A review of hydrogel-based composites for biomedical applications: enhancement of hydrogel properties by addition of rigid inorganic fillers
Source abstract
Abstract
There is a growing demand for three-dimensional scaffolds for expanding applications in regenerative medicine, tissue engineering, and cell culture techniques. The material requirements for such three-dimensional structures are as diverse as the applications themselves. A wide range of materials have been investigated in the recent decades in order to tackle these requirements and to stimulate the anticipated biological response. Among the most promising class of materials are inorganic/organic hydrogel composites for regenerative medicine. The generation of synergetic effects by hydrogel composite systems enables the design of materials with superior properties including biological performance, stiffness, and degradation behavior in vitro and in vivo. Here, we review the most important organic and inorganic materials used to fabricate hydrogel composites. We highlight the advantages of combining different materials with respect to their use for biofabrication and cell encapsulation as well as their application as injectable materials for tissue enhancement and regeneration.
Source: openaire · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: 3D Printing in Biomedical Research · Bone Tissue Engineering Materials · Hydrogels: synthesis, properties, applications
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (100+)
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1. Lodish H, Berk A, Zipursky LS, Matsudaira P, Baltimore D, Darnell JE (2002) Molecular cell biology. W.H. Freemann and Company, New York
2. Lee J, Cuddihy MJ, Kotov NA (2008) Three-dimensional cell culture matrices: state of the art. Tissue Eng Part B Rev 14:61–8610.1089/teb.2007.0150 ↗
3. Huh D, Hamilton GA, Ingber DE (2011) From 3D cell culture to organs-on-chips. Trends Cell Biol 21:745–75410.1016/j.tcb.2011.09.005 ↗
4. Haycock JW (2011) 3D cell culture. Springer Science and Business Media, New York10.1007/978-1-60761-984-0 ↗
5. Gaharwar AK, Peppas NA, Khademhosseini A (2014) Nanocomposite hydrogels for biomedical applications. Biotechnol Bioeng 111:441–45310.1002/bit.25160 ↗
6. Rezwan K, Chen QZ, Blaker JJ, Boccaccini AR (2006) Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering. Biomaterials 27:3413–343110.1016/j.biomaterials.2006.01.039 ↗
7. Carrow JK, Gaharwar AK (2015) Bioinspired polymeric nanocomposites for regenerative medicine. Macromol Chem Phys 216:248–26410.1002/macp.201400427 ↗
8. Vashist A, Ahmad S (2015) Hydrogels in tissue engineering: scope and applications. Curr Pharm Biotechnol 16:606–62010.2174/138920101607150427111651 ↗
9. Orive G, Hernández RM, Gascón AR, Calafiore R, Chang TMS, de Vos P, Hortelano G, Hunkeler D, Lacík I, Shapiro AMJ, Pedraz JL (2003) Cell encapsulation: promise and progress. Nat Med 9:104–10710.1038/nm0103-104 ↗
10. Uludag H, de Vos P, Tresco PA (2000) Technology of mammalian cell encapsulation. Adv Drug Deliv Rev 42:29–6410.1016/S0169-409X(00)00053-3 ↗
11. Hunt NC, Grover LM (2010) Cell encapsulation using biopolymer gels for regenerative medicine. Biotechnol Lett 32:733–74210.1007/s10529-010-0221-0 ↗
12. Zhao X, Kim J, Cezar CA, Huebsch N, Lee K, Bouhadir K, Mooney DJ (2011) Active scaffolds for on-demand drug and cell delivery. Proc Natl Acad Sci USA 108:67–7210.1073/pnas.1007862108 ↗
13. Cezar CA, Kennedy SM, Mehta M, Weaver JC, Gu L, Vandenburgh H, Mooney DJ (2014) Biphasic ferrogels for triggered drug and cell delivery. Adv Healthc Mater 3:1869–187610.1002/adhm.201400095 ↗
14. Ferris CJ, Gilmore KG, Wallace GG, In Het Panhuis M (2013) Biofabrication: an overview of the approaches used for printing of living cells. Appl Microbiol Biotechnol 97:4243–425810.1007/s00253-013-4853-6 ↗
15. Ivanova O, Williams C, Campbell T (2013) Additive manufacturing (AM) and nanotechnology: promises and challenges. Rapid Prototyp J 19:353–36410.1108/RPJ-12-2011-0127 ↗
16. Liu Y, Kim E, Ghodssi R, Rubloff GW, Culver JN, Bentley WE, Payne GF (2010) Biofabrication to build the biology-device interface. Biofabrication 2:02200210.1088/1758-5082/2/2/022002 ↗
17. Billiet T, Vandenhaute M, Schelfhout J, vanVlierberghe S, Dubruel P (2012) A review of trends and limitations in hydrogel-rapid prototyping for tissue engineering. Biomaterials 33:6020–604110.1016/j.biomaterials.2012.04.050 ↗
18. Schexnailder P, Schmidt G (2009) Nanocomposite polymer hydrogels. Colloid Polym Sci 287:1–1110.1007/s00396-008-1949-0 ↗
19. Thoniyot P, Tan MJ, Karim AA, Young DJ, Loh XJ (2015) Nanoparticle-hydrogel composites: concept, design, and applications of these promising, multi-functional materials. Adv Sci. doi:10.1002/advs.20140001010.1002/advs.201400010 ↗
20. Kretlow JD, Mikos AG (2007) Review: mineralization of synthetic polymer scaffolds for bone tissue engineering. Tissue Eng 13:927–93810.1089/ten.2006.0394 ↗
21. Sanchez C, Julián B, Belleville P, Popall M (2015) Applications of hybrid organic-inorganic nanocomposites. J Mater Chem 15:3559–359210.1039/b509097k ↗
22. Hule RA, Pochan DJ (2007) Polymer nanocomposites for biomedical applications. MRS Bull 32:354–35810.1557/mrs2007.235 ↗
23. Boccaccini AR, Erol M, Stark WJ, Mohn D, Hong Z, Mano JF (2010) Polymer/bioactive glass nanocomposites for biomedical applications: a review. Compos Sci Technol 70:1764–177610.1016/j.compscitech.2010.06.002 ↗
24. Peppas NA, Hilt JZ, Khademhosseini A, Langer R (2006) Hydrogels in biology and medicine: from molecular principles to bionanotechnology. Adv Mater 18:1345–136010.1002/adma.200501612 ↗
25. Hoffman AS (2002) Hydrogels for biomedical applications. Adv Drug Deliv Rev 54:3–1210.1016/S0169-409X(01)00239-3 ↗
26. Annabi N, Tamayol A, Uquillas JA, Akbari M, Bertassoni LE, Cha C, Camci-Unal G, Dokmeci MR, Peppas NA, Khademhosseini A (2014) 25th anniversary article: rational design and applications of hydrogels in regenerative medicine. Adv Mater 26:85–12410.1002/adma.201303233 ↗
27. de las Heras Alarcón C, Pennadam S, Alexander C (2005) Stimuli responsive polymers for biomedical applications. Chem Soc Rev 34:276–28510.1039/b406727d ↗
28. Jeong B, Gutowska A (2002) Lessons from nature: stimuli-responsive polymers and their biomedical applications. Trends Biotechnol 20:305–31110.1016/S0167-7799(02)01962-5 ↗
29. Huebsch N, Kearney CJ, Zhao X, Kim J, Cezar CA, Suo Z, Mooney DJ (2014) Ultrasound-triggered disruption and self-healing of reversibly cross-linked hydrogels for drug delivery and enhanced chemotherapy. Proc Natl Acad Sci USA 111:9762–976710.1073/pnas.1405469111 ↗
30. Kennedy S, Bencherif S, Norton D, Weinstock L, Mehta M, Mooney DJ (2014) Rapid and extensive collapse from electrically responsive macroporous hydrogels. Adv Healthc Mater 3:500–50710.1002/adhm.201300260 ↗
31. Kearney CJ, Skaat H, Kennedy SM, Hu J, Darnell M, Raimondo TM, Mooney DJ (2015) Switchable release of entrapped nanoparticles from alginate hydrogels. Adv Healthc Mater 4:1634–163910.1002/adhm.201500254 ↗
32. Drury JL, Mooney DJ (2003) Hydrogels for tissue engineering: scaffold design variables and applications. Biomaterials 24:4337–435110.1016/S0142-9612(03)00340-5 ↗
33. Kim JK, Kim HJ, Chung JY, Lee JH, Young SB, Kim YH (2014) Natural and synthetic biomaterials for controlled drug delivery. Arch Pharm Res 37:60–6810.1007/s12272-013-0280-6 ↗
34. Seliktar D (2012) Designing cell-compatible hydrogels for biomedical applications. Science 336:1124–112810.1126/science.1214804 ↗
35. Engel J, Bächinger HP (2005) Structure, stability and folding of the collagen triple helix. Top Curr Chem 247:7–3310.1007/b103818 ↗
36. Walters BD, Stegemann JP (2014) Strategies for directing the structure and function of three-dimensional collagen biomaterials across length scales. Acta Biomater 10:1488–150110.1016/j.actbio.2013.08.038 ↗
37. Fratzl P, Misof K, Zizak I, Rapp G, Amenitsch H, Bernstorff S (1997) Fibrillar structure and mechanical properties of collagen. J Struct Biol 122:119–12210.1006/jsbi.1998.3966 ↗
38. White DJ, Puranen S, Johnson MS, Heino J (2004) The collagen receptor subfamily of the integrins. Inter J Biochem Cell Biol 36:1405–141010.1016/j.biocel.2003.08.016 ↗
39. Heino J (2000) The collagen receptor integrins have distinct ligand recognition and signaling functions. Matrix Biol 19:319–32310.1016/S0945-053X(00)00076-7 ↗
40. Brown RA, Wiseman M, Chuo CB, Cheema U, Nazhat SN (2005) Ultrarapid engineering of biomimetic materials and tissues: fabrication of nano- and microstructures by plastic compression. Adv Funct Mater 15:1762–177010.1002/adfm.200500042 ↗
41. Bitar M, Salih V, Brown RA, Nazhat SN (2007) Effect of multiple unconfined compression on cellular dense collagen scaffolds for bone tissue engineering. J Mater Sci Mater Med 18:237–24410.1007/s10856-006-0685-1 ↗
42. Hu X, Cebe P, Weiss AS, Omenetto F, Kaplan DL (2012) Protein-based composite materials. Mater Today 15:208–21510.1016/S1369-7021(12)70091-3 ↗
43. Sarker B, Lyer S, Arkudas A, Boccaccini AR (2013) Collagen/silica nanocomposites and hybrids for bone tissue engineering. Nanotechnol Rev 2:427–44710.1515/ntrev-2013-0012 ↗
44. Allison DD, Grande-Allen KJ (2006) Hyaluronan: a powerful tissue engineering tool. Tissue Eng 12:2131–214010.1089/ten.2006.12.2131 ↗
45. Burdick JA, Prestwich GD (2011) Hyaluronic acid hydrogels for biomedical applications. Adv Healtc Mater 23:H41–H5610.1002/adma.201003963 ↗
46. Burdick JA, Chung C, Jia X, Randolph MA, Langer R (2005) Controlled degradation and mechanical behavior of photopolymerized hyaluronic acid networks. Biomacromolecules 6:386–39110.1021/bm049508a ↗
47. Kuo JW, Prestwich GD (2010) Hyaluronic acid. In: Materials of biological origin—materials analysis and implant uses, comprehensive biomaterials. Elsevier10.1016/B978-0-08-055294-1.00073-8 ↗
48. Augst AD, Kong HJ, Mooney DJ (2006) Alginate hydrogels as biomaterials. Macromol Biosci 6:623–63310.1002/mabi.200600069 ↗
49. Draget KI, Skjåk-Bræk G, Smidsrød O (1997) Alginate based new materials. Int J Biol Macromol 21:47–5510.1016/S0141-8130(97)00040-8 ↗
50. Kong HJ, Kaigler D, Kim K, Mooney DJ (2004) Controlling rigidity and degradation of alginate hydrogels via molecular weight distribution. Biomacromolecules 5:1720–172710.1021/bm049879r ↗
51. Bouhadir KH, Lee KY, Alsberg E, Damm KL, Anderson KW, Mooney DJ (2001) Degradation of partially oxidized alginate and its potential application for tissue engineering. Biotechnol Prog 17:945–95010.1021/bp010070p ↗
52. Sarker B, Papageorgiou DG, Silva R, Zehnder T, Gul-E-Noor F, Bertmer M, Kaschta J, Chrissafis K, Detsch R, Boccaccini AR (2014) Fabrication of alginate-gelatin crosslinked hydrogel microcapsules and evaluation of the microstructure and physic-chemical properties. J Mater Chem B 2:1470–148210.1039/c3tb21509a ↗
53. Venkatesan J, Bhatnagar I, Manivasagan P, Kang KH, Kim SK (2015) Alginate composites for bone tissue engineering: a review. Int J Biol Macromol 72:269–28110.1016/j.ijbiomac.2014.07.008 ↗
54. Balakrishnan B, Jayakrishnan A (2005) Self-cross-linking biopolymers as injectable in situ forming biodegradable scaffolds. Biomaterials 26:3941–395110.1016/j.biomaterials.2004.10.005 ↗
55. Liao H, Zhang H, Chen W (2009) Differential physical, rheological, and biological properties of rapid in situ gelable hydrogels composed of oxidized alginate and gelatin derived from marine or porcine sources. J Mater Sci Mater Med 20:1263–127110.1007/s10856-009-3694-4 ↗
56. Sarker B, Singh R, Silva R, Roether JA, Kaschta J, Detsch R, Schubert DW, Cicha I, Boccaccini AR (2014) Evalulation of fibroblasts adhesion and proliferation on alginate-gelatin crosslinked hydrogels. PLoS One 9:e10795210.1371/journal.pone.0107952 ↗
57. Grigore A, Sarker B, Fabry B, Boccaccini AR, Detsch R (2014) Behavior of encapsulated MG-63 cells in RGD and gelatine-modified alginate hydrogels. Tissue Eng Part A 20:2140–215010.1089/ten.tea.2013.0416 ↗
58. Rowley JA, Madlambayan G, Mooney DJ (1999) Alginate hydrogels as synthetic extracellular matrix material. Biomaterials 20:45–5310.1016/S0142-9612(98)00107-0 ↗
59. Hill SE, Ledward DA, Mitchell JR (1998) Functional properties of food macromolecules. Springer, Berlin
60. Park H, Park K, Shalaby WSW (2011) Biodegradable hydrogels for drug delivery. CRC Press, Boca Raton
61. Atala A, Mooney DJ (2013) Synthetic biodegradable polymer scaffolds. Springer, New York
62. Pluen A, Netti PA, Jain RK, Berk DA (1999) Diffusion of macromolecules in agarose gels: comparison of linear and globular configuarations. Biophys J 77:542–55210.1016/S0006-3495(99)76911-0 ↗
63. Pernodet N, Maaloum M, Tinland B (1997) Pore size of agarose gels by atomic force microscopy. Electrophoresis 18:55–5810.1002/elps.1150180111 ↗
64. Wang H, Hansen MB, Löwik DWPM, van Hest JCM, Li Y, Jansen JA, Leeuwenburgh SCG (2011) Oppositely charged gelatin nanospheres as building blocks for injectable and biodegradable gels. Adv Healthc Mater 23:H119–H12410.1002/adma.201003908 ↗
65. Boanini E, Bigi A (2011) Biomimetic gelatin–octacalcium phosphate core–shell microspheres. J Colloid Interface Sci 362:594–59910.1016/j.jcis.2011.06.061 ↗
66. Bigi A, Panzavolta S, Rubini K (2004) Relationship between triple-helix content and mechanical properties of gelatin films. Biomaterials 25:5675–568010.1016/j.biomaterials.2004.01.033 ↗
67. Ross-Murphy SB (1992) Structure and rheology of gelatin gels: recent progress. Polymer 33:2622–262710.1016/0032-3861(92)91146-S ↗
68. Pezron I, Djabourov M, Leblond J (1991) Conformation of gelatin chains in aqueous solutions: 1. A light and small-angle neutron scattering study. Polymer 32:3201–321010.1016/0032-3861(91)90143-7 ↗
69. Fialho AM, Moreira LM, Granja AT, Popescu AO, Hoffmann K, Sá-Correia I (2008) Occurrence, production, and application of gellan: current state and perspectives. Appl Microbiol Biotechnol 79:889–90010.1007/s00253-008-1496-0 ↗
70. Giavasis I, Harvey LM, McNeil B (2000) Gellan gum. Crit Rev Biotechnol 20:177–21110.1080/07388550008984169 ↗
71. Madihally SV, Matthew HWT (1999) Porous chitosan scaffolds for tissue engineering. Biomaterials 20:1133–114210.1016/S0142-9612(99)00011-3 ↗
72. Suh JKF, Matthew HWT (2000) Application of chitosan-based polysaccharide biomaterials in cartilage tissue engineering: a review. Biomaterials 21:2589–259810.1016/S0142-9612(00)00126-5 ↗
73. Chandy T, Sharma CP (1990) Chitosan-as a biomaterial. Biomater Artif Cells Artif Organs 18:1–2410.3109/10731199009117286 ↗
74. Kleinman HK, Martin GR (2005) Matrigel: basement membrane matrix with biological activity. Semin Cancer Biol 15:378–38610.1016/j.semcancer.2005.05.004 ↗
75. Hughes CS, Postovit LM, Lajoie GA (2010) Matrigel: a complex protein mixture required for optimal growth of cell culture. Proteomics 10:1886–189010.1002/pmic.200900758 ↗
76. Daamen WF, Veerkamp JH, van Hest JC, van Kuppevelt TH (2007) Elastin as a biomaterial for tissue engineering. Biomaterials 28:4378–439810.1016/j.biomaterials.2007.06.025 ↗
77. Kundu S (2014) Silk biomaterials for tissue engineering and regenerative medicine. Woodhead Publishing, Cambridge
78. Chang C, Zhang L (2011) Cellulose-based hydrogels: present status and application prospects. Carbohydr Polym 84:40–5310.1016/j.carbpol.2010.12.023 ↗
79. Chien KB, Chung EJ, Shah RN (2014) Investigation of soy protein hydrogels for biomedical applications: materials characterization, drug release, and biocompatibility. J Biomater Appl 28:1085–109610.1177/0885328213497413 ↗
80. Paliwal R, Palakurthi S (2014) Zein in controlled drug delivery and tissue engineering. J Control Release 189:108–12210.1016/j.jconrel.2014.06.036 ↗
81. Bailey FE, Koleske JV (2012) Poly(ethylene oxide). Elsevier, London
82. Ulery BD, Nair LS, Laurencin CT (2011) Biomedical applications of biodegradable polymers. J Polym Sci Part B 49:832–86410.1002/polb.22259 ↗
83. Helmy R (2012) Biotechnology—molecular studies and novel applications for improved quality of human life. InTech
84. Lin CC, Anseth KS (2008) PEG hydrogels for the controlled release of biomolecules in regenerative medicine. Pharm Res 26:631–64310.1007/s11095-008-9801-2 ↗
85. Falco EE, Patel M, Fisher JP (2008) Recent developments in cyclic acetal biomaterials for tissue engineering applications. Pharm Res 25:2348–235610.1007/s11095-008-9620-5 ↗
86. Betz MW, Modi PC, Caccamese JF, Coletti DP, Sauk JJ, Fisher JP (2008) Cyclic acetal hydrogel system for bone marrow stromal cell encapsulation and osteodifferentiation. J Biomed Mater Res A 86:662–67010.1002/jbm.a.31640 ↗
87. Lee KY, Mooney DJ (2001) Hydrogels for tissue engineering. Chem Rev 101:1869–187910.1021/cr000108x ↗
88. Lu S, Anseth KS (1999) Photopolymerization of multilaminated poly(HEMA) hydrogels for controlled release. J Control Release 57:291–30010.1016/S0168-3659(98)00125-4 ↗
89. Meyvis TKL, De Smedt SC, Demester J (2000) Influence of the degradation mechanism of hydrogels on their elastic and swelling properties during degradation. Macromolecules 33:4717–472510.1021/ma992131u ↗
90. Schild HG (1992) Poly(N-isopropylacrylamide): experiment, theory and application. Prog Polym Sci 17:163–24910.1016/0079-6700(92)90023-R ↗
91. Seiffert S, Weitz DA (2010) Microfluidic fabrication of smart microgels from macromolecular precursors. Polymer 51:5883–588910.1016/j.polymer.2010.10.034 ↗
92. Galaec IY, Mattiasson B (1999) “Smart” polymers and what they could do in biotechnology and medicine. Trends Biotechnol 17:335–34010.1016/S0167-7799(99)01345-1 ↗
93. Cooper SL, Bamford CH, Tsuruta T (1995) Polymer biomaterials in solution, as interfaces and as solids. Springer, New York
94. Nichol JW, Koshy ST, Bae H, Hwang CM, Yamanlar S, Khademhosseini A (2010) Cell-laden microengineered gelatin methacrylate hydrogels. Biomaterials 31:5536–554410.1016/j.biomaterials.2010.03.064 ↗
95. Van Vlierberghe S, Dubruel P, Schacht E (2011) Biopolymer-based hydrogels as scaffolds for tissue engineering applications: a review. Biomacromolecules 12:1387–140810.1021/bm200083n ↗
96. Yoshida T, Lai TC, Kwon GS, Sako K (2013) pH- and ion-sensitive polymers for drug delivery. Expert Opin Drug Deliv 10:1497–151310.1517/17425247.2013.821978 ↗
97. Bourges X, Weiss P, Daculsi G, Legeay G (2002) Synthesis and general properties of silated-hydroxypropyl methylcellulose in prospect of biomedical use. Adv Colloid Interface Sci 99:215–22810.1016/S0001-8686(02)00035-0 ↗
98. Engineer C, Parikh J, Raval A (2011) Review on hydrolytic degradation behavior of biodegradable polymers from controlled drug delivery system. Trends Biomater Artif Organs 25:79–85
99. Lyu SP, Untereker D (2009) Degradability of polymers from implantable biomedical devices. Int J Mol Sci 10:4033–406510.3390/ijms10094033 ↗
100. Kilpadi KL, Chang PL, Bellis SL (2001) Hydroxylapatite binds more serum proteins, purified integrins, and osteoblast precursor cells than titanium or steel. J Biomed Mater Res 57:258–26710.1002/1097-4636(200111)57:2<258::AID-JBM1166>3.0.CO;2-R ↗