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Current Drug Targets

Author(s): Xinyue Zhai, Yuqian Wu and Huaping Tan*

DOI: 10.2174/1389450124666230605150303

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Gelatin-based Targeted Delivery Systems for Tissue Engineering

Page: [673 - 687] Pages: 15

  • * (Excluding Mailing and Handling)

Abstract

Gelatin is an attractive material for drug delivery and tissue engineering applications due to its excellent biocompatibility and biodegradability, which has been utilized as cell, drug, and gene carriers. Gelatin is less immunogenic compared to collagen and its precursor and retains informational signals, such as RGD (Arg-Gly-Asp) sequence, thus promoting cell adhesion and proliferation. To tune the mechanical strength and bioactivity, gelatin can be easily modified via chemical reactions and physical methods to obtain various derivatives. Furthermore, gelatin-based biomaterials can be achieved through chemical immobilization of specific molecules and physical combination with other biopolymers. This review focuses on the recent advances of gelatin and its derivatives as biomaterials in the field of drug delivery, including cell scaffolds for tissue engineering applications.

Graphical Abstract

[1]
Liu X, Ma L, Mao Z, Gao C. Chitosan-based biomaterials for tissue repair and regeneration. Adv Polym Sci 2011; 244: 81-127.
[http://dx.doi.org/10.1007/12_2011_118]
[2]
Lee CH, Singla A, Lee Y. Biomedical applications of collagen. Int J Pharm 2001; 221(1-2): 1-22.
[http://dx.doi.org/10.1016/S0378-5173(01)00691-3] [PMID: 11397563]
[3]
Drury JL, Mooney DJ. Hydrogels for tissue engineering: Scaffold design variables and applications. Biomaterials 2003; 24(24): 4337-51.
[http://dx.doi.org/10.1016/S0142-9612(03)00340-5] [PMID: 12922147]
[4]
Tan H, Chu CR, Payne KA, Marra KG. Injectable in situ forming biodegradable chitosan–hyaluronic acid based hydrogels for cartilage tissue engineering. Biomaterials 2009; 30(13): 2499-506.
[http://dx.doi.org/10.1016/j.biomaterials.2008.12.080] [PMID: 19167750]
[5]
Tian X-H, Wang Z-G, Meng H, et al. Tat peptide-decorated gelatin-siloxane nanoparticles for delivery of CGRP transgene in treatment of cerebral vasospasm. Int J Nanomedicine 2013; 8: 865-76.
[http://dx.doi.org/10.2147/IJN.S39951] [PMID: 23576867]
[6]
Bott K, Upton Z, Schrobback K, et al. The effect of matrix characteristics on fibroblast proliferation in 3D gels. Biomaterials 2010; 31(32): 8454-64.
[http://dx.doi.org/10.1016/j.biomaterials.2010.07.046] [PMID: 20684983]
[7]
Nichol JW, Koshy ST, Bae H, Hwang CM, Yamanlar S, Khademhosseini A. Cell-laden microengineered gelatin methacrylate hydrogels. Biomaterials 2010; 31(21): 5536-44.
[http://dx.doi.org/10.1016/j.biomaterials.2010.03.064] [PMID: 20417964]
[8]
Giraudier S, Hellio D, Djabourov M, Larreta-Garde V. Influence of weak and covalent bonds on formation and hydrolysis of gelatin networks. Biomacromolecules 2004; 5(5): 1662-6.
[http://dx.doi.org/10.1021/bm049670d] [PMID: 15360272]
[9]
Tan H, Wan L, Wu J, Gao C. Microscale control over collagen gradient on poly(l-lactide) membrane surface for manipulating chondrocyte distribution. Colloids Surf B Biointerfaces 2008; 67(2): 210-5.
[http://dx.doi.org/10.1016/j.colsurfb.2008.08.019] [PMID: 18838254]
[10]
Zhang X, Pan Y, Li S, et al. Doubly crosslinked biodegradable hydrogels based on gellan gum and chitosan for drug delivery and wound dressing. Int J Biol Macromol 2020; 164: 2204-14.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.08.093] [PMID: 32798543]
[11]
Kommareddy S, Amiji M. Poly(ethylene glycol)–modified thiolated gelatin nanoparticles for glutathione-responsive intracellular DNA delivery. Nanomedicine 2007; 3(1): 32-42.
[http://dx.doi.org/10.1016/j.nano.2006.11.005] [PMID: 17379167]
[12]
Ulubayram K, Aksu E, Gurhan SID, Serbetci K, Hasirci N. Cytotoxicity evaluation of gelatin sponges prepared with different cross-linking agents. J Biomater Sci Polym Ed 2002; 13(11): 1203-19.
[http://dx.doi.org/10.1163/156856202320892966] [PMID: 12518800]
[13]
Tan H, Hu X. Injectable in situ forming glucose-responsive dextran-based hydrogels to deliver adipogenic factor for adipose tissue engineering. J Appl Polym Sci 2012; 126(S1): E180-7.
[http://dx.doi.org/10.1002/app.36737]
[14]
Tan H, Li H, Rubin JP, Marra KG. Controlled gelation and degradation rates of injectable hyaluronic acid-based hydrogels through a double crosslinking strategy. J Tissue Eng Regen Med 2011; 5(10): 790-7.
[http://dx.doi.org/10.1002/term.378] [PMID: 22002922]
[15]
Sun R, Shi J, Guo Y, Chen L. Studies on the particle size control of gelatin microspheres. Front Chem China 2009; 4(2): 222-8.
[http://dx.doi.org/10.1007/s11458-009-0031-x]
[16]
Tan H, Marra KG. Injectable, biodegradable hydrogels for tissue engineering applications. Materials 2010; 3(3): 1746-67.
[http://dx.doi.org/10.3390/ma3031746]
[17]
Sun J, Tan H. Alginate-based biomaterials for regenerative medicine applications. Materials 2013; 6(4): 1285-309.
[http://dx.doi.org/10.3390/ma6041285] [PMID: 28809210]
[18]
Tan H, DeFail AJ, Rubin JP, Chu CR, Marra KG. Novel multiarm PEG-based hydrogels for tissue engineering. J Biomed Mater Res A 2010; 92(3): 979-87.
[PMID: 19291691]
[19]
Tan H, Zhou Q, Qi H, Zhu D, Ma X, Xiong D. Heparin interacting protein mediated assembly of nano-fibrous hydrogel scaffolds for guided stem cell differentiation. Macromol Biosci 2012; 12(5): 621-7.
[http://dx.doi.org/10.1002/mabi.201100502] [PMID: 22454284]
[20]
Tan H, Ramirez CM, Miljkovic N, Li H, Rubin JP, Marra KG. Thermosensitive injectable hyaluronic acid hydrogel for adipose tissue engineering. Biomaterials 2009; 30(36): 6844-53.
[http://dx.doi.org/10.1016/j.biomaterials.2009.08.058] [PMID: 19783043]
[21]
Lai JY, Hsieh AC. A gelatin-g-poly(N-isopropylacrylamide) biodegradable in situ gelling delivery system for the intracameral administration of pilocarpine. Biomaterials 2012; 33(7): 2372-87.
[http://dx.doi.org/10.1016/j.biomaterials.2011.11.085] [PMID: 22182746]
[22]
Kosmala JD, Henthorn DB, Brannon-Peppas L. Preparation of interpenetrating networks of gelatin and dextran as degradable biomaterials. Biomaterials 2000; 21(20): 2019-23.
[http://dx.doi.org/10.1016/S0142-9612(00)00057-0] [PMID: 10966010]
[23]
Ohya S, Nakayama Y, Matsuda T. Material design for an artificial extracellular matrix: Cell entrapment in poly (N-isopropylacrylamide) (PNIPAM)-grafted gelatin hydrogel. J Artif Organs 2001; 4(4): 308-14.
[http://dx.doi.org/10.1007/BF02480023]
[24]
Ohya S, Matsuda T. Poly (N-isopropylacrylamide) (PNIPAM)- grafted gelatin as thermoresponsive three-dimensional artificial extracellular matrix: molecular and formulation parameters vs. cell proliferation potential. J Biomater Sci Polym Ed 2005; 16(7): 809-27.
[http://dx.doi.org/10.1163/1568562054255736] [PMID: 16128290]
[25]
Park SN, Park JC, Kim HO, Song MJ, Suh H. Characterization of porous collagen/hyaluronic acid scaffold modified by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide cross-linking. Biomaterials 2002; 23(4): 1205-12.
[http://dx.doi.org/10.1016/S0142-9612(01)00235-6] [PMID: 11791924]
[26]
Potiwiput S, Tan H, Yuan G, et al. Dual-crosslinked alginate/carboxymethyl chitosan hydrogel containing in situ synthesized calcium phosphate particles for drug delivery application. Mater Chem Phys 2020; 241: 122354.
[http://dx.doi.org/10.1016/j.matchemphys.2019.122354]
[27]
Bigi A, Cojazzi G, Panzavolta S, Rubini K, Roveri N. Mechanical and thermal properties of gelatin films at different degrees of glutaraldehyde crosslinking. Biomaterials 2001; 22(8): 763-8.
[http://dx.doi.org/10.1016/S0142-9612(00)00236-2] [PMID: 11246944]
[28]
Xing L, Ma Y, Tan H, et al. Alginate membrane dressing toughened by chitosan floccule to load antibacterial drugs for wound healing. Polym Test 2019; 79: 106039.
[http://dx.doi.org/10.1016/j.polymertesting.2019.106039]
[29]
Vandelli MA, Rivasi F, Guerra P, Forni F, Arletti R. Gelatin microspheres crosslinked with d,l-glyceraldehyde as a potential drug delivery system: preparation, characterisation, in vitro and in vivo studies. Int J Pharm 2001; 215(1-2): 175-84.
[http://dx.doi.org/10.1016/S0378-5173(00)00681-5] [PMID: 11250103]
[30]
Qian S, Yan Z, Xu Y, et al. Carbon nanotubes as electrophysiological building blocks for a bioactive cell scaffold through biological assembly to induce osteogenesis. RSC Advances 2019; 9(21): 12001-9.
[http://dx.doi.org/10.1039/C9RA00370C] [PMID: 35516980]
[31]
Xing L, Sun J, Tan H, et al. Covalently polysaccharide-based alginate/chitosan hydrogel embedded alginate microspheres for BSA encapsulation and soft tissue engineering. Int J Biol Macromol 2019; 127: 340-8.
[http://dx.doi.org/10.1016/j.ijbiomac.2019.01.065] [PMID: 30658141]
[32]
Ren B, Chen X, Ma Y, et al. Dynamical release nanospheres containing cell growth factor from biopolymer hydrogel via reversible covalent conjugation. J Biomater Sci Polym Ed 2018; 29(11): 1344-59.
[http://dx.doi.org/10.1080/09205063.2018.1460140] [PMID: 29609508]
[33]
Ren B, Chen X, Du S, et al. Injectable polysaccharide hydrogel embedded with hydroxyapatite and calcium carbonate for drug delivery and bone tissue engineering. Int J Biol Macromol 2018; 118(Pt A): 1257-66.
[http://dx.doi.org/10.1016/j.ijbiomac.2018.06.200]
[34]
Ma Y, Xin L, Tan H, et al. Chitosan membrane dressings toughened by glycerol to load antibacterial drugs for wound healing. Mater Sci Eng C 2017; 81: 522-31.
[http://dx.doi.org/10.1016/j.msec.2017.08.052] [PMID: 28888006]
[35]
Bigi A, Cojazzi G, Panzavolta S, Roveri N, Rubini K. Stabilization of gelatin films by crosslinking with genipin. Biomaterials 2002; 23(24): 4827-32.
[http://dx.doi.org/10.1016/S0142-9612(02)00235-1] [PMID: 12361622]
[36]
Sung HW, Liang IL, Chen CN, Huang RN, Liang HF. Stability of a biological tissue fixed with a naturally occurring crosslinking agent (genipin). J Biomed Mater Res 2001; 55(4): 538-46.
[http://dx.doi.org/10.1002/1097-4636(20010615)55:4<538::AID-JBM1047>3.0.CO;2-2] [PMID: 11288082]
[37]
Hellio-Serughetti D, Djabourov M. Gelatin hydrogels cross-linked with bis(vinylsulfonyl)methane (BVSM): 1. The chemical networks. Langmuir 2006; 22(20): 8509-15.
[http://dx.doi.org/10.1021/la060375j] [PMID: 16981770]
[38]
Lopes CMA, Felisberti MI. Mechanical behaviour and biocompatibility of poly(1-vinyl-2-pyrrolidinone)–gelatin IPN hydrogels. Biomaterials 2003; 24(7): 1279-84.
[http://dx.doi.org/10.1016/S0142-9612(02)00448-9] [PMID: 12527269]
[39]
Tan H, Xiao C, Sun J, Xiong D, Hu X. Biological self-assembly of injectable hydrogel as cell scaffold via specific nucleobase pairing. Chem Commun 2012; 48(83): 10289-91.
[http://dx.doi.org/10.1039/c2cc35449g] [PMID: 22983594]
[40]
Kurisawa M, Chung JE, Yang YY, Gao SJ, Uyama H. Injectable biodegradable hydrogels composed of hyaluronic acid–tyramine conjugates for drug delivery and tissue engineering. Chem Commun 2005; 34(34): 4312-4.
[http://dx.doi.org/10.1039/b506989k] [PMID: 16113732]
[41]
Jin R, Hiemstra C, Zhong Z, Feijen J. Enzyme-mediated fast in situ formation of hydrogels from dextran–tyramine conjugates. Biomaterials 2007; 28(18): 2791-800.
[http://dx.doi.org/10.1016/j.biomaterials.2007.02.032] [PMID: 17379300]
[42]
Oudgenoeg G, Hilhorst R, Piersma SR, et al. Peroxidase-mediated cross-linking of a tyrosine-containing peptide with ferulic acid. J Agric Food Chem 2001; 49(5): 2503-10.
[http://dx.doi.org/10.1021/jf000906o] [PMID: 11368627]
[43]
Sakai S, Hirose K, Taguchi K, Ogushi Y, Kawakami K. An injectable, in situ enzymatically gellable, gelatin derivative for drug delivery and tissue engineering. Biomaterials 2009; 30(20): 3371-7.
[http://dx.doi.org/10.1016/j.biomaterials.2009.03.030] [PMID: 19345991]
[44]
Park KM, Lee Y, Son JY, Oh DH, Lee JS, Park KD. Synthesis and characterizations of in situ cross-linkable gelatin and 4-arm-PPO-PEO hybrid hydrogels via enzymatic reaction for tissue regenerative medicine. Biomacromolecules 2012; 13(3): 604-11.
[http://dx.doi.org/10.1021/bm201712z] [PMID: 22263670]
[45]
Nguyen KT, West JL. Photopolymerizable hydrogels for tissue engineering applications. Biomaterials 2002; 23(22): 4307-14.
[http://dx.doi.org/10.1016/S0142-9612(02)00175-8] [PMID: 12219820]
[46]
Halstenberg S, Panitch A, Rizzi S, Hall H, Hubbell JA. Biologically engineered protein-graft-poly(ethylene glycol) hydrogels: A cell adhesive and plasmin-degradable biosynthetic material for tissue repair. Biomacromolecules 2002; 3(4): 710-23.
[http://dx.doi.org/10.1021/bm015629o] [PMID: 12099815]
[47]
Li H, Wang DQ, Liu BL, Gao LZ. Synthesis of a novel gelatin–carbon nanotubes hybrid hydrogel. Colloids Surf B Biointerfaces 2004; 33(2): 85-8.
[http://dx.doi.org/10.1016/j.colsurfb.2003.08.014]
[48]
Liu Y, Chan-Park MB. A biomimetic hydrogel based on methacrylated dextran-graft-lysine and gelatin for 3D smooth muscle cell culture. Biomaterials 2010; 31(6): 1158-70.
[http://dx.doi.org/10.1016/j.biomaterials.2009.10.040] [PMID: 19897239]
[49]
Gattás-Asfura KM, Weisman E, Andreopoulos FM, et al. Nitrocinnamate-functionalized gelatin: Synthesis and “smart”hydrogel formation via photo-cross-linking. Biomacromolecules 2005; 6(3): 1503-9.
[http://dx.doi.org/10.1021/bm049238w] [PMID: 15877371]
[50]
Fan M, Ma Y, Tan H, et al. Covalent and injectable chitosan-chondroitin sulfate hydrogels embedded with chitosan microspheres for drug delivery and tissue engineering. Mater Sci Eng C 2017; 71: 67-74.
[http://dx.doi.org/10.1016/j.msec.2016.09.068] [PMID: 27987759]
[51]
Van Den Bulcke AI, Bogdanov B, De Rooze N, Schacht EH, Cornelissen M, Berghmans H. Structural and rheological properties of methacrylamide modified gelatin hydrogels. Biomacromolecules 2000; 1(1): 31-8.
[http://dx.doi.org/10.1021/bm990017d] [PMID: 11709840]
[52]
Liu Y, Chan-Park MB. Hydrogel based on interpenetrating polymer networks of dextran and gelatin for vascular tissue engineering. Biomaterials 2009; 30(2): 196-207.
[http://dx.doi.org/10.1016/j.biomaterials.2008.09.041] [PMID: 18922573]
[53]
Shin H, Olsen BD, Khademhosseini A. The mechanical properties and cytotoxicity of cell-laden double-network hydrogels based on photocrosslinkable gelatin and gellan gum biomacromolecules. Biomaterials 2012; 33(11): 3143-52.
[http://dx.doi.org/10.1016/j.biomaterials.2011.12.050] [PMID: 22265786]
[54]
Hu X, Li D, Zhou F, Gao C. Biological hydrogel synthesized from hyaluronic acid, gelatin and chondroitin sulfate by click chemistry. Acta Biomater 2011; 7(4): 1618-26.
[http://dx.doi.org/10.1016/j.actbio.2010.12.005] [PMID: 21145437]
[55]
Tan H, Rubin JP, Marra KG. Injectable in situ forming biodegradable chitosan-hyaluronic acid based hydrogels for adipose tissue regeneration. Organogenesis 2010; 6(3): 173-80.
[http://dx.doi.org/10.4161/org.6.3.12037] [PMID: 21197220]
[56]
Tan H, Rubin JP, Marra KG. Direct synthesis of biodegradable polysaccharide derivative hydrogels through aqueous Diels-Alder chemistry. Macromol Rapid Commun 2011; 32(12): 905-11.
[http://dx.doi.org/10.1002/marc.201100125] [PMID: 21520481]
[57]
Tan H, Shen Q, Jia X, Yuan Z, Xiong D. Injectable nanohybrid scaffold for biopharmaceuticals delivery and soft tissue engineering. Macromol Rapid Commun 2012; 33(23): 2015-22.
[http://dx.doi.org/10.1002/marc.201200360] [PMID: 22941907]
[58]
Balakrishnan B, Jayakrishnan A. Self-cross-linking biopolymers as injectable in situ forming biodegradable scaffolds. Biomaterials 2005; 26(18): 3941-51.
[http://dx.doi.org/10.1016/j.biomaterials.2004.10.005] [PMID: 15626441]
[59]
Dawlee S, Sugandhi A, Balakrishnan B, Labarre D, Jayakrishnan A. Oxidized chondroitin sulfate-cross-linked gelatin matrixes: A new class of hydrogels. Biomacromolecules 2005; 6(4): 2040-8.
[http://dx.doi.org/10.1021/bm050013a] [PMID: 16004443]
[60]
Kuijpers AJ, Engbers GHM, Krijgsveld J, Zaat SAJ, Dankert J, Feijen J. Cross-linking and characterisation of gelatin matrices for biomedical applications. J Biomater Sci Polym Ed 2000; 11(3): 225-43.
[http://dx.doi.org/10.1163/156856200743670] [PMID: 10841277]
[61]
Thomas S. Alginate dressings in surgery and wound management- part 1. J Wound Care 2000; 9(2): 56-60.
[http://dx.doi.org/10.12968/jowc.2000.9.2.26338] [PMID: 11933281]
[62]
Bouhadir KH, Lee KY, Alsberg E, Damm KL, Anderson KW, Mooney DJ. Degradation of partially oxidized alginate and its potential application for tissue engineering. Biotechnol Prog 2001; 17(5): 945-50.
[http://dx.doi.org/10.1021/bp010070p] [PMID: 11587588]
[63]
Balakrishnan B, Mohanty M, Umashankar P, Jayakrishnan A. Evaluation of an in situ forming hydrogel wound dressing based on oxidized alginate and gelatin. Biomaterials 2005; 26(32): 6335-42.
[http://dx.doi.org/10.1016/j.biomaterials.2005.04.012] [PMID: 15919113]
[64]
Tan H, Huang D, Lao L, Gao C. RGD modified PLGA/gelatin microspheres as microcarriers for chondrocyte delivery. J Biomed Mater Res B Appl Biomater 2009; 91B(1): 228-38.
[http://dx.doi.org/10.1002/jbm.b.31394] [PMID: 19388090]
[65]
Tan H, Wu J, Huang D, Gao C. The design of biodegradable microcarriers for induced cell aggregation. Macromol Biosci 2010; 10(2): 156-63.
[http://dx.doi.org/10.1002/mabi.200900160] [PMID: 19714563]
[66]
Wang J, Tabata Y, Morimoto K. Aminated gelatin microspheres as a nasal delivery system for peptide drugs: Evaluation of in vitro release and in vivo insulin absorption in rats. J Control Release 2006; 113(1): 31-7.
[http://dx.doi.org/10.1016/j.jconrel.2006.03.011] [PMID: 16707188]
[67]
Curcio M, Gianfranco Spizzirri U, Iemma F, et al. Grafted thermo-responsive gelatin microspheres as delivery systems in triggered drug release. Eur J Pharm Biopharm 2010; 76(1): 48-55.
[http://dx.doi.org/10.1016/j.ejpb.2010.05.008] [PMID: 20580821]
[68]
Iemma F, Spizzirri UG, Muzzalupo R, Puoci F, Trombino S, Picci N. Spherical hydrophilic microparticles obtained by the radical copolymerisation of functionalised bovine serum albumin. Colloid Polym Sci 2004; 283(3): 250-6.
[http://dx.doi.org/10.1007/s00396-004-1071-x]
[69]
Vandelli MA, Romagnoli M, Monti A, et al. Microwave-treated gelatin microspheres as drug delivery system. J Control Release 2004; 96(1): 67-84.
[http://dx.doi.org/10.1016/j.jconrel.2004.01.009] [PMID: 15063030]
[70]
Chen H, Xing X, Tan H, et al. Covalently antibacterial alginate- chitosan hydrogel dressing integrated gelatin microspheres containing tetracycline hydrochloride for wound healing. Mater Sci Eng C 2017; 70(Pt 1): 287-95.
[http://dx.doi.org/10.1016/j.msec.2016.08.086] [PMID: 27770893]
[71]
Chen X, Fan M, Tan H, et al. Magnetic and self-healing chitosan-alginate hydrogel encapsulated gelatin microspheres via covalent cross-linking for drug delivery. Mater Sci Eng C 2019; 101: 619-29.
[http://dx.doi.org/10.1016/j.msec.2019.04.012] [PMID: 31029355]
[72]
Kato K, Uchida E, Kang E-T, Uyama Y, Ikada Y. Polymer surface with graft chains. Prog Polym Sci 2003; 28(2): 209-59.
[http://dx.doi.org/10.1016/S0079-6700(02)00032-1]
[73]
Bikram M, West JL. Thermo-responsive systems for controlled drug delivery. Expert Opin Drug Deliv 2008; 5(10): 1077-91.
[http://dx.doi.org/10.1517/17425247.5.10.1077] [PMID: 18817514]
[74]
Gupta AK, Gupta M, Yarwood SJ, Curtis ASG. Effect of cellular uptake of gelatin nanoparticles on adhesion, morphology and cytoskeleton organisation of human fibroblasts. J Control Release 2004; 95(2): 197-207.
[http://dx.doi.org/10.1016/j.jconrel.2003.11.006] [PMID: 14980768]
[75]
Ethirajan A, Schoeller K, Musyanovych A, Ziener U, Landfester K. Synthesis and optimization of gelatin nanoparticles using the miniemulsion process. Biomacromolecules 2008; 9(9): 2383-9.
[http://dx.doi.org/10.1021/bm800377w] [PMID: 18666795]
[76]
Wang H, Boerman OC, Sariibrahimoglu K, Li Y, Jansen JA, Leeuwenburgh SCG. Comparison of micro- vs. nanostructured colloidal gelatin gels for sustained delivery of osteogenic proteins: Bone morphogenetic protein-2 and alkaline phosphatase. Biomaterials 2012; 33(33): 8695-703.
[http://dx.doi.org/10.1016/j.biomaterials.2012.08.024] [PMID: 22922022]
[77]
Dombu CY, Betbeder D. Airway delivery of peptides and proteins using nanoparticles. Biomaterials 2013; 34(2): 516-25.
[http://dx.doi.org/10.1016/j.biomaterials.2012.08.070] [PMID: 23046753]
[78]
Balthasar S, Michaelis K, Dinauer N, von Briesen H, Kreuter J, Langer K. Preparation and characterisation of antibody modified gelatin nanoparticles as drug carrier system for uptake in lymphocytes. Biomaterials 2005; 26(15): 2723-32.
[http://dx.doi.org/10.1016/j.biomaterials.2004.07.047] [PMID: 15585276]
[79]
Tseng C, Wang T, Dong G, et al. Development of gelatin nanoparticles with biotinylated EGF conjugation for lung cancer targeting. Biomaterials 2007; 28(27): 3996-4005.
[http://dx.doi.org/10.1016/j.biomaterials.2007.05.006] [PMID: 17570484]
[80]
Wang H, Hansen MB, Löwik DWPM, et al. Oppositely charged gelatin nanospheres as building block for injectable and biodegradable gels. Adv Mater 2011; 23(12): H119-24.
[http://dx.doi.org/10.1002/adma.201003908]
[81]
Yan J, Miao Y, Tan H, et al. Injectable alginate/hydroxyapatite gel scaffold combined with gelatin microspheres for drug delivery and bone tissue engineering. Mater Sci Eng C 2016; 63: 274-84.
[http://dx.doi.org/10.1016/j.msec.2016.02.071] [PMID: 27040220]
[82]
Ishikawa H, Nakamura Y, Jo J, Tabata Y. Gelatin nanospheres incorporating siRNA for controlled intracellular release. Biomaterials 2012; 33(35): 9097-104.
[http://dx.doi.org/10.1016/j.biomaterials.2012.08.032] [PMID: 22985993]
[83]
Kadengodlu PA, Aigaki T, Abe H, Ito Y. Cationic cholesterol- modified gelatin as an in vitro siRNA delivery vehicle. Mol Biosyst 2013; 9(5): 965-8.
[http://dx.doi.org/10.1039/c2mb25424g] [PMID: 23303468]
[84]
Peng LH, Wei W, Qi XT, et al. Epidermal stem cells manipulated by pDNA-VEGF165/CYD-PEI nanoparticles loaded gelatin/β-TCP matrix as a therapeutic agent and gene delivery vehicle for wound healing. Mol Pharm 2013; 10(8): 3090-102.
[http://dx.doi.org/10.1021/mp400162k] [PMID: 23808658]
[85]
Pan Y, Xiao C, Tan H, et al. Covalently injectable chitosan/chondroitin sulfate hydrogel integrated gelatin/heparin microspheres for soft tissue engineering. Int J Polym Mater 2021; 70(3): 149-57.
[http://dx.doi.org/10.1080/00914037.2019.1695210]
[86]
Young S, Wong M, Tabata Y, Mikos AG. Gelatin as a delivery vehicle for the controlled release of bioactive molecules. J Control Release 2005; 109(1-3): 256-74.
[http://dx.doi.org/10.1016/j.jconrel.2005.09.023] [PMID: 16266768]
[87]
Huang Y, Onyeri S, Siewe M, Moshfeghian A, Madihally SV. in vitro characterization of chitosan–gelatin scaffolds for tissue engineering. Biomaterials 2005; 26(36): 7616-27.
[http://dx.doi.org/10.1016/j.biomaterials.2005.05.036] [PMID: 16005510]
[88]
Liu X, Ma PX. Phase separation, pore structure, and properties of nanofibrous gelatin scaffolds. Biomaterials 2009; 30(25): 4094-103.
[http://dx.doi.org/10.1016/j.biomaterials.2009.04.024] [PMID: 19481080]
[89]
Lee SB, Kim YH, Chong MS, Hong SH, Lee YM. Study of gelatin-containing artificial skin V: fabrication of gelatin scaffolds using a salt-leaching method. Biomaterials 2005; 26(14): 1961-8.
[http://dx.doi.org/10.1016/j.biomaterials.2004.06.032] [PMID: 15576170]
[90]
Fan H, Hu Y, Zhang C, et al. Cartilage regeneration using mesenchymal stem cells and a PLGA–gelatin/chondroitin/hyaluronate hybrid scaffold. Biomaterials 2006; 27(26): 4573-80.
[http://dx.doi.org/10.1016/j.biomaterials.2006.04.013] [PMID: 16720040]
[91]
Kido Y, Jo J, Tabata Y. A gene transfection for rat mesenchymal stromal cells in biodegradable gelatin scaffolds containing cationized polysaccharides. Biomaterials 2011; 32(3): 919-25.
[http://dx.doi.org/10.1016/j.biomaterials.2010.09.056] [PMID: 20947158]
[92]
Fujita N, Matsushita T, Ishida K, et al. An analysis of bone regeneration at a segmental bone defect by controlled release of bone morphogenetic protein 2 from a biodegradable sponge composed of gelatin and β-tricalcium phosphate. J Tissue Eng Regen Med 2012; 6(4): 291-8.
[http://dx.doi.org/10.1002/term.432] [PMID: 21706776]
[93]
Liu Y, Lu Y, Tian X, et al. Segmental bone regeneration using an rhBMP-2-loaded gelatin/nanohydroxyapatite/fibrin scaffold in a rabbit model. Biomaterials 2009; 30(31): 6276-85.
[http://dx.doi.org/10.1016/j.biomaterials.2009.08.003] [PMID: 19683811]
[94]
Tan H, Gong Y, Lao L, Mao Z, Gao C. Gelatin/chitosan/hyaluronan ternary complex scaffold containing basic fibroblast growth factor for cartilage tissue engineering. J Mater Sci Mater Med 2007; 18(10): 1961-8.
[http://dx.doi.org/10.1007/s10856-007-3095-5] [PMID: 17554603]
[95]
Tan H, Wu J, Lao L, Gao C. Gelatin/chitosan/hyaluronan scaffold integrated with PLGA microspheres for cartilage tissue engineering. Acta Biomater 2009; 5(1): 328-37.
[http://dx.doi.org/10.1016/j.actbio.2008.07.030] [PMID: 18723417]
[96]
Xu CY, Inai R, Kotaki M, Ramakrishna S. Aligned biodegradable nanofibrous structure: A potential scaffold for blood vessel engineering. Biomaterials 2004; 25(5): 877-86.
[http://dx.doi.org/10.1016/S0142-9612(03)00593-3] [PMID: 14609676]
[97]
Li M, Mondrinos MJ, Gandhi MR, Ko FK, Weiss AS, Lelkes PI. Electrospun protein fibers as matrices for tissue engineering. Biomaterials 2005; 26(30): 5999-6008.
[http://dx.doi.org/10.1016/j.biomaterials.2005.03.030] [PMID: 15894371]
[98]
Li M, Guo Y, Wei Y, MacDiarmid A, Lelkes P. Electrospinning polyaniline-contained gelatin nanofibers for tissue engineering applications. Biomaterials 2006; 27(13): 2705-15.
[http://dx.doi.org/10.1016/j.biomaterials.2005.11.037] [PMID: 16352335]
[99]
Lee J, Tae G, Kim YH, Park IS, Kim SH, Kim SH. The effect of gelatin incorporation into electrospun poly(l-lactide-co-ɛ-caprolactone) fibers on mechanical properties and cytocompatibility. Biomaterials 2008; 29(12): 1872-9.
[http://dx.doi.org/10.1016/j.biomaterials.2007.12.029] [PMID: 18234330]
[100]
Gámez Sazo RE, Maenaka K, Gu W, Wood PM, Bunge MB. Fabrication of growth factor- and extracellular matrix-loaded, gelatin-based scaffolds and their biocompatibility with Schwann cells and dorsal root ganglia. Biomaterials 2012; 33(33): 8529-39.
[http://dx.doi.org/10.1016/j.biomaterials.2012.07.028] [PMID: 22906605]
[101]
Hu JJ, Chao WC, Lee PY, Huang CH. Construction and characterization of an electrospun tubular scaffold for small-diameter tissue-engineered vascular grafts: A scaffold membrane approach. J Mech Behav Biomed Mater 2012; 13: 140-55.
[http://dx.doi.org/10.1016/j.jmbbm.2012.04.013] [PMID: 22854316]
[102]
Lee SJ, Liu J, Oh SH, Soker S, Atala A, Yoo JJ. Development of a composite vascular scaffolding system that withstands physiological vascular conditions. Biomaterials 2008; 29(19): 2891-8.
[http://dx.doi.org/10.1016/j.biomaterials.2008.03.032] [PMID: 18400292]