Hostname: page-component-745bb68f8f-lrblm Total loading time: 0 Render date: 2025-01-13T09:12:30.676Z Has data issue: false hasContentIssue false
  • English
  • Français

Gelatin-based hydrogels for biomedical applications

Published online by Cambridge University Press:  03 October 2017

Panupong Jaipan ,
Alexander Nguyen  and
Roger J. Narayan
Panupong Jaipan
Affiliation:
Department of Material Science & Engineering, North Carolina State University, Box 7907, Raleigh, NC 27695, USA
Alexander Nguyen
Affiliation:
Joint Department of Biomedical Engineering, University of North Carolina and North Carolina State University, Box 7115, Raleigh, NC 27695, USA
Roger J. Narayan*
Affiliation:
Department of Material Science & Engineering, North Carolina State University, Box 7907, Raleigh, NC 27695, USA Joint Department of Biomedical Engineering, University of North Carolina and North Carolina State University, Box 7115, Raleigh, NC 27695, USA
*
Address all correspondence to Roger J. Narayan at roger_narayan@msn.com
Get access

Abstract

Gelatin-based hydrogels derived from hydrolysis of collagen have been extensively used in pharmaceutical and medical applications because of their biocompatibility and biodegradability. For example, gelatin-based hydrogels are finding use in drug delivery and tissue engineering because they are able to promote cell adhesion and proliferation. In addition, these hydrogels can be used as wound dressings due to their attractive fluid absorbance properties. Manufacturing technologies such as ultraviolet stereolithography and two-photon polymerization can be used to prepare structures containing photosensitive gelatin-based hydrogels. This review describes the preparation of gelatin-based hydrogels and use of these materials for biomedical applications.

Type
Biomaterials for 3D Cell Biology Prospective Articles
Information
MRS Communications , Volume 7 , Issue 3 , September 2017 , pp. 416 - 426
Copyright
Copyright © Materials Research Society 2017 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Buhus, G., Peptu, C., Popa, M., and Desbrieres, J.: Controlled release of water soluble antibiotics by carboxymethylcellulose-and gelatin-based hydrogels crosslinked with epichlorohydrin. Cellulose Chem. Technol. 43, 141–151 (2009).Google Scholar
2.Hennink, W.E. and Van Nostrum, C.F.: Novel crosslinking methods to design hydrogels. Adv. Drug Deliv. Rev. 54, 13–36 (2002).Google Scholar
3.Li, J.: Biomaterials Engineering and Processing Series, Engineering Materials for Biomedical Applications, ed, Teoh, S.H., World Scientific Pub: New Jersey, 2004, Vol. 1, Chapter 7, pp. 7-1–7-14.Google Scholar
4.Williams, S.J., Wang, Q., MacGregor, R.R., Siahaan, T.J., Stehno-Bittel, L., and Berkland, C.: Adhesion of pancreatic beta cells to biopolymer films. Biopolymers 91, 676–685 (2009).Google Scholar
5.Tabata, Y. and Ikada, Y.: Vascularization effect of basic fibroblast growth factor released from gelatin hydrogels with different biodegradabilities. Biomaterials 20, 2169–2175 (1999).Google Scholar
6.Vandelli, M.A., Rivasi, F., Guerra, P., Forni, F., and Arletti, R.: Gelatin microspheres crosslinked with D, L-glyceraldehyde as a potential drug delivery system: preparation, characterization, in vitro and in vivo studies. Int. J. Pharm. 215, 175–184 (2001).Google Scholar
7.Drury, J.L. and Mooney, D.J.: Hydrogels for tissue engineering: scaffold design variables and applications. Biomaterials 24, 4337–4351 (2003).Google Scholar
8.Coviello, T., Matricardi, P., Marianecci, C., and Alhaique, F.: Polysaccharide hydrogels for modified release formulations. J. Control. Release 119, 5– (2007).Google Scholar
9.Bigi, A., Cojazzi, G., Panzavolta, S., Roveri, N., and Rubini, K.: Stabilization of gelatin films by crosslinking with genipin. Biomaterials 23, 4827–4832 (2002).Google Scholar
10.Pierce, B.F., Pittermann, E., Ma, N., Gebauer, T., Neffe, A.T., Holscher, M., Jung, F., and Lendlein, A.: Viability of Human Mesenchymal stem cells seeded on crosslinked entropy-elastic gelatin-based hydrogels. Macromol. Biosci. 12, 312–321 (2012).Google Scholar
11.Van Den Bulcke, A.I., Bogdanov, B., Rooze, N.D., Schacht, E.H., Cornelissen, M., and Berghmans, H.: Structural and Rheological properties of methacrylamide modified gelatin hydrogels. Biomacromolecules 1, 31–38 (2000).Google Scholar
12.Neumann, P.M., Zur, B., and Ehrenreich, Y.: Gelatin-based sprayable foam as a skin substitute. J. Biomed. Mater. Res. 15, 9–18 (1981).Google Scholar
13.Zhou, D. and Ito, Y.: Inorganic material surfaces made bioactive by immobilizing growth factors for hard tissue engineering. RSC Adv. 3, 11095–11106 (2013).Google Scholar
14.Draye, J.P., Delaey, B., Van de Voorde, A., Van Den Bulcke, A., De Reu, B., and Schacht, E.: In vitro and in vivo biocompatibility of dextran dialdehyde cross-linked gelatin hydrogel films. Biomaterials 19, 1677–1687 (1998).Google Scholar
15.Won, Y.W. and Kim, Y.H.: Recombinant human gelatin nanoparticles as a protein drug carrier. J. Control. Release 127, 154–161 (2008).Google Scholar
16.Chang, W.H., Chang, Y., Lai, P.H., and Sung, H.W.: A genipin-crosslinked gelatin membrane as wound-dressing material: in vitro and in vivo studies. J. Biomater. Sci., Polym. Ed. 14, 481–495 (2003).Google Scholar
17.Crescenzi, V., Francescangeli, A., and Taglienti, A.: New gelatin-based hydrogels via enzymatic networking. Biomacromolecules 3, 1384–1391 (2002).Google Scholar
18.Peppas, N.A., Bures, P., Leobandung, W., and Ichikawa, H.: Hydrogels in pharmaceutical formulations. J. Pharm. Biopharm. 50, 27–46 (2000).Google Scholar
19.Hoch, E., Schuh, C., Hirth, T., Tovar, G.E.M., and Borchers, K.: Stiff gelatin hydrogels can be photo-chemically synthesized from low viscous gelatin solutions using molecularly functionalized gelatin with a high degree of methacrylation. J. Mater. Sci. Mater. Med. 23, 2607–2617 (2012).Google Scholar
20.Shirahama, H., Lee, B.H., Tan, L.P., and Cho, N.J.: precise tuning of facile one-pot gelatin methacryloyl (GelMA) synthesis. Sci. Rep. 6, 1–11 (2016).Google Scholar
21.Pierce, B.F., Tronci, G., Roble, M., Neffe, A.T., Jung, F., and Lendlein, A.: Photocrosslinked co-networks from glycidylmethacrylated gelatin and poly(ethylene glycol) methacrylates. Macromol. Biosci. 12, 484–493 (2012).Google Scholar
22.Loessner, D., Meinert, C., Kaemmerer, E., Martine, L.C., Yue, K., Levett, P.A., Klein, T.J., Melchels, F.P.W., Khademhosseini, A., and Hutmacher, D.W.: Functionalization, preparation and use of cell-laden gelatin methacryloyl-based hydrogels as modular tissue culture platforms. Nat. Protoc. 11, 727–746 (2016).Google Scholar
23.Tsang, K.M.C., Annabi, N., Ercole, F., Zhou, K., Karst, D.J., Li, F., Haynes, J.M., Evans, R.A., Thissen, H., Khademhosseini, A., and Forsythe, J.S.: Facile one-step micropatterning using photodegradable methacrylated gelatin hydrogels for improved cardiomyocyte organization and alignment. Adv. Funct. Mater. 25, 977–986 (2015).Google Scholar
24.Wang, Z., Abdulla, R., Parker, B., Samanipour, R., Ghosh, S., and Kim, K.: A simple and high-resolution stereolithography-based 3D bioprinting system using visible light crosslinkable bioinks. Biofabrication 7, 045009 (2015).Google Scholar
25.Hutmacher, D.W., Sittinger, M., and Risbud, M.V.: Scaffold-based tissue engineering: rationale for computer-aided design and solid free-form fabrication systems. Trends Biotechnol. 22, 354–362 (2004).Google Scholar
26.Yeong, W., Chua, C., Leong, K., and Chandrasekaran, M.: Rapid prototyping in tissue engineering: challenges and potential. Trends Biotechnol. 22, 643–652 (2004).Google Scholar
27.Nichol, J.W., Koshy, S.T., Bae, H., Hwang, C.M., Yamanlar, S., and Khademhosseini, A.: Cell-laden microengineered gelatin methacrylate hydrogels. Biomaterials 31, 5536–5544 (2010).Google Scholar
28.Ovsianikov, A., Deiwick, A., Vlierberghe, S.V., Dubruel, P., Moller, L., Drager, G., and Chichkov, B.: Laser fabrication of three-dimensional CAD scaffolds from photosensitive gelatin for applications in tissue engineering. Biomacromolecules 12, 851–858 (2011).Google Scholar
29.Zalesskii, A.D., Danil'chenko, N.A., Barbashov, Y.V., Zapadinskii, B.I., and Sarkisov, O.M.: Multiphoton polymerization with the holographic control of femtosecond and continuous laser radiation. Russ. J. Phys. Chem. B 6, 357–361 (2012).Google Scholar
30.Gittard, S.D., Nguyen, A., Obata, K., Koroleva, A., Narayan, R.J., and Chichkov, B.N.: Fabrication of microscale medical devices by two-photon polymerization with multiple foci via a spatial light modulator. Biomed. Opt. Express 2, 3167–3178 (2011).Google Scholar
31.Koroleva, A., Deiwick, A., Nguyen, A., Wolter, S.S., Narayan, R., Timashev, P., Popov, V., Bagratashvili, V., and Chichkov, B.: Osteogenic differentiation of human mesenchymal stem cells in 3-D Zr-Si organic-inorganic scaffolds produced by two-photon polymerization technique. PLoS ONE 10, e0118164 (2015).Google Scholar
32.Guven, O., Sen, M., Karadag, E., and Saraydin, D.: A review on the radiation synthesis of copolymeric hydrogels for adsorption and separation purposes. Radiat. Phys. Chem. 56, 381 (1999).Google Scholar
33.Sen, M., Yakar, A., and Guven, O.: Determination of average molecular weight between cross-links (Mc) from swelling behaviors of diprotic acid-containing hydrogels. Polymer 40, 2696 (1999).Google Scholar
34.Sen, M., Uzun, C., and Guven, O.: Controlled release of terbinafine hydrochloride from pH sensitive poly (acrylamide/maleic acid) hydrogels. Int. J. Pharm. 203, 149 (2000).Google Scholar
35.Eid, M., Abdel-Ghaffar, M.A., and Dessouki, A.M.: Effect of maleic acid content on the thermal stability, swelling behavior, and network structure of gelatin-based hydrogels prepared by gamma irradiation. Nucl. Instrum. Methods Phys. Res. B 267, 91–98 (2009).Google Scholar
36.Karageorgiou, V. and Kaplan, D.: Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials 26, 5474–5491 (2005).Google Scholar
37.Bose, S., Roy, M., and Bandyopadhyay, A.: Recent advances in bone tissue engineering scaffolds. Trends Biotechnol. 30, 546–554 (2012).Google Scholar
38.Augst, A.D., Kong, H.J., and Mooney, D.J.: Alginate hydrogels as biomaterials. Macromol. Biosci. 6, 623–633 (2006).Google Scholar
39.Schlossmacher, U., Schroder, H.C., Wang, X., Feng, Q., Diehl-Seifert, B., Neumann, S., Trautwein, A., and Muller, W.E.G.: Alginate/silica composite hydrogel as a potential morphogenetically active scaffold for three-dimensional tissue engineering. RSC Adv. 3, 11185–11194 (2013).Google Scholar
40.Suarez-Gonzalez, D., Barnhart, K., Saito, E., Vanderby, R., Hollister, S.J., and Murphy, W.L.: Controlled nucleation of hydroxyapatite on alginate scaffolds for stem cell-based bone tissue engineering. J. Biomed. Mater. Res. A 95, 222–234 (2010).Google Scholar
41.Ito, A., Mase, A., Takizawa, Y., Shinkai, M., Honda, H., Hata, K.I., Ueda, M., and Kobayashi, T.: Transglutaminase-mediated gelatin matrices incorporating cell adhesion factors as a biomaterial for tissue engineering. J. Biosci. Bioeng. 95, 196–199 (2003).Google Scholar
42.Chang, C.H., Liu, H.C., Lin, C.C., Chou, C.H., and Lin, F.H.: Gelatin-chondroitin-hyaluronan tri-copolymer scaffold for cartilage tissue engineering. Biomaterials 24, 4853–4858 (2003).Google Scholar
43.Xia, W., Liu, W., Cui, L., Liu, Y., Zhong, W., Liu, D., Wu, J., Chua, K., and Cao, Y.: Tissue engineering of cartilage with the use of chitosan-gelatin complex scaffolds. J. Biomed. Mater. Res. B 71, 373–380 (2004).Google Scholar
44.Eslaminejad, M.B., Mirzadeh, H., Mohamadi, Y., and Nickmahzar, A.: Bone differentiation of marrow-derived mesenchymal stem cells using β-tricalcium phosphate-alginate-gelatin hydrid scaffolds. J. Tissue Eng. Regener. Med. 1, 417–424 (2007).Google Scholar
45.Tseng, H.J., Tsou, T.L., Wang, H.J., and Hsu, S.-H.: Characterization of chitosan-gelatin scaffolds for dermal tissue engineering. J. Tissue Eng. Regener. Med. 7, 20–31 (2013).Google Scholar
46.Liu, X. and Ma, P.X.: Phase separation, pore structure, and properties of nanofibrous gelatin scaffolds. Biomatperials 30, 4094–4103 (2009).Google Scholar
47.Meng, Z.X., Wang, Y.S., Ma, C., Zheng, W., Li, L., and Zheng, Y.F.: Electrospining of PLGA/gelatin randomly-oriented and aligned nanofibers as potential scaffolds in tissue engineering. Mater. Sci. Eng. C 30, 1204–1210 (2010).Google Scholar
48.Panzavolta, S., Gioffre, M., Focarete, M.L., Gualandi, C., Foroni, L., and Bigi, A.: Electrospun gelatin nanofibers: optimization of genipin cross-linking to preserve fiber morphology after exposure to water. Acta Biomater. 7, 1702–1709 (2011).Google Scholar
49.Hutmacher, D.W. and Cool, S.: Concepts of scaffold-based tissue engineering-the rationale to use solid free-form fabrication techniques. J. Cell. Mol. Med. 11, 654–669 (2007).Google Scholar
50.Derby, B.: Printing and prototyping of tissues and scaffolds. Science 338, 921–926 (2012).Google Scholar
51.Luo, Y., Lode, A., Akkineni, A.R., and Gelinsky, M.: Concentrated gelatin/alginate composites for fabrication of predesigned scaffolds with a favorable cell response by 3D plotting. RSC Adv. 5, 43480–43488 (2015).Google Scholar
52.Kashyap, N., Kumar, N., and Kumar, M.: Hydrogels for pharmaceutical and biomedical applications. Crit. Rev. Ther. Drug Carrier Syst. 22, 107–150 (2005).Google Scholar
53.Young, S., Wong, M., Tabata, Y., and Mikos, A.G.: Gelatin as a delivery vehicle for the controlled release of bioactive molecule. J. Control. Release 109, 256–274 (2005).Google Scholar
54.Einerson, N.J., Stevens, K.R., and Kao, W.J.: Synthesis and physicochemical analysis of gelatin-based hydrogels for drug carrier matrices. Biomaterials 24, 509–523 (2002).Google Scholar
55.Rathna, G.V.N., Mohan Rao, D.V., and Chatterji, P.R.: Hydrogels of gelatin-sodium carboxymethyl cellulose: synthesis and swelling kinetics. J. Mater Sci., Pure Appl. Chem. A33, 1199–1207 (1996).Google Scholar
56.Liu, C., Zhang, Z., Liu, X., Ni, X., and Li, J.: Gelatin-based hydrogels with β-cyclodextrin as a dual functional component for enhanced drug loading and controlled release. RSC Adv. 3, 25041–25049 (2013).Google Scholar
57.Rohanizadeh, R., Swain, M., and Mason, R.J.: Gelatin sponges (Gelfoam) as a scaffold for osteoblasts. Mater. Sci., Mater. Med. 19, 1173–1182 (2008).Google Scholar
58.Van Vlierberghe, S., Cnudde, V., Dubruel, P., Masschaele, B., Cosijns, A., De Paepe, I., Jacobs, P.J.S., Van Hoorebeke, L., Remon, J.P., and Schacht, E.: Porous gelatin hydrogels: 1. Cryogenic formation and structure analysis. Biomacromolecules 8, 331–337 (2007).Google Scholar
59.Van Vlierberghe, S., Dubruel, P., Lippens, E., Cornelissen, M., and Schacht, E.: Correlation between cryogenic parameters and physico-chemical properties of porous gelatin cryogels. J. Biomater. Sci., Polym. Ed. 20, 1417–1438 (2009).Google Scholar
60.Shastri, V.P. and Lendlein, A.: Materials in regenerative medicine. Adv. Mater. 21, 323–3234 (2009).Google Scholar
61.Shastri, V.P. and Lendlein, A.: Engineering materials for regenerative medicine. MRS Bull. 35, 571–577 (2010).Google Scholar
62.Engler, A.J., Sen, S., Sweeney, H.L., and Discher, D.E.: Matrix elasticity directs stem cell lineage specification. Cell 126, 677–689 (2006).Google Scholar
63.Nava, M.M., Raimondi, M.T., Credi, C., Marco, C.D., Turri, S., Cerullo, G., and Osellame, R.: Interactions between structural and chemical biomimetism in synthetic stem cell niches. Biomed. Mater. 10, 015012 (2015).Google Scholar
64.Joddar, B. and Ito, Y.: Artificial niche substrates for embryonic and induced pluripotent stem cell cultures. J. Biotechnol. 168, 218–228 (2013).Google Scholar
65.Angele, P., Muller, R., Schumann, D., Englert, C., Zellner, J., Johnstone, B., Yoo, J., Hammer, J., Fierlbeck, J., Anglle, M.K., Nerlich, M., and Kujat, R.: Characterization of esterified hyaluronan-gelatin polymer composites suitable for chondrogenic differentiation of mesenchymal stem cells. J. Biomed. Mater. Res. A 91A, 416–427 (2009).Google Scholar
66.Bian, L., Guvendiren, M., Mauck, R.L., and Burdick, J.A.: Hydrogels that mimic developmentally relevant matrix and N-Cadherin interactions enhance MSC chondrogenesis. Proc. Natl. Acad. Sci. USA 110, 10117–10122 (2013).Google Scholar
67.Mandrycky, K., Wang, Z., Kim, K., and Kim, D-H.: 3D bioprinting for engineering complex tissues. Biotechnol. Adv. 34, 422–434 (2016).Google Scholar
68.Akkineni, A.R., Ahlfeld, T., Lode, A., and Gelinsky, M.: A versatile method for combining different biopolymers in a core/shell fashion by 3D plotting to achieve mechanically robust constructs. Biofabrication 8, 045001 (2016).Google Scholar
69.Moroni, L., Hendriks, J.A.A., Schotel, R., de Wijn, J.R., and van Blitterswijk, C.A.: Design of biphasic polymeric 3-dimensional fiber deposited scaffolds for cartilage tissue engineering applications. Tissue Eng. 13, 361–371 (2007).Google Scholar
70.Winter, G.D.: Formation of the scab and the rate of epithelialization of superficial wounds in the skin of the young domestic pig. Nature 193, 293–294 (1962).Google Scholar
71.Barnett, S.E. and Irving, S.J.: Studies of wound healing and the effect of dressings. In High Performance Biomaterials, Szycher, M., ed, Technonic: Lancaster; 1991. pp. 583–620.Google Scholar
72.Quinn, K.J., Courtney, J.M., Evans, J.H., and Gaylor, J.D.S.: Principles of burn dressings. Biomaterials 6, 369–377 (1985).Google Scholar
73.Choi, Y.S., Hong, S.R., Lee, Y.M., Song, K.W., Park, H.M., and Nam, Y.S.: Studies on gelatin-containing artificial skin: II. Preparation and characterization of crosslinked gelatin-hyaluronate sponge. J. Biomed. Mater. Res. (Appl. Biomater.) 48, 631–639 (1999).Google Scholar
74.Balakrishnan, B., Mohanty, M., Umashankar, P.R., and Jayakrishnan, A.: Evaluation of an in situ forming hydrogel wound dressing based on oxidized alginate and gelatin. Biomaterials 26, 6335–6342 (2005).Google Scholar