Three-dimensional printing as a cutting-edge, versatile and personalizable vascular stent manufacturing procedure: Toward tailor-made medical devices

In e na ional Jou nal o Biop in ing Volume 9 Issue 2 (2023) h ps://doi.o g/10.18063/ijb. 9i2.664 219 REVIEW ARTICLE Th ee-dimensional p in ing as a cu ing-edge, e sa ile and pe sonalizable ascula s en manu ac u ing p ocedu e: Towa d ailo -made medical de ices Fa ima Ga cia-Villen1,2,3*, Fe nando López-Zá aga4, Cesa Vise as5,6, Sand a Ruiz-Alonso1,2,3, Fouad Al-Hakim1,2,3, I ene Diez-Aldama1, Lau a Saenz-del-Bu go1,2,3, Denis Scaini7*, Jose Luis Ped az1,2,3 1NanoBioCel G oup, School o Pha macy, Uni e si y o he Basque Coun y (UPV/EHU), 01006, Vi o ia-Gas eiz, Spain 2Biomedical Resea ch Ne wo king Cen e in Bioenginee ing, Bioma e ials and Nanomedicine (CIBER-BBN), 01006, Vi o ia-Gas eiz, Spain 3Bioa aba, NanoBioCel Resea ch G oup, 01009, Vi o ia-Gas eiz, Spain 4Depa men o Vascula and In e en ional Radiology, Ála a Uni e si y Hospi al, In eg a ed Heal h O ganiza ion o Ála a (Osakide za), Spain 5Depa men o Pha macy and Pha maceu ical Technology, School o Pha macy, Uni e si y o G anada (UGR), Campus o Ca uja, 18071 s/n, G anada, Spain 6Andalusian Ins i u e o Ea h Sciences, CSIC-Uni e si y o G anada, A da. de Las Palme as 4, 18100, A milla, G anada, Spain 7Join Resea ch Labo a o y (JRL). School o Pha macy, Uni e si y o he Basque Coun y (UPV/ EHU), 01006, Vi o ia-Gas eiz, Spain (This a icle belongs o he Special Issue: 3D Tissue Enginee ing and Biop in ing o Eme ging Applica ions) Abs ac Vascula s en s (VS) ha e e olu ionized he ea men o ca dio ascula diseases, as e idenced by he ac ha he implan a ion o VS in co ona y a e y disease (CAD) pa ien s has become a ou ine, easily app oachable su gical in e en ion o he ea men o s enosed blood essels. Despi e he e olu ion o VS h oughou he yea s, mo e e icien app oaches a e s ill equi ed o add ess he medical and scien i ic challenges, especially when i comes o pe iphe al a e y disease (PAD). In his ega d, h ee-dimensional (3D) p in ing is en isaged as a p omising al e na i e o upg ade VS by op imizing he shape, dimensions and s en backbone (c ucial o op imal mechanical p ope ies), making hem cus omizable o each pa ien and each s enosed lesion. Mo eo e , he combina ion o 3D p in ing wi h o he me hods could also upg ade he inal de ice. This e iew ocuses on he mos ecen s udies using 3D p in ing echniques o p oduce VS, bo h by i sel and in combina ion wi h o he echniques. The inal aim is o p o ide an o e iew o he possibili ies and limi a ions o 3D p in ing in he manu ac u ing o VS. Fu he mo e, he cu en si ua ion o CAD and PAD pa hologies is also add essed, hus highligh ing he main weaknesses o he al eady exis ing VS and iden i ying esea ch gaps, possible ma ke niches and u u e di ec ions. Keywo ds: S en ; Th ee-dimensional p in ing; Endo ascula p os hesis; A he oscle- osis; Pe iphe al a e y disease; Co ona y a e y disease *Co esponding au ho s: Fa ima Ga cia-Villen ([email p o ec ed]) Denis Scaini ([email p o ec ed]) Ci a ion: Ga cia-Villen F, López- Zá aga F, Vise as C, e al., 2023, Th ee-dimensional p in ing as a cu ing-edge, e sa ile and pe sonalizable ascula s en manu ac u ing p ocedu e: Towa d ailo -made medical de ices. In J Biop in , 9(2): 664. h ps://doi.o g/10.18063/ijb. 9i2.664 Recei ed: Augus 09, 2022 Accep ed: Oc obe 11, 2022 Published Online: Janua y 9, 2023 Copy igh : © 2023 Au ho (s). This is an Open Access a icle dis ibu ed unde he e ms o he C ea i e Commons A ibu ion License, pe mi ing dis ibu ion and ep oduc ion in any medium, p o ided he o iginal wo k is p ope ly ci ed. Publishe ’s No e: Whioce Publishing emains neu al wi h ega d o ju isdic ional claims in published maps and ins i u ional a ilia ions. In e na ional Jou nal o Biop in ing Co ona y and pe iphe al a e y disease. S a e o he a . Volume 9 Issue 2 (2023) h ps://doi.o g/10.18063/ijb. 9i2.664 220 1. In oduc ion A he oscle osis and h ombosis a e ascula condi ions ha ep esen one o he majo causes o dea h wo ldwide[1-3], hus placing a subs an ial medical and economic bu den o socie y. The p og essi e and ch onic accumula ion o a in a e y walls, which is ini ially asymp oma ic, can ul ima ely lead o he p oduc ion o a he oma ha blocks he essel lumen, hus jeopa dizing blood ci cula ion. Mo eo e , a he oma plaques can also su e om up u es, causing local p oblems such as h ombosis, a e ial wall ulce s, and dissec ion. I a he oscle osis happens in co ona y a e ies (co ona y a e y disease [CAD]), he blockage o he blood low could lead o myoca dial in a c ion and ul ima ely, dea h. I s enosis is loca ed in o he blood essels o he pe iphe al ci cula o y sys em, i is known as pe iphe al a e y disease (PAD). E en i PAD can a ec any blood essel, i is mo e common in he lowe ex emi ies han in he a ms. I is also wo h o cla i y ha PAD and CAD could ha e di e en causes, bu a he oscle osis emains one o he mos common causes. Di e en medical app oaches can be pe o med depending on he isk, age, s age o he condi ion, ype o lesion, e c. No mally, when he a e y blockage is se e e, ca diologi s eso o endo ascula p ocedu es o open ascula econs uc ion. Rega ding endo ascula p ocedu es, balloon angioplas y o endo ascula s en a e he mos ex ended me hods o ea ing he complica ions o a he oscle osis. Up o 42% o CAD pa ien s ha e PAD, and hal o hose pa ien s a e asymp oma ic[4]. Acco ding o Baue sachs e al., “wo ldwide da a showed app oxima ely 5%–8% p e alence o CAD and 10%–20% p e alence o PAD, dependen on he s udy design, a e age age, gende , and geog aphical loca ion”[5]. Ano he ecen epo om he Ame ican Hea Associa ion s a es ha he li e ime isk o PAD has been es ima ed be ween 19% and 30% depending on he ace, om whi e o black people, espec i ely[6]. Ch onic ulce a ion is one o he majo p oblems o PAD, which could ul ima ely lead o ampu a ion. Ulce a ion in hese pa ien s is ela ed o dis u bed mic oci cula ion, swelling and edema[7]. Due o he silen na u e o a he oscle osis, i is e y common o pa ien s o su e om ca dio ascula e en s, hus needing hospi aliza ion, su ge y, and pha macological ea men s. Bo h CAD and PAD ha e demons a ed o be a signi ican economic bu den on di e en heal h sys ems (Figu e 1A). In pa icula , PAD ep esen s a highe economic expense han CAD, especially due o a wo se p ognosis. In pa ien s wi h PAD, ca diac complica ions a e he majo cause o mo bidi y and mo ali y. Mo eo e , he pe iphe al lesions a e mo e complex and as e han co ona y ones[8]. Acco ding o a ecen ma ke s udy made by IMARC G oup Company, hey expec he ascula s en (VS) ma ke o s eadily g ow in he coming yea s. They asc ibe his g ow h o he inc easing end o ge ia ic popula ion as well as o a ise in he incidence a e o PAD, ao ic aneu ysm and ischemic hea disease[9]. Ne e heless, i we look in o he global VS ma ke by p oduc ype, i is also clea ha he majo i y o he e o s a e cen e ed on co ona y s en s (Figu e 1B), elega ing pe iphe al s en s o a seconda y place, despi e being he condi ion wi h he mos economic expendi u e. In iew o he abo e, Figu e 1. (A) Economic bu den caused by CAD and PAD in F ance, Ge many, and Canada. Le : a e age cumula i e 1-yea and 2-yea di ec medical cos s associa ed wi h hospi aliza ion/pa ien o bo h CAD and PAD (H s ands o “hospi aliza ion”). Ex ac ed om Smolde en e al.[145] Righ : A e age hospi aliza ion and annual medica ion cos s pe pa ien in Canada. Ex ac ed om Baue sachs e al.[5]. Ba s numbe s co espond o amoun in eu os. (B) Global ascula s en s ma ke sha e by p oduc ype. EVAR s ands o “endo ascula ao ic epai .” Values ex ac ed om[9]. In e na ional Jou nal o Biop in ing Co ona y and pe iphe al a e y disease. S a e o he a . Volume 9 Issue 2 (2023) h ps://doi.o g/10.18063/ijb. 9i2.664 221 small imp o emen s in PAD ea men could b ing abou signi ican di e ences no only o he pa ien s, bu also o he en i e heal h ca e sys em. Angioplas y, also known as pe cu aneous ansluminal co ona y angioplas y (PTCA) o pe cu aneous ansluminal angioplas y in pe iphe al ci cula ion, is an in e en ional p ocedu e o open na owed essels. Balloon angioplas y in ol es opening he s enosed essel by in la ing a ca he e -balloon in he s enosed a ea. Once he ca he e eaches he desi ed zone, he a ached balloon in la es o la en he a he oma plaque agains he a e y walls. Subsequen ly, he de ice (balloon and ca he e ) is wi hd awn and he ascula essel emains opened. Balloon angioplas y p o ides sho - e m bene i s wi h some imp o emen s in pa ency. In s en p ocedu e, on he o he hand, VS is placed in he ea ed a ea a e he la ening o a he oma. VS a e cylind ical medical de ices ac ing as endop o hesis. VS implan a ion aims o suppo he walls o a blood essel du ing a ce ain pe iod o ime and p e en es enosis. Once he VS is implan ed in he desi ed posi ion, i s inal scope is o exe pe manen p essu e agains he essel walls, ac ing as a sca old o keep he a e y o ein open un il he isk o ull closu e inishes. VS can also be used as low di e sion de ices o ea aneu ysm. In his p ocedu e, he s en edi ec s he blood low and elimina es he p essu e on he aneu ysm, educing he up u e isk. Dis ega ding he ype o in e en ion, he ul ima e objec i e agains a he oscle osis complica ions is o gua an ee blood ci cula ion in he long e m a e he essel opening, also e e ed o as pa ency. The pa ency is he s a e o quali y o being open, unblocked, o unobs uc ed. E en as i seems simple, ull pa ency a e angioplas y is s ill a challenge. Al hough VS is an inno a ion in ca diology ha has helped sa ing millions o li es wo ldwide, hey s ill ha e some d awbacks and weak poin s in pe iphe al ascula disease ha equi e a en ion. The p esen e iew ocuses on he mos ecen s udies using h ee-dimensional (3D) p in ing echniques o p oduce VS, bo h by i sel and in combina ion wi h o he echniques. Due o he complexi y o bo h disease and ea men s/medical de ices used, he i s pa o he e iew is de o ed o he mos common ypes o VS, hei cha ac e is ics, and p oduc ion echniques. The pape also ocuses on he use o 3D p in ing (3DP) by e iewing he mos ecen s udies ha ha e app oached his echnique o he manu ac u ing o VS. The ul ima e aim o his e iew is o o e a a ional o e iew o he s eng hs and weaknesses o 3DP in he de elopmen o hese medical de ices, iden i ying esea ch gaps, possible ma ke niches, and easible u u e di ec ions. 1.1. Types o ascula s en s and hei ea u es VS ha e been in use since 1977[10]. F om ha momen onwa d, di e en aspec s conce ning VS, such as he ype o ma e ials used and he implan a ion and p oduc ion echnology, ha e signi ican ly e ol ed. Any inno a ion in VS ield comes wi h new challenges a ise, ei he in he manu ac u ing p ocess o in he inal pe o mance o he medical de ice. The join e o o he scien i ic communi y in he sea ch o he ull-pa ency VS has gi en ise o he de elopmen o a wide a ie y o ca dio ascula s en s, which a e cu en ly a ailable in he ma ke (Table 1). Figu e 2A ep esen s di e en ypes o VS depending on hei pe manence in he human body, he implan a ion me hodology and he he apeu ic ac i i y oge he wi h hei ela i e p esence in he cu en ma ke (Figu e 2B). Pe manen s en s o non- eso bable s en s a e made o ma e ials ha do no su e deg ada ion unde physiological condi ions. The i s VS we e ba e me al s en s (BMS), which we e made o s ainless s eel and nickel- i anium alloy ( i s - gene a ion s en s). I is possible o ind cobal , ch omium, pla inum/i idium and pla inum/ch omium, o an alum BMS[11]. One o he main incon eniences o BMS a e he long- e m side e ec s: al hough hey help o main ain he angioplas y esul and hey possess excellen mechanical p ope ies, he emaining o he medical de ice wi hin he ascula essel could lead o ascula inju y, in lamma ion, h ombosis, and o he ca dio ascula complica ions, such as in-s en es enosis in he long e m[8,12]. Acco ding o Uhlemann e al., BMS ha e app oxima ely a 30% chance o es enosis wi hin 6 mon hs[13]. Mo eo e , hei pe manen p esence may in e e e wi h u u e ca diac in e en ions. The co osion o me allic VS migh accele a e o igge a he oscle osis as well as elease some oxic ions causing long- e m in lamma o y esponses[14]. BMS can be coa ed wi h di e en subs ances, aiming o modi y hei supe icial p ope ies and imp o e hei mechanical, biological, and he apeu ic pe o mance. S en su ace coa ing has been used o imp o e VS biocompa ibili y and mi iga e oxici y. Bea ing in mind ha he in e nal pa o he s en is in in ima e con ac wi h blood low, hey mus be ully biocompa ible and able o a oid pla ele , p o ein, and o he molecules adhesion while maximizing he adhe ence o speci ic cells such as endo helial cells. Coa ing p ocess enables o con ol and educe co osion (oxida ion) and he elease o undesi able elemen s o chemicals[15,16]. The ca ego y “coa ed s en s” usually o e laps wi h “d ug-elu ing s en s” (DES), since o ganic coa ings (mainly polyme s such as poly(e hylene), polyu e hane, polylac ides…) can ac as d ug ese oi s wi h con olled d ug elease p ope ies. In e na ional Jou nal o Biop in ing Co ona y and pe iphe al a e y disease. S a e o he a . Volume 9 Issue 2 (2023) h ps://doi.o g/10.18063/ijb. 9i2.664 222 Table 1. Some o he comme cialized VS o ca dio ascula sys em classi ied by ma e ial (polyme o me allic) and o he impo an ea u es Comme cial name o he s en Polyme ic Me allic O he ea u es Blood essel ype SE DES BRS Co ona y Pe iphe al Ao a Vascu lex®5 and 6 F ✓ ✓ ✓ Vascu lex® 2-LOC ✓ ✓ ✓ Vascu lex® 3-LOC ✓ ✓ ✓ Resis an and RESISTANT XL ✓ ✓ ✓ ✓ XoloTM ✓ ✓ ✓ Easy Flype ✓ ✓ ✓ Easy HiFlype ✓ ✓ ✓ Easy lex ✓ ✓ Heli lex TI ✓ ✓ ✓ ✓ Championi TM ✓ ✓ ✓ PMSX ✓ ✓ ✓ S.M.A.R.T. Con olTM ✓ ✓ ✓ Neu o o m A las ✓ ✓ ✓ E-XL ✓ ✓ Acclino® Flex S en ✓ ✓ ✓ Zeus SX ✓ ✓ ✓ Jagua ✓ ✓ ✓ Disco e y 5FTM ✓ ✓ ✓ Sinus XL ✓ ✓ ✓ MC-Pe iphe al 6F ✓ ✓ ✓ Fineben ✓ ✓ ✓ LVISTM ✓ ✓ ✓ P64 ✓ ✓ ✓ Biomimics 3DTM ✓ ✓ ✓ Silken lexTM Iliac ✓ ✓ ✓ Facile ✓ ✓ CGUARDTM ✓ ✓ MERES 100TM ✓ ✓ ✓ ✓ MER ✓ ✓ ✓ Acce o® ✓ ✓ ✓ CMCP001 ✓ ✓ Eucalimus ✓ ✓ ✓ ✓ ITRIXII ✓ ✓ ✓ ✓ Desol eTM ✓ ✓ ✓ Ad an a V12 ✓ ✓ ✓ Fan om® ✓ ✓ ✓ ✓ Neo asTM Si olimus-elu ing ✓ ✓ ✓ ✓ Gu ea e ® ✓ ✓ ✓ Pa ne ® ✓ ✓ ✓ Co o lex® ISAR Neo ✓ ✓ ✓ (Con inued) In e na ional Jou nal o Biop in ing Co ona y and pe iphe al a e y disease. S a e o he a . Volume 9 Issue 2 (2023) h ps://doi.o g/10.18063/ijb. 9i2.664 223 Comme cial name o he s en Polyme ic Me allic O he ea u es Blood essel ype SE DES BRS Co ona y Pe iphe al Ao a Co o lex® Blue Neo ✓ ✓ Co o lex® Blue Ul a ✓ ✓ Eu olimusTM ✓ ✓ ✓ E-Magic® PLUS ✓ ✓ ✓ Bioma ix AlphaTM ✓ ✓ ✓ Bioma ix ✓ ✓ ✓ ✓ ✓ Neo lexTM ✓ ✓ ✓ ✓ CRE8TMEVO ✓ ✓ ✓ DES-CRE8TM ✓ ✓ ✓ Ti an Op imax ✓ ✓ ✓ Helios LD ✓ ✓ ✓ ✓ BiomimeTM ✓ ✓ ✓ ✓ ✓ EVERPRO ✓ ✓ ✓ ✓ ✓ MOVYRAP ✓ ✓ ✓ ✓ ✓ TWINRAP ✓ ✓ ✓ ✓ ✓ AVIPLUS ✓ ✓ ✓ ✓ ✓ Xlimus Se ies ✓ ✓ ✓ ✓ ✓ O si o ✓ ✓ ✓ ✓ ✓ Zil e ® PTX® ✓ ✓ ✓ ✓ DynamxTM ✓ ✓ ✓ ✓ ✓ Fi ehawk® ✓ ✓ ✓ ✓ ✓ Ab axTM ✓ ✓ ✓ ✓ Angioli e BTK ✓ ✓ ✓ ✓ Bioss Expe ✓ ✓ ✓ ✓ ✓ SequenceTM ✓ ✓ ✓ ✓ ✓ Yukon® Choice PC ✓ ✓ ✓ ✓ Decen S ✓ ✓ ✓ ✓ ✓ P ono a ✓ ✓ ✓ ✓ ✓ In epideTM ✓ ✓ ✓ Xplosion+TM ✓ ✓ ✓ ✓ ✓ Nile® PAX ✓ ✓ ✓ Inspi on ✓ ✓ ✓ ✓ ✓ Cygnus II ✓ ✓ S el eTM ✓ ✓ A hospico ✓ ✓ C onus Plus ✓ ✓ Besmoo h ✓ ✓ Mg ua d p ime ✓ ✓ Ch omaTM ✓ ✓ CCFlex ✓ ✓ (Con inued) In e na ional Jou nal o Biop in ing Co ona y and pe iphe al a e y disease. S a e o he a . Volume 9 Issue 2 (2023) h ps://doi.o g/10.18063/ijb. 9i2.664 224 Comme cial name o he s en Polyme ic Me allic O he ea u es Blood essel ype SE DES BRS Co ona y Pe iphe al Ao a NexgenTM ✓ ✓ Twin lex ✓ ✓ And as en ✓ ✓ BMS ✓ ✓ Rena u al M ✓ ✓ ✓ ✓ Rena u al P ✓ ✓ ✓ ✓ Magma is ✓ ✓ ✓ Ama an h Fo i udeTM ✓ ✓ ✓ Bio eedomTM Ul a ✓ ✓ ✓ Cob a PZFTM ✓ ✓ Ca aniaTM ✓ ✓ ✓ P opass ✓ ✓ Nano+TM ✓ ✓ ✓ Elu ia™ ✓ ✓ ✓ Epic™ ✓ ✓ ✓ Exp ess™ LD Exp ess™ SD ✓ ✓ Inno a™ ✓ ✓ ✓ P omus PREMIER™ ✓ ✓ ✓ ✓ P omus ELITE™ ✓ ✓ ✓ ✓ SYNERGY™ ✓ ✓ ✓ ✓ ✓ REBEL™ ✓ ✓ SYNERGY™ XD ✓ ✓ ✓ ✓ ✓ SYNERGY MEGATRON™ ✓ ✓ ✓ ✓ ✓ Zil e ® ✓ ✓ ✓ Zil e ® Vena TM ✓ ✓ ✓ Zil e ® PTX® ✓ ✓ ✓ Magma is® RMS ✓ ✓ ✓ ✓ ✓ O si o Mission ✓ ✓ ✓ ✓ ✓ PRO-Kine ic Ene gy ✓ ✓ PK Papy us ✓ ✓ As on ✓ ✓ ✓ As on Pulsa ✓ ✓ ✓ Pulsa -18 ✓ ✓ ✓ Pulsa 18 T13 ✓ ✓ ✓ Pulsa -35 ✓ ✓ ✓ Dynamic ✓ ✓ Dyne ic®-35 ✓ ✓ Dynamic enal ✓ ✓ iVolu ion ✓ ✓ ✓ Res o e ✓ ✓ SS, s ainless s eel; SE, sel -expandable; DES, d ug-elu ing s en ; BRS, bio eso bable. Table 1. Con inued In e na ional Jou nal o Biop in ing Co ona y and pe iphe al a e y disease. S a e o he a . Volume 9 Issue 2 (2023) h ps://doi.o g/10.18063/ijb. 9i2.664 225 Bio eso bable (BRS) VS a e made o biodeg adable ma e ials, which can be deg aded o e ime unde physiologic condi ions un il o al disappea ance. Fo a p ope unc ioning, o al BRS VS deg ada ion mus occu a a desi able, p edic able a e, lea ing behind a na i e ascula essel ully epai ed[15,17]. In ac , he con ol and p edic ion o hei biodeg ada ion a e is s ill he main challenge in he p oduc ion and imp o emen o his g oup o VS. Despi e some excep ions such as BRS me allic s en s made o Mg, Ti, and Zn, biodeg adabili y is a p ope y usually associa ed o subs ances and molecules wi h poo e mechanical p ope ies han me als (polyme s). This means ha he majo pa o he ing edien s used o he p oduc ion o BRS VS unde ake poo e mechanical suppo when compa ed wi h BMS[12]. DES a e VS ha ca y ac i e subs ances in hei s uc u e, which a e p og essi ely eleased o ob ain a ce ain he apeu ic e ec . DES p e en o educe some o he BMS side e ec s: h ombosis, neoin imal sca issue o ma ion, es enosis, e c. In addi ion o he main ac i e subs ances loaded in o DES, o he subs ances also include an i h ombo ic d ugs (hepa in), an ip oli e a i e (pacli axel, ac inomycin D), immunosupp essi e (si olimus) and an i-in lamma o y (dexame hasone) d ugs[18]. The use o pacli axel has been pa icula ly use ul in he p e en ion o in-s en es enosis acco ding o [8]. Recen ly, he e iew o Beshchasna e  al. has epo ed ha nanopa icles and genes can also be loaded in o DES[15]. The e o e, DES a e conside ed Modi ied D ug Deli e y Sys ems (MDDS) since hey mus p o ec , ca y, and con ol d ug elease owa d he essel walls o he bloods eam. These medical de ices a e commonly made o d ug–polyme coa ing o di ec d ug immobiliza ion on he s en su ace[15,18]. The mos common echniques o load d ugs on s en s u s a e sp ay coa ing and dip coa ing. Rega ding sp ay coa ing, a nozzle, which c ea es d ople s o app oxima ely 10 μm in diame e , sp ays he d ug solu ion o d ug/polyme composi e solu ion o e he s en s u s. Fo dip coa ing, he whole s en is dipped in o he d ug o d ug/polyme solu ion in epea ed occasions. The excess o ma e ial o e he s en is hen emo ed by spinning o o he echniques[19]. DES can be di e en ia ed in o i s and second gene a ion o hi d gene a ion, wi h he o me one including non-bio eso bable DES and he la e one belonging o BRS DES[15]. Figu e 2. (A) Classi ica ion o VS based on hei deg adabili y, ype o blood essel ( o ea CAD o PAD) and implan a ion me hodology. (B) Rela i e amoun o VS comme cially a ailable in he ma ke . BRS s ands o “bio eso bable s en s,” SS “s ainless s eel,” SE “sel -expandable s en ,” and DES “d ug-elu ing s en .” The sec o g aph is d awn acco ding o he in o ma ion a ailable in Table 1. In e na ional Jou nal o Biop in ing Co ona y and pe iphe al a e y disease. S a e o he a . Volume 9 Issue 2 (2023) h ps://doi.o g/10.18063/ijb. 9i2.664 226 S en s can also be di e en ia ed by he implan a ion p ocedu e, which is designed depending on he pa icula i ies o he s en i sel . Balloon expandable s en s a e anspo ed o he desi ed zone moun ed a ound an in la able de ice called “balloon.” Once in he desi ed a ea, he balloon is in la ed un il a ce ain poin , o cing he s en o expand o he desi ed dimensions and gua an eeing he opening o he essel (Figu e 3, op). The co esponding coun e pa a e sel -expandable s en s, which a e also anspo ed wi h a ca he e o he desi ed a ea. None heless, in his pa icula case, he s en is c imped inside a hin ube ha deploys i once in he co ec posi ion (Figu e 3, bo om). Tha is, sel -expandable s en s a e able o expand on hei own, due o hei high adial o ce, whe eas balloon-expandable s en s mus be dila ed o be implan ed. Each placemen s a egy demands di e en s en mechanical p ope ies and geome ies. As s a ed by K ankenbe g e  al., “whe eas sel -expanding s en s a e o high elas ici y bu apply low adial ou wa d o ce, balloon-expandable s en s a e igid bu suppo high adial ou wa d o ce and allow o be placed wi h g ea e p ecision”[20]. Finally, VS can also be di e en ia ed based on he ype o blood essel: pe iphe al o co ona y (Figu e 2A). The signi ican success o co ona y s en ing has encou aged he ansla ion o his echnology o he ea men o PAD Figu e 3. Schema ic ep esen a ion o VS implan a ion p ocedu es. Top: balloon-media ed s en deli e y; bo om: sel -expanding s en deli e y. In e na ional Jou nal o Biop in ing Co ona y and pe iphe al a e y disease. S a e o he a . Volume 9 Issue 2 (2023) h ps://doi.o g/10.18063/ijb. 9i2.664 227 ha a ec s pe iphe al blood essels, such as emo al, iliac o popli eal a e ies, among o he s[21]. In ac , he endo ascula ea men o PAD s ill yields unsa is ac o y pa ency a es[22] o no signi ican di e ences be ween s en ing and pe cu aneous ansluminal angioplas y (PTA) in he lowe ex emi ies[23]. Among subjec s wi h diabe es, he isk o PAD is o en se e e and associa ed wi h ex ensi e a e ial calci ica ion, hus leading o a pa icula ype o lesion ha could complica e he s en ing p ocedu e. De ini ely, PAD and CAD espond di e en ly owa d he same pa hology and in e en ion, due o di e en ial ea u es and cha ac e is ics summa ized in Table 2. The di e en ial ana omy o co ona y and pe iphe al a e ies (size, bi u ca ions, elas ici y, and cu a u e) in luences he shea s ess and blood u bulences, indica ing he need o adjus he VS o he idiosync asy o each essel. The blood low and blood p essu e and pe usion is be e egula ed in he hea due o excellen au o egula ion mechanisms o hese essels, hus gua an eeing op imal blood low[24]; on he o he hand, o he o gans such as skele al muscle and splanchnic ci cula ions show mode a e au o egula ion[25]. I blood p essu e d ops o below he au o egula o y ange due o pa hologies such as s enosis, he dis al essels will be maximally dila ed in an a emp o gua an ee p ope blood low, hus causing u he p essu e educ ions. When s en ing pe iphe al blood essels, he mode a ed au o egula ion o blood p essu e and low could hinde he unc ion o he essel in main aining he open lumen. Because o his, s en s wi h be e adial o ce a e desi able o PAD. Ano he ac o o bea in mind is blood oxygena ion o he issues in he dis al egion o he s enosed essel. When i comes o he hea , he low is igh ly coupled o oxygen demand (when ca diac O2 consump ion inc eases, he e is an inc ease in co ona y blood low)[24], indica ing ha i is mo e easily compensa ed in CAD. In he case o PAD, he mode a ed p essu e au o egula ion o he pe iphe al issues could lead o oxygen-s a a ion o he dis al issues as well as in lamma ion, hypoxia, edema, ulce a ion, and, ul ima ely, ampu a ion in he long e m. The lowe blood oxygena ion in PAD wo sens he p ognosis o he ea men s, including s en ing. Ano he ac o o conside when designing and implan ing a s en is he ex en o he s enosed lesion: in CAD, no mally he size o he s enosed a ea is smalle and mo e localized (always wi h excep ions), while in PAD, he lesions can be much longe and usually loca ed be ween muscle and bone issue. The lesion size and i s loca ion imply ha he s en will be subjec ed o highe le el o mo emen s and s esses (e.g., displacemen , ac u e, c ushing). The e o e, mo e lexible VS a e p e e ed o PAD, while he VS is allowed o be a li le s i e o CAD because i will no be subjec ed o so much mo emen s. 2. Desi able s en ea u es In gene al, he pe ec VS has he abili y o be c imped in ag eemen wi h he implan a ion me hodology (balloon o sel -expansion), and has good expandabili y a io wi h enough adial s eng h and minimal ecoil. VS mus also be lexible and ully biocompa ible, as well as able o p e en o a oid h ombosis and es enosis a e implan a ion[26]. These desi able p ope ies and ea u es a e in ima ely ela ed o he s en aw ma e ials, hei combina ions, and he in insic ea u es o each o hem as well as he manu ac u ing p ocess and pos -p ocesses. Ne e heless, he geome y and design o he VS a e likewise impo an o con ol he inal p ope ies o he medical de ice, including he mechanical p ope ies[27]. Unde hese ci cums ances, he s udy o he geome y and dimensions o VS is a ield o s udy on i s own due o he my iad o possibili ies. In his sense, compu a ional s udies ha e p o en hemsel es as use ul ools o analyze and p edic he in luence o s en design on he inal pe o mance. Good expandabili y is he p ope y o a ma e ial o expand (ac i e expansion o sel -expandabili y) o o be expanded (passi e expansion). VS implan ed wi h a balloon a e passi ely expanded by he in la ion o he balloon. The e o e, he ma e ials used o he manu ac u ing o balloon-expandable s en s need o be mo e plas ic han elas ic. On he con a y, sel -expandabili y o VS e e s o he abili y o he medical de ice o expand wi hou he use o an ex e nal o ce and o e ain he inal shape. This can Table 2. Di e en ial p ope ies and ea u es o pe iphe al and co ona y blood essels in luencing he pa ency o PAD and CAD s en ing Di e en ial cha ac e is ic Co ona y blood essels Pe iphe al blood essels Blood low Excellen au o egula ion (60–200 mm Hg) o main ain no mal blood low unde ao ic p es- su e changes[24]. Mode a e au o egula ion (50–70 mmHg). S enosis could educe dis al p essu es below he au o egula o y ange causing maximally dila ed essels and u he p essu e educ ions[25] Blood oxygena ion Flow igh ly coupled o oxygen demand due o high basal oxygen consump ion by hea [24]. Mode a e p essu e au o egula ion could lead o issue hypoxia. Ex en o he s enosed lesion Smalle , localized lesions. Much longe lesions, usually loca ed be ween muscle and bone. In e na ional Jou nal o Biop in ing Co ona y and pe iphe al a e y disease. S a e o he a . Volume 9 Issue 2 (2023) h ps://doi.o g/10.18063/ijb. 9i2.664 234 O he MEX-based s udies ha e also been epo ed easible me hodologies o p in ing VS, e en i hese echniques depend on semisolid-like ma e ials. Some plas ic ma e ials can be dissol ed in ce ain sol en s ha le behind a solid s uc u e a e e apo a ion. Pa icula ly, PCL, PLGA, and polye hylene glycol (PEG) we e dissol ed, ex uded and subsequen ly coa ed wi h si olimus by means o ul asonic sp ay me hod[69]. This 3DP me hodology enables he p oduc ion o a helical, biocompa ible BRS and DES wi h success ul esul s in i o and in i o. Si olimus- coa ed BRS was able o educe neoin imal hype plasia in male pigs o 4 weeks compa ed o he co esponding coun e pa wi hou si olimus, oge he wi h educed h ombosis and in lamma ion. This e ec i eness has been ela ed o he con olled elease o si olimus o 31 days. I is also wo h o men ion ha he in i o s en implan a ion was pe o med wi hou much complica ions, p o ing ha 3DP s en s a e sui able o eal ea men s. MEX 3DP has Figu e 6. (A) Til ed s uc u es p in ed (scale ba : 1 cm). (B) S eps o in i o deploymen es ing. Di e en ames, om (a) o (d), show he shape memo y e ec o PGDA a e pho oc osslinking and he mal cu ing. E ec i e deploymen inside a comp essed silicone ube. (C) Resul s o in i o s udies in mouse ao a; (a) images a e implan a ion and (b) a e 14 days; (c), (d), (e), and ( ) co espond o di e en s aining echniques o middle/inne (c and e) and ou e laye s (d and ) o newly o med issue a e 14 days o VS implan a ion. Black a ows indica e inne elas- in laye and g een a ows indica e ou e elas in laye ; (g) endo helial cells s ained wi h VE-cadhe in an ibody (g een) and cell nuclei s ained wi h DAPI (blue); (h) myo ib oblas s ( ed) and nuclei s ained wi h DAPI (blue). Rep oduced wi h pe mission om [64] 2021, Ac a Bioma e ialia. In e na ional Jou nal o Biop in ing Co ona y and pe iphe al a e y disease. S a e o he a . Volume 9 Issue 2 (2023) h ps://doi.o g/10.18063/ijb. 9i2.664 235 enabled he p oduc ion o pa ien -speci ic polyme -ca bon BRS[70]. This s udy p o es ha pa ien -speci ic s en ing p ocess based on MEX 3DP is easible and p omising. Fib in-di ec ed adio-opaque con as helps o ob ain he mold and shape o he lesion, om which he 3D design o he s en is p epa ed. The ex usion-based p in ing p ocess o he BRS was ca ied ou as a la ec angula slab ha was subsequen ly olded and success ully deployed in o a pig hea . Lee e al. ha e ecen ly p oduced a BRS wi h pneuma ic-based 3DP[14]. The elec onic mic oscopy e ealed ha all o he PLA s ands we e smoo h, uni o m and clea ly connec ed wi hou su ace damage (Figu e 8A), gua an eeing absence o auma and s uc u al s abili y du ing implan a ion. To enhance biocompa ibili y and an i-coagula ion ac i i y, hepa in was in oduced h ough su ace modi ica ion wi h polydopamine (PDA) and polye hyleneimine (PEI) as in e media es. This coa ing allows o no only a highe hyd ophilici y, bu also he c osslinking o hepa in ca boxyl g oups wi h amino g oups o PEI in he s en su ace[14]. Success ul in i o s udies we e epo ed, wi h inhibi ed neoin ima hype plasia and absence o h ombosis. These pe o mances can be en i ely Figu e 7. (A) Pulling pla o m o deposi ion p ocess o e he sac i icial mold ob ained by means o 3DP. (B) Shaped ni inol wi es o be used in he inal s en . (C) Final aspec o ao ic me al-PU s en s wi h di e en shapes (b anched and s aigh ). Rep oduced wi h pe mission om [68] 2020, Medical Enginee ing and Physics. Figu e 8. (A) Scanning elec on mic oscopy o p in ed PLA s en s: (a) ull PLA s en ; (b) en i e su ace image; (c) ex e io connec ion; (d) in e io connec ion. (B) Con ocal lase scanning mic oscopy (CLSM) o smoo h muscle cells (SMC, ed) and endo helial cells (EC, g een) seeded o e he p o- duced s en s. PLA s ands o pu e PLA s en s; PLADP s ands o PLA s en s a e PEI immobiliza ion; PLADPH e e s o s en s loaded wi h hepa in a e su ace modi ica ion. Ba cha s ep esen he pe cen age o cellula p oli e a ion (bo h SMC and EC) a day 1 and day 3, hus demons a ing signi ican di e ences be ween samples. Rep oduced wi h pe mission om [14] 2019, Chemical Enginee ing. In e na ional Jou nal o Biop in ing Co ona y and pe iphe al a e y disease. S a e o he a . Volume 9 Issue 2 (2023) h ps://doi.o g/10.18063/ijb. 9i2.664 236 asc ibed o he p esence and con ol elease o hepa in. On he o he hand, he unc ional g oups in he s en su ace did in luence he medical de ice in e ac ion wi h cells and mechanical p ope ies. The amine- ich su ace o he s en wi h PDA and immobilized PEI p omo ed apid smoo h muscle cells (SMC) p oli e a ion, while he opposi e happened o he hepa in-loaded s en (Figu e8B). On he o he hand, hepa in-loaded s en inc eased endo helial cells (EC) p oli e a ion (Figu e 8B) and ni ic oxide gene a ion, which is desi able o a good pa ency. The combina ion o PLA, PDA, and PEI enhanced segmen al comp ession, bending and o esho ening es s. E en i he addi ion o hepa in weakened he mechanical pe o mance, i enhanced he s en lexibili y[14]. Mo e ecen ly, a MEX 3D p in e has been used o ob ain a BRS, pho ocu able, shape memo y cyclodex in-PCL-pacli axel (βCD-PCL-PTX) s en , which has app op ia e ensile s eng h, elas ici y, and bu s ing p essu e[71]. Mo e ecen ly, SC-3DP has also been p oposed o he p oduc ion o VS medical de ices. As p e iously emphasized, SC-3DP is conside ed a PBF o MEX 3DP, depending on he ing edien s and he p in ing p ocess. Singh e al. used his echnique o ob ain a PCL-ca bonyl i on powde (CIP) s en -like s uc u es[72], meaning ha hey wo ked wi h a polyme ic base dissol ed in an o ganic sol en ha e apo a ed as ex uded. No sin e ing is equi ed and debinding occu s by e apo a ion o he o ganic sol en . The au ho s highligh ed he ac ha no o he p e ious s udies ha e e e epo ed he use o his 3DP p ocess as a VS manu ac u ing echnique. Ne e heless, no VS 3D cons uc s we e p oduced, bu he a en ion was ocused on he e ec o CIP as a PCL ein o cemen as well as on he inal biological pe o mance o he p in ed composi e. The ole, p ope ies and po en ial use ulness o CIP will be add essed in la e sec ions. 4.2. Va pho opolyme iza ion 3DP as ascula s en manu ac u ing echnique As p e iously men ioned, VPP 3DP echniques wo k wi h a liquid aw ma e ial ha unde goes solidi ica ion by di e en mechanisms, depending on bo h he ma e ial i sel and he speci ic 3DP me hodology used. Fo he p oduc ion o VS, pho oc osslinkable esins and polyes e s a e able o p o ide sui able mechanical p ope ies a e cu ing; he e o e, hey can be used as ascula endop o hesis. Mic o-con inuous liquid in e ace p in ing (mic o CLIP) is a echnique ha wo ks wi h a simila p inciple o ha o DLP. The speed, ep oducibili y, and ideli y o his 3DP possess a high po en ial in he p oduc ion o in si u, ailo -made BRS. Van Li h e al. used a cus omized mic o CLIP o he p oduc ion o a pho ocu able, an ioxidan and bio eso bable me ac yla ed bioma e ial (poly(1,12- dodecame hylene ci a e), mPDC) by mixing ci ic acid and 1,12-dodecanediol, THF[73]. The pho ocu ing p ocess ans o ms he ini ial ma e ial in o a bio eso bable one, which can be used as a bioma e ial ink o he p oduc ion o VS and shows in i o deg ada ion o 25% (PBS, 37°C) wi hin 6 mon hs. Upon deploymen , he ab ica ed s en was able o sel -expand p ope ly, eaching he o iginal diame e in jus 3 min. This sel -expansion was epo ed o be as e han he expansion o o he comme cial BRS, aking ime om 3 o 8 min. Mo eo e , he inal mechanical p ope ies o hese 3D-p in ed BRS we e compa able o ba e-me al ni inol s en s, making hem a easible o mula ion o he p oduc ion o cus omizable, pe sonalized BRS. La e , au ho s epo ed an in-p ocess calib a ion me hod o he same mic o CLIP p in ing p ocess, aiming o educe he o al ab ica ion ime om 70min o 20-11 min depending on he laye slicing hickness o he s en [74]. They also op imized he ing edien s and concen a ions du ing he p in ing p ocess by including wo pho oini ia o s: i gacu e and e hyl 4-dime hylamino benzoa e (EDAB). This combina ion enabled g ea e c osslinking and made possible s u geome ies. Pho oc osslinkable, elas ome ic polyes e s such as me ac yla ed poly(dodecanediol ci a e) (mPDC) can be used as aw ma e ials o he p oduc ion o 3D cons uc s by means o DLP. mPDC polyme has p o en o be biodeg adable and biocompa ible and possess elas ic beha io , making i sui able o he p oduc ion o sel - expandable BRS[75,76]. Oli ei a e al. de eloped a BRS, DES based on mPDC and ni ic oxide, and used DLP as 3DP echnology o p oduce a small diame e VS (Figu e 9A)[75]. Wi h espec o o he ac i e subs ances, ni ic oxide has p o en o be mo e ad an ageous o s en s in e ms o cellula p oli e a ion, biocompa ibili y and es enosis. Mo eo e , ni ic oxide is bene icial o main ain he muscula onus o he ascula u e unde ea men , con ol blood p essu e and inhibi pla ele adhesion. Al hough he au ho s p oposed his app oach o a co ona y s en , i s ansla ion in o a pe iphe al one could be mo e bene icial i blood p essu e and muscle one o he pe iphe al essels a e lowe wi h espec o co ona y a e ies. Mo eo e , i has ecen ly been demons a ed ha he ni ic oxide sys em and i s egula o s a e comp omised in PAD[77]. Ni ic oxide elease was achie ed by he S-ni osa ion o N-ace yl-d-penicillamine (SNAP) o he 3D-p in ed cons uc ia liquid adso p ion[75]. The sel -expanding p ope ies o he s en we e con i med due o good elas ic esponse up o 50% s ain. In ac , he s en comple ely eco e ed i s ini ial dimensions a e being collapsed and c imped (Figu e 9C). Ne e heless, he au ho s s a ed ha an op imal cu e is needed o he mechanical p ope ies o be maximized, meaning ha he DLP p in ing p ocess In e na ional Jou nal o Biop in ing Co ona y and pe iphe al a e y disease. S a e o he a . Volume 9 Issue 2 (2023) h ps://doi.o g/10.18063/ijb. 9i2.664 237 (Figu e 9B) mus be p e iously op imized. The elease o ni ic oxide om mPDC/SNAP BRS is di ec ly ela ed o he su ace in con ac wi h he aqueous biological medium, sugges ing ha he modula ion o he inal s en geome y can be an impo an a iable o con ol he ni ic oxide elease[75]. This can be in e p e ed as ollows: 3DP enables he p oduc ion o cus omized VS in e ms o no only dimensions, bu also pa icula he apeu ic needs when i comes o DES. 4.3. Ma e ial je ing 3DP as ascula s en manu ac u ing echnique MJT 3DP is based on he deposi ion o liquid d ople s. I is complica ed o ob ain in ica e, high- esolu ion s uc u es such as hose equi ed o he p oduc ion o VS by his 3DP echnique. Mo eo e , he manu ac u ing o MJT- p in ed cons uc s depends on he apid solidi ica ion o ins an aneous cu ing (such as pho o-c osslinking) o he d ople s as hey a e deposi ed, in an a emp o minimize he liquid ink o low o e he p e iously deposi ed laye . Unde hese ci cums ances, MJT is a challenging echnique when i comes o VS. None heless, i can be o g ea use ulness in combina ion wi h o he me hods. In an a emp o imp o e he d ug coa ing p ocess o s en s u s, Scou a is e al. e e ed MJT 3DP o as a eliable, obus , and ep oducible echnique in con olling and gua an eeing he p ope d ug-coa ing o an in a ascula Figu e 9. (A) Pho og aphs and scanning elec on mic oscopy o mDPC-SNAP s en . (B) Schema ic ep esen a ion o he DLP p in e used. (C) S ess– s ain comp ession cu es o uncu ed and pos -cu ed mPDC s en s a di e en imes and wi h di e en diame e s (a and b). Pho og aphs ames o a s en o 6 mm diame e du ing s ess–s ain comp ession es (c–e). Rep oduced wi h pe mission om [75] 2021, Biop in ing. In e na ional Jou nal o Biop in ing Co ona y and pe iphe al a e y disease. S a e o he a . Volume 9 Issue 2 (2023) h ps://doi.o g/10.18063/ijb. 9i2.664 238 s en [19]. The quali y o s en d ug-coa ing is c ucial o wo main easons: (i) i in luences he d ug elease a e, and (ii) i a ec s he supe icial ex u e o he VS as an i egula coa ing could lead o ough su aces. The e o e, a smoo h s en su ace would minimize he inju y o blood essels du ing he implan a ion o he medical de ice. They aimed o imp o e he adi ional s en d ug-coa ing p ocedu es, he eby educing he ime equi ed and ma e ial was e. Thus, hey MJT-p in ed PLA/sim as a in and PLA/ pacli axel solu ions o e di e en al eady-exis ing BMS (P esillionTM and Cyphe TM s en s) by means o a piezod i en dispense . The au ho s epo ed ha “ ips wi h 300 pL aqueous d ople olume a e sui able o s en coa ing (…) while smalle olumes (100 pL) esul ed in clogging o he nozzle”[19]. Ano he impo an ac o o bea in mind is he ol age used, since an inadequa e ol age could lead o bubble o ma ion inside he ink ip, jeopa dizing he p in abili y. The compa ison be ween he inal coa ing o wo comme cial s en s wi h di e en geome ies indica es he need o MJT d ug-coa ing op imiza ion acco ding o he shape o each medical de ice o a oid i egula d ug- coa ing. The in i o d ug elease p o iles o sim as a in and pacli axel, sepa a ely, e ealed bu s elease o he i s 5 days, ollowed by a i s -o de elease un il day 30 in bo h cases. A success ul implan a ion in male Wis a a s was epo ed, wi hou in lamma o y and cy o oxici y esponse wi hin 7 days. The e o e, MJT-p in ing o s en d ug-coa ing can be used o op imize and maximize he pe o mance o DES. 4.4. Powde bed usion 3DP as ascula s en manu ac u ing echnique PBF 3DP is usually associa ed o s ong, ha d ma e ials. In ac , me al powde s a e mos equen ly used in PBF 3DP echniques o ob ain me allic VS. Despi e he long- e m complica ions and disad an ages o pe manen me allic s en s, hey a e he mos widely used (Table 1, Figu e 2). Ne e heless, in e ms o cu ing-edge echnologies and esea ch, he e o s a e cen e ed on BRS, DES, which means ha he numbe o s udies dealing wi h PBF 3DP echniques is sca ce. Lase -cu ing and b aiding a e he mos commonly used manu ac u ing echniques o he p oduc ion o me allic VS. When i comes o 3DP, PBF is commonly used o p in me allic ma e ials. Demi and P e i ali demons a ed he easibili y and con enience o PBF and he subsequen elec ochemical polishing o p oduce a CoC s en wi h espec o he con en ional manu ac u ing cycles (mic o ube p oduc ion ollowed by lase -cu ing)[37]. In his echnique, di e en scan s a egies can be ollowed (pa allel o concen ic scanning), gi ing ise o di e en esul s. The au ho s highligh ed he impo ance o a p ope s en design and manu ac u ing o ien a ion oge he wi h some basic ules du ing PBF p in ing p ocess. Wi h PBF p in ing, laye plane suppo s a e needed when angles smalle han 45° a e c ea ed; o e hanging egions up o 1 mm can be buil wi hou suppo s; minimum gaps o 0.3mm a e ecommended be ween sepa a e ea u es, e c.[37] Acco ding o hese equi emen s, hey designed a s en wi h hexagonal, zig-zag pa e n o ming a closed cell wi hou lex-connec o s (Figu e 10A). This geome y a oided he equi emen s o suppo s uc u es du ing PBF 3DP. Thei a en ion was clea ly cen e ed on he op imiza ion o he 3DP manu ac u ing, no in he inal p ope ies o he inal s en , so he ensile s eng h, ecoil and a igue esis ance we e no cha ac e ized in his s udy. Depending on he lase scanning pa e n, he lase pulse du a ion and peak powe mus be op imized. They also concluded ha inc eased peak powe and pulse du a ion educed su ace oughness. Fo he pa icula geome ical design o his VS, he pa allel s a egy ga e ise o i egula geome y, hickness, and su ace oughness, hus highligh ing he inadequacy o his s a egy o he p oduc ion o mic o-geome ies (Figu e 10C). On he con a y, concen ic scanning and highe p in abili y we e achie ed (Figu e 10C). Addi ionally, PBF 3DP p oduces i ems wi h e y ough su aces, implying ha pos -p ocessing echniques such elec o-polishing a e compulso y o educe ha m du ing s en implan a ion (Figu e 10B)[37]. Despi e he ac ha me allic subs a es a e he mos equen in PBF, he e a e also some excep ions. Fo ins ance, some yea s ago, Flege e  al. adap ed he PBF 3DP echnique o p oduce a BRS ascula s en made o PLLA and PCL[78]. Since his 3DP echnique equi es powde y aw ma e ials o he p in ing p ocess, PLLA and PCL polyme s we e subjec ed o sol en -e apo a ion p ocesses o ob ain homogeneous, small pa icles so ha hey could hen be used in PBF; bo h PCL and PLLA pa icles possessed good lowabili y, egula sphe ical shape, na ow pa icle size dis ibu ion, and high densi y. Mo eo e , he lase o he PBF p in e was adap ed by adding a powe a enua o . The a en ion o his s udy was he e o e cen e ed on he abili y o p oduce s en s om hese aw ma e ials and o moni o he s abili y o he esul an ing edien s a e he PBF p in ing and gamma- i adia ion s e iliza ion. The biocompa ibili y o he s en s and he ma e ials was assessed using human a e ial smoo h muscle cells (haSMCs), human umbilical ein endo helial cells (HUVECs), and endo helial p ogeni o cells (EPCs). Fi s , he manu ac u ing o PCL and PLLA powde pa icles did no jeopa dize hei biocompa ibili y, unlike he p in ing p ocess, which educed me abolic ac i i y o he EPCs. The au ho s asc ibed his esul o he p esence o polyme iza ion ini ia o s in s en In e na ional Jou nal o Biop in ing Co ona y and pe iphe al a e y disease. S a e o he a . Volume 9 Issue 2 (2023) h ps://doi.o g/10.18063/ijb. 9i2.664 239 su aces. Gamma-i adia ion was an e ec i e s e iliza ion p ocedu e, al hough i also a ec ed he s uc u e o he polyme s and hei biological pe o mance. haSMCs p oli e a ion and me abolic ac i i y we e inhibi ed due o su ace modi ica ions o he polyme s du ing s e iliza ion, while EPCs we e una ec ed. Flege e al. highligh ed his esul as a posi i e one, since i “migh a o he p e en ion o neoin imal hype plasia in s en ed essels”[78]. This s udy demons a ed he e sa ili y o 3DP echniques o be adap ed o p in a wide a ie y o ma e ials, meaning ha none o hem can be dismissed as use ul ally in he p oduc ion o medical de ices in u u e. 5. Compu a ional s udies and 3D p in ing Se e al s udies ha e demons a ed ha s en design ea u es a e o g ea impo ance o a success ul ea men due o co ela ions wi h h ombosis and in- es enosis isk[33,79,80]. Fo be e cla i y and unde s anding o his sec ion, a schema ic ep esen a ion o he mos impo an s en pa s and hei nomencla u e a e included in Figu e 11A. The implan ed VS induces dis u bances in blood low and al e s shea s ess o wall essels a he s u le el. These ac o s highly in luence he pa hophysiological mechanisms leading o VS complica ions[81]. Focusing on he s uc u al and geome ical design o VS, he i s manu ac u ed s en s could be classi ied in o slo ed geome ies and coil geome ies. The o me ones possessed highe adial s eng h bu lacked lexibili y, as compa ed o hei coil coun e pa s. A e wa d, VS geome ies ha e g ea ly e ol ed and changed, wi h mo e complica ed and pe ec ed geome ies included, and a e adap ed o hei inal scope (Table 3). Nowadays, coil s en geome ies a e mo e commonly used o non- ascula s en s, being mo e equen o ind helical spi al designs o VS. Wo en (b aided o kni ed) designs can be made o mo e han one s and (made o di e en ma e ials) and hey a e adi ionally used o he p oduc ion o sel -expandable VS, al hough balloon-expandable examples can also be ound. VS wi h indi idual ings equen ly use zig-zag wi e (s u s) ha should be a ached o one ano he o o m he inal s en o ascula p os hesis. I indi idual ings a e connec ed o each o he wi h a ce ain consis en pa e n, he s en possesses he so-called “sequen ial ing connec ion.” In his occasion, he zig-zag s u s a e connec ed h ough “b idges,” “hinges,” o “nodes,” placed in e e y s u in lec ion poin ( egula connec ion), in a subse o in lec ion poin s al e na ing wi h unconnec ed ones (pe iodic connec ion) o hey can be placed o join he ou e adii (peak-peak b idging elemen s) o o join inne adii wi h ou e adii (peak- alley b idging elemen s). The s en b idges can ha e di e en shapes such as V, L, N, W, S shapes, e c., as well as mul iple shapes all combined in he same s uc u e (Figu e 11C). These connec ions play an impo an ole in he op imiza ion o he inal pe o mance o he s en , especially in hei Figu e 10. (A) Digi al s en p o o ype op imized o PBF 3DP. (B) Scanning elec on mic oscopy images o p in ed VS a e elec ochemical polishing; images a he uppe panel belong o VS p oduced by ha ching PBF scanning, whe eas images a he lowe panel co espond o a s en p oduced wi h concen ic scanning PBF. (C) Scanning elec on mic oscopy images o 3DP CoC VS p oduced by ha ching ( op) o concen ic s a egy lase scanning (bo om) and hei di e ences. Lase pulse du a ion is indica ed in each case. Rep oduced wi h pe mission om [37] 2019, Ma e ials & Design. In e na ional Jou nal o Biop in ing Co ona y and pe iphe al a e y disease. S a e o he a . Volume 9 Issue 2 (2023) h ps://doi.o g/10.18063/ijb. 9i2.664 240 mechanical p ope ies, as ecen ly e iewed by Pan e al.[82] Wi hin hese s en s, i is possible o di e en ia e be ween “closed cells” and “open cells” (Table 3)[28]. Nowadays, i is also possible o ind comme cial s en s wi h di e en s u wid h in he same de ice, such as NIRxcellTM s en sys em (Figu e 11B) and o he s wi h non-uni o m cell sizes and shapes (Figu e 11D). The p epa a ion o di e en s en designs and he expe imen al s udy o hei co ela ion wi h s en pe o mance and u u e complica ions is no easible om an expe imen al poin o iew due o he milieu o possible designs (Table 3), dimensions, ma e ials, hemodynamics, e c., oge he wi h he long- e m s udies and he numbe o eplica es. Fo example, some au ho s and manu ac u e s ad oca e o s en s wi h hinne s u s o imp o e and aid e-endo helializa ion[83,84], bu his can signi ican ly in luence he VS deli e abili y, lexibili y, ic ion, amoun o essel wall co e age, and d ug deli e y, i applicable. In his ega d, compu a ional s udies o in silico s udies a e o g ea use ulness, enabling digi al simula ions o p edic he inal p ope ies and pe o mance o a pa icula s en . F om a medical poin o iew, 3DP is an especially obus , e sa ile echnique o he manu ac u ing o pe sonalized, in si u VS p io o he su gical in e en ion and adap ed o he pa icula ype o lesion and blood essel. F om he esea ch poin o iew, 3DP is also use ul in he p oduc ion o s en s wi h di e en geome ies enabling he s udy o he in luence ha each design would be upg aded o as a medical de ice. The e o e, 3DP is he pe ec me hod o apidly con i ming o denying compu a ional s udies. Mis a e  al. used compu a ional s udies o explo e di e en PCL-GR geome ies and simula e he de o ma ion o he s en du ing c imping and expansion[70]. The simula ions helped o disce n he mos op imal s en design, hus accele a ing he p oduc ion o he CAD model o 3DP. In a simila way, Cab e a e al. used compu a ional s udies o ansla e he esul s in o a physical polyme p o o ype h ough FDM 3DP[85]. The idea was o ab ica e a s en wi h a lexible, BRS he moplas ic co-polyes e elas ome (TPC) ha ing physical p ope ies simila o ha o a comme cially a ailable ni inol s en , including sel -expanding abili y. Compu a ional s udies enabled he an icipa ion and adjus men o he inal s en pe o mance by changing he wid h, hickness, and s u numbe . A e selec ing he desi able s en pa ame e s, dimensions and geome y as well as ob aining adequa e c imping and c ush compu a ional esul s, he TPC s en was p in ed wi h FDM. The expe imen al mechanical s udies we e in ag eemen wi h he compu a ional models, con i ming he abili y o compu a ional simula ions o build ealis ic p o o ypes. Figu e 11. (A) Schema ic ep esen a ion o s en pa s and nomencla u e. (B) Geome ical design o comme cial NIRxcell s en , which possesses di e en s u wid hs wi hin he same s uc u e. (C) Some examples o s u connec ions. (D) Non-uni o m Poisson’s a io s en 2D s uc u e. Rep oduced wi h pe mission om [82] 2021, Mic omachines. In e na ional Jou nal o Biop in ing Co ona y and pe iphe al a e y disease. S a e o he a . Volume 9 Issue 2 (2023) h ps://doi.o g/10.18063/ijb. 9i2.664 241 6. The impo ance o ing edien s o he manu ac u ing o ascula s en s In he de elopmen o ca dio ascula g a s and s en s, he use o ma e ial such as nanocomposi es has g ea ly e ol ed h oughou he yea s. A nanocomposi e is a ma e ial o he e ogeneous composi ion (o ganic, ino ganic o hyb ids) including ing edien s mixed a he nanome e scale. Usually, nanocomposi es a e made o a polyme ic- like ma ix hos ing ano he ing edien wi h unc ional ac i i y ( he apeu ic, c osslinking, ein o cing, e c.). Apa om he composi ion and ing edien concen a ion, he p oduc ion me hodology is also impo an o he success ul nanocomposi e pe o mance, including p oduc ion echnique, ype o ing edien s, eac ions/in e ac ions be ween he nanocomposi e componen s, among o he s[86]. Clays, ca bon, me als and glass ing edien s ha e p o en hei use ulness as nanocomposi e ein o cing o ille s, enabling no only he ca iage and deli e y o he apeu ic ing edien s, bu also he imp o emen o mechanical ea u es and heology. When i comes o medical de ices, he biocompa ibili y o he nanocomposi e is c ucial o gua an ee hei sa e y a e implan a ion. In he pa icula case o ca dio ascula medical de ices ( ascula g a s and VS), ca bon-based ing edien s (ca bon nano ubes, g aphene, e c.) ha e p o en hei biocompa ibili y[86]. G aphi e, g aphene, and ca bon nano ubes a e allo opic ca bon o ms, which di e om each o he by spa ial disposi ion. G aphene is a monolaye o ca bon a oms linked o each o he o ming a hexagonal honeycomb la ice. G aphi e, on he o he hand, occu s when g aphene laye s a e s acked in he z-plane and held oge he by an de Waals o ces. Ca bon nano ubes (CNT) a e ubula g aphene shee s. Depending on he numbe o ubula shee s, CNT can be di ided in o single-walled CNT ( ypically abb e ia ed as SWCNT) o mul i-walled CNT, which is when mo e han wo laye s a e combined (MWCNT). The main in e es o hese syn he ic ma e ials lies in hei biocompa ibili y. Vellayappan e al. e iewed he use ulness o hese ma e ials in he de elopmen o ascula g a s and s en s[86]. Ca bon-based ma e ials a e use ul as an icoagulan ing edien s and can p omo e cellula g ow h Table 3. Classi ica ion and ea u es o mos equen ly used VS designs and geome ies Geome y Scheme S eng hs Weaknesses Helical spi al • High lexibili y (minimal in e nal connec ion poin s) • Can be subjec ed o elonga ion and comp ession du ing deli e y • Lack o longi udinal suppo Wo en (b aided, kni ed) • O e ema kable co e age o he s enosed egion • F equen ecoil e en s a e expansion • Radial s eng h dependen on axial ixa ion o hei ends Indi idual ings • Use ul as ascula g a s • Easy o p oduce • Highly lexible • Ve sa ile • Requi e addi ional suppo o connec ion wi h o he pieces/ ings Sequen ial ings Closed cells (peak- o-peak connec ions) • Regula b idging elemen s lead o imp o ed s eng h • Op imal sca olding and suppo • Flex connec o s (wi h di e en shapes) allow o highe lexibili y due o plas ic de o ma ion o he b idging elemen du ing implan a ion • Gene ally less lexible han opened s uc u es, especially i oo much b idging, igid connec ions a e used Open cells (peak- o-peak, peak- o- alley, my iad o hyb id combina ions). • Longi udinal lexibili y hanks o unconnec ed s u s egions • Peak- o- alley connec ions op imize sca olding due o highe alignmen • Peak- o- alley sac i ices s eng h wi h espec o peak- o-peak connec ions Table cons uc ed based on he e iew o S oeckel e al.[28]. In e na ional Jou nal o Biop in ing Co ona y and pe iphe al a e y disease. S a e o he a . Volume 9 Issue 2 (2023) h ps://doi.o g/10.18063/ijb. 9i2.664 242 and mechanical p ope ies o polyme s such as a PLGA, PCL, PCLA (poly(L-lac ide-co-ε-cap olac one))[87-92]. Fo he pa icula case o mechanical ein o cemen , he homogeneous dispe sion o ca bon nano ubes is c ucial o asce ain op imal mechanical s eng h[92]. Consequen ly, he e is no di ec ela ionship be ween he amoun o CNT and he mechanical imp o emen , since e y high concen a ion could lead o he e ogeneous dispe sion, which hinde s he mechanical pe o mance o he nanocomposi e. G aphene (GR) has demons a ed o be a use ul ing edien o imp o e bo h mechanical p ope ies o VS and con ol d ug elease om d ug-elu ing VS. The li e a u e ega ding 3DP and GR is cu en ly sca ce, bu he e a e clea indica ions o he use ulness o g aphene as an ing edien o imp o e he mechanical and biological p ope ies o s en s. Ca bon is one o he ma e ials wi h highe hemocompa ibili y due o chemical ine ness, minimal pla ele ac i a ion and a o able con o ma ional changes[93]. Coa ing is he mos common s a egy o add GR o VS[94-96]. Ni inol VS coa ed wi h GR had imp o ed biological p ope ies compa ed o i s coun e pa [94]. B ie ly, GR coa ing inhibi ed pla ele ac i a ion and was ully biocompa ible wi h smoo h muscle cells. Likewise, excellen bio- and hemocompa ibili y was epo ed o a coa ed s ainless s eel VS[96]. In his occasion, a coa ing mix u e con aining poly(3,4-e hylenedioxy hiophene) polys y ene sul ona e (PEDOT:PSS), g aphene oxide (GO), and hepa in was deposi ed o e he s ainless s eel VS (SUS316) by elec ochemical polyme iza ion. This p ocess ga e ise o a s en wi h high hyd ophilic na u e, which can p e en pla ele adhesion ollowing implan a ion. GO con ibu ed he mos o his e ec , while he ole o hepa in was he minimum. The au ho s hypo hesized ha he nega i e cha ge o GO c ea ed a epulsing o ce agains plasma p o eins and pla ele s (also wi h a nega i e ne cha ge)[96]. On he opposi e side, GR has also been shown o be a use ul coa ing in BRS s en s. Magnesium alloy s en s a e BRS VS wi h good mechanical p ope ies. None heless, hese s en s su e s om a apid deg ada ion and insu icien biocompa ibili y. Laye -by-laye deposi ion me hod was ecen ly used o coa magnesium alloy VS wi h GR unc ionalized wi h chi osan[95]. The au ho s s a ed ha he esul an bioac i e mul ilaye coa ing endowed magnesium alloy wi h excellen in i o deg ada ion esis ance. Addi ionally, good blood compa ibili y ( educed hemolysis and pla ele adhesion) and imp o ed exp ession o ascula endo helial g ow h ac o (VEGF) and ni ic oxide we e asc ibed o he GR- based coa ing. The s udy o Mis a e  al. is one o he ew dealing wi h 3DP, g aphene, and VS[70]. A BRS s en made o PCL and g aphene and loaded wi h niclosamide and inosi ol phospha e epo ed good an icoagula ion and an i es enosis pe o mance. The compa ison o he 3D-p in ed s en wi h and wi hou g aphene helps disce n he in luence o he ino ganic ing edien on he s en pe o mance. The p esence o 4% o g aphene inc eased he Young’s modulus o PCL and demons a ed be e esis ance unde a e y wall p essu e a e deploymen . By he same oken, PCL–g aphene s en had a be e con ol o niclosamide and inosi ol phospha e elease. One o he limi a ions o 3DP o he p oduc ion o VS lies in he ac ha mos o he ma e ials used a e polyme ic, bu no all o hem a e able o be deployed inside he essels. In his ega d, shape memo y polyme s (SMP), also known as “sma ” o “in elligen ma e ials” a e cu en ly on he spo ligh , no only o 3DP in gene al[97], bu also in he p oduc ion o VS. In ac , sma ma e ials such as shape memo y alloys (such as ni inol) ha e al eady been used o ab ica e VS, and mos o hem ha e been comme cialized. SMP a e polyme ic sma ma e ials wi h he abili y o change hei shape while subjec ed o some igge s such as empe a u e, elec omagne ic ields, pho o-ac i a ion, elec o-ac i a ion, con ac wi h wa e (swelling), pH medium changes, e c. Dis ega ding he igge ing s imulus, all hese sma ma e ials a e used in a wo-s ep manne [97,98]. The “p og amming s ep” is he shape-memo y c ea ion p ocess, whe e he pe manen , o iginal shape is changed o a seconda y ( empo a y) one by subjec ing he ma e ial o ex e nal s ess o ces (mechanical s ess). Unde hese ci cums ances, he SMP acqui es a desi able shape and main ains i a e s ess emo al. Then, a e he exposu e o he shaped s uc u e o o he non- mechanical igge s (e.g., hea , ligh , pH change), i is able o eco e he o iginal, pe manen shape by e e ing he shape i acqui es du ing he applica ion o mechanical o ces. Hence, SMP ha e he abili y o s o e mechanical s ess and elease i unde non-mechanical s imuli. Depending on he na u e o he ma e ial, he mechanism o shape modi ica ion is di e en . Fo he pa icula case o SMP, hey sha e he p esence o “pe manen ne poin s” o “pe manen links” in hei in e nal ne wo k s uc u e and “ empo a y links” o “swi ches.” The pe manen links a e esponsible o he pe manen shape, he so-called “memo y e ec ,” and he e o e, hese ne poin s a e no a ec ed by mechanical de o ma ion. On he o he hand, swi ches a e o med du ing mechanical s ess due o he con o ma ional eedom o some o he polyme chains. The de o ma ion ob ained du ing he p og amming s ep can be s abilized by he o ma ion o hese “ empo a y links” wi hin he polyme s uc u e. When i comes o he mal- sensi i e polyme s, he di e ence be ween pe manen links and empo a y links lies in he exis ence o mo e han In e na ional Jou nal o Biop in ing Co ona y and pe iphe al a e y disease. S a e o he a . Volume 9 Issue 2 (2023) h ps://doi.o g/10.18063/ijb. 9i2.664 243 one he mal ansi ion. Those domains wi h he highes he mal ansi ion (glass ansi ion empe a u e, Tg o mel ing empe a u e, Tm) a e esponsible o he memo y shape o pe manen shape, whe eas swi ching domains ha possess he second highes he mal ansi ion (Tg o Tm) is esponsible o he empo a y shape[97,98]. SMP also possesses use ul p ope ies, such as ligh weigh , la ge elas ic modulus and lexibili y, as well as biodeg adabili y[97]. A polyu e hane SMP was success ully used o ob ain a bi u ca ed s en deployable in jus one s ep[65,66]. When ascula s enosis occu s in a bi u ca ed essel ( essel wi h Y-shaped lumen), wo cylind ical s en s mus be inse ed and subsequen ly joined, which complica es he in e en ion. Thanks o he in insic p ope ies o SMP, Kim e  al. we e able o ab ica e a one-piece, bi u ca ed s en combining wo di e en geome ical designs: he unk o he s en (main essel) possessed a con en ional wa y pa e n, whe eas he bi u ca ed zone was designed wi h a “ki igami-like” s uc u e (Figu e 12A). Ki igami is a supe se o o igami wi h he addi ion o cu ing[66]. Fo deploymen , an in elligen s a egy was also applied: he wo bi u ca ed essels will be olded and i ed wi h one ano he (like a puzzle) o o m a ull, cylind ical piece ha is will be aken o he deploymen a ea (Figu e 12B). Once he e, he olded b anches will bi u ca e and deployed in bo h essels in jus one s ep a e he applica ion o empe a u e as a igge (Figu e 12C)[65,66]. The main d awback o his pa icula s en was he misma ch be ween he empe a u e ha igge s he SMP o un old (55°C–60°C) and he empe a u e o he human body. A ecen s udy demons a es he possibili y o modi ying he glass ansi ion empe a u e o SMP, b inging i close o a mo e physiological empe a u e ange[64]. The au ho s syn he ized biodeg adable poly(glyce ol dodecanoa e (PGD, ansi ion empe a u e o 22.5°C–43.6°C) and subsequen ly modi ied i o ob ain poly(glyce ol dodecanoa e ac yla e) (PGDA) h ough glyce ol and docecanedioic polycondensa ion. The esul an ma e ial wa pho ocu able and showed a inal ansi ion empe a u e o 20°C–37°C, which was much close o he physiological ange. A e being p in ed and pho ocu ed wi h UV ligh , he PGDA cons uc was he mally cu ed a 145°C in an o en. Then, he cons uc was de o med o c ea e he “c imped s a e” o he s en . Wi h u he hea ing abo e he ansi ion empe a u e (20°C–37°C), he s en eco e ed i s ini ial s a e wi hin 8 seconds. Simila mechanical p ope ies be ween he p in ed s en and he so biological issues a 37°C was ound, demons a ing mechanical adap a ion Figu e 12. Design and eal aspec o bi u ca ed sel -expandable s en p oduced by FMD using a shape memo y polyme . The bi u ca ed b anch is able o de o m un il he o ma ion o a single condui , he eby allowing implan a ion. The sui abili y o his VS o deploymen in a bi u ca ed essel was es ed in a silicon, anspa en mold. Scale ba s: 20 mm. Rep oduced wi h pe mission om [66] 2018, Scien i ic Repo s. In e na ional Jou nal o Biop in ing Co ona y and pe iphe al a e y disease. S a e o he a . Volume 9 Issue 2 (2023) h ps://doi.o g/10.18063/ijb. 9i2.664 250 18. Ooi OC, Mullany CJ, Rihal CS, 2007, Re ascula iza ion op ions o ischemic hea disease: Co ona y a e y bypass g a ing and pe cu aneous co ona y in e en ion, in Ca dio ascula The apeu ics: A Companion o B aunwald’s Hea Disease, 3 d ed., E. M. An man and M. S. Saba ine, Eds. W.B. Saunde s, 157–177. 19. Scou a is N, Chai F, Mau el B, e  al., 2015, De elopmen and biological e alua ion o inkje p in ed d ug coa ings on in a ascula s en . Mol Pha m, 13(1):125–133. h ps://doi.o g/10.1021/ACS.MOLPHARMACEUT.5B00570 20. K ankenbe g H, e al., 2017, Sel -expanding e sus balloon- expandable s en s o iliac a e y occlusi e disease: The andomized ICE ial. JACC Ca dio asc In e , 10(16):1694– 1704. h ps://doi.o g/10.1016/J.JCIN.2017.05.015 21. Fo nell D, 2019, T ends in co ona y, ca o id and pe iphe al s en s | DAIC. Diagn In e Ca diol. h ps://www.dica diology.com/a icle/ ends-co ona y- ca o id-and-pe iphe al-s en s (Accessed Ap il 02, 2022) 22. an Haels STW, Pee e s Weem SMO, Moll FL, e al., 2016, Cu en s a us and u u e pe spec i es o bio eso bable s en s in pe iphe al a e ial disease. J Vasc Su g, 64(4): 1151–1159.e1. h ps://doi.o g/10.1016/J.JVS.2016.05.044 23. Medical Ad iso y Sec e a ia , 2010, S en ing o pe iphe al a e y disease o he lowe ex emi ies: An e idence-based analysis. On Heal h Technol. Assess Se , 10(18):1–88. Accessed: Ap il 02, 2022 [Online]. A ailable. h ps://pubmed.ncbi.nlm.nih.go /23074395/ 24. Klabunde RE, 2017, Co ona y ana omy and blood low. Ca dio asc Physiol Concep s. h ps://www.c physiology.com/Blood Flow/BF001 (Accessed Ap il 02, 2022). 25. Klabunde RE, 2010, Au o egula ion o o gan blood low. Ca dio as Physiol Concep s. h ps://www.c physiology.com/Blood Flow/BF004 (Accessed Ap il 02, 2022). 26. Mani G, Feldman MD, Pa el D, e al., 2007, Co ona y s en s: A ma e ials pe spec i e. Bioma e ials, 28(9):1689–1710. h ps://doi.o g/10.1016/J.BIOMATERIALS.2006.11.042 27. Lachowi ze M, 2008, Assessing adial es s o endo ascula implan s. Med De ice Diagn Ind. h ps://www.mddionline.com/news/assessing- adial- es s- endo ascula -implan s (Accessed Feb ua y 02, 2022). 28. S oeckel D, Bonsigno e C, Duda S, 2002, A su ey o s en designs. Minim In asi e The Allied Technol, 11(4):137–147. Accessed: Feb ua y 02, 2022 [Online]. A ailable. h ps://sci-hub. u/h ps://www. and online.com/doi/ abs/10.1080/136457002760273340 29. Abhyanka AD, Thakka AS, 2012, In i o assessmen o s en ecoil o biodeg adable polyme -coa ed cobal – ch omium si olimus-elu ing co ona ys en sys em. Indian Hea J, 64(6):546. h ps://doi.o g/10.1016/J.IHJ.2012.07.005 30. Lee MS, Banka G, 2016, In-s en es enosis. In e Ca diol Clin, 5(2):211–220. h ps://doi.o g/10.1016/J.ICCL.2015.12.006 31. Modi K, Soos MP, Mahajan K, 2021, S en h ombosis. S a Pea ls 1–15. Accessed: Feb ua y 03, 2022 [Online]. A ailable. h ps://www.ncbi.nlm.nih.go /books/NBK441908/ 32. Reejhsinghani R, Lo i AS, 2015, P e en ion o s en h ombosis: Challenges and solu ions. Vasc Heal h Risk Manag, 2015(11):93–106. h ps://doi.o g/10.2147/VHRM.S43357 33. Kolandai elu K, Swamina han R, Gibson WJ, e  al., 2011, S en h ombogenici y ea ly in high- isk in e en ional se ings is d i en by s en design and deploymen and p o ec ed by polyme -d ug coa ings. Ci cula ion, 123(13):1400–1409. h ps://doi.o g/10.1161/CIRCULATIONAHA.110.003210 34. Ho a E, Ha a H, Kamiya T, e  al., 2018, Non- he mal a mosphe ic p essu e plasma-induced IL-8 exp ession is egula ed ia in acellula K + loss and subsequen ERK ac i a ion in human ke a inocy e HaCaT cells. A ch Biochem Biophys, 644:64–71. h ps://doi.o g/10.1016/j.abb.2018.03.005 35. C ček L, Ho áko á M, 2019, Plasma modi ied polyme ic ma e ials o implan applica ions, in Non-The mal Plasma Technology o Polyme ic Ma e ials. Applica ions in Composi es, Nanos uc u ed Ma e ials and Biomedical Fields., S. Thomas, M. Moze ič, U. C elba , e al., Eds. Else ie , 367–407. 36. Guo R, He Y, Li H, e al., 2020, De elopmen o 3D-p in ed sul a ed chi osan modi ied bio eso bable s en s o co ona y a e y disease. F on Bioeng Bio echnol, 8(462):1–12. h ps://doi.o g/10.3389/ bioe.2020.00462 37. Demi AG, P e i ali B, 2017, Addi i e manu ac u ing o ca dio ascula CoC s en s by selec i e lase mel ing. Ma e Des, 119:338–350. h ps://doi.o g/10.1016/J.MATDES.2017.01.091 38. Zou Q, Xue W, Lin J, e al., 2016, Mechanical cha ac e is ics o no el polyes e /NiTi wi es b aided composi e s en o he medical applica ion. Resul s Phys, 6:440–446. h ps://doi.o g/10.1016/J.RINP.2016.07.007 39. Ahlhelm F, Kau mann R, Ahlhelm D, e al., 2009, Ca o id a e y s en ing using a no el sel -expanding b aided nickel- In e na ional Jou nal o Biop in ing Co ona y and pe iphe al a e y disease. S a e o he a . Volume 9 Issue 2 (2023) h ps://doi.o g/10.18063/ijb. 9i2.664 251 i anium s en : Feasibili y and sa e y po cine ial. Ca dio asc In e Radiol, 32(5):1019–1027. h ps://doi.o g/10.1007/S00270-009-9572-0 40. Ueng KC, Wen SP, Lou CW, e al., 2016, S ainless s eel/ni inol b aid co ona y s en s: B aiding s uc u e s abili y and cu sec ion ea men e alua ion. J Ind Tex , 45(5):965–977. h ps://doi.o g/10.1177/1528083714550054 41. Ma i P, Lampus F, Bene en o D, e al., 2019, T ends in use o 3D p in ing in ascula su ge y: A su ey. In Angiol, 38(5):418–424. h ps://doi.o g/10.23736/S0392-9590.19.04148-8 42. Memon S, F iend E, Samuel SP, e  al., 2021, 3D p in ing o ca o id a e y and ao ic a ch ana omy: Implica ions o p ep ocedu al planning and ca o id s en ing. J In asi e Ca diol, 33(9):E723–E729. Accessed: Decembe 30, 2021 [Online]. A ailable. h ps://pubmed.ncbi.nlm.nih.go /34473073/ 43. Val e de I, Gomez G, Cose ia JF, e al., 2015, 3D p in ed models o planning endo ascula s en ing in ans e se ao ic a ch hypoplasia. Ca he e Ca dio asc In e , 85(6):1006–1012. h ps://doi.o g/10.1002/CCD.25810 44. Sun Z, Jansen S, 2019, Pe sonalized 3D p in ed co ona y models in co ona y s en ing. Quan Imaging Med Su g, 9(8):1356–1367. h ps://doi.o g/10.21037/QIMS.2019.06.21 45. Bo man J, Mahmood F, Sche me ho n M, e  al., 2019, Use o 3-dimensional p in ing o c ea e pa ien -speci ic abdominal ao ic aneu ysm models o p eope a i e planning. J Ca dio ho ac Vasc Anes h, 33(5):1442–1446. h ps://doi.o g/10.1053/J.JVCA.2018.08.011 46. Ba ón V, Gue a a R, 2019, Th ee-dimensional p in ing- guided enes a ed endo ascula ao ic aneu ysm epai using open sou ce so wa e and physician-modi ied de ices. J Vasc Su g Cases Inno Tech, 5(4):566–571. h ps://doi.o g/10.1016/J.JVSCIT.2019.08.006 47. Young L, Ha b SC, Pu i R, e al., 2020, Pe cu aneous co ona y in e en ion o an anomalous co ona y ch onic o al occlusion: The added alue o h ee-dimensional p in ing. Ca he e Ca dio asc In e , 96(2):330–335. h ps://doi.o g/10.1002/CCD.28625 48. Walke JL, San o o M, 2017, P ocessing and p oduc ion o bio eso bable polyme sca olds o issue enginee ing, in Bio eso bable Polyme s o Biomedical Applica ions: F om Fundamen als o T ansla ional Medicine, G. Pe ale and J. Hilbo n, Eds. Woodhead Publishing, 181–203. 49. Singh R, Singh S, Hashmi MSJ, 2016, Implan ma e ials and hei p ocessing echnologies, in Ma e ials Science and Ma e ials Enginee ing, Else ie . 50. Mohapa a S, Ka RK, Biswal PK, e al., 2022, App oaches o 3D p in ing in cu en d ug deli e y. Senso s In , 3(100146): 1–10. h ps://doi.o g/10.1016/J.SINTL.2021.100146 51. Schwab A, Le a o R, D’Es e M, e  al., 2020, P in abili y and shape ideli y o bioinks in 3D biop in ing. Chem Re , 120(19):11028–11055. h ps://doi.o g/10.1021/acs.chem e .0c00084 52. Ga cia-Villen F, Ruiz-Alonso S, La uen e-Me chan M, e al., 2021, Clay mine als as bioink ing edien s o 3D p in ing and 3D biop in ing: Applica ion in issue enginee ing and egene a i e medicine. Pha maceu ics, 13(1806):1–46. [Online]. A ailable. h ps://pubmed.ncbi.nlm.nih.go /34834221/ 53. Mani a PG, Ga cia-O ue I, San os-Vizcaino E, e al., 2021, 3D biop in ing o unc ional skin subs i u es: F om cu en achie emen s o u u e goals. Pha maceu icals, 14(362): 1–25. [Online]. A ailable. h ps://www.mdpi.com/1424-8247/14/4/362 54. Jamee R, A a Y, Bin Nase I, e  al., 2021, The p omising ise o biop in ing in e olu ionalizing medical science: Ad ances and possibili ies. Regen The , 18:133–145. h ps://doi.o g/10.1016/J.RETH.2021.05.006 55. Begum S, Ka im ANM, Ansa i MNM, e  al., 2020, Nanoma e ials, in Encyclopedia o Renewable and Sus ainable Ma e ials, ol. 1, S. Hashmi and I. A. Choudhu y, Eds. Else ie , 515–539. 56. Song X, Zhai W, Huang R, e  al., 2022, Me al-based 3D-p in ed mic o pa s & s uc u es, in Encyclopedia o Ma e ials: Me als and Alloys, ol. 4, F. G. Caballe o, Ed. Else ie , 448–461. 57. Zhu C, Liu T, Qian F, e  al., 2017, 3D p in ed unc ional nanoma e ials o elec ochemical ene gy s o age. Nano Today, 15:107–120. h ps://doi.o g/10.1016/J.NANTOD.2017.06.007 58. Xu C, Bouchemi A, L’Espé ance G, e al., 2017, Sol en -cas based me al 3D p in ing and seconda y me allic in il a ion. J Ma e Chem C, 5(40):10448–10455. h ps://doi.o g/10.1039/C7TC02884A 59. Gue a AJ, Cano P, Rabione M, e  al., 2018, 3D-p in ed PCL/PLA composi e s en s: Towa ds a new solu ion o ca dio ascula p oblems. Ma e ials (Basel, Swi ze land), 11(9): 1–13. h ps://doi.o g/10.3390/MA11091679 60. Gue a AJ, Ciu ana J, 2018, 3D-p in ed bioabso dable polycap olac one s en : The e ec o p ocess pa ame e s on i s physical ea u es. Ma e Design, 137:430–437. h ps://doi.o g/10.1016/J.MATDES.2017.10.045 In e na ional Jou nal o Biop in ing Co ona y and pe iphe al a e y disease. S a e o he a . Volume 9 Issue 2 (2023) h ps://doi.o g/10.18063/ijb. 9i2.664 252 61. Wu Z, Zhao J, Wu W, e al., 2017, A no el 3D addi i e manu ac u ing machine o biodeg adable s en s. P oc Manu , 13:718–723. h ps://doi.o g/10.1016/J.PROMFG.2017.09.118 62. Wu Z, e  al., 2018, Radial comp essi e p ope y and he p oo -o -concep s udy o ealizing sel -expansion o 3D p in ing polylac ic acid ascula s en s wi h nega i e Poisson’s a io s uc u e. Ma e ials (Basel), 11(8):1357. h ps://doi.o g/10.3390/MA11081357 63. Jia H, Gu SY, Chang K, 2018, 3D p in ed sel -expandable ascula s en s om biodeg adable shape memo y polyme . Ad Polym Technol, 37(8):3222–3228. h ps://doi.o g/10.1002/ADV.22091 64. Zhang C, Cai D, Liao P, e al., 2021, 4D p in ing o shape- memo y polyme ic sca olds o adap i e biomedical implan a ion. Ac a Bioma e , 122:101–110. h ps://doi.o g/10.1016/J.ACTBIO.2020.12.042 65. Kim D, Kim T, Lee YG, 2019, 4D p in ed bi u ca ed s en s wi h ki igami-inspi ed s uc u es. J Vis Exp, 149(e59746):1–9. h ps://doi.o g/10.3791/59746 66. Kim T, Lee Y-G, 2018, Shape ans o mable bi u ca ed s en s. Sci Rep, 8(13911):1–9. h ps://doi.o g/10.1038/s41598-018-32129-3 67. Zhang Y, Zhao J, Yang G, e  al., 2019, Mechanical p ope ies and deg ada ion o d ug elu ed bio eso bable ascula sca olds p epa ed by h ee-dimensional p in ing echnology. J Bioma e Sci Polym Ed, 30(7):547–560. h ps://doi.o g/10.1080/09205063.2019.1586303 68. Lei Y, Chen X, Li Z, e  al., 2020, A new p ocess o cus omized pa ien -speci ic ao ic s en g a using 3D p in ing echnique. Med Eng Phys, 77:80–87. h ps://doi.o g/10.1016/j.medengphy.2019.12.002 69. Pa k SA, Lee SJ, Lim KS, e  al., 2015, In i o e alua ion and cha ac e iza ion o a bio-abso bable d ug-coa ed s en ab ica ed using a 3D-p in ing sys em. Ma e Le , 141: 355–358. h ps://doi.o g/10.1016/J.MATLET.2014.11.119 70. Mis a SK, Os adhossein F, Babu R, e al., 2017, 3D-p in ed mul id ug-elu ing s en om g aphene-nanopla ele -doped biodeg adable polyme composi e. Ad Heal hc Ma e , 6(1700008):1–14. h ps://doi.o g/10.1002/ADHM.201700008 71. Zhou Y, Zhou D, Cao P, e al., 2021, 4D p in ing o shape memo y ascula s en based on βCD-g-polycap olac one. Mac omol Rapid Commun, 42(14):2100176. h ps://doi.o g/10.1002/MARC.202100176 72. Singh J, Kau T, Singh N, e  al., 2020, Biological and mechanical cha ac e iza ion o biodeg adable ca bonyl i on powde /polycap olac one composi e ma e ial ab ica ed using h ee-dimensional p in ing o ca dio ascula s en applica ion. P oc Ins Mech Eng H, 234(9):975–987. h ps://doi.o g/10.1177/0954411920936055 73. Van Li h R, Bake E, Wa e H, e al., 2016, 3D-p in ing s ong high- esolu ion an ioxidan bio eso bable ascula s en s. Ad Ma e Technol, 1(9): 1–7. h ps://doi.o g/10.1002/ADMT.201600138 74. Wa e HOT, Fa sheed AC, Aka B, e al., 2018, High-speed on- demand 3D p in ed bio eso bable ascula sca olds. Ma e Today Chem, 7:25–34. h ps://doi.o g/10.1016/J.MTCHEM.2017.10.002 75. de Oli ei a MF, da Sil a LCE, de Oli ei a MG, 2021, 3D p in ed bio eso bable ni ic oxide- eleasing ascula s en s. Biop in ing, 22(e00137): 1–10. h ps://doi.o g/10.1016/J.BPRINT.2021.E00137 76. Yang J, Webb AR, Picke ill SJ, e  al., 2006, Syn hesis and e alua ion o poly(diol ci a e) biodeg adable elas ome s. Bioma e ials, 27(9):1889–1898. h ps://doi.o g/10.1016/J.BIOMATERIALS.2005.05.106 77. Ismaeel A, Papou si E, Mise lis D, e  al., 2020, The ni ic oxide sys em in pe iphe al a e y disease: Connec ion wi h oxida i e s ess and biop e ins. An ioxidan s, 9(7):1–16. h ps://doi.o g/10.3390/ANTIOX9070590 78. Flege C, Vog F, Höges S, e  al., 2013, De elopmen and cha ac e iza ion o a co ona y polylac ic acid s en p o o ype gene a ed by selec i e lase mel ing. J Ma e Sci Ma e Med, 24(1):241–255. h ps://doi.o g/10.1007/S10856-012-4779-Z 79. Ellio MR, Kim D, Molony DS, e al., 2019, Es ablishmen o an au oma ed algo i hm u ilizing op ical cohe ence omog aphy and mic o-compu ed omog aphy imaging o econs uc he 3-D de o med s en geome y. IEEE T ans Med Imaging, 38(3):710–720. h ps://doi.o g/10.1109/TMI.2018.2870714 80. Wiesen L, Spea A, Nonn A, 2022, Compu a ional analysis o he e ec s o geome ic i egula i ies on he in e ac ion o an addi i ely manu ac u ed 316L s ainless s eel s en and a co ona y a e y. J Mech Beha Biomed Ma e , 125:1–12. h ps://doi.o g/10.1016/J.JMBBM.2021.104878 81. Chias a C, Mazzi V, Lodi Rizzini M, e al., 2022, Co ona y a e y s en ing a ec s wall shea s ess opological skele on. J Biomech Eng. 144(6):061002, 1–11. h ps://doi.o g/10.1115/1.4053503 82. Pan C, Han Y, Lu J, 2021, S uc u al design o ascula s en s: A e iew. Mic omachines, 12(7):770. h ps://doi.o g/10.3390/MI12070770 In e na ional Jou nal o Biop in ing Co ona y and pe iphe al a e y disease. S a e o he a . Volume 9 Issue 2 (2023) h ps://doi.o g/10.18063/ijb. 9i2.664 253 83. Habib A, Finn AV, 2015, Endo helializa ion o d ug elu ing s en s and i s impac on dual an i-pla ele he apy du a ion. Pha macol Res, 93:22–27. h ps://doi.o g/10.1016/J.PHRS.2014.12.003 84. Nguyen DT, Smi h AF, Jiménez JM, 2021, S en s u s eamlining and hickness educ ion p omo e endo helializa ion. J R Soc In e ace, 18(181):1–14. h ps://doi.o g/10.1098/RSIF.2021.0023 85. Cab e a MS, Sande s B, Goo OLGM, e  al., 2017, Compu a ionally designed 3D p in ed sel -expandable polyme s en s wi h biodeg ada ion capaci y o minimally in asi e hea al e implan a ion: a p oo -o -concep s udy. 3D P in Addi Manu , 4(1):19–29. h ps://doi.o g/10.1089/3DP.2016.0052/ASSET/IMAGES/ LARGE/FIGURE8.JPEG 86. Vellayappan MV, Balaji A, Sub amanian AP, e  al., 2015, Mul i ace ed p ospec s o nanocomposi es o ca dio ascula g a s and s en s. In J Nanomed, 10:2785–2803. h ps://doi.o g/10.2147/IJN.S80121 87. Chou TC, Fu E, Wu CJ, e  al., 2003, Chi osan enhances pla ele adhesion and agg ega ion. Biochem Biophys Res Commun, 302(3):480–483. h ps://doi.o g/10.1016/S0006-291X(03)00173-6 88. Wickham AM, Islam MM, Mondal D, e  al., 2014, Polycap olac one– hiophene-conjuga ed ca bon nano ube meshes as sca olds o ca diac p ogeni o cells. J Biomed Ma e Res Pa B Appl Bioma e , 102(7):1553–1561. h ps://doi.o g/10.1002/JBM.B.33136 89. S ou DA, Yoo J, San iago-Mi anda AN, e  al., 2012, Mechanisms o g ea e ca diomyocy e unc ions on conduc i e nanoenginee ed composi es o ca dio ascula applica ion. In J Nanomed, 7:5653–5669. h ps://doi.o g/10.2147/IJN.S34574 90. Ma ioli-Belmon e M, Vozzi G, Whulanza Y, e  al., 2012, Tuning polycap olac one–ca bon nano ube composi es o bone issue enginee ing sca olds. Ma e Sci Eng C, 32(2):152–159. h ps://doi.o g/10.1016/J.MSEC.2011.10.010 91. Chakoli AN, Wan J, Feng JT, e al., 2009, Func ionaliza ion o mul iwalled ca bon nano ubes o ein o cing o poly(l- lac ide-co-ε-cap olac one) biodeg adable copolyme s. Appl Su Sci, 256(1):170–177. h ps://doi.o g/10.1016/J.APSUSC.2009.07.103 92. Lee HH, Shin US, Jin GZ, e al., 2011, Highly homogeneous ca bon nano ube-polycap olac one composi es wi h a ious and con ollable concen a ions o ionically-modi ied- MWCNTs. Bull Ko ean Chem Soc, 32(1):157–161. h ps://doi.o g/10.5012/BKCS.2011.32.1.157 93. A abi H, Mi zadeh H, Ahmadi SH, e al., 2004, In i o and in i o hemocompa ibili y e alua ion o g aphi e coa ed polyes e ascula g a s. In J A i O gans 27(8):691–698. h ps://doi.o g/10.1177/039139880402700807 94. Podila R, Moo e T, Alexis F, e al., 2013, G aphene coa ings o biomedical implan s. J Vis Exp, 73(e50276):1–9. h ps://doi.o g/10.3791/50276 95. Gao F, Hu Y, Li G, e al., 2020, Laye -by-laye deposi ion o bioac i e laye s on magnesium alloy s en ma e ials o imp o e co osion esis ance and biocompa ibili y. Bioac Ma e , 5(3):611–623. h ps://doi.o g/10.1016/J.BIOACTMAT.2020.04.016 96. Yang MC, Tsou HM, Hsiao YS, e al., 2019, Elec ochemical polyme iza ion o PEDOT-g aphene oxide-hepa in composi e coa ing o an i- ouling and an i-clo ing o ca dio ascula s en s. Polyme s (Basel), 11(9):1–15. h ps://doi.o g/10.3390/POLYM11091520 97. Alshebly YS, Na ea M, Mohamed Ali MS, e  al., 2021, Re iew on ecen ad ances in 4D p in ing o shape memo y polyme s. Eu Polym J, 159:110708. h ps://doi.o g/10.1016/J.EURPOLYMJ.2021.110708 98. Melocchi A, Uboldi M, Ce ea M, e  al., 2021, Shape memo y ma e ials and 4D p in ing in pha maceu ics. Ad D ug Deli Re , 173:216–237. h ps://doi.o g/10.1016/J.ADDR.2021.03.013 99. Xu J, Zhang Y, Feng YB, e al., 2018, Elec omagne ic and mechanical p ope ies o ca bonyl i on powde - illed me hyl inyl silicone ubbe du ing he mal aging. Polym Compos, 39(8):2897–2903. h ps://doi.o g/10.1002/PC.24286 100. Waksman R, Pakala R, Ba ou R, e al., 2008, Sho - e m e ec s o bioco odible i on s en s in po cine co ona y a e ies. J In e Ca diol, 21(1):15–20. h ps://doi.o g/10.1111/J.1540-8183.2007.00319.X 101. Peus e M, Hesse C, Schloo T, e  al., 2006, Long- e m biocompa ibili y o a co odible pe iphe al i on s en in he po cine descending ao a. Bioma e ials, 27(28):4955–4962. h ps://doi.o g/10.1016/J.BIOMATERIALS.2006.05.029 102. Peus e M, Wohlsein P, B ügmann M, e al., 2001, A no el app oach o empo a y s en ing: Deg adable ca dio ascula s en s p oduced om co odible me al- esul s 6-18 mon hs a e implan a ion in o New Zealand whi e abbi s. Hea , 86(5):563–569. h ps://doi.o g/10.1136/HEART.86.5.563 103. Liu B, Zheng YF, 2011, E ec s o alloying elemen s (Mn, Co, Al, W, Sn, B, C and S) on biodeg adabili y and in i o biocompa ibili y o pu e i on. Ac a Bioma e , 7(3):1407–1420. h ps://doi.o g/10.1016/J.ACTBIO.2010.11.001 In e na ional Jou nal o Biop in ing Co ona y and pe iphe al a e y disease. S a e o he a . Volume 9 Issue 2 (2023) h ps://doi.o g/10.18063/ijb. 9i2.664 254 104. Khoo ZX, Liu Y, An J, e al., 2018, A e iew o selec i e lase mel ed NiTi shape memo y alloy. Ma e ial, 11:519. h ps://doi.o g/10.3390/MA11040519 105. Bi i CA, Fiocchi J, Valenza F, 2020, e  al., Selec i e lase mel ing o NiTi shape memo y alloy: P ocessabili y, mic os uc u e, and supe elas ici y. Shape Mem Supe elas ici y, 6(3):342–353. h ps://doi.o g/10.1007/S40830-020-00298-8/FIGURES/11 106. Sa a i MS, Bo dba ‐Khiabani A, Khalil‐alla i J, e al., 2022, Addi i e manu ac u ing: An oppo uni y o he ab ica ion o nea ‐ne ‐shape NiTi implan s. J Manu Ma e P ocess, 6(3):1–22. h ps://doi.o g/10.3390/JMMP6030065 107. Hassani FA, Peh WYX, Gammad GGL, e al., 2017, A 3D p in ed implan able de ice o oiding he bladde using shape memo y alloy (SMA) ac ua o s. Ad Sci, 4(11):1–10. h ps://doi.o g/10.1002/ADVS.201700143 108. Tong A, Pham QL, Aba ema co P, e  al., 2021, Re iew o low-cos 3D biop in e s: S a e o he ma ke and obse ed u u e ends. SLAS Technol, 26(4):333–366. h ps://doi.o g/10.1177/24726303211020297 109. Choona a YE, Du Toi LC, Kuma P, e al., 2016, 3D-p in ing and he e ec on medical cos s: A new e a? Expe Re Pha macoecon Ou comes Res, 16(1):23–32. h ps://doi.o g/10.1586/14737167.2016.1138860 110. an Tonde L, Labuschagné FJWJ, 2021, Sys ema ic li e a u e e iew o he e ec o laye ed double hyd oxides on he mechanical p ope ies o ubbe . Polyme , 13:3716. h ps://doi.o g/10.3390/POLYM13213716 111. Coppola B, Cappe i N, Di Maio L, e  al., 2017, Laye ed silica e ein o ced polylac ic acid ilamen s o 3D p in ing o polyme nanocomposi es, 1–4. h ps://doi.o g/10.1109/RTSI.2017.8065892 112. Papageo giou DG, Li Z, Liu M, e  al., 2020, Mechanisms o mechanical ein o cemen by g aphene and ca bon nano ubes in polyme nanocomposi es. Nanoscale, 12(4. Royal Socie y o Chemis y): 2228–2267. h ps://doi.o g/10.1039/c9n 06952 113. Coleman JN, Khan U, Gun’ko YK, 2006, Mechanical ein o cemen o polyme s using ca bon nano ubes. Ad Ma e , 18(6):689–706. h ps://doi.o g/10.1002/ADMA.200501851 114. Kim H, Ryu KH, Baek D, e  al., 2020, 3D p in ing o polye hylene e eph hala e glycol-sepioli e composi es wi h nanoscale o ien a ion. ACS Appl Ma e In e aces, 12(20):23453–23463. h ps://doi.o g/10.1021/acsami.0c03830 115. Zhou K, Dey M, Ayan B, e al., 2021, Fab ica ion o PDMS mic o luidic de ices using nanoclay- ein o ced Plu onic F-127 as a sac i icial ink. Biomed Ma e , 16(4):45005. h ps://doi.o g/10.1088/1748-605X/abe55e 116. Gu Z, Rol e BE, Xu ZP, e al., 2012, An ibody- a ge ed d ug deli e y o inju ed a e ies using laye ed double hyd oxide nanopa icles. Ad Heal hc Ma e , 1(5):669–673. h ps://doi.o g/10.1002/ADHM.201200069 117. Gu Z, Rol e B, Thomas A, e al., 2013, Res enosis ea men s using nanopa icle-based d ug deli e y sys ems. Cu Pha m Des, 19(35):6330–6339. h ps://doi.o g/10.2174/1381612811319350009 118. Gu Z, Rol e BE, Xu ZP, e al., 2010, Enhanced e ec s o low molecula weigh hepa in in e cala ed wi h laye ed double hyd oxide nanopa icles on a ascula smoo h muscle cells. Bioma e ials, 31(20):5455–5462. h ps://doi.o g/10.1016/J.BIOMATERIALS.2010.03.050 119. Ishiha a S, Machino T, Deguchi K, e al., 2021, Disposable ni ic oxide gene a o based on a s uc u ally de o med ni i e- ype laye ed double hyd oxide. Ino g Chem, 60(21):16008–16015. h ps://doi.o g/10.1021/ACS.INORGCHEM.1C00456 120. Russell SE, González Ca ballo JM, O ellana-Ta a C, e al., 2017, A compa ison o coppe and acid si e zeoli es o he p oduc ion o ni ic oxide o biomedical applica ions. Dal T ans, 46(12):3915–3920. h ps://doi.o g/10.1039/C7DT00195A 121. Doyle RA, Russell SE, Mo is RE, 2019, Ni ic oxide p oduc ion om ni i e by a se ies o zeoli es p oduced ia he ADOR ou e. Mic opo ous Mesopo ous Ma e , 280:367–371. h ps://doi.o g/10.1016/J.MICROMESO.2019.02.019 122. Jung SY, Kim HM, Hwang S, e al., 2020, Physicochemical p ope ies and hema ocompa ibili y o laye ed double hyd oxide-based an icance d ug me ho exa e deli e y sys em. Pha m, 12:1210. h ps://doi.o g/10.3390/PHARMACEUTICS12121210 123. Gu Z, Yan S, Cheong S, e al., 2018, Laye ed double hyd oxide nanopa icles: Impac on ascula cells, blood cells and he complemen sys em. J Colloid In e ace Sci, 512:404–410. h ps://doi.o g/10.1016/J.JCIS.2017.10.069 124. Vaiana CA, Leona d MK, D ummy LF, e al., 2011, Epide mal g ow h ac o : Laye ed silica e nanocomposi es o issue egene a ion. Biomac omolecules, 12(9):3139–3146. h ps://doi.o g/10.1021/bm200616 125. Wu K, Feng R, Jiao Y, e  al., 2017, E ec o halloysi e nano ubes on he s uc u e and unc ion o impo an mul iple blood componen s. Ma e Sci Eng C, 75:72–78. h ps://doi.o g/10.1016/J.MSEC.2017.02.022 In e na ional Jou nal o Biop in ing Co ona y and pe iphe al a e y disease. S a e o he a . Volume 9 Issue 2 (2023) h ps://doi.o g/10.18063/ijb. 9i2.664 255 126. De lin JJ, Ki che S, Kozen BG, e  al., 2011, Compa ison o Chi oFlex®, CELOXTM, and QuikClo ® in con ol o hemo hage. J Eme g Med, 41(3):237–245. h ps://doi.o g/h p://dx.doi.o g/10.1016/j. jeme med.2009.02.017 127. Ran Y, e al., 2010, QuikClo comba gauze use o hemo hage con ol in mili a y auma: Janua y 2009 Is ael De ense Fo ce Expe ience in he Gaza S ip—A p elimina y epo o 14 cases. P ehosp Disas e Med, 25(6):584–588 [Online]. A ailable: h p://jou nals.camb idge.o g/ac ion/display Abs ac ? omPage=online&aid=8257157& ileId= S1049023X00008797 128. Choi SJ, Oh JM, Choy JH, 2008, Sa e y aspec o ino ganic laye ed nanopa icles: Size-dependency in i o and in i o. J Nanosci Nano echnol, 8(10):5297–5301. h ps://doi.o g/10.1166/JNN.2008.1143 129. Tahmasebi-Bi gani Z, Sola i-Hashjin M, Pei o i H, e  al., 2010, Laye ed double hyd oxide: A new ce amid-based hemos a ic agen ?, in Ce amic T ansac ions, ol. 218, R. Na ayan, M. Singh, and McKi ick, Eds. Wiley-Ame ican Ce amic Socie y, 53–57. 130. Mahesh V, Joseph AS, Mahesh V, e al., 2021, In es iga ion on he mechanical p ope ies o addi i ely manu ac u ed PETG composi es ein o ced wi h OMMT nanoclay and ca bon ibe s. Polym Compos, 42:2380–2395. h ps://doi.o g/10.1002/pc.25985 131. Coppola B, Cappe i N, Di Maio L, e al., 2018, 3D p in ing o PLA/clay nanocomposi es: In luence o p in ing empe a u e on p in ed samples p ope ies. Ma e ials (Basel), 11(1947):1–17. h ps://doi.o g/10.3390/ma11101947 132. Paspali A, Bao Y, Gawne DT, e al., 2018, The in luence o nanos uc u e on he mechanical p ope ies o 3D p in ed polylac ide/nanoclay composi es. Compos Pa B Eng, 152:160–168. h ps://doi.o g/10.1016/j.composi esb.2018.07.005 133. Adepu S, Luo H, Ramak ishna S, 2021, Hepa in- agged PLA- PEG copolyme -encapsula ed biochanin A-loaded (Mg/Al) LDH nanopa icles ecommended o non- h ombogenic and an i-p oli e a i e s en coa ing. In J Mol Sci, 22(11):5433. h ps://doi.o g/10.3390/IJMS22115433/S1 134. Xiao R, Huang WM, Xiao R, e al., 2020, Hea ing/sol en esponsi e shape-memo y polyme s o implan biomedical de ices in minimally in asi e su ge y: Cu en s a us and challenge. Mac omol Biosci, 20(8):2000108. h ps://doi.o g/10.1002/MABI.202000108 135. Bha ia M, Bha ia S, Siddha ha, 2022, Sma ma e ials o ca dio ascula de ices. Ma e Today P oc, 53:307–309. h ps://doi.o g/10.1016/J.MATPR.2021.12.591 136. Jiang JJ, Hu Y, Chen X, e  al., 2018, De elopmen and applica ion o shape memo y in elligen composi es. Cailiao Gongcheng/J Ma e Eng, 46(8):1–13. h ps://doi.o g/10.11868/J.ISSN.1001-4381.2018.000344 137. Hua W, Shi W, Mi chell K, e  al., 2022, 3D p in ing o biodeg adable polyme ascula s en s: A e iew. Chin J Mech Eng Addi Manu F on , 1(2):100020. h ps://doi.o g/10.1016/J.CJMEAM.2022.100020 138. Kluska E, G uda P, Majca-Nowak N, 2018, The accu acy and he p in ing esolu ion compa ison o di e en 3D p in ing echnologies. T ans Ae osp Res, 2018(3):69–86. h ps://doi.o g/10.2478/TAR-2018-0023 139. Nul y A, 2022, A compa ison o ueness and p ecision o 12 3D p in e s used in den is y. BDJ Open, 8(1):1–9. h ps://doi.o g/10.1038/s41405-022-00108-6 140. Chae MP, Chung RD, Smi h JA, e al., 2021, The accu acy o clinical 3D p in ing in econs uc i e su ge y: Li e a u e e iew and in i o alida ion s udy. Gland Su g, 10(7): 2293. h ps://doi.o g/10.21037/GS-21-264 141. Ho Kim J, Pinha a-Bap is a OH, Ay es AP, e  al., 2022, Accu acy compa ison among 3D-p in ing echnologies o p oduce den al models. Appl Sci, 12(8425):1–9. 142. Nguyen PD, Nguyen TQ, Tao QB, e al., 2022, A da a-d i en machine lea ning app oach o he 3D p in ing p ocess op imisa ion. Vi ual Phys P o o yp 17(4):768–786. h ps://doi.o g/10.1080/17452759.2022.2068446 143. Gong X, Zeng D, G oene eld-Meije W, e al., 2022, Addi i e manu ac u ing: A machine lea ning model o p ocess- s uc u e-p ope y linkages o machining beha io o Ti- 6Al-4V. Ma e Sci Addi Manu , 1(1):6. h ps://doi.o g/10.18063/MSAM.V1I1.6 144. Sing SL, Kuo CN, Shih CT, e al., 2021, Pe spec i es o using machine lea ning in lase powde bed usion o me al addi i e manu ac u ing. Vi ual Phys P o o yp 16(3):372–386. h ps://doi.o g/10.1080/17452759.2021.1944229 145. Smolde en KG, Wang K, De Pou ou ille G, e  al., 2012, Two-yea ascula hospi alisa ion a es and associa ed cos s in pa ien s a isk o a he o h ombosis in F ance and Ge many: Highes bu den o pe iphe al a e ial disease. Eu J Vasc Endo asc Su g, 43(2):198–207. h ps://doi.o g/10.1016/J.EJVS.2011.09.016