Re iew a icle
Nanoma e ial-based sca olds endowed wi h haloch omic p ope ies o
skin healing pu poses
Ana R.M. Ribei o
a
, B una A.S. Oli ei a
a
, Ana Isabel Ba bosa
b
, Ca a ina L. Seab a
b
,
Sale e Reis
b
, Helena P. Felguei as
a,*
a
Cen e o Tex ile Science and Technology (2C2T), Uni e si y o Minho, Campus de Azu ´
em, 4800-058 Guima ˜
aes, Po ugal
b
Associa e Labo a o y o G een Chemis y (LAQV), Ne wo k o Chemis y and Technology (REQUIMTE), Depa men o Chemical Sciences, Facul y o Pha macy,
Uni e si y o Po o, 4050-313 Po o, Po ugal
ARTICLE INFO
Keywo ds:
Biomedical sca olds
Elec ospinning
Haloch omism
Nanoma e ials
ABSTRACT
Recen ly, biomedical enginee ing has seen signi ican ad ancemen s in nanoma e ial-based sca olds o issue
enginee ing and wound healing. Inco po a ing haloch omic p ope ies wi hin hese sca olds has ga ne ed
subs an ial in e es due o hei eal- ime moni o ing abili ies o accessing issue g ow h and egene a ion. This
e iew p esen s a comp ehensi e analysis o ecen ad ancemen s in nanoma e ial-based sca olds wi h hal-
och omic unc ionali ies o skin biomedical applica ions. This discussion e ol es a ound he a ious classes o
nanoma e ials used in sca old ab ica ion, including bu no limi ed o elec ospun nanoma e ials, polyme ic
nanoma e ials (bo h o na u al and syn he ic o igins), and nanoma e ials based on bio-composi es, each o e ing
dis inc ad an ages and limi a ions in e ms o mechanical p ope ies, biocompa ibili y, and unabili y o hal-
och omic esponse. Emphasis is placed on in eg a ing haloch omic moie ies, such as pH-sensi i e dyes, in o he
sca old ma ices, wi h a ocus on main aining op imal cy ocompa ibili y and bio unc ionali y. A key ocus is
gi en o ecen in i o s udies showcasing he po en ial o haloch omic nanoma e ial-based sca olds in clinical
applica ions. The no el y o his s udy lies in p o iding a s uc u ed amewo k o unde s anding he in e ac ion
be ween haloch omic nanoma e ials and biomedical sca olds, iden i ying challenges, and p oposing u u e
esea ch di ec ions o enhance hei diagnos ic and he apeu ic po en ial.
1. In oduc ion
Nano echnology is an eme ging ield o esea ch ha deals wi h
syn hesizing ma e ials a nanome ic scale. Nanoma e ials, cha ac e -
ized by hei unique physicochemical p ope ies and small size, o e
dis inc i e ad an ages in he design o biomedical sca olds, including
he abili y o ci cula e along he body wi hou dis up ing blood low and
o esis exc e ion by he enal canal and o he complemen sys ems [1,
2]. These ma e ials, anging om nanopa icles and nano ibe s o
nanocomposi es, p o ide ailo ed s uc u al biocompa ibili y, ole a-
bili y and mechanical cha ac e is ics ha closely mimic he na i e
ex acellula ma ix [3–5]. This simila i y is essen ial o p omo ing
cellula adhesion, p oli e a ion, and di e en ia ion, gene a ing a
mic oen i onmen ideal o issue egene a ion and e ec i e wound
healing. They can be applied o a ious ypes o sca olds, such as ma s
p oduced by elec ospinning, hyd ogels, o a combina ion o bo h,
known as composi es.
Wound managemen is a c ucial pa o heal hca e, impac ing pa-
ien s’ quali y o li e and placing a inancial s ain on he heal hca e
sys em. The ad ancemen o sma bandages o e s signi ican p omise
o wound moni o ing and p ecise ea men [6].
The use o nanoma e ials in medicine has enabled inno a i e s a-
egies o enhance diagnos ics, ea men s, and he apeu ics [7].
Exploi ing he unique p ope ies o nanoma e ials, such as hei high
su ace a ea o olume a io and unab le su ace chemis y, has enabled
he de elopmen o sma d essings, a ge ed d ug deli e y sys ems and
biosenso s wi h unp eceden ed p ecision [8]. O e he las decade, in
Eu ope, he use o nanoma e ials in medicine has been on he ise,
d i en by signi ican esea ch and de elopmen e o s in academia,
indus y, and go e nmen - unded ini ia i es [2,9]. Sma d essings a e
an a ea o applica ion in which nano echnology has acili a ed he
de elopmen o highly sensi i e solu ions (de ices, new d essings, e c.)
* Co esponding au ho .
E-mail add esses: [email p o ec ed] (A.R.M. Ribei o), [email p o ec ed] (B.A.S. Oli ei a), [email p o ec ed] (A.I. Ba bosa), ca i.
[email p o ec ed] (C.L. Seab a), [email p o ec ed] (S. Reis), [email p o ec ed] (H.P. Felguei as).
Con en s lis s a ailable a ScienceDi ec
Jou nal o D ug Deli e y Science and Technology
jou nal homepage: www.else ie .com/loca e/jdds
h ps://doi.o g/10.1016/j.jdds .2025.106950
Recei ed 26 No embe 2024; Recei ed in e ised o m 26 Feb ua y 2025; Accep ed 18 Ap il 2025
Jou nal o D ug Deli e y Science and Technology 108 (2025) 106950
A ailable online 19 Ap il 2025
1773-2247/© 2025 The Au ho s. Published by Else ie B.V. This is an open access a icle unde he CC BY license ( h p://c ea i ecommons.o g/licenses/by/4.0/ ).
ha can de ec low amoun s o biomolecules in bodily luids such as
blood and u ine, acili a ing ea ly de ec ion and disease/wound man-
agemen wi h high sensi i i y and speci ici y [9,10].
Ch omic p ope ies allied o sma d essings ep esen an inno a i e
s a egy o medical ea men s. The abili y o isually moni o changes
in he sca old en i onmen and he e olu ion o egene a ion and
healing p ocesses opens a new enue o wound ea men s a egies
[11]. In biomedical applica ions, ch omic nanoma e ials can be
designed o espond in eal- ime o speci ic biological igge s o
changes in physiological condi ions such as pH, empe a u e, he p es-
ence o mic oo ganisms, and biochemical signals ha a e essen ial o
p ese ing heal h s a us [12]. pH- esponsi e nanoma e ials, which un-
de go colo changes in acidic o basic en i onmen s a e commonly
ound in biological sys ems (haloch omism). The inco po a ion o hal-
och omic elemen s in o nanoma e ial-based sca olds no only enhances
hei unc ionali y bu also unlocks he po en ial o inno a i e di-
agnos ics and he apeu ic ools [13]. Fu u e haloch omic d essings
di e om comme cially a ailable ones by hei abili y o change colo
in esponse o pH changes in a wound. This colo change can indica e he
wound’s condi ion, such as in ec ion o healing p og ess, p o iding
eal- ime, non-in asi e moni o ing. T adi ional bandages lack his dy-
namic eedback capabili y and only se e as a p o ec i e co e ing
wi hou p o iding in o ma ion abou he wound’s s a e and equi ing
cons an emo al o he bandage, o en damaging he newly o med
issue and in e up ing he healing p ocess [14,15].
This e iew aims o explo e he syne gis ic ela ionship be ween
nanoma e ial sca olds and haloch omic agen s in he con ex o
biomedicine, ocusing on he la es de elopmen s and applica ions o
hese sma sca olds in he ield o skin healing. Addi ionally, he
challenges and u u e di ec ions in binding he ull po en ial o nano-
ma e ials wi h haloch omic p ope ies o ad ancing biomedical ech-
nologies will be add essed. This e iew highligh s as well he challenges
associa ed wi h he s abili y o haloch omic species unde physiological
condi ions, emphasizing he impo ance o ailo ed su ace modi ica-
ions and encapsula ion s a egies o mi iga e po en ial cy o oxici y and
deg ada ion e en s. Finally, he po en ial pa hways o u u e esea ch
o hese sma nanoma e ial-based sca olds in clinical se ings a e dis-
cussed, seeking o s imula e c ea i e app oaches o ad ancing he
design o such cons uc s o each imp o ed diagnos ic and he apeu ic
unc ionali ies.
2. Biomedical sca olds based on nanoma e ials
Nanoma e ial-based sca olds ha e widesp ead in e es in biomedi-
cine due o hei abili y o eplica e he na u al en i onmen o body
issues, mimicking he ex acellula ma ix, and p o iding s uc u al
suppo and mechanical p o ec ion [16]. These sca olds play an
impo an ole in issue enginee ing and wound managemen o
epai ing, imp o ing, and main aining issue o ma ion [17].
In Oc obe 2011, he Eu opean Commission de ined nanoma e ials
as na u al, inciden al, o manu ac u ed ma e ials ha con ain unbound
o agglome a e pa icles, whe e 50 % o mo e o he pa icles, mus be
be ween 1 and 100 nm [18]. These ma e ials ha e inno a i e physical
(la ge speci ic su ace a ea, small size) chemical ( esis ance o co osion,
high eac i i y, ca aly ic abili y), and biological p ope ies (biodeg ad-
abili y, biocompa ibili y, low immunogenici y, e c.), a o ing mo e
e ec i e cellula in e ac ions compa ed wi h mic o and mac oscale
ma e ials [16,18,19]. The inco po a ion o nanoma e ials in o biomed-
ical sca olds has demons a ed posi i e e ec s on cell adhesion,
iabili y, p oli e a ion, and mig a ion, h ough biochemical, bioelec-
ical, o biomechanical signals [16,20,21]. Despi e he p omising po-
en ial o hese sca olds, issue enginee ing and wound managemen
aces challenges, such as he lack o sui able bioma e ials, di icul ies in
eplica ing issue cha ac e is ics in i o, and he absence o p ecise
con ol o e he physiological s uc u e o he sca olds [22].
In he p oduc ion o biomedical sca olds based on nanoma e ials,
polyme s a e used and classi ied acco ding o hei o igin as na u al o
syn he ic, and acco ding o chemical composi ion, as o ganic o ino -
ganic [16,23,24]. Bo h na u al and syn he ic polyme s ha e been
explo ed as biocompa ible and biodeg adable ma e ials o de eloping
o nano-sca olds. Na u al nanoma e ials, which come om mic oo -
ganisms, human issues, animals, o plan sou ces, a e gene ally
non- oxic bu ha e high cos s due o p ocessing and insula ion. Also,
hei p ope ies’ ep oducibili y is limi ed [24,25].
In u n, syn he ic ma e ials, a e mo e easily ob ained wi h he
desi able ea u es and hei a ailabili y is no as limi ed. Howe e , like
na u al ma e ials, hey may exhibi ba ch o ba ch a ia ion o e en
p oduc ion cos s [24]. Syn he ic ma e ials can be ca ego ized as
biodeg adable (such as polyes e s, poly-anhyd ides, and poly-
phosphoes e s) and non-biodeg adable (such as polye hylene and
polye hylene e eph hala e) [24,26,27].
The use o mul iple na u al and syn he ic polyme s, o bo h, is a
s a egy adop ed o p o ide a a ie y o physicochemical and biological
cha ac e is ics, o e ing mechanical and biochemical suppo o cells
and con olling egene a ion [20,26,28].
Na u ally-de i ed bioma e ials used in sca olds ha e ad an ages in
wound healing, issue enginee ing, d ug deli e y, in ec ious disease
diagnos ics, and egene a i e medicine [20,29–31]. Based on he spec-
i ici y o he s uc u al design, i is possible o dis inguish se e al ypes
o sca olds, including ib ous, hyd ogels, mic osphe e-based sys ems,
acellula , and composi e s uc u es [32]. Fo op imizing
h ee-dimensional (3D) sca olds, nume ous manu ac u ing echniques
ha e been used, including con en ional elec ospinning, sol en cas-
ing/pa icle leaching, he mally induced phase sepa a ion (TIPS),
eeze d ying, gas oaming, powde oaming, sol-gel, e c. Inno a i e
apid p o o yping echniques, such as used deposi ion modelling,
binde je ing echnique, s e eoli hog aphy, inkje p in ing, selec i e
lase sin e ing, lase -assis ed biop in ing, me al-based addi i e
manu ac u ing and di ec cell w i ing, a e, h ough he deposi ion o
o e lapping laye s, also able o p oduce nano-sca olds in 3D [17,33].
Each app oach al e s he sca olds’ a chi ec u e, in luencing po e size,
s uc u e, in e connec i i y, and mechanical p ope ies [32].
In his sec ion, di e en ypes o nano-sca olds a e discussed o
unde s and how hei p ope ies con ibu e o he biomedical pu pose.
Elec ospun nanoma e ials a e highligh ed and inally, bio-composi e
sca olds a e p esen ed as an app oach o combining di e en ypes o
nanoma e ials.
2.1. Polyme -sou ced nanoma e ials
Polyme ic nanoma e ials e e o ma e ials wi h dimensions a he
nanome e scale, and hey exhibi excep ional op ical, mechanical,
elec ical and ca aly ic p ope ies. Thei cha ac e is ics can be adjus ed
as needed, con olling he size, shape, syn hesis condi ions and unc-
ionaliza ion [34]. Due o hei unique p ope ies and unc ionali y,
polyme ic nanoma e ials ind se e al applica ions, om accina ion o
cell and gene he apies, as well as in he design o inno a i e de ices
aimed a new wound ea men s a egies [18]. In gene al, hey possess
high su ace- o- olume a io, adjus able s uc u e, small size and
biocompa ibili y [18,35].
Rega ding polyme ic nanopa icles, he e a e wo dis inc ypes: (1)
nanosphe es, cha ac e ized by solid and homogeneous s uc u es, in
which he ac i e compound and polyme a e equally dispe sed and (2)
nanocapsules, which exhibi a hollow, oily o aqueous s uc u e, wi h
he ac i e elemen s housed in a ese oi , which is su ounded by a
polyme ic memb ane [35,36]. Polyme ic nanopa icles (PNPs) s and ou
as p omising ehicles in he con olled deli e y o d ugs and egene a-
i e issue enginee ing [37,38]. Lu e al. de eloped sil e -deco a ed
mesopo ous silica nanopa icles (Ag-MSNs) by means o disul ide
bonds (addi ion o bis (3- ie hoxysilyl p opyl) disul ide). The s udy
demons a ed ha Ag-MSNs possess obus adhesi e p ope ies and
e ec i e an ibac e ial ac i i y, o e ing a p omising solu ion o he
A.R.M. Ribei o e al.
Jou nal o D ug Deli e y Science and Technology 108 (2025) 106950
2
apid and sa e closu e o skin wounds. Fu he mo e, Ag-MSNs p o ed o
be biodeg adable and biocompa ible, minimizing cellula and sys emic
oxici y du ing he healing p ocess. These esul s indica ed ha poly-
me ic nanoma e ials, especially hose de i ed om Ag-MSNs, ep esen
an inno a i e and p omising app oach o he de elopmen o ad anced
issue adhesi es wi h signi ican po en ial o clinical applica ions in
egene a i e medicine [39]. On he o he hand, polyme ic nano-
composi es (PNCs), a e made o a ma ix, he polyme , and a ein-
o cemen o nano ille . Commonly, hese a e ligh weigh and
cos -e ec i e and can be molded in o di e en shapes and sizes, mak-
ing i possible o con ol su ace a ea, op ical p ope ies, ca aly ic ac-
i i y and magne ic beha iou [40]. Th ough he inco po a ion o small
amoun s o nano ille s, imp o emen s in he composi e p ope ies,
he mal, chemical, mechanical o elec ical, a e ecognized [41]. In a
s udy conduc ed by Yao e al., a ma ix o me hac yla e hyalu onic acid
mic oneedles encapsula ed in me al-o ganic s uc u es o zinc h ough
he molding me hod was in es iga ed in o de o p omo e wound
healing. The ma ix demons a ed excellen an ibac e ial ac i i y due o
he con olled elease o zinc ions, as well as ci ocompa ibili y.
Fu he mo e, he mic oneedles ma ix was deg adable, allowing he
con inuous elease o he ac i e ing edien and, h ough ha , p omo ing
issue egene a ion. The s udy highligh ed he e ec i eness o mic o-
needles in accele a ing epi helial egene a ion and neo ascula iza ion,
ep esen ing a p omising ea men s a egy o wounds [42].
The e a e also polyme ic nano ibe s, which can be modi ied wi h
polysaccha ides, p o eins, pep ides, na u al ex ac s and e en g ow h
ac o s [43]. Gene ally, nano ibe s wi h applica ions in biomedicine a e
p oduced h ough elec ospinning, since his echnique is ema kable
o i s e sa ili y in e ms o polyme s o usage, ibe diame e , and
possibili y o la ge-scale p oduc ion.
2.1.1. Polyme ic nano ibe s: shaping sca olds’ a chi ec u e
Elec ospinning is a simple, economical, e sa ile and p omising
echnique ha allows he p oduc ion o nano ibe s wi h adjus able
s uc u es, p ope ies and unc ions, is aluable o he cons uc ion o
sca olds o a ious applica ions in indus y and esea ch [44]. When
p oduced by his echnique, he nanoma e ial exhibi s exclusi e
in insic p ope ies, highligh ing adjus able size dis ibu ion, good
connec i i y, ease o unc ionaliza ion wi h bioac i e molecules, s uc-
u al s abili y, uni o mi y, composi ional di e si y, and s uc u al lex-
ibili y, augmen ing hei appeal [24,45]. The e o e, inding po en ial
uses in se e al a eas, co e ing he ield o ene gy, en i onmen , issue
enginee ing and biomedical enginee ing, since hey a e non- oxic,
biodeg adable and biocompa ible, hus being able o en e in o di ec
and indi ec con ac wi h biological sys ems [46,47]. The echnique is
based on elec os a ic a ac ion and in ol es he p oduc ion o
ex emely na ow ibe s, wi h diame e s anging om a ew nanome e s
o se e al mic ome e s in scale. A polyme ic solu ion is ejec ed om a
needle wi h a speci ic diame e by he in luence o an elec os a ic ield,
induced by high ol age anging om 1 o 30 kV [48]. The esul ing je
is collec ed by an opposi ely cha ged collec o o assemble he ejec ed
ibe s [49,50]. Elec ospinning allows consis en p oduc ion o sca olds
wi h a la ge su ace a ea. Elec ospun nano ibe s can be p oduced om
na u al o syn he ic polyme s, and he mix u e o hese polyme s adjus s
he unc ionali y o he esul ing nano ibe s, o e ing a ema kable di-
e si y o composi ion and p ope ies [51–53]. This echnique s ands
ou o i s abili y o mimic he cha ac e is ics o he cellula ma ix, as
hey p esen a highly po ous 3D ne wo k wi h excellen in e -
connec i i y [24,54].
The concen a ion, iscosi y, su ace ension, polyme s uc u e,
molecula weigh , sol en ype and conduc i i y o he polyme ic solu-
ion can in luence he e iciency o he p ocess. The in ensi y o he
elec ic ield, he dis ance om he ip o he collec o and he low a e
a e p ocess pa ame e s ha can also a ec e iciency. Finally, he e a e
en i onmen al pa ame e s, such as humidi y, p essu e, ai eloci y and
empe a u e, which play a c ucial ole. All hese pa ame e s di ec ly
a ec he su ace mo phology, diame e and ex u e o he ibe s p o-
duced [45,51,55,56].
Despi e he dis inc and ad an ageous cha ac e is ics, elec ospun
sca olds s ill p esen limi a ions, such as low cell pene a ion due o he
high packing densi y o he nano ibe laye s, esul ing in ex emely
small po es, which can comp omise cell mig a ion, ascula iza ion and
adequa e issue in e ac ion, po en ially a ec ing issue egene a ion and
cell unc ion [49]. Ano he limi a ion is he inadequa e load suppo . Fo
uses as weigh -bea ing cell issues, elec ospun nano ib ous ma s should
each 150 MPa, which due o hei high po osi y, is ex emely ha d o
accomplish [49,57,58]. The use o oxic sol en s (i.e., o ganic), and low
p oduc i i y a e also among he limi a ions o he s anda d elec o-
spinning echnique [59]. To o e come se e al o hese limi a ions
combina ions o o ganic wi h ino ganic componen s, na u al wi h syn-
he ic, na u al wi h ino ganic, e c., ha e been p oposed o enhance in-
di idual componen p ope ies o e en gene a e syne gis ic e ec s [61].
Saeed e al. examined a h ee-laye d essing p oduced h ough elec o-
spinning, using polycap olac one (PCL), poly inyl alcohol (PVA), and
cu cumin. This d essing se es o abso b wound exuda es, main ain
wound mois u e, and le e age cu cumin’s an ibac e ial p ope ies,
add essing gaps ound in o he con en ional d essings, combining
wound p o ec ion wi h an ibac e ial p ope ies. The addi ion o he PVA
laye ipled he abso p ion capaci y, signi ican ly enhancing exuda e
abso p ion and educing o eign body esidues in wounds. Wi h 16 %
(w/ ) cu cumin con en , he d essing displayed an ibac e ial ac i i y,
e ec i ely elimina ing bo h G am-posi i e and G am-nega i e bac e ia
wi hin 48 h [60]. Baya e al. used elec ospinning o p oduce chi osan
nano ibe s loaded wi h b omelain (ex ac con aining p o eoly ic en-
zymes ex ac ed om plan s o he B omeliaceae amily, which includes
pineapple) a 2 % and 4 % (w/ ) o ea skin bu ns. The e ec i eness o
his ea men was e alua ed h ough he educ ion o he bu ned a ea
and his ological analysis. Nano ibe s loaded wi h 2 % (w/ ) b omelain
demons a ed supe io p ope ies and imp o ed e iciency in healing
skin bu ns compa ed o hose loaded wi h 4 % (w/ ) b omelain. In his
way, chi osan nano ibe s wi h 2 % (w/ ) b omelain p o e o be a
p omising na u al opical ea men o de mal egene a ion in cases o
bu ns [61]. Teixei a e al. de eloped elec ospun ma s c oss-linked wi h
glu a aldehyde apo , made om cellulose ace a e (CA) combined wi h
PVA, o ea ch onic wounds. Ma s we e unc ionalized wi h he an i-
mic obial pep ide Cys-pexiganan and he immuno egula o y pep ide
Tige 17. A e analysis, hey ound ha Tige 17 accele a ed plasma
coagula ion, educing he o ma ion o clo s, and making i p omising
o wound healing. Based on his s udy, elec ospinning ma s con aining
PVA and CA, especially in he op imized a io o 90/10 % ( / ), showed
p omise o ea ing wounds by con ibu ing o he adequa e abso p ion
o exuda es and e ec i eness in comba ing bac e ial in ec ion [62].
2.1.2. Polyme ic nano-composi e sca olds
The in elligen combina ion o di e en nanoma e ials plays a
c ucial ole in he skin healing ield. Indeed, he bio-nanocomposi es
(BNCs), also known as biohyb id ma e ials, g een composi es o nano-
biocomposi es, a e made o a biopolyme and an ino ganic solid [63,64].
These ma e ials a e classi ied unde a g oup o composi e ma e ials wi h
di e se componen s, each possessing dis inc p ope ies like an imic o-
bial o an ioxidan ac i i y and a e me ged unde a ying condi ions
including speci ic empe a u es o he p esence o a sol en [65]. This
in ol es combining na u al elemen componen s such as biopolyme s,
including polysaccha ides (cellulose, aga , chi osan), p o eins and
nucleic acids wi h ino ganic componen s (nano- ein o cemen s), such as
i anium dioxide, zinc oxide, among o he s, on a nanome ic scale,
endowing hem wi h unique p ope ies and making hem a p omising
al e na i e o syn he ic ma e ials [66–69].
Nano- ein o ce s exhibi a ema kable su ace- o- olume a io, hus
op imizing in e ac ions wi h he polyme ic ma ix, esul ing in
imp o ed ma e ial pe o mance, e en a educed amoun s o nano ille .
This disc epancy a ises om he highe densi y o binding si es,
A.R.M. Ribei o e al.
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3
acili a ing s onge adhesion be ween he nano ille and he polyme ic
ma ix. Nano- ein o cemen s p o ide mo e ac i e in e ac ion si es,
enabling a mo e e icien and uni o m dis ibu ion wi hin he composi e
ma e ial compa ed o con en ional composi es, which need la ge p o-
po ions o achie e simila ou comes [70]. The pe o mance o
bio-nanocomposi es depends on he dispe sion o nanopa icles in he
polyme ma ix, wi h such dispe sion being a ec ed by he ype o sol-
en , mixing me hod and size o he nanopa icles. Techniques such as
plasma modi ica ion, g a ing o coa ing wi h bio-moie ies and chemical
modi ica ions, a e used o modi y he su ace o he nano ille s,
con ibu ing o inc easing he biocompa ibili y [71].
In bio-nanocomposi es, he cen al challenge is o imp o e pe o -
mance by combining he p ope ies o he componen s. Polyme s, being
biocompa ible and biodeg adable, complemen he mechanical and
he mal p ope ies o he ino ganic pa , hus b idging he gap be ween
unc ional and s uc u al ma e ials [69].
Compa ed o isola ed na u al ma e ials, bio-composi e ma e ials
o e se e al ad an ages, such as a igue esis ance, abili y o esis
impac s, igidi y, co osion esis ance, biodeg adabili y, he mal con-
duc i i y e iciency, low ela i e densi y, en i onmen ally iendly
was e s ages, ligh weigh and high speci ic esis ance [72]. Addi ion-
ally, due o hei ema kable an imic obial ac i i y, hese ma e ials can
unc ion as ac i e agen s o e ec i ely inac i a e pa hogenic mic oo -
ganisms [73].
Bio-nanocomposi es can be classi ied acco ding o o igin, size, and
shape o ein o cemen s and ypes o ma ices used. Based on he shape
o he ein o cing pa icles, BNCs can be ca ego ized in o: (1) pa icle
BNCs, which a e hose ha use dimensional pa icles as ein o cemen
and educe pe meabili y, o make composi es non- lammable, and o
dec ease he cos s; (2) BNCs wi h elonga ed pa icles, which use elon-
ga ed pa icles such as cellulose nano ibe s as ein o cemen , p o iding
be e biomechanical beha iou due o he high aspec a io o he
ein o cemen ; and (3) BNCs ein o ced by laye ed pa icles, also called
laye ed polyme nanocomposi es, which a e di ided acco ding o he
dispe sion a e in he ma ix in mic o-composi es, loccula ed/phase-
sepa a ed nanocomposi es, in e cala ed and ex olia ed nanocomposi es
[74].
BNCs ind se e al applica ions as d ug deli e y sys ems, accines,
wound d essings and issue enginee ing, due o hei biocompa ibili y,
and inhe en non- oxici y, impo an o he p ope unc ion o he
human body wi hou igge ing side e ec s [68,75]. These a e s ill being
explo ed o applica ions in he elec onics, en i onmen al, ene gy, and
cosme ic indus ies, bioac i e implan s, among many o he s [65,76].
As o healing pu poses, he e is apid epai when wounds a e
ea ed wi h d essings con aining BNCPs. Recen ly, Baghe i e al. used
composi e nanoma e ials, namely sil e nanopa icles (AgNPs) and zinc
oxide (ZnO) inco po a ed in o chi osan (CS) and polye hylene oxide
(PEO) nano ibe s, o de elop wound d essings wi h an ioxidan and
an imic obial p ope ies. The esul s demons a ed ha he composi e
nanoma e ials p esen ed syne gis ic an ioxidan and an imic obial ac-
i i y [77]. Also, Kho asani e al. de eloped and cha ac e ized hepa-
inized hyd ogels composed o PVA, CS and zinc oxide nanopa icles
(ZnO-NPs) in ended o use as wound d essings. They concluded ha he
addi ion o ZnO-NPs imp o ed he mechanical and he mal p ope ies,
esul ing in a s uc u e wi h po osi y a o able o wound healing.
Fu he mo e, a mo e sus ained elease a e o hepa in was obse ed in
he p esence o ZnO-NPs, while cell iabili y and an ibac e ial ac i i y
showed p omise. Da a sugges ed ha PVA/CS/ZnO-NPs/hepa in
hyd ogels may be e ec i e in p omo ing wound healing, p esen ing a
po en ially aluable app oach o de eloping new ma e ials o wound
ca e [78]. Simila ly, Yang e al., in es iga ed he inco po a ion o gold
nanopa icles (AuNPs) in o elec ospun PCL and gela in nano ibe s in
o de o de elop wound ca e d essings agains mul i-d ug esis an
bac e ia (MDRB). AuNPs we e coa ed wi h 6-aminopenicillanic acid,
which exhibi ed excellen biocompa ibili y. A e se en days o cul u e,
a signi ican ise in he elease o gold was obse ed compa ed o he
ini ial day. This sugges ed ha he AuNPs we e eleased o e ime,
which indica ed he abili y o he nano ibe s o ap and elease AuNPs,
and hus, be able o emedia e a wound in ec ion by MDRB, which could
be c ucial o ins iga ing egene a ion [79]. Finally, Masud e al. de el-
oped a wound d essing composed o CS, ZnO-NPs and polye hylene
glycol (PEG) c oss-linked wi h sodium ipolyphospha e (STPP). The
bio-nanocomposi e was p epa ed by a simple solu ion mixing and
cas ing me hod. The objec i e was o con ol he elease o gen amicin
(an an ibio ic) o imp o e healing by s opping he p oli e a ion o mi-
c oo ganisms. ZnO-NPs we e inco po a ed o p o ide an imic obial
p ope ies. In i o and in i o es s con i med he biocompa ibili y,
enhanced an ibac e ial ac i i y, and mo e e ec i e healing wi h he
gen amicin-loaded bio-nanocomposi e compa ed o comme cial hyd o-
gel d essings [80].
3. Ch omism o nanoma e ials
One in iguing phenomenon ha has ga ne ed conside able a en-
ion in he nanoma e ials ield is ch omism, known as he abili y o
ma e ials o exhibi e e sible and unable changes in colo in esponse
o ex e nal s imuli, ypically obse ed in solids and liquids [81]. Ch o-
mic nanoma e ials, wi h hei dynamic colo -changing capabili ies, hold
immense p omise o applica ions anging om senso s o sma coa -
ings and biomedical de ices [82]. Exhibi ing his pa icula ch omic
beha io on nanoma e ials is ad an ageous due o hei enhanced
su ace- o- olume a io, unable op ical p ope ies, and po en ial o
unc ionaliza ion a he molecula le el. The ch omic beha io obse ed
in nanoma e ials can be a ibu ed o a ious mechanisms, including
changes in he elec onic, con o ma ional, c ys al, and physical s uc-
u e o he ma e ial o su ace chemis y [83]. When ex e nal s imuli
induce s uc u al changes in he ma e ial, he e is a co esponding shi
in op ical abso p ion cha ac e is ics due o modi ica ions in elec on
densi y and, consequen ly, he ma e ial unde goes a colo changes [84].
Va ious ypes o ch omism, such as pho och omism, he moch omism,
sol a och omism, elec och omism, mechanoch omism and hal-
och omism ha e been disco e ed, each igge ed by speci ic s imuli,
espec i ely ligh , empe a u e, sol en , elec ic po en ial, mechanical
o ces o pH [85,86]. Among he di e en ypes o ch omism, hal-
och omism has ga ne ed signi ican in e es due o i s sensi i i y o pH
a ia ions, which a e c i ical indica o s o physiological and pa holog-
ical s a es. Haloch omic nanoma e ials change colo in esponse o al-
e a ions in he local ionic concen a ion, making hem highly use ul o
eal- ime pH moni o ing in wound healing and issue enginee ing
applica ions.
3.1. Haloch omism
Haloch omic ma e ials change colo based on he acidi y o alka-
lini y o hei su oundings in esponse o he p esence o speci ic ions o
changes in ionic concen a ion. This ype o ch omism is o en used in
pH indica o s, whe e he colo o he indica o is co ela ed wi h he pH
o he solu ion [13,87]. This sensi i i y is ha nessed h ough ca e ully
enginee ed s uc u es o unc ional g oups ha unde go e e sible al-
e a ions, o en in ol ing p o ona ion and dep o ona ion o unc ional
g oups in esponse o changes in pH, leading o shi s in elec onic
con igu a ion and op ical abso p ion p ope ies. Se e al compounds
ound in na u e exhibi haloch omism unde speci ic condi ions [88].
An hocyanins a e na u al pigmen s abundan ly ound in a ious plan s,
pa icula ly in ui s (i.e., be ies) and ege ables (i.e., ed cabbage and
ed adish). These compounds demons a e haloch omism by al e ing
hei colo based on he pH o hei su oundings (Fig. 1) [89]. They
se e as excellen pH indica o s due o hei dis inc colo changes,
anging om ed o pu ple o blue-g een. Al hough hese compounds a e
no exclusi ely haloch omic, hei abili y o unde go colo changes in
esponse o en i onmen al ac o s makes hem in aluable in a ious
applica ions [90]. Pa icula ly in pH de ec ion and colo ime ic assays,
A.R.M. Ribei o e al.
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4
na u al haloch omic compounds o e simplici y, a o dabili y, and
eco- iendliness, hus inding widesp ead usage in labo a o ies, in-
dus ies, and educa ional se ings [91]. Haloch omism also p esen s
e sa ile applica ions in biomedicine, including pH sensing o moni-
o ing cellula en i onmen s, disease s a es and wound healing; d ug
deli e y sys ems ha enable con olled elease in esponse o pH
changes, and biomedical imaging o enhanced con as in pa hological
issues [92,93]. In eg a ion o haloch omism in o biomedical esea ch
holds p omise o ad ancing diagnos ics, he apeu ics, and eal- ime
moni o ing o physiological p ocesses, ul ima ely con ibu ing o
imp o ing pa ien ca e and ou comes [15]. Mo eo e , haloch omism in
nanoma e ials wi hin he medical con ex p o ides in aluable insigh s
in o he impo ance o his ea u e in p o iding isual signals o al e -
a ions occu ing a he molecula o cellula scale ha unc ion as a
diagnos ic ool, ea men managemen and e alua ion o issue egen-
e a ion and in eg a ion [94].
The unde lying mechanisms behind haloch omism in nanoma e ials
o en in ol e in e ac ions a he nanoscale le el. These ma e ials un-
de go p o ona ion o dep o ona ion based on he su ounding pH,
leading o a ia ions in elec on densi y and op ical p ope ies. Fo
ins ance, changes in he concen a ion o ions may induce s uc u al
modi ica ions in he nanoma e ial, in luencing hei elec onic con ig-
u a ions and subsequen ly al e ing hei op ical p ope ies [95]. Many
o ganic compounds con ain unc ional g oups ha can gain o lose
p o ons depending on he pH o he solu ion. The addi ion o emo al o
p o ons can lead o changes in he elec onic s uc u e o he molecule,
esul ing in a shi in i s abso p ion spec um and, hence, i s colo . This
dynamic beha io can be uned by selec ing speci ic haloch omic dyes,
modi ying nanoma e ial su aces, o inco po a ing hyb id s uc u es
ha enhance s abili y and esponse ime [96].
This esponsi eness p o ides a basis o designing senso s capable o
de ec ing imely changes (minu e) in he su ounding en i onmen .
Unde s anding and ha nessing he haloch omic p ope ies o nano-
ma e ials opens a enues o he de elopmen o inno a i e echnologies
wi h enhanced unc ionali y and sensi i i y.
Howe e , he applica ion o haloch omism in biomedical con ex s
s ill aces signi ican challenges, despi e i s widesp ead use in o he in-
dus ies such as ex iles and chemis y. One o he main obs acles lies in
he complexi y o he biological en i onmen , whe e ac o s such as pH,
empe a u e, humidi y, and he p esence o bodily luids can in e e e
wi h he s abili y and accu acy o haloch omic esponses. Besides ha ,
haloch omic ma e ials mus be biocompa ible and sa e o di ec con ac
wi h he body, which is no always easy o ensu e. In indus ial sec o s,
condi ions a e mo e con olled, allowing o he e icien use o hese
echnologies wi hou he same cons ain s imposed by biological a i-
abili y [97].
3.1.1. Nano-sca olds wi h haloch omic beha iou
The eme ging ield o nanoma e ial-based sca olds exploi s he
p ope ies o haloch omism, in oducing a dynamic dimension o he
design and unc ionali y o sca olds employed in issue enginee ing,
egene a i e medicine and heal h moni o ing [98]. A pe ec example o
he impo ance o pH is in wound healing. pH se es as a c ucial
bioma ke , in luencing he p og ession om in lamma ion o issue
egene a ion. Ch onic wounds o en exhibi an alkaline en i onmen
(pH 7.2–8.9), whe eas healing wounds shi owa ds a neu al- o-acidic
pH. This pH ansi ion is essen ial o cellula ac i i ies such as enzyme
unc ion, mic obial balance, and issue emodeling. By in eg a ing
pH-sensi i e haloch omic nanoma e ials in o biomedical sca olds,
wound healing can be con inuously moni o ed, educing he need o
in asi e diagnos ic me hods and enabling imely in e en ions [99].
Di e en s ages o wound healing a e linked wi h speci ic pH anges,
wi h wounds healing be e in acidic condi ions. Con e sely, alkaline
en i onmen s can lead o he de elopmen o ch onic wounds [99].
Th oughou healing, he wound en i onmen shi s om alkaline o
neu al and hen acidic. Moni o ing wound pH, as an indica o o
healing, is sugges ed o de e mining e ec i e ea men s a egies
[100]. This p esen a aluable app oach o imp o ing diagnos ic and
he apeu ic ou comes in egene a i e medicine. By inco po a ing hal-
och omic dyes and pH-sensi i e nanoma e ials in o sca olds, hese
sys ems enable eal- ime moni o ing o en i onmen al changes, o e ing
a non-in asi e means o assessing issue healing. The mechanis ic in-
sigh s in o haloch omic beha io allow o u he unc ionaliza ion and
op imiza ion o enhance sca old e iciency [101,102]. Also, in some
occasions, i is in e es ing o inco po a e an imic obial and an i ungal
p ope ies, p o iding dual unc ionali y (ac ing as bo h pH senso s and
ac i e agen s agains mic obial con amina ion) [103]. Typically con-
s uc ed om nanos uc u ed polyme s o hyb id sys ems (nano-
composi es), haloch omic nano-sca olds achie e an imic obial and
an i ungal e icacy h ough he inco po a ion o nanopa icles loaded
wi h an ibio ics, essen ial oils, o e en isola ed an ibio ics, which ensu e
b oad-spec um g ow h inhibi ion o bac e ia and ungi [104,105].
The inco po a ion o haloch omic elemen s in o biomedical sca olds
allows o eal- ime, isually obse able esponses o changes in he
local mic oen i onmen . This capabili y holds po en ial o moni o ing
and unde s anding cellula ac i i ies, issue healing and g ow h, and he
o e all pe o mance o he sca old wi hin he body [95]. The
colo -changing aspec p o ides a no el means o assessing he heal h
and in eg a ion o he sca old wi h hos issues. One o he no able
ad an ages o his app oach lies in i s po en ial diagnos ic applica ions
and con inuous moni o ing. The haloch omic beha io can se e as a
isual indica o o speci ic physiological condi ions, such as a ia ions in
pH, ion concen a ion, o he p esence o ce ain biomolecules and mi-
c oo ganisms. Howe e , haloch omic subs ances do no exhibi a com-
ple e spec um o colo s ac oss all pH le els because, beyond ce ain
le els o acidi y, he conjuga ed sys em emains unchanged. The di e se
shades obse ed s em om a ia ions in he concen a ions o hal-
och omic molecules possessing dis inc conjuga ed sys ems [96,106].
This diagnos ic capabili y could signi ican ly impac he ea ly de ec ion
o pa hological changes o he success o issue egene a ion, pa ing he
way o mo e pe sonalized and e ec i e he apeu ic in e en ions
[107]. Fu he mo e, he adap abili y o haloch omic biomedical sca -
olds o di e en issue ypes and en i onmen s enhances hei e sa-
ili y. Tailo ing he colo esponse o speci ic signals acili a es he
de elopmen o sma sca olds ha can dynamically adjus o he needs
o di e se issues o disease s a es [108]. This adap abili y is c ucial o
c ea ing biomime ic en i onmen s ha p omo e op imal cell g ow h and
issue egene a ion. While he ield is s ill in i s beginnings, he po en ial
o biomedical sca olds wi h haloch omic beha io o e olu ionize
egene a i e medicine and ex ile biomedical enginee ing (haloch omic
d essings) is e iden (Fig. 2) [109,110]. Con inued esea ch and de el-
opmen in his a ea hold he p omise o no only imp o ing ou unda-
men al unde s anding o issue enginee ing and wound healing bu also
igge ing a new e a o sma , esponsi e implan s o d essings wi h
enhanced diagnos ic and he apeu ic capabili ies. As esea ch goes
deepe in o he de ails o haloch omic ma e ials and hei in e ac ion
wi h biological sys ems, he p ospec s o inno a i e applica ions in
heal hca e con inue o expand [110].
Fig. 1. – Colou shi o di e en pH solu ions in con ac wi h a ed cabbage
haloch omic na u al ex ac . (Fo in e p e a ion o he e e ences o colo in his
igu e legend, he eade is e e ed o he Web e sion o his a icle.)
A.R.M. Ribei o e al.
Jou nal o D ug Deli e y Science and Technology 108 (2025) 106950
5
Fig. 2. – Haloch omic wound d essing wi h d ug deli e y sys em p ope ies wi h applica ion on wound healing and issue egene a ion. Adap ed om Re . [110]
wi h CCBY 4.0 pe mission.
Table 1
Applica ions o nanoma e ials based haloch omic biomedical sca olds in he ield o skin egene a ion and wound healing.
Nanoma e ial Design S a egy Haloch omic Molecule Fea u es pH
Range
Applica ion Re .
Elec ospun
nano ibe s
Elec ospinning o poly (me hyl me hac yla e-
co-me hac ylic acid) (PMMA-co-MAA) and
poly (ac ylic acid) (PAA) ibe s encapsula ed
wi h haloch omic b omo hymol blue (BTB)
BTB - Syn he ic pH indica o ; 5.0–8.0 Ch onic wound
managemen and
moni o ing
[119]
Elec ospun
nano ibe s
Chi osan/PCL nano ib ous ma ix blended
wi h haloch omic dyes Me hyl Red and Rose
Bengal
Syn he ic pH indica o s;
Bo h haloch omic dyes possess a unc ional ca boxyl-g oup
ha is a ailable o coupling wi h chi osan, wi hou
dis up ing he ch omopho e and lea ing haloch omism
in ac ;
0.0–12.0 Wound d essing [118]
Elec ospun
nano ibe s
Sodium algina e (SA) and PVA nano ib ous
ma loaded wi h an hocyanins ex ac ed om
black ca o (BC)
Black ca o na u al ex ac wi h haloch omic p ope ies;
Good wa e solubili y, excep ional colo esis ance a high
empe a u es, and ligh s abili y;
4.0–10.0 Wound healing
moni o ing
[94]
Elec ospun
nano ibe s
PCL and PCL/chi osan (80:20) nano ibe s
loaded wi h Ni azine Yellow dye
Ni azine Yellow dye - Syn he ic pH indica o ; 2.0–11.0 pH-senso wi h
an imic obial
p ope ies o di e se
medical applica ions
[117]
Hyd ogel Me hac yla e-chi osan c osslinked wi h
me hylenebisac ylamide (MBAA) hyd ogel
embedded wi h ed cabbage ex ac
Red cabbage na u al ex ac wi h haloch omic p ope ies;
An ioxidan , an i-in lamma o y, an icance , an ibac e ial,
an i ungal, and an i i al agen ;
2.0–11.0 pH-sensi i e wound
d essing
[113]
Hyd ogel SA ilms con aining haloch omic Cli o ia
e na ea Linn. lowe ex ac loaded wi h gallic
acid and eso cinol as model d ugs
Cli o ia e na ea Linn. lowe ex ac ;
An ioxidan agen
5.0–9.0 pH-sensing o he
ansde mal di usion
o d ugs
[122]
Hyd ogel Haloch omic hyd ogel-based d essing
(GelDe m®) ha eleases he an ibio ic
gen amicin
Red cabbage na u al ex ac wi h haloch omic p ope ies;
An ioxidan , an i-in lamma o y, an icance , an ibac e ial,
an i ungal, and an i i al agen ;
4.0–9.2 Colo ime ic
measu emen o pH and
elease o an ibio ic
agen s a he wound
si e
[123]
Nanopa icles Bac e ial nanocellulose-based wound d essing
imp egna ed wi h meso-po ous silica
nanopa icles (MSNs) loaded wi h BTB pH-
esponsi e dye
BTB - Syn he ic pH indica o ; 5.0–8.0 Real- ime pH wound
moni o ing
[112]
Nanopa icles Red-cabbage based an hocyanin ch omopho e
ex ac was encapsula ed in o algina e NPs ia
c osslinking and immobilized in o co on
gauze medical ab ics
Red cabbage na u al ex ac wi h haloch omic p ope ies;
An ioxidan , an i-in lamma o y, an icance , an ibac e ial,
an i ungal, and an i i al agen ;
4.5–8.0 Real- ime de ec o o
wound healing p og ess
moni o ing
[120]
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3.1.2. Haloch omism o skin egene a ion and wound healing
The in eg a ion o haloch omic ea u es in o biomedical sca olds has
no ewo hy implica ions in issue enginee ing, pa icula ly in he
con ex o skin egene a ion and wound healing (Table 1). This inno-
a i e app oach b ings a dynamic and esponsi e elemen o he design
o sca olds, o e ing unique ad an ages o moni o ing and enhancing
he success o skin issue enginee ing [108]. Howe e , sca olds mus be
de eloped keeping in mind he basic equi emen s o biocompa ibili y,
biodeg adabili y, and causing minimal immune eac ions and side e -
ec s [110]. Despi e signi ican p og ess being made in he c ea ion o
new bandage ma e ials, only a ew o hem can o e medical s a
diagnos ic in o ma ion abou he wound’s biomolecula composi ion.
Cu en ly, much o he ea men is done by obse a ion, and he
accompanying heal hca e p o ide ’s c i ical judgmen and expe ience
a e c ucial. E en hough some o he cu en he apies, such as skin
g a s, skin subs i u ions, nega i e p essu e wound he apy, and o he s,
can be help ul, hey ypically necessi a e p ocedu es o su gical in e -
en ion. Nec osis, sepsis, and e en mo ali y can esul om mic obial
in ec ion a he si e o he wound, which can signi ican ly slow down he
healing p ocess [111].
The haloch omic beha io allows o he eal- ime isualiza ion o
cellula ac i i ies wi hin he sca old. As skin cells p oli e a e and
di e en ia e, he colo changes in he sca old can se e as a di ec in-
dica o o hese p ocesses [112]. This eal- ime moni o ing is i al o
assessing he heal h and s eng h o he enginee ed skin issue. Wi h ha
in mind, he colo -changing p ope ies can be ha nessed as diagnos ic
indica o s o he heal h o he enginee ed skin [113]. Speci ic colo
shi s in esponse o a ia ions in pH o he p esence o ce ain bio-
molecules can p o ide ea ly wa nings o po en ial issues (in ec ion,
excessi e elease o exuda es, in e up ion o he wound healing p o-
cess), allowing o quick in e en ion and adjus men o ea men
s a egies. Colo changes may indica e a heal hy ascula iza ion p ocess,
o e ing insigh s in o he blood supply c i ical o he su i al and
unc ionali y o he egene a ed skin. [114]. This ea u e aids in op i-
mizing he o e all success o issue enginee ing p ocesses and wound
healing.
The adap abili y o haloch omic beha io enables he cus omiza ion
o sca old esponses o speci ic en i onmen al ac o s in luencing skin
egene a ion. The abili y o isually ack cellula ac i i ies, diagnose
ea ly issues, op imize in eg a ion, and ailo esponses o en i onmen al
ac o s con ibu es o he c ea ion o sma and esponsi e sca olds
[115]. Va ia ions in colo in esponse o changes in pH o o he ele an
pa ame e s can be adjus ed o mimic he dynamic condi ions o he skin
mic oen i onmen , os e ing imp o ed cellula esponses and issue
de elopmen [94,115]. Also, haloch omic sca olds can p o ide a isu-
ally in ui i e means o heal hca e p o essionals o moni o he p og ess
o skin egene a ion. This ea u e acili a es enhanced pa ien moni-
o ing, allowing o imely adjus men s in ea men plans and s a egies
based on he eal- ime eedback p o ided by he colo -changing sca old
[116].
Pakolpakçıl e al. ocused hei esea ch on de eloping a no el
wound d essing o pH moni o ing based on sodium algina e (SA) and
poly inyl alcohol (PVA) nano ib ous ma loaded wi h he na u al an-
hocyanins ex ac ed om black ca o (BC). The nano ib ous ma s we e
p oduced by elec ospinning and he immobiliza ion o an hocyanins
was ca ied ou h ough di ec blending in he polyme ic solu ion. A
d essing wi h haloch omic p ope ies ha exhibi ed a isual pH g ading
be ween pH 4–10, demons a ing ha PVA/SA/BC nano ib ous ma can
be used as a pH-sensi i e wound d essing o moni o ing he healing
p og ess was ob ained [94]. Also demons a ing he po en ial o elec-
ospinnable sca olds, bo h Schoolae , E. e al., and Van de Schue en,
L. e al., de eloped nano ib ous ma ixes by blending haloch omic dyes
wi h polyme ic solu ions o ob ain nano ib ous pH-sensi i e wound
d essings and opening doo s o a b oadening o he selec ion o sui able
dye-ma ix combina ions owa ds colo changes in he pH- ange wi hin
he neu al o alkaline pH- egion [117,118]. The s udy om Basel
Bazbouz M., and T onci, G., also highligh s he clinical diagnos ic po-
en ial o inco po a ing haloch omic p ope ies in o nanoma e ials o
wound healing. By de eloping a wo-laye ib ous de ice ia elec o-
spinning, he esea che s c ea ed a ma e ial capable o bo h exuda e
managemen and in ec ion de ec ion h ough isual colo changes. The
use o b omo hymol blue (BTB) in PMMA-co-MAA ibe s enabled
pH-sensi i e colo shi s, signaling in ec ion-induced alkalini y. The
indings demons a e how nanoma e ial design can enhance wound
moni o ing, o e ing a p omising app oach o eal- ime in ec ion
de ec ion in ch onic wound ca e [119]. Following ano he s a egy,
Alaysuy, O. e al., aimed a de eloping a no el mul i unc ional wound
d essing wi h he abili y o p o ec , cu e and sense he healing p ocess.
Haloch omism was p o ided by ed cabbage an hocyanin ex ac , a
compound known no only o i s haloch omic p ope ies, bu also o i s
abili y o unc ion as an ioxidan , an i-in lamma o y, an icance , an i-
bac e ial, an i ungal, and an i i al agen . The an hocyanin ch omo-
pho ic ex ac was encapsula ed a di e en concen a ions in o
algina e-based NPs, o ming a hyd ogel sca old, and immobilized in o
co on gauze o p o ide a sma he apeu ic pH- esponsi e wound d ess
o unc ion as an an imic obial and bioch omic ma ix p o iding a
com o able d ess senso o moni o he wound s a us [120]. Simila ly,
Eskilson, O. e a ., ab ica ed a pH-sensi i e hyd ogel-based wound
d essing by imp egna ing meso-po ous silica nanopa icles (MSNs) wi h
a pH- esponsi e dye, as a new e ec i e s a egy o apid colo ime ic
assessmen o wound pH, ha can be u he o encapsula ion and
elease o bioac i e compounds o ea men o ha d- o-heal wounds
[112]. Mi ani, B. e al., pa en ed GelDe m®, a mul i unc ional wound
d essing wi h signi ican clinical diagnos ic po en ial o in ec ion
de ec ion and ea men . By inco po a ing a pH-sensi i e colo ime ic
esponse, GelDe m can isually indica e bac e ial in ec ions, while also
enabling con olled an ibio ic elease o a ge ed ea men . In i o and
ex i o es s con i med i s accu acy, compa able o comme cial diag-
nos ic sys ems. Addi ionally, i s in eg a ion wi h sma phone-based
wi eless moni o ing allows pa ien s o ack wound condi ions
emo ely, imp o ing elemedicine capabili ies. Designed o compa i-
bili y wi h comme cial pa ches, his sys em o e s a non-i i a ing,
pa ien - iendly solu ion o managing ch onic and acu e wounds,
holding p omise o applica ions in auma, su ge y, and diabe es ca e
[121].
4. Conclusion and u u e pe spec i es
The in eg a ion o haloch omic p ope ies in o nanoma e ial-based
biomedical sca olds ep esen s a cu ing-edge and p omising a enue
in he ield o bioma e ials. The e e sible colo changes in esponse o
en i onmen al s imuli, add a dynamic dimension o he unc ionali y o
biomedical sca olds applied o wound healing and skin egene a ion.
This holds signi ican po en ial o eal- ime moni o ing o physiological
condi ions wi hin he body. This ea u e is pa icula ly ad an ageous in
he de elopmen o no el wound d essings, sma implan s and issue
sca olds, whe e he isual indica ion o changes a he molecula o
cellula le el can se e as a diagnos ic ool o aid in he assessmen o
issue egene a ion and in eg a ion. Mo eo e , he haloch omic p op-
e ies con ibu e o he e sa ili y o hese nanoma e ial-based sca olds,
allowing o ailo ed esponses o he unique mic oen i onmen s o
di e en issues. This adap abili y is c ucial o op imizing he apeu ic
ou comes and minimizing undesi ed side e ec s. The ield is s ill in
de elopmen , and u he esea ch is needed o ully explo e he scope o
applica ions and e ine he design p inciples o hese haloch omic
nanoma e ials. Despi e hei po en ial, haloch omic nanoma e ials in
biomedical sca olds ace se e al challenges ha mus be add essed o
acili a e hei p ac ical implemen a ion in clinical se ings. One o he
p ima y conce ns is he s abili y o haloch omic dyes and nanoma e ials
unde physiological condi ions. Many pH-sensi i e dyes may deg ade o
lose hei esponsi eness due o p olonged exposu e o bodily luids,
empe a u e luc ua ions, and enzyma ic ac i i y. Encapsula ion and
A.R.M. Ribei o e al.
Jou nal o D ug Deli e y Science and Technology 108 (2025) 106950
7
polyme s abiliza ion s a egies mus be de eloped o enhance he
longe i y and eliabili y o hese ma e ials. Ano he c i ical challenge is
biocompa ibili y and po en ial cy o oxici y. Some haloch omic com-
pounds, pa icula ly syn he ic dyes, may elici ad e se biological e-
sponses. Fu u e esea ch should p io i ize he de elopmen o
biodeg adable and non- oxic haloch omic agen s, such as hose de i ed
om na u al sou ces like an hocyanins. In eg a ion wi h exis ing med-
ical de ices and scalabili y also p esen signi ican obs acles. The
ab ica ion o haloch omic sca olds should be compa ible wi h la ge-
scale p oduc ion echniques while main aining consis ency in ma e ial
p ope ies. Addi ionally, egula o y app o al o new haloch omic bio-
ma e ials may equi e ex ensi e p eclinical and clinical alida ion,
necessi a ing collabo a ions be ween esea che s, indus y, and egula-
o y agencies. Finally, cus omiza ion and adap abili y o di e se wound
ypes and pa ien condi ions emain an open esea ch a ea. The abili y o
adjus he sensi i i y and esponse ime o haloch omic sca olds o
di e en applica ions, such as diabe ic ulce s o su gical wounds, would
expand hei usabili y and clinical impac . As he unde s anding o he
in e ac ion be ween nanoma e ials, haloch omism, and biological sys-
ems de elops, he po en ial o inno a i e diagnos ic and he apeu ic
solu ions con inues o g ow. One o he key u u e pe spec i es lies in
hei use o ad anced sensing and de ec ion echnologies. Haloch omic
nanoma e ials could e olu ionize medical diagnos ics by p o iding
eal- ime, non-in asi e moni o ing o physiological pa ame e s such as
pH le els in biological luids on ch onic wounds.
CRediT au ho ship con ibu ion s a emen
Ana R.M. Ribei o: W i ing – e iew & edi ing, W i ing – o iginal
d a , In es iga ion. B una A.S. Oli ei a: W i ing – o iginal d a ,
In es iga ion. Ana Isabel Ba bosa: W i ing – e iew & edi ing, In es-
iga ion. Ca a ina L. Seab a: W i ing – e iew & edi ing, Supe ision,
Funding acquisi ion. Sale e Reis: W i ing – e iew & edi ing, Supe -
ision, Funding acquisi ion. Helena P. Felguei as: W i ing – e iew &
edi ing, Supe ision, P ojec adminis a ion, Funding acquisi ion.
Decla a ion o compe ing in e es
The au ho s decla e he ollowing inancial in e es s/pe sonal e-
la ionships which may be conside ed as po en ial compe ing in e es s:
Helena P. Felguei as epo s inancial suppo was p o ided by Foun-
da ion o Science and Technology. Ana Ri a M. Ribei o epo s inancial
suppo was p o ided by Founda ion o Science and Technology. I
he e a e o he au ho s, hey 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 .
Acknowledgmen s
This esea ch was unded by he Po uguese Founda ion o Science
and Technology (FCT) ia g an UID/CTM/00264/2020 o Cen e o
Tex ile Science and Technology (2C2T) on i s componen s base
(h ps://doi.o g/10.54499/UIDB/00264/2020) and p og amma ic
(h ps://doi.o g/10.54499/UIDP/00264/2020). A.R.M.R. acknowl-
edges FCT o PhD schola ship 2021.08627.BD, and H.P.F. o Auxilia y
Resea che con ac 2021.02720.CEECIND.
Da a a ailabili y
No da a was used o he esea ch desc ibed in he a icle.
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