ease o
hyd ogen bonds by he p esence o chi osan. The ilms ha we e es ed
exhibi ed he absence o cy o oxici y using NIH/3T3 cells. Howe e , he
p esence o AgNPs showed a sligh inhibi ion o NIH/3T3 cell g ow h,
below 5 % [109].
The signi ican inc ease in an ibio ic esis ance poses a majo global
heal h challenge [143]. A mul i unc ional nanocomposi e based on BNC,
gela ine (1 w .%), and selenium NPs (SeNPs) (30 mmol L
-1
) has also been
de eloped o add ess he an ibio ic esis ance issue. SeNPs can ecognize
and dis inguish be ween bac e ia and heal hy mammalian cells in
addi ion o being non- oxic. In a wo k by Mao and co-wo ke s (2021),
SeNPs a e used along wi h gela ine o unc ionalize BNC hyd ogel. The
inco po a ion o SeNPs has shown an ibac e ial e ec . The p esence o
SeNPs has acili a ed ROS gene a ion and induced oxida i e s ess o
des oy he bac e ia. The coa ing wi h gela ine educed he po osi y o
he hyd ogel which helps in he con ol elease o SeNPs. Cy o oxici y
was es ed using NIH/3T3 cells, and he samples p epa ed using con-
cen a ions o H
2
SeO
3
below 0.06 mol L
−1
we e ound o be non- oxic.
These accele a ed he wound healing p ocess by p omo ing g anula-
ion issue o ma ion, collagen deposi ion, and angiogenesis, by
educing he in lamma o y esponse. The mechanical esul s sugges ed
ha he ensile s eng h and Young´s modulus imp o ed wi h he addi-
ion o gel due o he o ma ion o hyd ogen bonds and e en mo e wi h
he addi ion o an op imized amoun o SeNPs. This composi e mee s a
wide ange o equi emen s o wound d essing applica ions. Biocom-
pa ibili y, biodeg adabili y, hemocompa ibili y, excellen mechanical
p ope ies, high swelling capaci y, lexibili y, ema kable wound heal-
ing, as well as an ioxidan , an i-in lamma o y, and an imic obial ac i -
i ies, a e among he achie ed ea u es. A syne gis ic e ec be ween
gela ine and SeNPs has been es ablished [144].
Schizophyllan (SPG) is an ex acellula polysaccha ide ob ained
om ungus Schizophyllum commune wi h good an imic obial, an ioxi-
dan , an i-w inkle, and mois u izing e ec s and can also p omo e cell
p oli e a ion and egene a ion. Hence, aminoalkylsilane g oups and SPG
we e simul aneously used by Hamedi e al. (2021) o modi y he BNC
hyd ogel. The ea e , ZnONPs we e loaded on unc ionalized BNC. The
ob ained samples we e es ed agains E. coli and S. au eus and showed
inhibi ion e ec . Supp ession o he espi a o y chain enzymes by he
eleased Zn
2+
ions and addi ionally gene a ion o a huge amoun o ROS
can be he ac o s leading o he dea h o bac e ia. Conside ing he cell
iabili y o mo e han 70 % om cy o oxic es s, i can be unde s ood
ha he samples a e non- oxic o ib oblas s and he p esence o SPG can
lead o cell p oli e a ion and hus p omo e a smoo h wound healing
p ocess. The swelling beha iou o he samples wi h SPG imp o ed in
compa ison wi h BNC due o he hyd ophilic na u e o SPG and he
o ma ion o hyd ogen bonds wi h wa e molecules. Howe e , he
addi ion o ZnONPs educed he swelling a io due o he chela ion o
ZnONPs wi h he hyd ophilic si es o he polyme . Ne e heless, he
swelling a io emained highe han ha o he p is ine BNC. The
hyd ogen bonding be ween he OH g oups in he polyme and oxygen
bonds in he NPs esul ed in imp o ed ensile s eng h o he hyd ogel
[110].
Nanozymes a e able o egula e ROS le els o p o ide good an i-
bac e ial e ec . Hence, a s udy in es iga ing he e ec s o enzyme-based
wound d essing was conduc ed by Zhang e al (2022). In his s udy, a
nanocomposi e was de eloped using polyp opylene (PP) en eloped BNC
and hollow mesopo ous nanoca alys i on (Fe@HCMS) oge he wi h
glucose oxidase (GluO
x
). The an ibac e ial esul s indica ed ha BNC/
PP/Fe@HCMS/GluO
x
has good an ibac e ial ac i i y agains S. au eus
and E. coli. No iceable hemocompa ibili y wi h abbi ed blood cells
wi h he hemolysis a io below 1.5 %. The composi e was able o educe
he bleeding. The cell iabili y was 81 %. The o ma ion o new epi-
he mal laye s in combina ion wi h a good an ibac e ial e ec due o he
con e sion o glucose o a hyd oxyl adical (•OH) a he wound si es has
p omo ed wound healing o BNC/PP/Fe@HCMS/GluO
x
[116]. Hyd o-
gels consis ing o algina e, casein, BNC and Fe
3
O
4
NPs syn hesized by
co-p ecipi a ion we e p epa ed by Pa wa e al. (2020). The FeO
3
NPs
p omo ed a ough su ace necessa y o cell adhesion. The swelling
p ope ies o he hyd ogel imp o ed wi h he addi ion o bo h BNC and
Fe
3
O
4
NPs a la ge concen a ions. This can be a ibu ed o he inc ease
o i egula po ous size ha acili a ed mo e wa e ake-up. The an i-
bac e ial ac i i y was obse ed in all he hyd ogels and he inhibi ion
zone is highe agains S. au eus in compa ison wi h E. coli. Cell iabili y
o e 80 % was ound o all samples when es ed agains mu ine em-
b yonic ib oblas s [111].
In a di e en s udy, Luo and co-wo ke s (2020) modi ied BNC wi h
maleic anhyd ide. The ea e i was used o syn hesize sphe ical-shaped
NPs, since maleic anhyd ide enhances he bonding be ween he BNC and
he ZnNPs. The an ibac e ial p ope ies o he sample we e g ea e
agains S. au eus in compa ison wi h E. coli. The inco po a ion o ZnO
has main ained adequa e po e size and po osi y o he sample and
enhanced he wa e apo pe meabili y. The wa e apo ansmission
a e was obse ed o be 2856.60 g m
-2
and his alue is well wi hin he
limi o a desi ed alue (2500–3000 g m
-2
) o a wound d essing ma e-
ial. The cy o oxici y esul s ha e sugges ed ha a lowe concen a ions
(5 w .%) o ZnO, i was non- oxic o he mouse ib oblas cells. No
i i a ion on he skin o 5 w .% ZnONPs bu a 20 w .% ZnONPs
exhibi ed i i a ion and c us o ma ion. The sample also showed a good
wound healing p ocess due o he imp o ed e-epi helializa ion and
wound con ac ion. The ensile s eng h and Young´s modulus inc eased
wi h he addi ion o ZnONPs and he p ope ies indica e ha he
memb anes we e lexible, com o able, and esilien [115]. Any po en-
ial cy o oxic e ec o ZnONPs seems o ha e been o e come by unc-
ionalizing BNC wi h bo ulin diphospha e (BDP). An an ioxidan ,
an i-bu n, and an i umo compound ha , acco ding o Melniko a
e al. (2021), when in combina ion wi h ZnO demons a ed good alues
o cell a ailabili y (L929 mouse ib oblas s) and no signi ican di e ence
compa ed o p is ine BNC. Fu he mo e, i p esen ed good wound
healing p ope ies due egula ion o oxygena ion and mic oci cula ion,
L. Mel o e al.
Applied Ma e ials Today 46 (2025) 102858
16
Table 5
Examples o BNC unc ionalized wi h o ganic compounds o wound d essings and wound healing applica ions.
Applica ion Compounds Inco po a ion me hod P ope ies Re .
NPs o complex (size; shape) D ugs o o he
componen s
Wound healing Comme cial
α
-13
′
-COOH (n.d.) n.d. Ex si u – imp egna ion
Con olled elease o
α
-13
′
-COOH (24 h)
[120]
P ese a ion o a mois en i onmen
Enhancemen o comp ession s eng h
Collagen deposi ion (10 days)
Facili a es de mal hickness (~150 %)
Wound healing Comme cial Collagen/chi osan (n.d.) n.d. Ex si u – imme sion
High swelling capaci y: 166 %, 15 min
[122]
Tensile s eng h: 128.6±4.7 kPa
Young’s modulus: 382.3±6.7 kPa
Elonga ion a es: 4.8±1.1 %
Densi y: 5.9±0.3 mg cm
-3
An imic obial ac i i y:
E. coli (97.6 %)
S. au eus (98.3 %)
K. xylinus (97.4 %)
Non-cy o oxic
Hemos a ic
Deg adable: 86 %, 30 days
P omo es ib oblas p oduc ion and
educes in lamma o y esponse (in i o)
Wound healing Comme cial Hyalu onic acid (n.d.) n.d. Ex si u – imp egna ion
Tensile s eng h: ~0.54–0.9 MPa
[130]
Young’s modulus: ~1.25–2 MPa
S ain a b eak: ~30–45 %
High wa e e en ion capaci y
Non-cy o oxic: Cell iabili y (L929) >80
%
Wound healing Ke a in (n.d., 83.73 nm) n.d.
In si u: 3 % w/ ke a in
unde s a ic
e men a ion
In si u: non-cy o oxic (L929 ib oblas s
and HS2 ke a inocy es)
[133]
Ex si u –imp egna ion Ex si u: non-cy o oxic. Cell iabili y
(L929, excep o he 1:1 a io BNC:
ke a in; HS2 ke a inocy es)
Waound healing Comme cial Gela ine (n.d.) n.d. Ex si u – imme sion
S ess-s ain: ~200–800 MPa
[135]
Tensile s eng h: ~110–785 MPa
Young’s modulus: ~20–35 GPa)
T anspa en : >75 % ansmi ance
Mode a e we abili y: <90º
Non-cy o oxic: Cell iabili y (NIH/3T3)
>87 %, 5 days
Hemocompa ible: ~0.3–1.1 %
Good wound healing abili y
Inhibi s sca o ma ion
P omo es angiogenesis
Biocompa ible (TNF-
α
, IL-6, and IL-1β)
Wound d essing Cu cumin (n.d.) n.d. Ex si u – imme sion
Mode a e wa e abso p ion capaci y:
~190–300 %
[126]
Sus ained elease (ini ial bu s in he
i s 8 h, maximum o 64 %)
An imic obial ac i i y (Log educ ion):
S. au eus (1.42–2.63)
E. coli (0.36–0.91)
Wound d essing Cu cumin (n.d.)
hyd oxyp opyl-
β-cyclodex in as
encapsula ing agen
Ex si u – imme sion
Humidi y abso p ion: 97.63±0.057 %
[127]
T anspa ency: 66.13±2.36 %
ansmi ance
Wa e apou pe meabili y:
2258.53–2460.63 g m
-2
/24 h
Biocompa ible
Hemocompa ible: <0.20 % (in i o)
Non-cy o oxic: Cell iabili y (A549) 60
%
Con olled elease o cu cumin: ~77 %
a 6 h and 82 % a 48 h
An imic obial ac i i y:
S. au eus (11.08±0.90 mm)
An ioxidan ac i i y: IC50=1087.49
±6.47 µg mL
-1
Wound d essing Chi osan/ cip o loxacin (n.d.) n.d. Ex si u – imme sion
Wa e apo pe meable: 12.34±0.10 g
m
-2
h
[135]
Sus ained an ibio ic elease: ~74 %, 6 h
An imic obial ac i i y: P. ae uginosa (4.3
mm)
S. au eus (5.5 mm)
(con inued on nex page)
L. Mel o e al.
Applied Ma e ials Today 46 (2025) 102858
17
Table 5 (con inued)
Applica ion Compounds Inco po a ion me hod P ope ies Re .
NPs o complex (size; shape) D ugs o o he
componen s
Non-cy o oxic: Cell iabili y (GM07492)
84.2 %
Wound d essing Chi osan NPs (n.d., 339–700 nm) n.d. Ex si u – imme sion
BNC/chi osan 2 %:
[137]
Young’s modulus: 2.06 MPa
Tensile s eng h: 0.95 MPa
Elonga ion a b eak: 68 %
An imic obial ac i i y: <99 % educ ion
agains S. au eus and E. coli
Non-cy o oxic
P omo es cell adhesion and p oli e a ion
Biocompa ible
S imula es collagen p oduc ion
Accep able in lamma o y esponse
Wound d essing
Comme cial Poly ([2-(me hac yloyloxy)
e hyl] ime hylammonium chlo ide) (10
and 40 w .%) (n.d.)
n.d. In si u – mixing and
polyme iza ion
UV-A and UV-B esis ance
[141]
High wa e abso p ion capaci y:
225–873 %, 48 h
S o age modulus: >1.7 GPa
Young’s modulus: ≥2.4 GPa
Elonga ion a b eak: >2.4 %
Non-cy o oxic: Cell iabili y (HaCaT)
72.4–81.4 %
An i ungal ac i i y (Log educ ion):
C. albicans (3.4–5.5)
Bu n wound
d essing Comme cial Collagen/chi osan (n.d.) n.d.
In si u – mixing o
collagen in cul u e
medium
Ex si u – imme sion in
chi osan
Mois u e con en : 95.5±0.10 %
[121]
Hemocompa ible: 1.51±0.01 %
Facili a es oxygen exchange: 76.8±0.07
% po osi y
Flexible: ensile s eng h o ~0.8 MPa
Mic obial educ ion
Non-cy o oxic: Cell iabili y
(mammalian cells) 90 %
Reduced healing p ocess ime (in i o)
Bu n wound
d essing Cu cumin (n.d.) n.d. Ex si u – imme sion
Non-cy o oxic
[122,125]
Enhances cellula adhesion
An imic obial ac i i y: E. coli (15±0
mm)
P. ae uginosa (16.3±0.4 mm)
S. yphimu ium (16±0 mm)
S. au eus (15.5±0.4 mm)
Imp o es wound healing p ocess: 64.25
%, 15 days
Reduces sca o ma ion
Inc eases cell p oli e a ion and collagen
p oduc ion
Bu n wound
d essing
Ac ylic acid/ ke a inocy es/ ib oblas s (n.
d.) n.d. Ex si u – mixing
Enhances wound healing: 77.34±6.21
%, 13 days [125,138]
Inc eases collagen deposi ion
Facili a es eepi helializa ion p ocess
Bu n wound
d essing ( hi d
deg ee)
Comme cial Timol (n.d.) n.d. Ex si u – imme sion
High wa e abso p ion capaci y: >400 g
m
-2
d
-1
[129,139]
An imic obial ac i i y:
S. au eus (40.33±1.15 mm)
E. coli (18.33±1.15 mm)
P. ae uginosa (20.67±0.57 mm)
K. pneumoniae (41.33±1.15 mm)
Non-cy o oxic: Cell iabili y (NIH/3T3)
88.81 %
Facili a es cell p oli e a ion
Enhances wound healing p ocess: 90.7
%, 20 days
Reduc ion in sca o ma ion
Ch onic wound
healing
Dehyd ogena i e polyme o coni e yl
alcohol (n.d.) n.d. Ex si u – imme sion
High swelling: ~74–97 %
[129,131]
Con olled and sus ained elease o 72 h
(ini ial bu s o 34 % in 1 h)
An imic obial ac i i y
Ch onic wound
d essing Comme cial Hyalu onic acid (n.d.) n.d. Ex si u – imp egna ion
High swelling capaci y: 3334.21
±353.54 %, 24 h [131,133]
Non-cy o oxic
n.d. – no de ined.
L. Mel o e al.
Applied Ma e ials Today 46 (2025) 102858
18
educ ion o oxida i e s ess, and hypoxia in a bu n wound [96].
The enhancemen o he mechanical p ope ies wi h he inco po a-
ion o AgNPs was also e i ied by Song e al. (2021), who p oduced a
hyd ogel based on PVA/BNC/AgNPs. Bo h he s ess a b eak and
elonga ion a b eak imp o ed, bu only a an op imized concen a ion o
AgNPs. This was due o AgNPs agglome a ion a highe concen a ions
ha dis u b he o ma ion o he hyd ogel ne wo k, con ibu ing o he
decline in p ope ies. These hyd ogels we e es ed o an ibac e ial ac-
i i y agains E. coli and S. au eus showing signi ican an ibac e ial e -
ec s. Good cy ocompa ibili y using L929 cells was e i ied. The addi ion
o AgNPs inc eased he e-epi helializa ion due o he an i-in lamma o y
ac i i ies, imp o ed angiogenesis and o ma ion o a hai ollicle [114].
Table 6
Examples o BNC unc ionalized wi h o ganic and ino ganic compounds o wound d essings and wound healing applica ions.
Applica ion Compounds Inco po a ion
me hod
P ope ies Re .
NPs o complex (size; shape) D ugs o o he
componen s
Bu n wound
healing ( hi d
deg ee)
AgNPs (n.d.) PDA In si u –
polyme iza ion
An imic obial ac i i y:
[87]
S. au eus (22.33±0.57 mm)
E. coli (12.00±1.00 mm)
P. ae uginosa (15.67±0.57 mm)
K. pneumoniae (15.00±0.00 mm)
Non-cy o oxic: Cell iabili y (NIH/3T3) >70 %
Wa e apo pe meabili y: ~400 g m
-2
d
-1
P omo es cell p oli e a ion, eepi helializa ion, and collagen
deposi ion (IL-1
α
, IL-6, Il-10, VEGF-A, VEGF-B, bFGF, TGF-
β1, TGF-β3, and SMAD-3)
E ec i e in wound healing: 94.35 % healing a e a 20 days
and 100 % a e 25 days
No sca o ma ion
Wound healing AgNPs (n.d., 42.71±17.97 nm)
/Cu cumin-Cyclodex ins n.d. In si u – imme sion
Non-cy o oxic: Cell iabili y (U251, MSTO and Panc 1) >80
%
[142]
Hemolysis: 6.85±1.12 %
An imic obial ac i i y: signi ican o P. ae uginosa, S.
au eus, and C. au is
An ioxidan ac i i y
Wound d essing Gela ine/SeNPs (n.d., 75 nm) n.d. In si u – imme sion
and educ ion
Tensile s eng h: ~0.74–0.85 MPa
[144]
Young’s modulus: ~2.77–3.08 MPa
Failu e s ain: ~33.4–40 %
High swelling: >2000 %
An ioxidan ac i i y: ~25–80 % 24 h
Deg adable: 100 %, 180 min
Con olled elease o SeNPs: ~20.4–25.2 %, 3 days
An imic obial ac i i y agains E. coli, MDR E. coli, S. au eus,
and MDR S. au eus
Non-cy o oxic a concen a ions below 60 mmol L
-1
Hemocompa ible: hemolysis a e <2 %
Facili a es wound healing (96 %, 14 days)
An i-in lamma o y ac i i y (TNF-
α
and IL-6)
P omo es ib oblas and collagen p oduc ion
P omo es angiogenesis
Biocompa ible (in i o, TNF-
α
, IL-6, and IL-1)
Wound d essing
Ag/g aphi ic ca bon ni ide(gCN)/
eucalyp us ex ac (EE)
Elec ospinning (wi h PVA)
PVA Imme sion (wi hou
PVA)
Release p o ile:
[145]
– BC/Ag/gCN/EE a e 30 h:
61% o Ag and 67% o EE
– PVA/BC/Ag/gCN/EE a e 12 h:
62% o Ag and 74% o EE
Biodeg adabili y:
– PVA/BC/Ag/gCN/EE ~44 %
– unc osslinked PVA/BC/Ag/gCN/EE 79 %
– c osslinked PVA/BC/Ag/gCN/EE imp o ed dissol abili y
signi ican ly
Mechanical p ope ies:
– BC/Ag/gCN/EE
ensile s eng h 6.99 MPa
Young Modulus 121.37 MPa
– unc osslinked PVA/BC/Ag/gCN/EE
ensile s eng h 6.56 MPa
Young Modulus 412.88 MPa
– PVA/BC/Ag/gCN/EE
ensile s eng h 8.44 MPa
Young Modulus 564.84 MPa
An ibac e ial: s ong an ibac e ial ac i i y agains E. coli and
S. au eus
Viabili y:
– BC/Ag/gCN/EE 89 ±2.31 %
– PVA/BC/Ag/gCN/EE 96 ±3.28 %
Sc a ch a ea educ ion:
– BC/Ag/gCN/EE 18.69%
– PVA/BC/Ag/gCN/EE 23.97 %
n.d. – no de ined.
L. Mel o e al.
Applied Ma e ials Today 46 (2025) 102858
19
Table 6 summa izes examples o BNC unc ionalized wi h o ganic and
ino ganic compounds o applica ion in wound d essings and wound
healing.
3.2. Implan s
Implan s assis as suppo , o as eplacemen o damaged body pa s,
and can also unc ion as deli e y agen s o o moni o ing o physio-
logical ac i i y. Once in oduced in o he body, medical implan s can
emain pe manen ly o se e hei pu pose o a empo a y e m. Ex-
amples o implan s a e a i icial join s, su gical meshes, b eas implan s,
cochlea implan s, in aocula lenses, pacemake s, o o he ca diac im-
plan s, and in au e ine con acep i e de ices. Medical body implan s
can be made o me al, plas ic, ce amic, skin, bone, o o he issues [146].
Biocompa ibili y and lack o oxici y a e wo essen ial ea u es o 3D
sca olds, in associa ion wi h he abili y o p omo e cell adhesion, p o-
li e a ion, and di e en ia ion. Ano he essen ial p ope y is i s po osi y,
which should enable cell in il a ion, ascula iza ion, nu ien ex-
change, and possess adequa e mechanical p ope ies. I has been ound
ha he implan mo phology should esemble ha o he ECM [147].
BNC is a bioma e ial applied in se e al biomedical applica ions (see
Table 7), a ibu ed o i s ou s anding mechanical, physical, and chem-
ical p ope ies. Fu he mo e, di e en sizes can be achie ed by egu-
la ing i s biosyn hesis [148]. Ne e heless, he lack o an imic obial,
an i-in lamma o y, and an ioxidan p ope ies limi s i s applica ion.
BNC modi ica ion adap abili y is ad an ageous o mi iga e his limi a-
ion, acili a ed by i s abundance o OH g oups and a neu al elec o-
s a ic cha ge [65]. The e o e, he isk o in ec ion o ejec ion a e
implan a ion can be easily mi iga ed o e en o e come i he igh
an imic obial agen s a e inco po a ed wi hin he implan ma ix,
a oiding he need o a second su ge y. An ex ensi e a ay o pos-
i i ely/nega i ely cha ged o ganic/ino ganic compounds can be in o-
duced using a ious me hods (in si u and ex si u), esul ing in composi es
ha ul il he equisi es o he biomedical ield [149,150]. BNC-based
unc ional composi es ha e been applied in he de elopmen o wound
d essings, cance he apy, d ug deli e y, biosenso s, and implan s [40,
151]. Some examples o implan s a e displayed in Fig. 7. Thei appli-
ca ion has been p io i ized o e syn he ic p oduc s due o hei hemo-
compa ibili y, biocompa ibili y, ease o s e iliza ion, and lack o
cy o oxici y [13]. Ano he no able p ope y is he deg adabili y o BNC
[152]. In speci ic con ex s, a sough -a e a ibu e in ol es he deg a-
da ion and abso p ion o ma e ials wi hin he body upon implan a ion,
pa icula ly wi hin issue enginee ing. This p ope y enhances cellula
p oduc ion, g ow h, and adhesion, acili a ing he g adual eplacemen
o he implan wi h newly egene a ed issue [153]. None heless, i can
be easily modi ied o inc ease deg adabili y (e.g., oxida ion p ocesses
[122], cellulase ea men , and adia ion [154]).
3.2.1. So issue implan s
BNC can be applied in he eplacemen o syn he ic so implan s,
namely, ca dio ascula sys ems (e.g., a i icial blood essels and hea
al e eplacemen ), ne ous sys em (e.g., ne e sca old and du a ma e
eplacemen ), oph halmic applica ions (e.g., a i icial co nea and con-
ac lenses), u ina y condui s, and skele al sys em (e.g., ca ilage
egene a ion, meniscus implan , a i icial ligamen / endon, ympanic
memb anes, and ocal co ds) [150,157,158].
3.2.1.1. Ino ganic compounds in so issue implan s. Acco ding o se e al
s udies, he ea men o neu ological diso de s like Pa kinson’s and
Alzheime ’s disease, o ce ical spinal co d inju y, can po en ially ely
on cell-based he apy based on neu al s em cells (NSC) o p o ec and
es o e damaged neu ons. Howe e , he e is an u gen need o egula e
he g ow h and di e en ia ion o hese cells and o ensu e he success ul
in eg a ion o implan ed issues essen ially, ansi ioning om he lab-
o a o y o clinical applica ion. Neu ogenesis, as wi h any cell cul u e, is
e y pa icula ega ding he su ounding physiological condi ions. The
su ace in which hey di e en ia e and g ow is o pa icula impo ance,
he e o e signi ican e o s ha e been made o de elop a sca old able o
p o ide he mic oen i onmen o de elop NSC. An example is a wo k
de eloped by Guo e al. (2021), who de eloped an elec ically conduc-
i e sca old by making use o he conduc i i y o 3D-g aphene (3D-G).
Despi e de biocompa ibili y o his ino ganic oam, he la ge po es o
100–300 µm signi ie ha cells enden ially a ach, p oli e a e and
di e en ia e along he walls and no on he inside. To simula e a mo e
ealis ic en i onmen , BNC was added o he 3D-G by cul u ing
K. xylinum on i s su ace. The esul ing supe io su ace a ea and
educed po e size p o ided a b oad a ay o oxygen g oups ha
inc eased biocompa ibili y, p oli e a ion, and di e en ia ion. In ac ,
p ima y co ical neu ons cul u ed on his composi e o med an in ense
neu onal ne wo k wi h g ea e ne wo k ac i i y han he one o med on
he g aphene oam alone. RNA-Seq analysis sugges ha he composi e
o e s a mo e p omising 3D conduc i e subs a e o neu al issue en-
ginee ing. Fu he mo e, he inco po a ion o BNC on o he 3D-G su ace
lowe s he Young’s modulus o he biopolyme o le els simila o so -
issue memb anes, since he ino ganic ma ix p esen s app oxima ely
1,000–2,000 MPa [159].
Endo helial cells a e impo an cons i uen s o he blood essels and
he lympha ic sys em, ope a ing as a selec i e ba ie o he anspo o
molecules be ween blood/lymph and issues. The blood essel endo-
helium laye is ex emely impo an in ascula in eg i y he e o e, an
in ac endo helium ensu es he no mal wo king o blood essels. I
egula es blood low, ascula one, angiogenesis, monocy e/leukocy e
Table 7
Examples o comme cialized BNC-based p oduc s speci ically de eloped o medical implan s.
Comme cial name (p oducing
bac e ia)
Company/dis ibu o Ac i e
compound
P ope ies Wound ype Re
SYn hesized Cellulose
(BASYC®) (n.d.)
Uni e si y Jena and Polyme Jena,
Ge many
None High mechanical s eng h Blood essel epai [24]
High wa e e en ion
Low oughness o inne ube
su ace
Xylos ® Po ous Su gical Mesh
(n.d.)
Xylos Co po a ion ®None Rein o cemen Abdominal and ho a ic de ec s [155]
Xylos ® Vessel Gua d (n.d.) Xylos Co po a ion ®None P o ec ion Co e o essels du ing an e io
e eb al su ge y
[155]
Go e-Tex® memb anes Go e-Tex®n.d. Pe iodon al issue
imp o emen
Den al implan [156]
Secu ian n.d. n.d. Tissue Tendon epai [156]
Rein o cemen ma ix
Gel oam™Pha macia & Upjohn Company LLC n.d. Tympanic memb ane
pe o a ions
Tissue epai [156]
n.d. – no de ined.
L. Mel o e al.
Applied Ma e ials Today 46 (2025) 102858
20
adhesion, pla ele agg ega ion, and acili a es no mal unc ions o is-
sues o o gans. Mal unc ion may esul in di e en pa hologies such as
aneu ysms, s oke and hea disease, diabe es, among o he s. In issue
enginee ed ascula g a s (TEVG), au ologous saphenous ein and
syn he ic ascula g a s a e used o ci cum en hese issues [160,161].
Modi ied syn he ic nondeg adable polyme s, biodeg adable syn he ic o
na u al polyme s ha e been used o cons uc ing ascula g a s, among
hem poly e a luo oe hylene (e-PTFE) o polye hylene e eph hala e
(PET). None heless, p oblems in seeding endo helial cells on o p os-
he ic g a s ia physical o ces (g a i a ional o hyd os a ic seeding)
could no ul il he p eclinical equi emen s. In addi ion, su ace hy-
d ophobici y o hyd ophilici y a e ano he majo issue. Hyd ophobic
su aces enden ially adso b non-speci ic p o eins, leading o pla ele
adhesion and h ombus o ma ion, whils highly hyd ophilic ma e ials
can hinde adhesion hus ull co e age o endo helial cells, disabling
long- e m applica ions o ascula g a s [161]. Biologically ac i e cells
a e able o achie e issue emodelling and eg ow h o inju ed blood
essels, bu i is a leng hy p ocess since cellula denuda ion occu s due o
he high dynamic shea s ess a he damaged si e, impai ing issue
g ow h. A magne ic ield g adien can po en ially a ge magne ic
NPs-loaded cells locally o he BNC su ace and be a e en ion pla o m
o inc ease cell homing a damaged ascula u e. The inco po a ion o
magne i e (Fe
3
O
4
) wi hin BNC was possible h ough in si u p ecipi a ion
o Fe
3+
and Fe
2+
. To a oid oxida ion, dex an was used o p o ec he
i on oxide NPs and imp o e cy ocompa ibili y. The cha ac e iza ion o
his magne ic hyd ogel showed a supe pa amagne ic beha iou since no
hys e esis loop was o med. The Young’s modulus o he composi e o
all he expe imen al samples (200–380 KPa) was highe han ha e-
po ed o heal hy ca o id walls du ing he ca diac cycle (130±15 KPa in
sys ole and 80±10 KPa in dias ole) and wi h no signi ican di e ences o
he un ea ed BNC memb ane (320.51±149.58 KPa). This shows he
mechanical sui abili y o he hyd ogel as ascula g a . The elease o
weakly bonded me al NPs was e i ied o 100 mM and 50 mM Fe
3+
con aining BNC, whils he 25 mM sample emained almos in a ian
h oughou he 8 days o expe imen . Cell iabili y ia li e/dead and
MTT assays p esen ed 90.56 % li e cells and 9.43 % dead cells o a o al
o 339 cells o he 25 mM Fe
3+
BNC, simila o p is ine BNC (98 % li e
cells o a o al o 227 cells). The o he concen a ions o Fe
3+
, 50 mM and
100 mM showed poo esul s o iabili y. Cul u ed human ao ic smoo h
muscle cells (HASMC) showed an ex ended mo phology and we e well
adhe ed o all he subs a es, seemingly p oli e a ing as e in p is ine
BNC and 25 mM magne ic BNC. Cell a ge ing was achie ed a low i on
oxide NPs concen a ion (25 mM), bu he cell co e age in he magne ic
BNC was lowe han he sys ems based on magne ized s eel s en s. The
eason can be due o he coa ing o he NPs wi h dex an, which is known
o esis cell adhesion [160]. Zhang e al. (2020) demons a ed a
non-in asi e and con enien me hod o emo ely egula e he adhesion
o endo helial cells based on an oscilla ing magne ic ield. BNC mem-
b anes we e modi ied using PEG-coa ed i on oxide NPs wi h g a ed
A g-Gly-Asp pep ide used as cell ancho s. Seeded mu ine endo helial
cells we e subjec ed o a magne ic ield a di e en equencies (0 Hz,
0.1 Hz, 2 Hz), and adhesion and g ow h o endo helial cells showed o be
signi ican ly oscilla ion equency dependen , wi h cell g ow h p omo-
ion unde lowe equency, leading o success ul endo helializa ion on
he modi ied BNC memb anes. The magne ic BNC composi e demon-
s a ed high mechanical s eng h wi h Young’s modulus o 1.75±0.3
MPa, only sligh ly lowe han p is ine BNC (2.21±0.4 MPa). Simila
ensile s eng h and elonga ion a b eak o BNC we e also e i ied. Cell
iabili y, illus a ed in Fig. 8, was analysed by he CCK-8 assay using
mu ine endo helial C166 cells. The esul s showed no educ ion o he
composi e (1 mg mL
-1
o 24 h) iabili y by mo e han 20 %. Inc eased
incuba ion o up o 7 days (a concen a ions highe han 125
μ
g mL
-1
)
caused some oxic e ec s, howe e , no enough o label i as
non-biocompa ible. Release o i on oxide NPs was less han 0.1 % a e
Fig. 7. Examples o so (blue boxes) and ha d (g ey boxes) BNC-based implan s. C ea ed wi h BioRende .com.
L. Mel o e al.
Applied Ma e ials Today 46 (2025) 102858
21
incuba ion o 14 days. C166 cells show highe co e age on
pep ide-modi ied memb anes han p is ine BNC, i espec i e o he
applied magne ic ield. The o me showed highe cell seeding densi y
and mo e ex ended cellula mo phology. The eason could be due o he
pep ide’s abili y o in e ac wi h he in eg in ecep o s on he cell
memb ane and enhance cell adhesion and a ini y [161]. Di e en ap-
plica ions o magne ic NPs include ac ua o s. These ma e ials p oduce
mechanical mo ion o o ce in esponse o an ex e nal s imulus. These
can be applied in o a ious medical de ices o implan able sys ems o
speci ic pu poses. Supe pa amagne ic i on oxide NPs (SPIONs) a e a
good example since hei applicabili y in biomedicine includes: d ug
deli e y, making use o hei a ge ing h ough an ex e nal magne ic
ield [162], con as agen s o magne ic esonance imaging o enhance
he isibili y o speci ic issues [163], and hype he mia he apy due o
he abili y o SPIONs o gene a e hea when exposed o an al e na ing
magne ic ield [164]. The inco po a ion o hese NPs wi hin BNC o be
po en ially used as ac ua o s was epo ed by Roig-Sanchez and
co-wo ke s (2021), who es ed a s a ic and agi a ed cul u e o BNC in he
p esence o SPIONs. Magne ic ac ua ion is con e ed by SPIONs. The
combina ion o pla inum NPs (P NPs) o AuNPs wi h SPIONs allows he
con olled mo ion o he hyd ogels by a magne ic ield and an H
2
O
2
oxida ion eac ion. These Janus P /SPIONs s uc u es inc eased by i e
imes he di ec ionali y and mo emen [165]. Table 8 summa izes ex-
amples o BNC unc ionalized wi h ino ganic compounds o so issue
implan applica ions.
3.2.1.2. O ganic compounds in so issue implan s. Loss o unc ion o
a icula ion and muscles due o ca ilage damage cons i u es a p oblem.
Such inju ies a e equen in he aging popula ion and a hle es. The
human body’s capaci y o sel - egene a ion aces limi a ions due o he
es ic ed p oli e a ion o chond ocy es, he absence o blood essels and
ne es, and he ela i ely low me abolic a e [158,166]. The p edomi-
nan ea men me hod in ol es au og a ing chond ocy es, specialized
cells ha s imula e he gene a ion o new ca ilage issue. None heless,
he demand o dual su ge ies and an ex ended eco e y pe iod has
p omp ed explo ing a bioma e ial-based app oach o ca ilage ans-
plan a ion [158]. Implan s equi e high po osi y o suppo chond ocy e
mig a ion and ECM p oduc ion. Howe e , BNC p esen s di e en sizes
Fig. 8. (a) Immuno luo escence s aining mic og aphs o inculin (g een), F-ac in ( ed), and nuclei (blue) a e incuba ion o C166 cells on BNC/magne ic BNC/
pep ide-g a ed magne ic BNC o 24 h unde “s a iona y”, “slow”, and “ as ” condi ions by applying a ious oscilla ion equencies (0, 0.1, and 2 Hz) o a mag-
ne ic ield. The un ea ed cells on each ype o memb ane a e con ol g oups. Scale ba s ep esen 50
μ
m. (b,c) Co esponding quan i ica ions o adhe ed cell densi y
and a ea. Da a a e shown as mean ±s anda d e o s (n =30). The s a is ical signi icance o he esul s was de e mined using one-way ANOVA, *, **, ***, and ****
ep esen he signi icance a p <0.05, p <0.01, p <0.005, and p <0.001. Rep oduced om Re . [161] wi h pe mission, Copy igh 2020, Ame ican Chemical Socie y.
L. Mel o e al.
Applied Ma e ials Today 46 (2025) 102858
22
and in e connec i i y ha may inhibi chond ocy e p oli e a ion [167].
Nume ous app oaches ha e been de eloped o adjus po e size, simila
o he ECM dimensions ( anging om 100 o 500 µm) [168]. These
me hodologies include lase d illing, pho o e icula ion, eeze-d ying,
and inco po a ing NPs/mic opa icles du ing syn hesis [123,169,170].
Pho o e icula ion o a BNC/me hac yla e gela ine hyd ogel dec eased
he po e size om 200 o 10 µm, a ibu ed o hyd ogen bonding.
No wi hs anding he educed po e size, chond ocy e g ow h and p o-
li e a ion we e success ul [171]. To inc ease he numbe o po es in
BNC, eeze-d ying becomes a p ac ical and cos -e ec i e me hod o
achie e his a ibu e. Li e al. (2017) de eloped a BNC-chi osan com-
posi e (1 w .%). The combina ion o he eeze-d ying p ocess and he
iscosi y enhancemen , esul ing om he p esence o chi osan,
con ibu ed o a subs an ial 50 % inc ease in po e size [172]. Heal hy
ca ilage has a high-wa e con en o abou 80 %, so he eplacemen
implan mus main ain his p ope y [154]. BNC exhibi s a no able ine
wa e e en ion capaci y, ende ing i sui able o ca ilage eplacemen
applica ions. Inco po a ing BNC in o ca ilage implan s mus acili a e
he p og ession o new issue de elopmen , a phenomenon e e ed o as
chond ogenesis [173]. Fu he mo e, BNC hyd ogels we e modi ied wi h
algina e and/o hyalu onic acid o achie e his p ope y. The composi e
BNC/chi osan/algina e/gela ine (80:20 % w/w) was e alua ed, p o-
mo ing cell adhesion, p oli e a ion, and cell di e en ia ion o chon-
d ocy es [174]. The p oduc ion o p in able a 3D hyd ogel o BNC and
me hac yloyl gela ine, demons a ed in Fig. 9 a-g, enhanced mechanical
p ope ies. A e 24 weeks o in i o implan a ion, he ea ca ilage
implan exhibi ed Young’s modulus (1.33±0.13 MPa) simila o he
modulus o elas ici y o human ea ca ilage (1.41±0.67 MPa). Cell
iabili y displayed p omising esul s, wi h alues exceeding 97 %
ollowing a 7-day es ing [175]. The in si u polyme iza ion modi ica ion
wi h an addi ional o ganic compound, PGA, esul ed in a bioma e ial
ha exhibi ed imp o ed mechanical p ope ies. This modi ica ion
enhanced bond in e ac ions, ampli ying elas ic eco e y a e
comp ession, ac u e s eng h, and enaci y. The composi e shows
p omising p ope ies in ca ilage applica ion, including excellen cell
iabili y [176]. Mo eo e , he applica ion o na u al p o eins was also
analysed o mechanical imp o emen . The in eg a ion o SF in o BNC,
ollowed by he eeze-d ying p ocedu e, e ealed an enhancemen in
comp essi e s eng h and de o ma ion. This imp o emen can be
a ibu ed o he c osslinking in e ac ion be ween BNC and SF [177]. All
he exempli ied examples indica e ha u ilizing hese o ganic ma e ials
did no comp omise he non-cy o oxici y o he inal composi es. The
high iabili y can be a ibu ed o he simila i y o BNC o he ECM o
hyaline ca ilage [168].
Se e e ca dio ascula condi ions equi e a ascula ansplan o
eplace obs uc ed pa hways. These eplacemen s may in ol e applying
al e na i e body issues ( om onesel o a dono ) o using a i icial
ascula g a s (e.g., blood essels o ca diac al es) [178]. Su gically,
syn he ic ma e ials a e employed o eplace la ge-diame e blood essels
( anging om 6 o 10 mm in diame e ), commonly u ilizing PTFE and
e-PTFE. Ne e heless, hese ma e ials a e inadequa e o eplacing
small-diame e essels (wi h diame e s less han 6 mm) due o hei
suscep ibili y o clo ing and es enosis. This inhe en limi a ion con-
s i u es he main obs acle p e en ing comme cially accessible p os he-
ses designed o his ype o essel [179]. BNC hemocompa ibili y makes
i a p omising choice o adequa ely eplacing bo h ypes o implan s
[180]. BASYC® (BAc e ial SYn hesized Cellulose) is a comme cially
a ailable BNC-based p oduc ha eplaces a i icial blood essels. I
ea u es a ubula con igu a ion and mechanical p ope ies esembling
na u al blood essels [24]. Applying his bioma e ial as a ca dio ascula
ube necessi a es he p ese a ion o blood essel cha ac e is ics,
including in e nal oughness and p essu e esis ance [13]. Fu he mo e,
issues ela ed o limi ed elas ici y and an i- h ombogenic p ope ies
mus be add essed o es ablish BNC as a iable p oduc . Fo his pu pose,
a c ucial modi ica ion is equi ed [178]. Fig. 9h illus a es a
PVA-modi ied BNC o applica ion in a i icial blood essels. The D-BNC
ube possesses a bigge ex e nal diame e and mo e homogeneous
cha ac e along he diame ic di ec ion and he S-BNC ube possesses
dense nano-cellulose close o he inne wall. The hyd ogen bonds a e
no ably educed wi hin he BNC ma ix inc easing he elas ici y/s e ch
a b eak. The mechanical p ope ies a e displayed in Fig. 9i-m. Highe
Young’s modulus, ensile s eng h, and elonga ion a b eak a e e i ied
Table 8
Examples o BNC unc ionalized wi h ino ganic compounds o so issue implan s applica ions.
Compounds Inco po a ion me hod P ope ies Re .
Applica ion NPs o complex
(size; shape)
D ugs o o he
componen s
Neu al issue enginee ing 3D-G (n.d.) n.d. In si u – cul u ing o K. xylinum on he 3D-G su ace
Non- oxic: Cell iabili y >99 %
[159]
Kep physiological le els o
s emness
Young’s modulus simila o so -
issue memb anes
Vascula g a s
Fe
3
O
4
(n.d.,
49.81 ±20.77
nm)
n.d. In si u – mixing and educ ion
Supe pa amagne ic beha iou
[160]
Young’s modulus: 200 – 380 KPa
Non- oxic: Cell iabili y (Human
ao ic smoo h muscle cells) 98 %
Cell a ge ing achie ed a low i on
oxide NPs concen a ion (25 mM)
Vascula g a s
I on oxide co e
(~10 nm)
PEG-coa ed i on
oxide (~26 nm)
n.d. Ex si u – mixing
Young’s modulus: 1.75 ±0.3 MPa
[161]
Tensile s eng h: 2.22 ±0.4 MPa
Elonga ion a b eak: 3.59 ±0.3 %
Non- oxic: Cell iabili y (mu ine
endo helial C166 ) >80 %
Release o i on oxide NPs: <0.1
%, 14 days
Ca go-deli e y sys ems,
he agnos ic, issue
enginee ing
SPIONs
(sphe ical, 7.1 ±
1.5 nm)
AuNPs
(sphe ical, 19 –
47 nm)
P NPs (n.d., 3
nm)
n.d.
In si u – mixing NPs in cul u e medium
Supe pa amagne ic beha iou [165]
Magne ic esponse in wa e owa d a magne ic ield a 10 mm
was di ec ly p opo ional o he SPIONs concen a ion:
[SPIONs] =2.50 mg mL
-1
– speed o 13.5 ±1.7 mm s
-1
n.d. – no de ined.
L. Mel o e al.
Applied Ma e ials Today 46 (2025) 102858
23
Fig. 9. P in abili y es o bac e ial nanocellulose (BNC)/gela in me hac yloyl (GelMA) hyd ogel o (a) PSH cha ac e s p in ed wi h BNC/GelMA hyd ogel, (b) cuboid
s uc u e a di e en laye s p in ed wi h BNC/GelMA hyd ogel, (c) human mandibula model p in ed wi h BNC/GelMA hyd ogel, (d) human nose model p in ed wi h
BNC/GelMA hyd ogel (e) Young’s modulus o egene a ed ca ilage (n =3), ( ) glycosaminoglycan (GAG) con en o egene a ed ca ilage (n =3), (g) To al collagen
con en o egene a ed ca ilage (n =3). **P <0.01, ***P <0.001, ****P <0.0001. (h) Mac o-mo phology o he (h.a) S-BNC ube, (h.b) D-BNC ube, (h.c) S-BNC/
PVA composi e ube, (h.d) D-BNC/PVA composi e ube and (h.e) PVA ube, (i-l) axial s e ch mechanical p ope ies o he PVA ube (a), S-BNC ube (b), D-BNC ube
(c), S-BNC/PVA composi e ube (d) and D-BNC/PVA composi e ube (e). Signi ican di e ences be ween g oups a e indica ed (*p <0.05), (m) ci cum e en ial
dynamic compliance o he S-BNC ube ( ed), D-BNC ube (blue), S-BNC/PVA ube (dashed ed), D-BNC/PVA ube (dashed blue) and PVA ube (black). Signi ican
di e ences be ween g oups a e indica ed (*p <0.05). Adap ed om Re . [175,181], unde he Licence CC BY 4.0, 2023, ACCSCIENCE Publishing and wi h pe mission,
Copy igh 2015, Royal Socie y o Chemis y, espec i ely.
L. Mel o e al.
Applied Ma e ials Today 46 (2025) 102858
24
o he D-BNC ube as a esul o he hicke ib es and a dense
nano- ib e ne wo k. Pe meabili y a ainmen was also success ul, as no
wa e leakage was de ec ed, and he e was an enhancemen in bu s
p essu e wi hou any cy o oxic e ec s [181]. Mo eo e , ensu ing he
mig a ion and p oli e a ion o endo helial cells on he implan su ace
holds ex eme impo ance in achie ing biocompa ibili y. The
BNC/chi osan/hepa in composi es signi ican ly acili a ed he adhesion
and g ow h o human saphenous ein endo helial cells (SVEC) and
endo helial p ogeni o cells (EPC). Con e sely, he BNC/hepa in com-
posi e exclusi ely exhibi ed hese e ec s in he second cell ype, EPC.
Bo h a ian s hold p omise o applica ion in small-diame e ascula
g a s, e ec i ely minimizing he po en ial o h ombogenici y and
augmen ing biocompa ibili y [182]. In addi ion, a chemical c osslinking
p ocess was employed o inco po a e hepa in in o BNC, unc ionalized
wi h SFNPs. The p oli e a ion o endo helial cells, apid endo heliali-
za ion, minimal p esence o in lamma o y cells, and absence o de-
g adabili y o 4 weeks we e obse ed [183]. Inco po a ing 1 % w/ ish
gela ine esul ed in apid endo helializa ion, wi h hemolysis a es
emaining below 1 % (demons a ing hemocompa ibili y) and an
enhanced le el o biocompa ibili y [184].
Replacing blood essels o ascula g a s smalle han 6 mm in
diame e p esen s challenges. Howe e , se e al mul i unc ional BNC
composi es exhibi p omising p ope ies. BNC/chi osan composi es
demons a ed no alle gic eac ions and e ec i ely supp essed in lam-
ma o y esponses o excessi e g ow h o egene a ed muscle issue. This
ul ils he c i e ia o biocompa ibili y and non-cy o oxici y [185]. In
i o, blood essel egene a ion was swi ly accomplished h ough in si u
modi ica ion o BNC wi h po a o s a ch. Po a o s a ch pa icles a highe
concen a ions (2% w/ ) expanded du ing he e men a ion p ocess,
esul ing in an inc ease in po e size (~28±6
μ
m) [186].
Co neal dys unc ion culmina es in ision loss, p omp ing he adop-
ion o an a i icial co nea as he op imal ea men app oach. The de-
mand o syn he ic al e na i es a ises om dono sca ci y. This
ansplan a ion echnique demons a es heigh ened e icacy owing o i s
non- ascula na u e [187]. The a i icial co nea should sa is y he
ollowing p e- equisi es: biocompa ibili y, mechanical s abili y, com-
o , igid s uc u e, anspa ency, and he abili y o enhance cell
adhesion and p oli e a ion [188]. In his con ex , hyalu onic acid can be
applied in co neal implan s. Aniso opic p ope ies and high ans-
pa ency (40 % highe han BNC) we e achie ed due o he inco po a ion
o his agen . The chemically c osslinked BNC/hyalu onic acid com-
posi e demons a ed conside able cy ocompa ibili y owa ds co neal
s omal cells and su u e s eng h compa able o he human eye [189].
The in eg a ion o his composi e in o BNC, wi hou equi ing a c oss-
linking agen , displayed se e al encou aging a ibu es. Mechanical
p ope ies and elas ici y, high po osi y, and excellen ansmi ance a e
some o he cha ac e is ics o he composi e [190]. Beyond hyalu onic
acid, inco po a ing PVA imp o es he op ical p ope ies h ough he
expansion o in e s i ial spaces o BNC, p omo ing inc eased ligh
ansmission. Mo eo e , his inclusion suppo s he di usion o oxygen
and essen ial nu ien s c ucial o cellula g ow h while demons a ing
minimal immunogenici y [191]. The e o e, he excellen abili y o
p omo e ligh ansmission, high wa e con en combined wi h UV
p o ec ion es ablishes PVA as a iable op ion o eplace
non-biocompa ible polyme hyl me hac yla e in co neal implan s and
con ac lenses [13].
PP-based implan s a e applied su gically o he ea men o he nias.
None heless, a educ ion in physicochemical p ope ies, accele a ed
deg ada ion in he human body, and i s non-ine na u e ha os e s
in ec ions and in lamma ion dec ease he e icacy o employing hese
syn he ic polyme s [192]. To mi iga e associa ed biological isks, an
in en i e bioma e ial, BNC, was combined wi h chi osan and applied o
a PP mesh. A e 3 mon hs o implan a ion, he composi e a ou ed
issue emodelling and demons a ed a dis inc absence o cy o oxici y.
Unlike PP-based he nia meshes, his includes minimal i i a ion and no
alle gic eac ions [193]. In addi ion o ea ing he nias, BNC can se e as
a subs i u e o a pe o a ed ympanic memb ane because o i s lexi-
bili y, biocompa ibili y, and anspa ency. Howe e , no necessi y o
modi ying BNC o his speci ic applica ion was iden i ied. PVA eme ges
as a plausible choice o modi ica ion o enhance ligh ansmission
[147].
Di e en al e na i es ha e been explo ed o p omo e he egene a-
ion o u ological issues, such as he case o u ina y condui s - a c i ical
componen in managing bladde cance ea men [147]. Ke a ocy es
we e cul u ed on a BNC/SF bi-laye sca old. SF encou aged cell p o-
li e a ion and mig a ion, while BNC suppo ed p ese ing epi helial
cells, which play a c ucial ole in u e h al econs uc ion [194].
Repai ing ne e inju ies is a complex and c ucial p ocess cha ac-
e ized by he challenges o limi ed egene a i e po en ial. An up-and-
coming solu ion lies in applying neu al implan s, pa icula ly high-
ligh ed by he BNC a ou able compa ibili y wi h Schwann cells [195].
In addi ion o biological p ope ies, ne e egene a ion implan s need
e ec i e elec ical conduc i i y o acili a e ne e impulses. Thus, Wu
e al. (2021) de eloped a 3D biop in ing sca olds o BNC (0.3 %)/algi-
na e (5 %)/gela ine me hac yla e (5 %) loaded wi h RSC96 cells ha
showed a good elec ical conduc i i y (6 ×10
-7
S m
-1
). The e ec o
in oducing RSC96 cells on neu al egene a ion was assessed, con i m-
ing he exp ession o nume ous mRNA genes associa ed wi h axon
g ow h, p oli e a ion egula ion, mig a ion con ol, Schwann cell
ma u a ion, and myelina ion. Following 21 days o in i o implan a ion,
no indica ions o in lamma ion o oxici y we e obse ed [196]. F om a
di e en pe spec i e, a scia ic ne e egene a ion was assessed using
an oxidized BNC composi e unc ionalized wi h chi osan NPs (in si u)
con aining ne e g ow h ac o s. The mic opo ous composi e exhibi ed
a no able educ ion o mic obial p oli e a ion, while he oxida ion o
BNC imp o ed i s biodeg adabili y. Schwann cell adhesion and p oli -
e a ion demons a ed simila esul s o comme cial g a s, and ne e
g ow h ac o s we e esponsible o e iden ne e epai (10 mm in 4
weeks) [197]. The elec ical signal be ween cells plays an impo an pa
in issue egene a ion. As a conduc i e ma e ial, ne e condui s a e able
o ansmi elec ical signals be ween cells in elec oac i e issue, hus
allowing ne e epai h ough he p omo ion o Schwann cells adhesion
and p oli e a ion o cons uc he connec ed bel when he Walle ian
degene a ion occu s. In pe iphe al ne e inju y, his is especially
impo an since i allows he b idge be ween he wo ends o damaged
ne es. Poly(3,4-e hylenedioxy hiophene) (PEDOT), a conduc i e
polyme ha has gained a signi ican in e es in issue enginee ing due
o i s biocompa ibili y and elec ical p ope ies, has been used in com-
bina ion wi h sul ona ed nano ib es (SNFs) and BNC o c ea e a ans-
pa en conduc i e memb ane. This composi e showed g ea
biocompa ibili y, high conduc i i y, and app op ia e mechanical
s eng h o be used o pe iphe al ne e epai , acco ding o in i o es s
on Sp ague Dawley a s [198].
O e all, composi es based on BNC modi ied wi h o ganic compounds
p esen p omising physicochemical and biological p ope ies o
eplacing syn he ic so implan s. Table 9 summa izes examples o BNC
unc ionalized wi h o ganic compounds o applica ion in so implan s.
3.2.2. Ha d issue implan s
Ha d issue implan s a e medical de ices used o suppo , eplace, o
epai ei he bone, ca ilage, o den al s uc u es. Typically, biocom-
pa ible ce amics and me als a e used o his pu pose, inc easingly allied
o biopolyme s due o hei excellen biocompa ibili y, adequa e me-
chanical p ope ies, po ous s uc u e, and enhanced os eogenic ac i i y
[200,201]. Fu he mo e, BNC is simila o he ECM, ha ing a b oad
spec um o applica ions, including bone in pe iodon al su ge y, ca i-
lage in he empo omandibula join , skin and o al mucosa, den in and
den al pulp, and has he abili y o be enginee ed in o bone issue. The
abili y o nanocellulose sca olds o ans e cells and g ow h ac o s o
damaged si es is unde s udy. In addi ion, su ace modi ica ion o p o-
mo e he bioac i i y o cellulose-based g a s is ano he a ea o in e es ,
in which bioac i e compounds a e linked o BNC o p omo e bone cell
L. Mel o e al.
Applied Ma e ials Today 46 (2025) 102858
25
Fig. 11. (a) H&E s aining analysis o newly o med bone alues: (le ) Compa ison o newly o med bone alues be ween di e en g oups, analyzed by One-way
analysis o a iance and LSD- es . * p <0.05; NS: no signi icance. E o ba s indica e s anda d de ia ions. ( igh ) Compa ison o newly o med bone alues be-
ween ou and eigh weeks, analyzed by independen -samples - es ; * p <0.05; NS: no signi icance. E o ba s indica e s anda d de ia ions. Cy o oxic e ec s and
a achmen o mice MC3T3-E1 cells on BNC, collagen, and collagen/BNC po ous mic osphe es (b) cell iabili y, (c) adhesion a e, (d) SEM images o cell a achmen .
Adap ed om Re . [8,219], wi h pe mission, Copy igh 2020, Else ie and unde he Licence CC BY 4.0, 2019, MDPI, espec i ely.
L. Mel o e al.
Applied Ma e ials Today 46 (2025) 102858
32
cells. Mo eo e , an in i o s udy pe o med on CT-26 cells subcu ane-
ously implan ed in emale Balb/c mice e idenced a signi ican educ ion
in he umou olume a e 10 days, alida ing he high po en ial o he
no el magne ic BNC-based sca olds o cance chemo he apy ea men
[227].
Pho o he mal he apy (PTT) and pho odynamic he apy (PDT) a e
al e na i e ea men s ha ha e conside ably enhanced he e ec i e-
ness o bac e ial in ec ions and cance ea men , o e coming he
esis ance o an ibio ics and an icance d ugs [228]. In PTT, he ea -
men is based on he local hea gene a ed by pho o he mal agen s unde
i adia ion a a speci ic wa eleng h. The inc ease in he empe a u e can
inhibi he bac e ia by des oying he cell memb ane, e apo a ing he
cellula luid, o dena u ing p o eins and enzymes [229]. The e ec o
PTT in cance cells is p o ein dena u a ion and empo a y cells inac i-
a ion, when he issue empe a u e inc eases up o 42 ◦C, long- e m
cells inac i a ion (43–45 ◦C), apid cell nec osis (45–48 ◦C), and
mic o ascula h ombosis and ischemia (48–60 ◦C) [230]. In PDT,
pho ochemical eac ions occu in ol ing molecula oxygen and speci ic
ligh wa eleng hs ha s imula e a pho osensi ize agen , gene a ing
ROS which can des oy a ge bac e ia o cance cells [231,232]. Fo
example, Ni e al. (2021) epo ed he de elopmen o a hyb id ma e ial
ha in eg a es pho odynamic, pho o he mal, and Ag-ion eleasing e -
ec s. Po ous Coo dina ion Ne wo k-224 (PCN-224) me al-o ganic
amewo ks (MOFs) NPs we e in si u g own on he su ace o Ti
3
C
2
MXene nanoshee s and hen il e ed on o BNC sca olds, ollowed by he
spu e ing o nanosil e using he magne on spu e ing me hod. The
pho o he mal pe o mance, shown in Fig. 13e, demons a es ha
PCN@Ti
3
C
2
-BNC eached up o 58.9 ◦C a e 300 s illumina ion, which
was highe han o PCN-BNC (38.3 ◦C) and Ti
3
C
2
-BNC (53.6 ◦C). These
esul s sugges ha he nanosil e co e ed on he su ace o Ti
3
C
2
and
Table 11
Examples o BNC unc ionalized wi h o ganic compounds o ha d issue implan s applica ions.
Applica ion NPs (size; shape) Sou ce Inco po a ion P ope ies Re .
Bone issue BMP-2 (n.d.) Collagen Ex si u – Imme sion
P oli e a ion a e: 105–130 %
[8]Good adhesion a e: 90.7 %
No mal bone di e en ia ion beha iou
Bone issue Hyd oxyapa i e (n.d.) n.d. Ex si u – Mixing
Po osi y: 314.14±23.2 µm
[218]
Tensile s eng h: 1.58±0.19 MPa
S ain a b eak: 3.97±2.27 %
Excellen cell iabili y
Bone egene a ion BMP-2 (n.d.) n.d. Ex si u –Loading Healing and bone egene a ion ema kably accele a ed [219]
n.d. – no de ined.
Fig. 12. Rep esen a ion o he mechanism o d ug deli e y, pho o he apy (PTT and PDT), and diagnosis (SERS) BNC-based implan s o cance he apy.
L. Mel o e al.
Applied Ma e ials Today 46 (2025) 102858
33
Fig. 13. (a) Rep esen a i e FESEM images o oxidized BNC, TB/oxidized BNC, ⍺PD-1@AuNCs/oxidized BNC, and TB/⍺PD-1@AuNCs/oxidized BNC. (b) Pho o-
he mal in a ed images o ⍺PD-1@AuNCs. (c) The empe a u e a ia ion cu e o ⍺PD-1@AuNCs. (d) Cy o oxici y o ⍺PD-1@AuNCs a di e en concen a ions. (e)
Su ace he mal images and ( ) empe a u e change o PCN-BNC, Ti
3
C
2
-BNC, PCN@Ti
3
C
2
-BNC and Ag-PCN@Ti
3
C
2
-BNC eco ded by an in a ed came a and illu-
mina ed by a 500 W Xe lamp wi h a 420 nm il e (31.45 W cm
-2
, 15 cm dis ance). (g) Pho o he mal hea ing cu es o Ag-PCN@Ti
3
C
2
-BNC o 5 ci cles. Adap ed om
Re . [233,238], wi h pe mission, Copy igh 2021, Else ie and wi h pe mission, Copy igh 2022, Sp inge Na u e, espec i ely.
L. Mel o e al.
Applied Ma e ials Today 46 (2025) 102858
34
PCN-224, weakened he pho on abso p ion abili y o Ti
3
C
2
nanoshee s.
The pho o he mal s abili y o Ag-PCN@Ti
3
C
2
-BNC (Fig. 13g) showed no
ele an changes in ele a ing and declining empe a u e in 5 ci cles.
Fu he mo e, hey ound ha unde isible ligh illumina ion o wo
ounds o 30 min (Xe lamp, 31.45 W cm
-2
), he an ibac e ial e iciency,
bo h agains G am posi i e and G am nega i e, was enhanced due o he
syne gy be ween PCN-224 and Ti
3
C
2
, by gene a ing 1O
2
and pho o-
he mal hea , espec i ely, which in u n boos s he nanosil e oxida ion
and accele a es Ag
+
ions elease. Wi h his s e iliza ion p ocess, i was
ob ained a 6-log uni and 99.99 % bac e ia inac i a ion which las ed o
6 mon hs o oom p ese a ion [233]. In ano he wo k, o inc ease he
pho odynamic ac i i y o MOFs, ca bon quan um do s (CQDs) (ene gy
dono s) we e encapsula ed in he PCN-224 po phy in-based MOFs
(accep o ) du ing a sol o he mal eac ion p ocess o cons uc luo es-
cence esonance ene gy ans e (FRET) pai s. Then, he syn hesized
CQDs@PCN-224 NPs we e immobilized in o he BNC memb ane using
an eco- iendly in si u biosyn he ic app oach whe e a compac
sandwich-like s uc u e o he BNC/MOFs memb ane was o med by i s
in e sion du ing he cul i a ion p ocess. This me hod p e en s MOFs
leakage du ing use as shown by a <1.5 % leaching. The ob ained
BNC/CQDs@PCN-224 composi e showed excellen an ibac e ial e i-
cacy when exposed o ligh o 30 min, >99.99 % o bo h S. au eus and
E. coli, good hemocompa ibili y ( abbi ed blood cells), and low cy o-
oxici y (L929 cells) [234]. Li e al. (2021) inco po a ed AuNRs in o BNC
memb anes as a pho o he mal agen , o achie e nea - in a ed (NIR)--
ac i a ed bac e icidal p ope ies, and u he coa ed wi h
phase- ansi ioned bo ine se um albumin (PTB) ilm, o imp o e he
blocking e iciency agains bio oulings, ob aining a dual- unc ional BNC
composi e. The esul ing BNC sca old p esen ed an i ouling p ope ies
agains he adso p ion o p o eins and he a achmen o bac e ia and
mammalian ib oblas s. Mo eo e , wi h 5 min o NIR i adia ion ligh ,
bo h G am posi i e and G am nega i e bac e ium could be ully elimi-
na ed due o he hea gene a ed om he inco po a ed AuNRs. In i o
biocompa ibili y e alua ion showed negligible cy o oxici y and in i o
es s using an in ec ed ull- hickness skin wound model in
Sp ague-Dawley a s showed good his ocompa ibili y wi h he wound
being almos ully closed on day 12 pos - ea men [235]. Zhang e al.
(2019) designed a ansde mal d ug a ge ing sys em o b eas cance
he apy based on BNC and lase -sensi ized magne ic NPs (LMNs).
Fe
3
O
4
NPs, which se ed as he magne ic co e, we e i s coa ed wi h
hyd ogels loaded wi h Dox and hema opo phy in monome hyl e he
(HMME). Then, he LMNs we e g a ed wi h olic acid o p omo e
cell-speci ic ecogni ion and binding. Finally, he NPs complex was
loaded on o he BNC sca old. When i adia ed (633 nm lase ), his
mul i unc ional he agnos ic sca old p oduces epea edly single oxy-
gen (O
−
) and eleases he an icance d ug Dox, hus combining bo h
pho odynamic he apy and chemo he apy. The pe o mance o his
sys em was e alua ed in i o using human b eas ca cinoma (MCF-7)
and human skin ib oblas s (HSF) cells, and in i o using Balb/c mice
bea ing MCF-7 cells. Fo he ea men , cells we e i adia ed wi h s a ic
magne ic ield (100 mT) o 6 h and He-Ne lase (633 nm, 100 mW cm
-2
)
o 10 min. In i o esul s showed ha he MCF-7 cells g ow h was
delayed 50 % in compa ison wi h he non- ea ed con ol g oup and in a
sc a ch/wound healing es he monolaye es o a ion was delayed by
82 % (24 h). Meanwhile, iabili y es s indica ed no inhibi ion in he
g ow h o HSF cells. Mo eo e , in i o chemo he apy and PDT measu ed
on Balb/c mice bea ing MCF7 cells wi h umou olumes o 100 mm
3
showed, on he 14
h
day, a dec ease o he umou olume o 40.8±5.4
mm
3
and umou g ow h inhibi ion a es o 80.38 %, while no e idence
o leukopenia o associa ed oxici y was obse ed [236]. Chu e al.
(2018) ook ad an age o he abili y o C
60
iso opes o gene a e abun-
dan ROS when exposed o ligh , o use hem in sca olds o PDT o ea
skin cance . Fulle ene C
60
NPs suspension was i s p epa ed by a sol en
exchange me hod, being a e wa d inco po a ed in o he BNC by ac-
uum il a ion. Resul s showed ha C
60
pa icles o diame e s less han
100 nm we e uni o mly dis ibu ed in he ul a ine BNC ne wo k and,
when exposed o ligh , he sca old exhibi ed excellen an ibac e ial
pe o mance due o he high des uc i e powe o ROS agains bac e ia.
Mo eo e , in i o cell expe imen s showed a high a e o cell dea h (80
%) owa d human epide moid ca cinoma cells A-143, gi ing ise o a
g ea po en ial o BNC/C
60
sca olds o ea ing skin cance [237].
Recen ly, Zhou e al. (2023) epo ed a mul i unc ional he apeu ic
sys em o be used as a e sa ile implan o a oiding he ecu ence o
head and neck squamous cell ca cinoma (HNSCC) a e esec ion, whe e
PTT was used o boos he immuno he apy media ed by he
an i-p og ammed dea h 1 (PD-1) an ibody. The sca old was p epa ed by
i s encapsula ing PD-1 in o gold nanocages (AuNCs) and hen, oge he
wi h h ombin (TB), hey we e inco po a ed in o oxidized BNC. The
pho o he mal ea men (Fig. 13b,c), consis ing o consecu i e NIR lase
i adia ion (808 nm, 1.0 W cm
-2
) o 5 min, on SCC7 cells was i s
e alua ed in i o, e ealing a no iceable educ ion in he cell p oli e -
a ion (Fig. 13d). The immuno he apeu ic sys em was u he e alua ed
in i o using SCC7 umou -bea ing mice whe e a umou was esec ed
a e eaching 100 mm
3
, lea ing a small amoun o umou behind.
Likewise, he NIR lase i adia ion ea men inhibi ed he umou
g ow h and supp essed he esidual umou ecu ence, wi h no
appa en oxici y. This e ec is a consequence o he inc eased in a-
cellula ROS le els ha igge ed umou py op osis, a ype o p o-
g ammed cell dea h, induced by he in lamma o y Caspase-1 clea age o
gasde min D p o ein, he inc ease in T-cell in il a ion, and he dec ease
in he numbe o immunosupp essi e cells. Field Emission Scanning
Elec on Mic oscopy (FESEM) images in Fig. 13a sugges ha he
p ope ies o he oxidized BNC we e main ained since no al e a ions in
i s s uc u e we e e i ied a e coa ing wi h TB. Fu he mo e, he
loading o TB and ⍺PD-1@AuNCs was con i med [238].
The ea ly diagnosis o cance o e s a supe io chance o a success ul
ea men . Su ace-enhanced Raman sca e ing (SERS) is an imaging
echnique wi h ul ahigh sensi i i y, s abili y, low cos , epea abili y,
and ease o use. I has he abili y o iden i y wi h high sensi i i y and
eliabili y he main bioma ke s which in ol e di e en biomolecules,
such as p o eins, nucleic acids, and lipids, dis inguishing umou cells
om no mal cells h ough inge p in signals [239–241]. In a s udy on
cance diagnosis, Fe ei a e al. (2019) de eloped a low-cos hyb id
subs a e based on BNC and in si u g own AgNPs o di ec SERS analysis
o exosomes. S a is ical p incipal componen analysis (PCA) was used o
classi y exosome-de i ed SERS signals ob ained om PBS solu ions o
exosomes isola ed om non umo igenic b eas epi helium (MCF-10A)
and b eas cance (MDA-MB-231) cell cul u es. This label- ee diag-
nos ic me hod allowed a umo al and non umo al exosomes disc imi-
na ion wi h a 95 % con idence [242]. Simila ly, Li e al. (2024) epo ed
he de elopmen o a SERS subs a e based on BNC and in si u syn hesis
o AgNPs, bu o de ec ion o glu a hione in se um. The moni o ing o
glu a hione can be used in cance de ec ion as he le els o his ipep-
ide small molecule a e highe in he se um o cance pa ien s. Fo SERS
measu emen s, Ellman’s eagen (DTNB) was added o colon cance ,
gas ic cance , and no mal se um dilu ed wi h PBS. Highe con en s o
glu a hione we e de ec ed in cance se um when compa ed wi h no mal
se um, being 2.6 imes highe in colon cance and 2.8 imes highe in
gas ic cance [243]. These wo ks show he easibili y and g ea po-
en ial o BNC/AgNPs subs a e o SERS applica ion in eal- ime and
ea ly cance diagnosis. Table 10 p esen s examples o he a ious ap-
plica ions o BNC in cance he apy.
Table 12
4. Conclusions and u u e pe spec i es
The cu en s a e o he a ega ding BNC in he biomedical ield,
especially i s use as wound d essings and body implan s, is desc ibed
abo e. Acco ding o he li e a u e, he g owing in e es in BNC is due o
i s no able in insic p ope ies such as excellen mechanical p ope ies,
high wa e e en ion, easy unc ionaliza ion, high pu i y. In ac , he
impo ance o BNC as a subs i u e o pe ochemical-based polyme s,
L. Mel o e al.
Applied Ma e ials Today 46 (2025) 102858
35
Table 12
BNC composi es in cance he apy applica ions.
Applica ion NPs (o complex) (size;
shape)
D ugs o o he
componen s
Inco po a ion me hod P ope ies Re .
D ug deli e y o b eas
cance ea men
NLCs (sphe ical, ~150
nm)
Doxo ubicin
(Dox) Ex si u – Imme sion
Dox elease: 50 % a e 24 h and sus ained o e
ime [223]
In i o an i umo e icacy (MDA-MB-231 cells)
T ea men o skin cance
and so issues in ec ed
by bac e ial pa hogens
Ag complex wi h 4-ami-
nobenzoic acid (Ag-
pABA) (n.d.)
n.d. Ex si u – Imme sion
An ip oli e a i e ac i i y agains eigh human
umo cell lines (U251, MCF-7, NCI-ADR/RES,
786-0, NCI-H460, PC-3, HT-29, and K562) [224]
Sus ained elease o Ag-pABA up o 120 h
T ea men o skin cance
Ag complex wi h
nimesulide (AgNMS) (n.
d.)
n.d. Ex si u – Imme sion
An ip oli e a i e ac i i y agains
adenoca cinoma (MCF-7, TGI =26.3 µM, PC-3,
TGI =22.8 µM, OVCAR-03, TGI =22.5 µM, and
HT-29, TGI =41.1 µM) cell lines
[225]
An ip oli e a i e e ec a AgNMS
concen a ions highe han 70 µM o he o he
cell lines
Inac i e ee NMS o all human umo s (TGI >
200 µM)
P oli e a ion o immo alized human
ke a inocy es HaCaT una ec ed by AgNMS
complex and NMS
Selec i e inhibi ion o SCC o SCC15 (TGI =67.3
µM) and UACC-62 (TGI =2.8 µM)
Less ac i e agains SCC o FaDu (TGI =107.2
µM) and SCC4 (TGI >400)
Sus ained elease o AgNMS complex o up o
216 h
An i umo al e icacy o he BNC sca old
con aining AgNMS (Balb/c mice wi h induced
SSCC cells)
D ug ca ie sys em wi h
an ibac e ial, an icance ,
and la icidal ac i i ies
CuO NPs (sphe ical, ~ 48
nm) n.d. Ex si u – Solu ion mixing and cas ing
An ibac e ial ac i i y (S. au eus, S. mu ans, S.
yphimu ium, E. coli, and P. luo escens)
[226]An icance : Caco-2, HepG-2, and MDA
An ila icidal ac i i y: A. aegyp i mosqui o in all
s ages o la al and pupal ins a
Chemo he apy (colon
cance )
Fe
3
O
4
NPs (sphe ical,
8–15 nm) n.d. Ex si u – Co-p ecipi a ion
An ibac e ial (8 s ains)
[227]Non-cy o oxic
An icance
Pho odynamic and
pho o he mal he apy o
mic obial disin ec ion
PCN-224 MOFs@Ti
3
C
2
MXene (n.d.) Nanosil e Ex si u – Fil a ion and spu e ing
An ibac e ial ac i i y:
[233]
S. au eus and E. coli (>99.99 %, 2 h o NIR ligh
exposu e
Cy o oxici y: Cell iabili y (L929 cells) 75.84
and 69.75 %, a e 12 and 24 h
Pho odynamic he apy o
mic obial disin ec ion
CQDs@PCN-224 MOFs
(sphe ical, 99.1 ±18.1
nm)
n.d. In si u – mixing in cul u e
medium +sonica ion
The mally s able a 265 ◦C
[234]
B eaking s ess: 12.5 MPa
Elonga ion a b eak: 27 %
An ibac e ial ac i i y: S. au eus and E. coli (>
99.99 %, 30 min o NIR ligh exposu e)
Good hemocompa ibili y: hemolysis a es <5 %
( abbi ed blood cells)
Non-cy o oxic. Cell iabili y (L929 cells) 88 %
Pho o he mal he apy o
mic obial disin ec ion
AuNRs ( od-like, 51
±7x15±3 nm;) PTB Ex si u – Imme sion
An i ouling (FITC-BSA p o ein, E. coli DH5
α
-
pBADDs bac e ia, and L929 cells)
[235]
An ibac e ial ac i i y: S. au eus and E. coli
(~100 %, 5 min o i adia ion o NIR ligh
exposu e)
Good biocompa ibili y wi h negligible
cy o oxici y in i o (L929 cells)
Skin wound healing pe o mance in i o
(Sp ague-Dawley a s)
D ug deli e y and
pho odynamic he apy
o b eas cance
ea men
Magne ic-hyd ogel
(Fe
3
O
4
-FA-NIPAm-AA)
NPs (MHNP) (n.d., ~106
nm
Dox and HMME Ex si u – Imme sion
In i o – cell g ow h delayed 50 % (MCF-7 cells)
and 82 % in a sc a ch/wound healing es
[236]
No inhibi ion in he g ow h o HSF cells
In i o – umou g ow h inhibi ion a es o 80.38
% (MCF7 cells)
No e idence o leukopenia o associa ed oxici y
Pho odynamic he apy o
skin cance ea men
Fulle ene C60 (n.d., <100
nm) n.d. Ex si u – Vacuum il a ion
An ibac e ial ac i i y agains E. coli and
S. au eus [237]
An i-cance (human-de i ed epide moid
ca cinoma A-431 cells)
Pho o he mal he apy and
immuno he apy AuNCs (cubic, 89.0 nm) PD-1 an ibody
and h ombin Ex si u – Imme sion
In i o – ma ked educ ion in cell p oli e a ion
(SCC7 cells) [238]
In i o – umou ecu ence inhibi ed wi hou
oxici y
(con inued on nex page)
L. Mel o e al.
Applied Ma e ials Today 46 (2025) 102858
36
such as polye hylene, polyp opylene, polyu e hane, poly e a luo o-
e hylene, and polye he e he ke one, which a e p e alen in es ablished
biomedical ma e ials, is clea . These polyme s o en su e om poo
biocompa ibili y, bo h sho - and long- e m, con a y o BNC, which can
lead o ch onic in lamma o y esponses and he o ma ion o ib ous
collagen capsules a ound hem. This, in u n, can esul in pain,
es ic ed mo emen , and e en nec osis.
In u n, he physical cha ac e is ics o he BNC’s ib ous ne wo k a e
pa icula ly well-sui ed o wound d essings and implan s because hey
closely esemble he ex acellula ma ix, especially i s componen ,
collagen. As a esul , i s use in blood essels and biosenso s is, also, o
pa icula in e es . In addi ion, he po en ial o ex ensi e modi ica ions,
unc ionaliza ion p ocesses, and ca ie applica ions enhances i s
di e se biomedical uses. In ac , since speci ic p ope ies can be easily
endowed o BNC, issue enginee ing seems o be one o he mos in e -
es ing a eas, e.g. by he inco po a ion o bioac i e molecules ha p o-
mo e cell g ow h leading o issue epai and egene a ion. The majo
numbe o s udies ound a e ocused on wound d essings and wound
healing, highligh ing he con inued de elopmen o BNC o hese ap-
plica ions, due o i s ele an p ope ies o biocompa ibili y, high
po osi y, wa e holding capaci y, and non oxici y. Fo so implan a ea,
ca ilage, ascula g a s/blood essels, and co nea a e he mos com-
mon applica ions, based on he a ou able mechanical p ope ies. Ha d
issue implan s a e majo ly based on bone issue egene a ion, ha ake
ad an age o i s nano sca old a chi ec u e. Ino ganic nanopa icles/
complexes s ill play an impo an ole in he unc ionaliza ion o BNC,
despi e he g owing e o s on using o ganic nanopa icles/complexes.
The displayed sepa a ion be ween ino ganic and o ganic nanopa icles/
complexes should assis in highligh ing i s in luence owa ds BNC and i s
applica ion goal, en isaging a endency o he mos e ec i e and o less
de imen al. Ne e heless, due o non-consis en cha ac e iza ion
me hodology displayed in he e e ences, i is ex emely p eca ious he
es ablishmen o a compa ison. Thus, o he de elopmen o u u e
applica ions, o bo h ino ganic and o ganic nanopa icles/complexes a
cohe en se o cha ac e iza ions should be p omo ed o allow a obus
compa ison be ween hese wo app oaches. Again, despi e he in iguing
physicochemical p ope ies o BNC, he e is no clea consensus on
es ing me hodology, especially ega ding pa ame e s and assay ypes.
Va ia ions assays, such as whe he hey a e conduc ed on ne e -d ied,
lyophilized, o d ied samples, and whe he empe a u e o acuum
condi ions a e used, a e also signi ican . The e o e, imp o ing he
s anda diza ion o me hodology s physicochemical p ope ies should
ocus on de ining he applica ions equi emen s and ea he ma e ial
a chi ec u e as a nano non-wo en ma e ial. Fu he mo e, al hough
cellulases capable o deg ading cellulose a e no p esen in he human
body, BNC is s ill exposed o mechanical s ess, oxida ion, and o he
ac o s ha could a ec i s long- e m use. The e o e, u he in es iga-
ion is needed o unde s and and co ela e all hese concep s in o de o
ake ad an age o he excellen p ope ies o his sus ainable ma e ial.
In conclusion, BNC unc ionalized wi h ino ganic and o ganic
nanopa icles/complexes clea ly display a wide se o ele an unc ions
and ac i i ies, ha may and should be explo ed in o he a eas. I s ib ous
na u e clea ly d i es i s use owa ds he ex ile indus y, in pa icula o
he de elopmen o ad anced mul i unc ional echnical ex iles, ha
comp ise a ple ho a o applica ions. The main ac o impai ing his shi
is i s ecalci an high p oduc ion cos . Howe e , he a ailable unding
o he implemen a ion o sus ainable indus ies, should p ess he
de elopmen o no el BNC p oduc ion me hodologies and u he lead
o low-cos cul u e media use bio-based on was e p oduc s. A lowe cos
BNC will p omp ly pe mea e wi hin ib e-based indus ies such as
packaging, au omo i e, and cons uc ion.
CRediT au ho ship con ibu ion s a emen
Liliana Mel o: W i ing – e iew & edi ing, W i ing – o iginal d a ,
Visualiza ion, Valida ion, Me hodology, In es iga ion, Concep ualiza-
ion. C´
a ia Al es: W i ing – e iew & edi ing, W i ing – o iginal d a ,
Visualiza ion, Valida ion, Me hodology, In es iga ion, Concep ualiza-
ion. Ma a Fe nandes: W i ing – e iew & edi ing, W i ing – o iginal
d a , Visualiza ion, Valida ion, Supe ision, Me hodology, In es iga-
ion, Concep ualiza ion. So ia Rocha: W i ing – e iew & edi ing,
W i ing – o iginal d a , Visualiza ion, Valida ion, Me hodology, In es-
iga ion. Behnaz Meh a ani: W i ing – e iew & edi ing, W i ing –
o iginal d a , Valida ion, Me hodology, In es iga ion. Ana Isabel
Ribei o: W i ing – e iew & edi ing, W i ing – o iginal d a , Valida ion,
Me hodology, In es iga ion. Sa a Aze edo: W i ing – o iginal d a ,
Valida ion, Me hodology, In es iga ion. Vanessa F. Ca doso: W i ing –
e iew & edi ing, Visualiza ion, Valida ion. ´
Osca Ca alho: Valida-
ion. Nuno Dou ado: Valida ion. An ´
onio J. Salgado: Valida ion.
And ea Zille: W i ing – e iew & edi ing, Visualiza ion, Valida ion,
Supe ision. Jo ge Pad ˜
ao: W i ing – e iew & edi ing, Visualiza ion,
Valida ion, Supe ision, Concep ualiza ion.
Decla a ion o compe ing in e es
The au ho s decla e ha hey ha e no known compe ing inancial
in e es s o pe sonal ela ionships ha could ha e appea ed o in luence
he wo k epo ed in his pape .
Acknowledgemen s
This wo k was unded by he Eu opean Regional De elopmen Fund
h ough he Ope a ional Compe i i eness P og am and he Na ional
Founda ion o Science and Technology o Po ugal (FCT) unde he
p ojec s UID/CTM/00264/2020 o Cen e o Tex ile Science and
Technology (2C2T) on i s componen s Base (10.54499/UIDB/00264/
2020) and p og amma ic (10.54499/UIDP/00264/2020). The au ho s
Liliana Mel o, C´
a ia Al es, Behnaz Meh a ani and Vanessa Ca doso also
acknowledge he g an s suppo ed by MCTES, FSE, UE and FCT, I.P.
2020.04919.BD (h ps://doi.o g/10.54499/2020.04919.BD), 2022.10
454.BD (h ps://doi.o g/10.54499/2022.10454.BD), 2022.13094.BD
(h ps://doi.o g/10.54499/2022.13094.BD), and 2020.02304.CEE-
CIND (h ps://doi.o g/10.54499/2020.02304.CEECIND/CP1600/CT0
025), espec i ely.
Table 12 (con inued)
Applica ion NPs (o complex) (size;
shape)
D ugs o o he
componen s
Inco po a ion me hod P ope ies Re .
Cance diagnosis (SERS) AgNPs (n.d., 92.1±51.57
nm) n.d. Ex si u – Mic owa e in si u AgNPs
syn hesis in o BNC
Enhancemen ac o s (EF): 10
4
o 10
5
( hodamine 6G, 10
−11
M)
[242]Di e en ia ion o umo al and non- umo al
exosomes: MCF-10A and MDA-MB-231 wi h 95
% con idence
Cance diagnosis (SERS) AgNPs (n.d., 65±10 nm) n.d. Ex si u – Soaking in ammonia
ollowed by in si u educ ion in sil e
i luo oace a e (CF3COOAg) solu ion
EF: 3.8 ±10
7
(glu a hione in se um o cance
(gas ic and colon), 2.9 ±10
–8
M)
[243]
n.d. – no de ined.
L. Mel o e al.
Applied Ma e ials Today 46 (2025) 102858
37
Da a a ailabili y
No da a was used o he esea ch desc ibed in he a icle.
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