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Biomaterials Research (2010) 14(2) : 66-77 <Review> Biomaterials Research 7 The Korean Society for Biomaterials w Recent R & D Trends of Medical Adhesives and Anti-adhesion Membranes y 1 Á½x 1 Á kš 1 Áw y 2 Á 2 Á» 3 Á 4 Áx { 5 Áw 6 Áw 1 * Jong Ho Lee 1, Hyeon Yong Kim 1, Tae Gon Jung 1, Inho Han 2, Jong-Chul Park 2, Ki Dong Park 3, Jae Bong Choi 4, Suong-Hyu Hyon 5, Dong Keun Han 6, and Dong-Wook Han 1 * 1 Š y Š, BK21 fš Š, 2 Š f Š fš Š, 3 j Š f Š Š 4 Š Š Š, 5 f Š g fš, 6 Š Š e f g 1 Department of Nanomedical Engineering, BK21 Nano Fusion Technology Division, Pusan National University, Busan 609-735, Korea 2 Department of Medical Engineering, Yonsei University College of Medicine, Seoul 120-752, Korea 3 Department of Molecular Science and Technology, Ajou University, Suwon 442-749, Korea 4 Division of Industrial & Mechanical Systems Engineering, Hansung University, Seoul 136-792, Korea 5 Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan 6 Biomaterials Research Center, Korea Institute of Science and Technology, Seoul 130-650, Korea (Received April 08, 2010/Acccepted April 12, 2010) In the case of surgical operation for the treatment of cancers, vascular diseases and diabetes mellitus, the use of medical (or biotissue) adhesives is gradually increasing instead of suturing. Together with this trend, the development of anti-adhesion membranes (or barriers) is rapidly increasing for preventing complications originated from post-operative tissue adhesions frequently occurring. In general, all medical devices should pass the testing for biological safety and effectiveness. Thus, newly developed medical adhesives and anti-adhesion membranes must be evaluated according to the well-regulated standard guidelines, such as ISO, OECD, ASTM, etc, under authorized institution, otherwise they cannot be commercialized. In this review, medical adhesives and anti-adhesion membranes were categorized and compared according to their use and materials followed by a brief description of the properties of products commercially available. Furthermore, this review dealt with the present state of commercialization, the size of market and the recent trends of research and development regarding medical adhesives and anti-adhesion membranes. Key words: Medical adhesives, Anti-adhesion membranes, Medical devices, Safety and Effectiveness f 65 f ff ef 2010 g h t f f 10%( 500 ) 2000 f Œ (7%) lfšf, 2019 (14%) 2026 t (20%) 2050 f u f h f (Figure 1). d u Š f l (2006 79.1 ) uhf v (2008 1.2, hv j 2e) f f f l Š ff, f Š d h f i Œ Œ lœf lhf } l Š f. Š, Œf Œ, fj,, ƒ f f f Š lœ fš f l v ff, ƒ f dš, Œ g lœf g Š f ef j 1-3e rlš f (Table 1). *sf hf: nanohan@pusan.ac.kr, Œ lœ f x eš d h Š (suture) f d(œf tild) hrh (medical or biotissue adhesives)f df l v f, il er(tissue adhesion) Figure 1. 2005 f vf( t). 66

f d hrh er l f u 67 Table 1. 2008 ef (f 10, t) e ef ( f /10 / ) 1 ( ) 139.5 2 Œ lœ 56.5 3 g lœ 43.4 4 f 26.0 5 20.7 6~10 ~ df 64.8 Š lf l eš er l (anti-adhesion membranes or barriers)f f lš Œf. f ˆŒ hf Š tild hrh er l Š t hf h (e ) Š Š. u f f d hrh er l f d g ƒl hˆ(œ) Œ g h f Š u Š f. ƒ, f d hrhf d, i f f Áf d hrh hi Á (hœ,, e, Š Š h e x, 2004) Áf d thr hf u Á (Š, Š Š e, 2005)f jd r f ŒdŠ. f d hrh Š Š Š if fš ilf hš ~ d edš t f fy. 1), Œ, Œd, hœd, x Š f ilf h, sf Š, l Œ, ev l f hf tild hrh d ff, f d Š hˆf hr d e Œ f. 2-4) f Š f d hrh hf lh ht z dš hrh t d thš f Œf Š, hrf l hf t Œ jf Š i f t lh Š eš f Š, Š f d Š g ŠdŠ. 5,6) Š ŒŠ i Š hf hrf i f df, tilf Š Š ~ tf f - f ŠŠl f Š g hš f jdš. 5,6) f hf h Šf Š ilf t f Œ fš hf ~f v Š hr f Š hr thš f ƒ f l Š hš g f d f. 1) f d hrh h g 20~30% h gš f xf f d hˆfl, d f d f h Šd f fiš f ef ev f hf. Table 2. f d hrhf hd g t ~/ Œ f hh } fƒ t/jš Œ f, f d / hr f, il h f d / hr f, g h d ~ vš t/ e tf vš ŒŠ e h z f / r l t h ˆŒ lš j il ild h, h, hd ƒ, f x, f x d x d hrh, Š l, l ƒ, f ƒ vs: 5) Š Š h e(kisti) x, hœ,, e, f d hrh hi, 2004 6) Š Š e(kist) Š, f d thrhf u, 2005 Table 3. hr y l f d hrhf d Œ f f t jš } fƒ, ƒ(mma) jš vš t vš d ~ f d ( h,, h h) ŒŠ hr l vs: 5) KISTI x, hœ,, e, f d hrh hi, 2004 tild hrh Table 2 f hd d f il dš x f il dš f } f, hr y l Table 3 f f Š. 5,6) f hf f d hrh, Œ, Œ,, Œd, hœd f d ƒ f ŠdŠl j f f f d. 5,6) È f f d, hrš Š È f Š f Š È r rš v Š h f elš Š È Š f lœ f Š È tf xe Š l Š g dœ f ild hrhf g } fƒ (cyanoacrylate), (fibrin), h (gelatin), d ~(polyurethane) ŒŠ hr l(mussel adhesive protein) f ff (Table 2) 5,6), g f d hrhf ƒlf f. Vol. 14, No. 2

68 fiœá dáh~ ÁŠfŒÁ isá Áug Á ÁŠ ÁŠ d Figure 2. ~ } fƒ hrhf t jšt jš h (vs: 6) KIST Š, f d thrhf u, 2005). Figure 3. } fƒf Š y l f (vs: 6) KIST Š, f d thrhf u, 2005). } fƒ } fƒ hrh hdf 20%, d f 75% rlš ff, f df h hf 5% fšl u f hrhf f f. 5) ƒ, thš, e h f til Šd f d hrh lœ, Š Š f t Š, f, e f l f j f Œ lš jf. 5) f Š } fƒ hrh Figure 2 f f Œ d h f l lf h f f Biomaterials Research 2010

f d hrh er l f u 69 Š Œ d f Š hr } v Š, f l hf f. 5,6) f ~ l Š hr l Š jšt f d ~ l Š Š Š (formaldehyde) h il f Š f ~. 5,6) Šd hrh t } fƒ hrh d f il f Š g f dšl ff (Figure 3), n- } fƒ f hdš f df hf d ff f f il w f h df hš f hf. 5,6) il s j f Œ f Œ f (blood coagulation) Š (fibrinogen)f e vš f Œ Šf s je r(crosslinking) ~, f f f il rfdf f hf f dš f (fibrin glue)f. f e 5), ƒ (thrombin), Œx (calcium chloride) Œ f ff(factor XIII) f Š ilhrh t f Š, Œ f Š dš Šf d f eš f hf fdš f. f d 5,6) hrh Œ d f Š d, f h r hœd, Œff lœ fd f. 5) hrf, f f ŠdŠ h r ef f l f h gh fd Œ (platelet) f gš, ilhš f d Š, h hš f l f Šh ghf l, h r f Š f e f h f. f 5) Š hf Š eš f Š jštf Š Š hr elš eš (aprotinin) f t Š Š hšš f f hœ jšt e (fibroblast) g l z (collagen) f il f tl z. 6) hr l ~ eš hi h f d f(fibroin), z, -L- ~ [poly(lglutamic acid)] f ŒŠŠ hr } z f. 5) h h (gelatin glue) t e f hrh h (G) i (R)f (F)f ~ (GRF)f f. f hrh ilhr f 5) l, h dš f t f l ff ffz f ~. GRF g hi f, f l f l l d f lœh e f lš f. Š, ŠeŠ l hrh h ~ d x f (carbodiimide)f ff fdš d hrh. 5) f h w f i (benzophenone) fš Œ h f Š Š ih z } fƒ(polyethylene glycol diacrylate) ŒfŠ lœh j ff, fh (excimer laser) i fš f Œ Š lœh f. 5) d ~ ild hrh d ~ hrh Œ hš f e f el ~ hrh lš, f f h f d ~ fš d ~ hrh j f. f hrh t il f f 5) Š il f r f f, fš f ŒŠ, Œ f ~ hf e f ~, Œ hrh Š ƒlf f, il Š Š f f ljf Š, hrhf h h f l Š. hf Š e f i f fƒ(diisocyanate) t f f fl Œ l Œ l i f fƒ dšf ed f. 5) ŒŠ e hr l ŒŠf i ( ) f hr lf Š ll e f, f Š e Š ŒŠf hr lf fdš f Šf thr hf. ŒŠf 7,8) fp-5(foot protein type 5) l hr z fdf Š fp-1 lf f f, hh hf ŒŠf fp-5 lf l d Š hr f elš. 7,8) fp-5 lf d Œ g } g d h, d, h e hh h Š. f Šf hrh 7-9) 40 mg f fdš d 1cmf h e 2 10 kgf t h rš f f l f. ŒŠ hr lf Š t Œ ~f fš f dˆ xf f d hrh, h, d hœ l l Š Œdf Š. ƒ i f d hr 7-9) h f f } fƒ hrh f l f Š f lf f t hš dš f r f d hrh fd f. g dœ f } fƒ, /h d ~ f d hrhf f Š Table 4. 6) Vol. 14, No. 2

70 fiœá dáh~ ÁŠfŒÁ isá Áug Á ÁŠ ÁŠ d Table 4. f d hrhf f d hrh g } f ƒ /h d ~ hš hr hr hr Œ ( ) Šg } } (ff) e ( h Š) ( h Š) e ~ (ff) (ff) f xf ( f) ( f) ff Š ff( ) ff( ) ff f f f h h h *( ) h vs: 6) KIST Š, f d thrhf u, 2005 Table 5. hœd d ƒf i ƒl i ƒl(g h) f jš fš j f, PMMA f thš f s f Š Calcium Phosphate + f Œ, Œ, Š Calcium Phosphate t f, fš hš, + e g tf dv fš Bis-GMA(3MA) j, d Š h thš vs: 6) KIST Š, f d thrhf u, 2005 g d f ild hrh hœd ( il)d ƒ(mma, methyl methacrylate) x d ƒ f f hf i f. hœd d ƒ Table 5 f f f. x d ƒf i d Table 6. w ³ h f d Š g 30 v ff, f d hrhf g 2000 j (KISTI)f } fƒ 2, 5 f g ht 10 f gf Œ Š 26% l Š v f f. h h 6) f f e f lh f fš f d hrhf df fr Œ Œ fl, Š f d h h f Š d f l f, u Š gf gf h. f d hrhf f g 5) (Yano Economic Research Institute) 2003 200 h g f f he (96%)Š ff, 10 700 f f Œ f h f (Figure 4). Table 6. x d ƒf i d i jd f x hd gxf hš Œ el f, j h / f hšh / hg / fg / x ih x fƒ f hšh / hg f f hšh f hx / hgx hšh / fgh l hgx f hšh Œx x ig / hg vs: 6) KIST Š, f d thrhf u, 2005 Figure 4. f f d hrh g hee(2003 j). f d hrhf d g f hrhf Š Š hf hœš f f l, Š f Œ h Š sxe gf s e Š f tš f d hrh gf Œf e, v, s fh f fš g f d w f. 5) hrh gf ht hrh gf 5% h f, fj f df 5% f f v. f ilhrh g 40 ef vh KISTI Š f d hrh g f e(2000 j)f Š f } fƒ g 16 ef v f ŠŠ f f d hrh g 50~60 ef vh. 5) Š f d hrh g hf 30~40%f gf wš, g hf 10% h wš f f Š f f d hrh g 2013 300 ef f w. 5) j p g } fƒ gf hf t f Biomaterials Research 2010

f d hrh er l f u 71 Table 7. } fƒ f d hrh hˆ Œ hˆ ~ hi( ) hˆ Œ - il f Š dšl f Histoacryl B. Braun Melsungen AG, f TissueSeal LLC, / 2007 n- FDA f Indermil Dermabond Covidien AG, / 2002 FDA f CLOSURE Medical Corp., Ethicon Inc. 1997 8e EU CE mark, 1998 8e FDA f hr } Š tš f w f. 5) Dermabond } fƒ hr h Š Closure Medical ft i fš t hf 200 e f t gf Œ Š f w w, g s Šd hrh Ethicon Š f Š h 50 j f (Table 7). 5,6) f Š Š ~f, B. Braun Š l Histoacryl f fš Š d jf, Ethicon Š l Dermabond fš j f. v h f hrhf g 2000 5 vh, g heef 2000 fh l g Œ f f f ll ff 2003 f 31% f g Š f h f. Haemacure v Š Hemaseel APR f 1998 FDAf ff f f TM gf hf Œ f, t gf 2s jfl, 80% f gf w, 2003 f gf 30%f g Š f Š. f f 5) d, 1999 hrh g 182 f, f l hf Œ f h f. 5) gf d 30~40 e 1996 f lœh d ilhrh Greenplast Š f ˆŒŠ g gf 80% f f heš ff, f Tisseel, Beriplast P f j f j f (Table 8). x f d hrh j d h Š t d f, hˆf Œ~ ƒ vœf Š f. hrh f f l, j lœh(hemostat or antihemorrhagic agent)f d f hˆ f f f f (Table 9). 10) Table 8. f d hrh hˆ Œ hˆ hi( ) hˆ Œ Tisseel Immuno AG, ƒ / Baxter Healthcare Corp., Hemaseel APR CoStasis DynaStat CryoSeal Beriplast P Evicel Artiss Greenplast 1998 FDA f Haemacure Corp., 1998 FDA f Cohesion Technologies Inc., 2000 FDA f ThermoGenesis Corp., 2001 FDA f, x f Behringwerke AG, f 2003 FDA f Ethicon Inc., Johnson & Johnson Co. Ltd., / 2008 FDA f Baxter Healthcare Corp., 2008 FDA f  f, Š 1996 KFDA f w } fƒ g Š f d hrh f dœ h hf j f., ƒ, Œx f f f f fš hr f, f ftf Œgf hi f fš f f f hf f. 1) Š, lœ ƒ, ilg f d Š e f d } fƒ hr h Š hr. u f f f Œ~ ilhrh dš f Œ Šl ff, f, }, z f fdš hhd dhœ h hrh ft f i h f Š f h h hr f gf Š Œ lš j f. 5) } fƒ hrh } fƒ t e hrh. Šd hrh } fƒ 2- } fƒ f d l t Š Š hhf f g, f, f Š } fƒ f t. 5,6) Š, Œ,, Œ l f Œ lœ f Œ, vœ f lœf x eš d h Š PEGŠe ƒ hrh dš Š. 6) 2003 3e, f l g (NIMS) d x ŒŠ f f f, f d h rh Š Š. f hrh Š g 5) t f ilf h hr, i hˆf d, hr f hˆf f Š xe Vol. 14, No. 2

72 fiœá dáh~ ÁŠfŒÁ isá Áug Á ÁŠ ÁŠ d Table 9. f d lœh hˆ Œ hˆ( ) jd g hi( ) hˆ Œ Bioglue bovine serum albumin and glutaraldehyde Cryolife, Gelfoam sponge and powder Pharmacia, / 2007 FDA f porcine gelatin Ethicon Inc., Johnson & Johnson Co. Ltd., Surgifoam sponge & powder / 2007 FDA f FloSealÂ& Baxter Healthcare Corp., FloSeal NT gelatin (bovine, porcine) 1999 FDA f with or without thrombin Surgiflo Ethicon Inc., Johnson & Johnson Co. Ltd., Avitene ultrafoam & flour Helistat & Helitene Instat & Instat MCH Surgicel Fibrillar & Nu-Knit bovine collagen / 2007 FDA f Davol Inc., C. R. Bard Inc., 2000 FDA f Integra LifeSciences Corp., 1999 EU CE mark, 2002 FDA f Ethicon Inc., Johnson & Johnson Co. Ltd., / 1980 s FDA f Ethicon Inc., Johnson & Johnson Co. Ltd., oxidized regenerated cellulose / 2008 FDA f Arista AH polysaccharide spheres Medafor Inc., / 2006 FDA f Thrombin-JMI Evithrom thrombin (human, bovine, recombinant) King Pharmaceuticals, 2007 FDA f Ethicon Inc., Johnson & Johnson Co. Ltd., / 2007 FDA f Zymogenetics Inc., 2008 FDA f Vitagel plasma, collagen and bovine thrombin Orthovita Inc., / 2006 FDA f Recothrom f ff, f hf hˆf hr f Š h f h. hrh t igš f z (citric acid)f Š Š f d lh dš if f d hrh Š h r f, f f. Š 5) hrh f hˆ f h, Š Š d f h tš f ff, f hf d f Œff sx e Š h Š f. 5) 2008 9ef KISTI Š(GTB) f NIMS h(, ~ ) Š t /, j (tartaric acid) f e Œ fš h l 10 nmf lf (albumin)f hrh Š. f hrhf Œ wh 11-13), 10 f u hr f jf hrh(, ) Š 3 f f f hr f f f h. f Š f hr j f e f Š Š h hrh jf t il jf z fš fš Š. KISTI Š(GTB) 2009 3e, x f Š f ŒŠf s hr l MEMS(microelectromechanical systems) f ~f Š f}h f Šf f h d f j Œ f d hrh Š. ŒŠf 14) hr hr lf f Š f ƒ f f. f f dš hœš ex hrh Š f f fdf, hœ Š ex il f Š f sf x l h f f. Š, f Š g f Š ˆt h Š fdf f f l -L- f [εpoly(l-lysine)] f fif ƒ (dextran)f g Š d f ilhrh Š Lydex Š (Figure 5). f Lydex thš f l g ŒŠ l t f hœ(gelation) ilf hr ~, i hrh Š hr j. Š, v l(prevention of pulmonary air leakage), g f eš f (amniotic membrane transplantation for ocular surface reconstruction) f (keratoplasty) Lydex hf hdš 2007 11e, 2008 7e 2009 6e f Š. 2-4) u l fš t ehf g iš f fdš, ŒŠ hr lf f z f Œ~f z fƒ(coacervate) thrh. f z f hr lf g fl 15) Biomaterials Research 2010

f d hrh er l f u 73 Figure 5. -L- f [ε-poly(l-lysine)] ƒ (dextran)f g Š ilhrh(lydex). (A) f f j Œ d ; Š f aldehyded dextran d (Liquid A)f, ε-poly(l-lysine) d (Liquid B)f seh ff, fš f d f static mixer Š ŒŠf f fdš LYDEX f Œ Œ Š. (B D) ŒŠ d f hœ(gelation) hrhf ƒ f ~. (E) Lydexf l g d ~ff hiš. Table 10. Š f g fdš f d hrh g Œ ƒl (d, t / h ) r polyvinyl alcohol, polyvinyl pyrrolidone polycaprolactone silicone + carbon nanotube poly(glycerol sebacate acrylate) poly(dimethylsiloxane) + poly(dopamine methacrylamide-comethoxyethyl acrylate) Tetronic + succinic anhydride + tyramine film (patch) membrane tape (patch) polymer pillar array hydrogel skin bioadhesive film 16, 17 wound closure, hemostat, air leakage sealant, modified with 2-isocyanatoethylmethacrylate, crosslinking via UV irradiation synthetic gecko tape (Á micropatterned carbon nanotube arrays) biodegradable, biocompatible elastomeric gecko-inspired nanopatterns flexible organic nanoadhesive as geckel, reflecting inspiration from both gecko & mussel injectable, biodegradable, in situ forming, crosslinking via enzymatic reaction 18 19 20 21 22 g f d f, if ŒŠhr l d Š hr f 2 f. ŒŠ hr l 80% hf tg j Š f (hyaluronic acid) 20% ŒŠŠ, z f f z fƒ. f lf hr f g fl f g f d ~eš h ƒ f l f, ft hš dš f thš f l f. Š hr f z fƒ ŒdŠ f} y f f d hrh h l Œd ff, Œgˆ ˆ t l ehf Œd f. PubMed lf fdš u 5 (2005 f ) f f SCI(E) h f d hrh Š f Š f g, Œ ƒl f i Š (Tables 10 & 11). f g Š Š f s e g fdš ff, Š ff d Š ( w)f f Œ~, s ff d j h(šf h Œf h) Œ~ h rh Š f f l fff f. erf h hf f il f h hf f f Š. g l l er f jd 26) dff, f Œ f f l Š l v f e xr dš hf t h hf f xe Œ f Š e f dš Vol. 14, No. 2

74 fiœá dáh~ ÁŠfŒÁ isá Áug Á ÁŠ ÁŠ d Table 11. s f g fdš f d hrh g Œ ƒl (d, t / h ) r poly(l-lysine) + aldehyded dextran (Lydex) human serum albumin + tartaric acid derivative mussel adhesive protein chondroitin sulfate + polyethylene glycol gel/powder h rœ erf Š h f. 26) Mechanical trauma, foreign body, desiccation, incomplete hemostasis, suture f er Œ f tlš f Š f Šj f ŠdŠ, jdš er l f f. d s j 26) f lš eš Š h d f jf(instillation)š Š (normal saline) Ringer s lactate dš. f d h Œf f dš er 26) l Š Š. 26), f, s g Œf h rf fl erf Š f h f. xe h erf Šf 27,28) Š, g f d f f Š lf e Š g e l Š Š. er l f 27,28) ih d f f tš f, ff df Œf f Š lf fš g, gfe df h Š hf f Š f. il erf f d Š ff, g l, l, g, f f eff, h x l f Œhf f h x hœf h hf Š Š 2r f Œf f df j. f Š erf 27,28) lš f s u ŒŠ, Š hf d Œf f Œ f eš il Œ ff(tissue-type plasminogen activator) Œ Œ ~ f f, Š Œ~f hf 29,30) g (physical barrier)f dš f d f. 27,28,31,32) h g f er f f fhš il f biodegradable, anti-microbial hemostat, air leakage sealant, adhesion-preventive gel biodegradable, injectable in situ forming DDS 11-13 complex coacervates recombinant hybrid complex with hyaluronic acid or fused with RGD peptide exš ilf xe ff er f lš fdf Š, fh f l Š f ff ff~l Š. 27,28) er l f Š s } hhh(intraperitoneal instillates) er r h(adhesion barriers)f l Œ~ f. g d f hh h (heparin), 33) x (carboxy methyl cellulose, CMC), 34) (hyaluronic acid, HA) 35) f hi h Œ~ Ringer s lactate, icodextrin(adept ), dextran- 70(Hyskon ) f d ~ff f (Table 12). er r h ƒ(teflon sheet), HA/CMCf Š (Seprafilm ) Œg (oxidized regenerated cellulose)f l (Interceed ) f f( ) Œ~ f (Table 13). Š / (poloxamer/alginate)f fdš f (thermosensitive) er l Š f. 36) d Œf d t f h s hœ d, f ~ff Œ~ Œ Š x(trocar)f Š er l f Š hdš d hf h. 27) g f f d f hf d Œ f f ~f er l f f f f (Tables 12 & 13). h d ~ff er l f f dextran e t jd g Š ADEPT Hyskon sodium hyaluronate ironf h ~ff Intergel f 1998 f FDA ff g dœ f. 2-4 15, 23, 24 hydrogel ph sensitive adhesive for wound healing 25 Table 12. d h ~f er l hˆ Œ hˆ( ) jd g hi( ) hˆ Œ ADEPT Hyskon Gynecare Intergel Guardix-sol 4% icodextrin solution 32% dextran-70 solution gel of sodium hyaluronate & iron gel of hyaluronic acid & sodium carboxymethyl cellulose Baxter AG, ƒ 2006 FDA f Coopersurgical Inc. / Abbott Laboratories / Hospira Inc., 1998, 2000, 2007 FDA f Lifecore Biomedical Inc., 2002 FDA f Biorane Co. Ltd., Hanmi Pharm. Co. Ltd., Š / 2006 KFDA f Biomaterials Research 2010

f d hrh er l f u 75 Table 13. f ~f er l hˆ Œ hˆ( ) jd g hi( ) hˆ Œ Interceed (TC7) Seprafilm SurgiWrap Guardix-MB oxidized regenerated cellulose hyaluronic acid + carboxymethylcellulose 70:30 poly(l-lactide-co-d,l-lactide) hyaluronic acid + sodium carboxymethyl cellulose Noramco, Inc. / Ethicon Inc., Johnson & Johnson Co. Ltd., / 1994, 1997 FDA f Genzyme Biosurgery Corp., 1996 FDA f Mast Biosurgery Inc., 2006 FDA f Biorane Co. Ltd., Hanmi Pharm. Co. Ltd., Š / 2006 KFDA f Table 14. Š f g fdš er l g Œ ƒl (d, t / h ) r polyethylene glycol + poly(l-lactic acid) sodium hyaluronate + sodium carboxymethyl cellulose hyaluronic acid (HA) hyaluronic acid (HA) + cellulose derivatives such as carboxymethylcellulose, hydroxypropylmethylcellulose & methylcellulose carboxymethyldextran (CMDX) + carboxymethylcellulose (CMC) hyaluronan (HA) oxidized dextran + N-carboxyethyl chitosan poly (lactic-co-glycolic acid) film anti-inflammatory drug, ibuprofen-loaded 32 membrane hydrogel hydrogel hydrogel hydrogel crosslinking with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide biodegradable, in situ cross-linkable, HA modified with adipic dihydrazide or aldehyde injectable, in situ cross-linkable, degradable by hyaluronidase, hydrazide-modified HA & aldehydemodified cellulose derivatives in situ cross-linkable, injectable, hydrazide-modified CMDX, aldehyde-modified CMC in situ cross-linkable, tissue-type plasminogen activatorloaded, HA modified with adipic dihydrazide or aldehyde hydrogel biodegradable, in situ crosslinkable 46 membrane bioabsorbable, electrospun nanofiber coated with hyaluronic acid 31 43 44 45 30 27 ff f ~ff Interceed er l f ut FDA ff f hˆf l jd (affusion) dš f, Šf Šd f g f Œg glf 8 h f Œ f Œ Š 2j t. if Š f f h Š hf ff, Š v vœ e g d erf e Š f f. x g Š Seprafilm f d, d f hhf iff d dš Š e f d f f ŠdŠ. f SurgiWrap f poly(l-lactide-co-d,l-lactide) g Š t Š f Šf Š Š e, h, if ŠdŠ hh h f. Š, l fš ˆf hyaluronic acid sodium carboxymethyl cellulose g Š Guardix-sol f  f f fš Š ˆf 2006 8e j f. thš f s f h ft ŠŠ Š l 2j h l t Š 1 e f v. Šhf hš t er l hh, f fl. h ~ff er ld Š / f h dš d e hf hdf Š f if h f l l l FDAf ff l Š. w f Š, thš g 1,000~ 10,000,000 g/molef f f e s ff, β(1 Á 3) & β(1 Á 4) z Š(glycosidic bonding) f D- (D-glucuronic acid) N- -D- z (N-acetyl-D-glucosamine)f 2 (disaccharide) etf f f l Œ ff f. 37-39) f Šilf d l(extracellular matrix, ECM) f jd f ƒš h~ ƒ Šh f h sx,, h il Šh fd e Vol. 14, No. 2

76 fiœá dáh~ ÁŠfŒÁ isá Áug Á ÁŠ ÁŠ d dš g f. f ilf Œ 37) ihš ECM f z e Œ ƒe} f ff, Š s xe h f e Œ jdš Šf Š. f x 37) xœ f fš f hf ƒ f ff, l ~ f Š e t f x f Š h dš Šf hf hiš lš f. 38-42) er l f d Š hf g fš il f hf htf lš erf Œ f lš. er l f f h h df d f h d Š d hf lf ~f jdš d. f f omentumf peritoneal graft vvf Š Š f f ŠdŠ dhfl Š h f. 26) PubMed lf fdš u 5 (2005 f ) f f SCI(E) h er l Š f Š f g, Œ ƒl f i Š (Table 14). f g Š Š f s e g fdš ff, j Šf h Œ~ hrh Š f f l fff f. u f Œ lœ f f dš l f x f f d hrh Š Š v f, il er Š lf l eš er l f df Š Š Œf. Š f tild hrh er lgf d f lš f f Š f, t fš f ŒdŠ Š d hˆ Š t hf h e f Š Š. 2009 ˆf ˆ ht d hf le(09142f 488) l h ges f le(k0006028) fš Š f f. š x 1. d, f, tg d f, Š Š h e(kisti) (2002). 2. M. Araki, H. Tao, N. Nakajima, H. Sugai, T. Sato, S. -H. Hyon, T. Nagayasu, and T. Nakamura, Development of new biodegradable hydrogel glue for preventing alveolar air leakage, J. Thorac. Cardiovasc. Surg., 134, 1241-1248 (2007). 3. M. Takaoka, T. Nakamura, H. Sugai, A. J. Bentley, N. Nakajima, N. J. Fullwood, N. Yokoi, S. -H. Hyon, and S. Kinoshita, Sutureless amniotic membrane transplantation for ocular surface reconstruction with a chemically defined bioadhesive, Biomaterials, 29, 2923-2931 (2008). 4. M. Takaoka, T. Nakamura, H. Sugai, A. J. Bentley, N. Nakajima, N. Yokoi, N. J. Fullwood, S. -H. Hyon, and S. Kinoshita, Novel sutureless keratoplasty with a chemically defined bioadhesive, Invest. Ophthalmol. Vis. Sci., 50, 2679-2685 (2009). 5. hœ,, e, f d hrh hi, Š Š h e(kisti) x (2004). 6. Š, f d thrhf u, Š Š e(kist) (2005). 7. D. S. Hwang, Y. Gim, H. J. Yoo, and H. J. Cha, Practical recombinant hybrid mussel bioadhesive fp-151, Biomaterials, 28, 3560-3568 (2007). 8. D. S. Hwang, S. B. Sim, and H. J. Cha, Cell adhesion biomaterial based on mussel adhesive protein fused with RGD peptide, Biomaterials, 28, 4039-4046 (2007). 9. D. S. Hwang, H. J. Yoo, J. H. Jun, W. K. Moon, and H. J. Cha, Expression of functional recombinant mussel adhesive protein Mgfp-5 in Escherichia coli, Appl. Environ. Microbiol., 70, 3352-3359 (2004). 10. W. D. Spotnitz and S. Burks, Hemostats, sealants, and adhesives: components of the surgical toolbox, Transfusion, 48,1502-1516 (2008). 11. S. Kakinoki, T. Taguchi, H. Saito, J. Tanaka, and T. Tateishi, Injectable in situ forming drug delivery system for cancer chemotherapy using a novel tissue adhesive: characterization and in vitro evaluation, Eur. J. Pharm. Biopharm., 66, 383-390 (2007). 12. R. Sethumadhavan, T. Taguchi, J. Tanaka, and T. Tateishi, Investigations on the interaction of tartaric acid derivative/ human serum albumin tissue adhesive with J774A.1 mouse macrophage cells through SEM, IL-6 cytokine and gene expression techniques, Biomed. Mater. Eng., 17, 209-217 (2007). 13. M. Iwasashi, M. Sakane, H. Saito, T. Taguchi, T. Tateishi, and Ochiai N, In vivo evaluation of bonding ability and biocompatibility of a novel biodegradable glue consisting of tartaric acid derivative and human serum albumin, J. Biomed. Mater. Res. A, 90, 543-548 (2009). 14. A. Doraiswamy, T. M. Dunaway, J. J. Wilker, and R. J. Narayan, Inkjet printing of bioadhesives, J. Biomed. Mater. Res. B, 89, 28-35 (2009). 15. S. Lim, Y. S. Choi, D. G. Kang, Y. H. Song, and H. J. Cha, The adhesive properties of coacervated recombinant hybrid mussel adhesive proteins, Biomaterials, 31, 3715-3722 (2010). 16. A. Nussinovitch, A. Gal, C. Padula, and P. Santi, Physical characterization of a new skin bioadhesive film, AAPS Pharm. Sci. Tech., 9, 458-463 (2008). 17. A. Gal and A. Nussinovitch, Plasticizers in the manufacture of novel skin-bioadhesive patches, Int. J. Pharm., 370, 103-109 (2009). 18. P. Ferreira, J. F. Coelho, and M. H. Gil, Development of a new photocrosslinkable biodegradable bioadhesive, Int. J. Pharm., 352, 172-181 (2008). 19. L. Ge, S. Sethi, L. Ci, P. M. Ajayan, A. Dhinojwala, Carbon nanotube-based synthetic gecko tapes, Proc. Natl. Acad. Sci. USA, 104, 10792-10795 (2007). 20. A. Mahdavi, L. Ferreira, C. Sundback, J. W. Nichol, E. P. Chan, D. J. Carter, C. J. Bettinger, S. Patanavanich, L. Chignozha, E. Ben- Joseph, A. Galakatos, H. Pryor, I. Pomerantseva, P. T. Masiakos, W. Faquin, A. Zumbuehl, S. Hong, J. Borenstein, J. Vacanti, R. Langer, Biomaterials Research 2010

f d hrh er l f u 77 and J.M. Karp, A biodegradable and biocompatible geckoinspired tissue adhesive, Proc. Natl. Acad. Sci. USA, 105, 2307-2312 (2008). 21. H. Lee, B. P. Lee, and P. B. Messersmith, A reversible wet/dry adhesive inspired by mussels and geckos, Nature, 448, 338-341 (2007). 22. K. M. Park, Y. M. Shin, Y. K. Joung, H. Shin, K. D. Park In situ forming hydrogels based on tyramine conjugated 4-Arm-PPO- PEO via enzymatic oxidative reaction, Biomacromolecules, 11, 706-712 (2010). 23. D. S. Hwang, S. B. Sim, and H. J. Cha, Cell adhesion biomaterial based on mussel adhesive protein fused with RGD peptide, Biomaterials, 28, 4039-4046 (2007). 24. D. S. Hwang, J. H. Waite, and M. Tirrell, Promotion of osteoblast proliferation on complex coacervation-based hyaluronic acid - recombinant mussel adhesive protein coatings on titanium, Biomaterials, 31, 1080-1084 (2010). 25. I. Strehin, Z. Nahas, K. Arora, T. Nguyen, and J. Elisseeff, A versatile ph sensitive chondroitin sulfate-peg tissue adhesive and hydrogel, Biomaterials, 31, 2788-2797 (2010). 26. uj, er l eš u l : erf er l eš, Medical Observer (2008). 27. f d, v, fe,, jœ, f, e, h e er lh f h, Šd Š l, 76, 73-80 (2009). 28. Œj, ie, j, d, ue,, r g, j, gf~, f,, Œ, l eœf er lhf, Šd Š l, 77, 7-14 (2009). 29. K. Falk, P. Bjorquist, M. Stromqvist, and L. Holmdahl, Reduction of experimental adhesion formation by inhibition of plasminogen activator inhibitor type 1, Br. J. Surg., 88, 286-289 (2001). 30. Y. Yeo, E. Bellas, C. B. Highley, R. Langer, and D. S. Kohane, Peritoneal adhesion prevention with an in situ cross-linkable hyaluronan gel containing tissue-type plasminogen activator in a rabbit repeated-injury model, Biomaterials, 28, 3704-3713 (2007). 31. f d, f, k g/ r Sodium Hyaluronate/Sodium Carboxymethyl Cellulose ff er l Š e, Membrane J., 15, 213-223 (2005). 32. J. H. Lee, A. K. Go, S. H. Oh, K. E. Lee, and S. H. Yuk, Tissue anti-adhesion potential of ibuprofen-loaded PLLA-PEG diblock copolymer films, Biomaterials, 26, 671-678 (2005). 33. R. P. Jansen, Failure of peritoneal irrigation with heparin during pelvic operations upon young women to reduce adhesions, Surg. Gynecol. Obstet., 166, 154-160 (1988). 34. H. D. Moll, D. F. Wolfe, J. Schumacher, and J. C. Wright, Evaluation of sodium carboxymethylcellulose for prevention of adhesions after uterine trauma in ewes, Am. J. Vet. Res., 53, 1454-1456 (1992). 35. B. Urman and V. Gomel, Effect of hyaluronic acid on postoperative intraperitoneal adhesion formation and reformation in the rat model, Fertil. Steril., 56, 568-570 (1991). 36. e, f Œ, f d, fe, v, flœ, f, g/ r f er lh(poloxamer/ Alginate/CaCl2 Mixture)f, Šd Š l, 71, 280-287 (2006). 37. S. Y. Kim, Research trends on polymeric hydrogels for tissue engineering applications, Tissue Eng. Regen. Med., 5, 14-25 (2008). 38. S. K. Hahn, J. K. Park, T. Tomimatsu, and T. Shimoboji, Synthesis and degradation test of hyaluronic acid hydrogels, Int. J. Biol. Macromol., 40, 374-380 (2007). 39. A. Maleki, A. L. Kjøniksen, and B. Nyström, Characterization of the chemical degradation of hyaluronic acid during chemical gelation in the presence of different cross-linker agents, Carbohydr. Res., 342, 2776-2792 (2007). 40. O. Jeon, S. J. Song, K. Lee, M. H. Park, S. -H. Lee, S. K. Hahn, S. Kim, and B. -S. Kim Mechanical properties and degradation behaviors of hyaluronic acid hydrogels cross-linked at various cross-linking densities, Carbohydr. Polym., 70, 251-257 (2007). 41. O. P. Varghese, W. Sun, J. Hilborn, and D. A. Ossipov, In situ cross-linkable high molecular weight hyaluronan-bisphosphonate conjugate for localized delivery and cell-specific targeting: a hydrogel linked prodrug approach, J. Am. Chem. Soc., 131, 8781-8783 (2009). 42. E. J. Oh, K. Park, K. S. Kim, J. Kim, J. A. Yang, J. H. Kong, M. Y. Lee, A. S. Hoffman, and S. K. Hahn, Target specific and longacting delivery of protein, peptide, and nucleotide therapeutics using hyaluronic acid derivatives, J. Control. Release, 141, 2-12 (2010). 43. Y. Yeo, C. B. Highley, E. Bellas, T. Ito, R. Marini, R. Langer, and D.S. Kohane, In situ cross-linkable hyaluronic acid hydrogels prevent post-operative abdominal adhesions in a rabbit model, Biomaterials, 27, 4698-4705 (2006). 44. T. Ito, Y. Yeo, C. B. Highley, E. Bellas, C. A. Benitez, and D. S. Kohane, The prevention of peritoneal adhesions by in situ crosslinking hydrogels of hyaluronic acid and cellulose derivatives, Biomaterials, 28, 975-983 (2007). 45. T. Ito, Y. Yeo, C. B. Highley, E. Bellas, and D. S. Kohane, Dextranbased in situ cross-linked injectable hydrogels to prevent peritoneal adhesions, Biomaterials, 28, 3418-3426 (2007). 46. C. A. Falabella, M. M. Melendez, L. Weng, and W. Chen, Novel macromolecular crosslinking hydrogel to reduce intraabdominal adhesions, J. Surg. Res., 159, 772-778 (2010). Vol. 14, No. 2