Skip to main content

Gelatin-based hydrogels for biomedical applications

  • Panupong Jaipan (a1), Alexander Nguyen (a2) and Roger J. Narayan (a1) (a2)

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.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Gelatin-based hydrogels for biomedical applications
      Available formats
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about sending content to Dropbox.

      Gelatin-based hydrogels for biomedical applications
      Available formats
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about sending content to Google Drive.

      Gelatin-based hydrogels for biomedical applications
      Available formats
Corresponding author
Address all correspondence to Roger J. Narayan at
Hide All
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, 141151 (2009).
2. Hennink W.E. and Van Nostrum C.F.: Novel crosslinking methods to design hydrogels. Adv. Drug Deliv. Rev. 54, 1336 (2002).
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. 7-17-14.
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, 676685 (2009).
5. Tabata Y. and Ikada Y.: Vascularization effect of basic fibroblast growth factor released from gelatin hydrogels with different biodegradabilities. Biomaterials 20, 21692175 (1999).
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, 175184 (2001).
7. Drury J.L. and Mooney D.J.: Hydrogels for tissue engineering: scaffold design variables and applications. Biomaterials 24, 43374351 (2003).
8. Coviello T., Matricardi P., Marianecci C., and Alhaique F.: Polysaccharide hydrogels for modified release formulations. J. Control. Release 119, 5– (2007).
9. Bigi A., Cojazzi G., Panzavolta S., Roveri N., and Rubini K.: Stabilization of gelatin films by crosslinking with genipin. Biomaterials 23, 48274832 (2002).
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, 312321 (2012).
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, 3138 (2000).
12. Neumann P.M., Zur B., and Ehrenreich Y.: Gelatin-based sprayable foam as a skin substitute. J. Biomed. Mater. Res. 15, 918 (1981).
13. Zhou D. and Ito Y.: Inorganic material surfaces made bioactive by immobilizing growth factors for hard tissue engineering. RSC Adv. 3, 1109511106 (2013).
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, 16771687 (1998).
15. Won Y.W. and Kim Y.H.: Recombinant human gelatin nanoparticles as a protein drug carrier. J. Control. Release 127, 154161 (2008).
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, 481495 (2003).
17. Crescenzi V., Francescangeli A., and Taglienti A.: New gelatin-based hydrogels via enzymatic networking. Biomacromolecules 3, 13841391 (2002).
18. Peppas N.A., Bures P., Leobandung W., and Ichikawa H.: Hydrogels in pharmaceutical formulations. J. Pharm. Biopharm. 50, 2746 (2000).
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, 26072617 (2012).
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, 111 (2016).
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, 484493 (2012).
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, 727746 (2016).
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, 977986 (2015).
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).
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, 354362 (2004).
26. Yeong W., Chua C., Leong K., and Chandrasekaran M.: Rapid prototyping in tissue engineering: challenges and potential. Trends Biotechnol. 22, 643652 (2004).
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, 55365544 (2010).
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, 851858 (2011).
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, 357361 (2012).
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, 31673178 (2011).
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).
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).
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).
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).
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, 9198 (2009).
36. Karageorgiou V. and Kaplan D.: Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials 26, 54745491 (2005).
37. Bose S., Roy M., and Bandyopadhyay A.: Recent advances in bone tissue engineering scaffolds. Trends Biotechnol. 30, 546554 (2012).
38. Augst A.D., Kong H.J., and Mooney D.J.: Alginate hydrogels as biomaterials. Macromol. Biosci. 6, 623633 (2006).
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, 1118511194 (2013).
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, 222234 (2010).
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, 196199 (2003).
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, 48534858 (2003).
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, 373380 (2004).
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, 417424 (2007).
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, 2031 (2013).
46. Liu X. and Ma P.X.: Phase separation, pore structure, and properties of nanofibrous gelatin scaffolds. Biomatperials 30, 40944103 (2009).
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, 12041210 (2010).
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, 17021709 (2011).
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, 654669 (2007).
50. Derby B.: Printing and prototyping of tissues and scaffolds. Science 338, 921926 (2012).
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, 4348043488 (2015).
52. Kashyap N., Kumar N., and Kumar M.: Hydrogels for pharmaceutical and biomedical applications. Crit. Rev. Ther. Drug Carrier Syst. 22, 107150 (2005).
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, 256274 (2005).
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, 509523 (2002).
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, 11991207 (1996).
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, 2504125049 (2013).
57. Rohanizadeh R., Swain M., and Mason R.J.: Gelatin sponges (Gelfoam) as a scaffold for osteoblasts. Mater. Sci., Mater. Med. 19, 11731182 (2008).
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, 331337 (2007).
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, 14171438 (2009).
60. Shastri V.P. and Lendlein A.: Materials in regenerative medicine. Adv. Mater. 21, 3233234 (2009).
61. Shastri V.P. and Lendlein A.: Engineering materials for regenerative medicine. MRS Bull. 35, 571577 (2010).
62. Engler A.J., Sen S., Sweeney H.L., and Discher D.E.: Matrix elasticity directs stem cell lineage specification. Cell 126, 677689 (2006).
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).
64. Joddar B. and Ito Y.: Artificial niche substrates for embryonic and induced pluripotent stem cell cultures. J. Biotechnol. 168, 218228 (2013).
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, 416427 (2009).
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, 1011710122 (2013).
67. Mandrycky K., Wang Z., Kim K., and Kim D-H.: 3D bioprinting for engineering complex tissues. Biotechnol. Adv. 34, 422434 (2016).
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).
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, 361371 (2007).
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, 293294 (1962).
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. 583620.
72. Quinn K.J., Courtney J.M., Evans J.H., and Gaylor J.D.S.: Principles of burn dressings. Biomaterials 6, 369377 (1985).
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, 631639 (1999).
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, 63356342 (2005).
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

MRS Communications
  • ISSN: 2159-6859
  • EISSN: 2159-6867
  • URL: /core/journals/mrs-communications
Please enter your name
Please enter a valid email address
Who would you like to send this to? *


Full text views

Total number of HTML views: 55
Total number of PDF views: 174 *
Loading metrics...

Abstract views

Total abstract views: 280 *
Loading metrics...

* Views captured on Cambridge Core between 3rd October 2017 - 17th January 2018. This data will be updated every 24 hours.