Abstract
The 3D polymer network of hydrogels got immense importance because of distinctive characteristics like high water content, flexible and soft nature, biodegradable, and biocompatible behavior. These materials can be produced by physical or chemical cross-linking of the usual natural and synthetic hydrophilic polymer chains into a 3D network structure. The resemblances of hydrogels with the living body tissues make these materials to be applied extensively in the biomedical field. The present study emphasizes the main characteristics and use of hydrogels in biomedical fields. This review provides the reader with a comprehensive detail of the polymer hydrogel based inventions and products as well as perspective on future potential developments.
Similar content being viewed by others
References
Malmsten M (2011) Antimicrobial and antiviral hydrogels. Soft Matt 7(19):8725–8736
Duquette D, Dumont M-J (2019) Comparative studies of chemical crosslinking reactions and applications of bio-based hydrogels. Polym Bull 76(5):2683–2710
Khan M, Shah LA, Khan MA, Khattak NS, Zhao H (2020) Synthesis of an un-modified gum arabic and acrylic acid based physically cross-linked hydrogels with high mechanical, self-sustainable and self-healable performance. Mater Sci Eng: C 116:111278
Portnov T, Shulimzon TR, Zilberman M (2017) Injectable hydrogel-based scaffolds for tissue engineering applications. Rev Chem Eng 33(1):91–107
Ali I, Shah LA (2020) Rheological investigation of the viscoelastic thixotropic behavior of synthesized polyethylene glycol-modified polyacrylamide hydrogels using different accelerators. Polym Bull 78:1–17
Hilderbrand AM, Ford EM, Guo C, Sloppy JD, Kloxin AM (2020) Hierarchically structured hydrogels utilizing multifunctional assembling peptides for 3D cell culture. Biomater Sci 8(5):1256–1269
Eliyahu-Gross S, Bitton R (2013) Environmentally responsive hydrogels with dynamically tunable properties as extracellular matrix mimetic. Rev Chem Eng 29(3):159–168
Lim KS, Martens P, Poole-Warren L (2018) Biosynthetic hydrogels for cell encapsulation. In: Li J, Osada Y, Cooper-White J (eds) Functional hydrogels as biomaterials. Springer, Berlin, pp 1–29
Salomé Veiga A, Schneider JP (2013) Antimicrobial hydrogels for the treatment of infection. Peptide Sci 100(6):637–644
Peppas N, Hilt J, Khademhosseini A, Langer R (2006) Hydrogels in biology and medicine: from molecular principles to bionanotechnology. Adv Mater 18:1345–1360
Tibbitt MW, Anseth KS (2009) Hydrogels as extracellular matrix mimics for 3D cell culture. Biotechnol Bioeng 103(4):655–663
Censi R, Di Martino P, Vermonden T, Hennink WE (2012) Hydrogels for protein delivery in tissue engineering. J Control Rel 161(2):680–692
Seliktar D (2012) Designing cell-compatible hydrogels for biomedical applications. Science 336(6085):1124–1128
Chirila TV, Constable IJ, Crawford GJ, Vijayasekaran S, Thompson DE, Chen Y-C, Fletcher WA, Griffin BJ (1993) Poly (2-hydroxyethyl methacrylate) sponges as implant materials: in vivo and in vitro evaluation of cellular invasion. Biomaterials 14(1):26–38
Yadav N, Chauhan MK, Chauhan VS (2020) Short to ultrashort peptide-based hydrogels as a platform for biomedical applications. Biomater Sci 8(1):84–100
Chao Y, Chen Q, Liu Z (2020) Smart injectable hydrogels for cancer immunotherapy. Adv Funct Mater 30(2):1902785
Andrgie AT, Mekuria SL, Addisu KD, Hailemeskel BZ, Hsu WH, Tsai HC, Lai JY (2019) Non-anticoagulant heparin prodrug loaded biodegradable and injectable thermoresponsive hydrogels for enhanced anti-metastasis therapy. Macromol Biosci 19(5):1800409
Burdick JA, Prestwich GD (2011) Hyaluronic acid hydrogels for biomedical applications. Adv Mater 23(12):H41–H56
Sato T, Uchida R, Tanigawa H, Uno K, Murakami A (2005) Application of polymer gels containing side-chain phosphate groups to drug-delivery contact lenses. J Appl Polym Sci 98(2):731–735
Rodriguez R, Alvarez-Lorenzo C, Concheiro A (2003) Interactions of ibuprofen with cationic polysaccharides in aqueous dispersions and hydrogels. Rheological and diffusional implications. Eur J Pharm Sci 20(4–5):429–438
Zumbuehl A, Ferreira L, Kuhn D, Astashkina A, Long L, Yeo Y, Iaconis T, Ghannoum M, Fink GR, Langer R (2007) Antifungal hydrogels. Proc Natl Acad Sci 104(32):12994–12998
Bharathi K, Pazhanisamy P (2018) Synthesis and characterization of poly (N-tert-amylacrylamide-co-acrylamide/2-Acrylamido-2-methylpropanesulphonic Acid Sodium Salt) zinc oxide nanocomposite hydrogels. Chem Sci 7(3):515–521
Bahram M, Mohseni N, Moghtader M (2016) An introduction to hydrogels and some recent applications. In: Majee SB (ed) Emerging concepts in analysis and applications of hydrogels. IntechOpen, London
Li J, Mooney DJ (2016) Designing hydrogels for controlled drug delivery. Nat Rev Mater 1(12):1–17
Fujita S, Hara S, Hosono A, Sugihara S, Uematsu H, Suye S-i (2020) Hyaluronic acid hydrogel crosslinked with complementary DNAs. Adv Polym Technol 2020:1–7
Chu T-W, Feng J, Yang J, Kopeček J (2015) Hybrid polymeric hydrogels via peptide nucleic acid (PNA)/DNA complexation. J Control Rel 220:608–616
Feeney M, Giannuzzo M, Paolicelli P, Casadei MA (2007) Hydrogels of dextran containing nonsteroidal anti-inflammatory drugs as pendant agents. Drug Deliv 14(2):87–93
Schoenmakers RG, Van De Wetering P, Elbert DL, Hubbell JA (2004) The effect of the linker on the hydrolysis rate of drug-linked ester bonds. J Control Rel 95(2):291–300
Fang Y, Tan J, Lim S, Soh S (2018) Rupturing cancer cells by the expansion of functionalized stimuli-responsive hydrogels. NPG Asia Mater 10(2):e465–e465
Jones DS, Andrews GP, Caldwell DL, Lorimer C, Gorman SP, McCoy CP (2012) Novel semi-interpenetrating hydrogel networks with enhanced mechanical properties and thermoresponsive engineered drug delivery, designed as bioactive endotracheal tube biomaterials. Eur J Pharm Biopharm 82(3):563–571
Coughlan D, Corrigan O (2008) Release kinetics of benzoic acid and its sodium salt from a series of poly (N-isopropylacrylamide) matrices with various percentage crosslinking. J Pharm Sci 97(1):318–330
Jones DS, Lorimer CP, McCoy CP, Gorman SP (2008) Characterization of the physicochemical, antimicrobial, and drug release properties of thermoresponsive hydrogel copolymers designed for medical device applications. J Biomed Mater Res Part B 85(2):417–426
Jones DS, Lorimer CJ, Andrews GP, McCoy CP, Gorman SP (2007) An examination of the thermorheological and drug release properties of zinc tetraphenylporphyrin-containing thermoresponsive hydrogels, designed as light activated antimicrobial implants. Chem Eng Sci 62(4):990–999
Yoshida T, Aoyagi T, Kokufuta E, Okano T (2003) Newly designed hydrogel with both sensitive thermoresponse and biodegradability. J Polym Sci Part A 41(6):779–787
Kofron MD, Laurencin CT (2006) Bone tissue engineering by gene delivery. Adv Drug Deliv Rev 58(4):555–576
Arrington ED, Smith WJ, Chambers HG, Bucknell AL, Davino NA (1996) Complications of iliac crest bone graft harvesting. Clin Orthopaed Relat Res 329:300–309
Kondiah PJ, Choonara YE, Kondiah PP, Marimuthu T, Kumar P, Du Toit LC, Pillay V (2016) A review of injectable polymeric hydrogel systems for application in bone tissue engineering. Molecules 21(11):1580
Vo TN, Ekenseair AK, Spicer PP, Watson BM, Tzouanas SN, Roh TT, Mikos AG (2015) In vitro and in vivo evaluation of self-mineralization and biocompatibility of injectable, dual-gelling hydrogels for bone tissue engineering. J Control Rel 205:25–34
Wang D, Hu Y, Liu P, Luo D (2017) Bioresponsive DNA hydrogels: beyond the conventional stimuli responsiveness. Acc Chem Res 50(4):733–739
Reif J, Chandran H, Gopalkrishnan N, LaBean T (2012) Self-assembled DNA nanostructures and DNA Devices. Nanofabrication handbook. pp 299–328
Yongzheng Xing EC, Yang Y, Chen P, Zhang T, Sun Y, Yang Z, Liu D (2011) Self-assembled DNA hydrogels with designable thermal and enzymatic responsiveness. Adv Mater 23(9):1117–1121
Shao Y, Jia H, Cao T, Liu D (2017) Supramolecular hydrogels based on DNA self-assembly. Acc Chem Res 50(4):659–668
Rajagopalan R, Yakhmi JV (2017) Nanotechnological approaches toward cancer chemotherapy. In: Nanostructures for cancer therapy. Elsevier, pp 211–240
Zhihao Li JW, Li Y, Liu X, Yuan Q (2018) Self-assembled DNA nanomaterials with highly programmed structures and functions. Mater Chem Front 2(3):423–436
Clark DP, Pazdernik NJ (2015) Biotechnology. Newnes, London
Kong G, Xiong M, Liu L, Hu L, Meng HM, Ke G, Tan W (2021) DNA origami-based protein networks: from basic construction to emerging applications. Chem Soc Rev 50:1846–1873
Praetorius F, Kick B, Behler KL, Honemann MN, Weuster-Botz D, Dietz H (2017) Biotechnological mass production of DNA origami. Nature 552(7683):84–87
Li F, Lyu D, Liu S, Guo W (2020) DNA Hydrogels and microgels for biosensing and biomedical applications. Adv Mater 32(3):1806538
Yan F, Kuang Y, Ren B, Wang J, Zhang D, Lin H, Yang B, Zhou X, Zhou H (2018) Highly efficient A· T to G· C base editing by Cas9n-guided tRNA adenosine deaminase in rice. Mol Plant 11(4):631–634
Watson BM, Vo TN, Tatara AM, Shah SR, Scott DW, Engel PS, Mikos AG (2015) Biodegradable, phosphate-containing, dual-gelling macromers for cellular delivery in bone tissue engineering. Biomaterials 67:286–296
Ma D, An G, Liang M, Liu Y, Zhang B, Wang Y (2016) A composited PEG-silk hydrogel combining with polymeric particles delivering rhBMP-2 for bone regeneration. Mater Sci Eng: C 65:221–231
Kawata M, Azuma K, Izawa H, Morimoto M, Saimoto H, Ifuku S (2016) Biomineralization of calcium phosphate crystals on chitin nanofiber hydrogel for bone regeneration material. Carbohydr Polym 136:964–969
Cui N, Qian J, Liu T, Zhao N, Wang H (2015) Hyaluronic acid hydrogel scaffolds with a triple degradation behavior for bone tissue engineering. Carbohydr Polym 126:192–198
Rimmer S (2011) Biomedical hydrogels: biochemistry, manufacture and medical applications. Elsevier, Amsterdam
Bouten PJ, Zonjee M, Bender J, Yauw ST, van Goor H, van Hest JC, Hoogenboom R (2014) The chemistry of tissue adhesive materials. Prog Polym Sci 39(7):1375–1405
Peppas NA (2010) Biomedical applications of hydrogels handbook. Springer Science & Business Media, Berlin
Panáček A, Kvitek L, Prucek R, Kolář M, Večeřová R, Pizúrová N, Sharma VK, Tj N, Zbořil R (2006) Silver colloid nanoparticles: synthesis, characterization, and their antibacterial activity. J Phys Chem B 110(33):16248–16253
Hernández-Sierra JF, Ruiz F, Pena DCC, Martínez-Gutiérrez F, Martínez AE, Guillén AdJP, Tapia-Pérez H, Castañón GM (2008) The antimicrobial sensitivity of Streptococcus mutans to nanoparticles of silver, zinc oxide, and gold. Nanomed Nanotechnol Biol Med 4(3):237–240
Morones JR, Elechiguerra JL, Camacho A, Holt K, Kouri JB, Ramírez JT, Yacaman MJ (2005) The bactericidal effect of silver nanoparticles. Nanotechnology 16(10):2346
Panáček A, Kolář M, Večeřová R, Prucek R, Soukupova J, Kryštof V, Hamal P, Zbořil R, Kvítek L (2009) Antifungal activity of silver nanoparticles against Candida spp. Biomaterials 30(31):6333–6340
Chaloupka K, Malam Y, Seifalian AM (2010) Nanosilver as a new generation of nanoproduct in biomedical applications. Trends Biotechnol 28(11):580–588
Yu H, Xu X, Chen X, Lu T, Zhang P, Jing X (2007) Preparation and antibacterial effects of PVA-PVP hydrogels containing silver nanoparticles. J Appl Polym Sci 103(1):125–133
Zan X, Kozlov M, McCarthy TJ, Su Z (2010) Covalently attached, silver-doped poly (vinyl alcohol) hydrogel films on poly (L-lactic acid). Biomacromol 11(4):1082–1088
Thomas V, Yallapu MM, Sreedhar B, Bajpai S (2007) A versatile strategy to fabricate hydrogel–silver nanocomposites and investigation of their antimicrobial activity. J Colloid Interf Sci 315(1):389–395
Rattanaruengsrikul V, Pimpha N, Supaphol P (2009) Development of gelatin hydrogel pads as antibacterial wound dressings. Macromol Biosci 9(10):1004–1015
Singh R, Singh D (2012) Radiation synthesis of PVP/alginate hydrogel containing nanosilver as wound dressing. J Mater Sci: Mater Med 23(11):2649–2658
Marchesan S, Qu Y, Waddington LJ, Easton CD, Glattauer V, Lithgow TJ, McLean KM, Forsythe JS, Hartley PG (2013) Self-assembly of ciprofloxacin and a tripeptide into an antimicrobial nanostructured hydrogel. Biomaterials 34(14):3678–3687
De Giglio E, Cometa S, Ricci M, Cafagna D, Savino A, Sabbatini L, Orciani M, Ceci E, Novello L, Tantillo G (2011) Ciprofloxacin-modified electrosynthesized hydrogel coatings to prevent titanium-implant-associated infections. Acta Biomater 7(2):882–891
Tsou T-L, Tang S-T, Huang Y-C, Wu J-R, Young J-J, Wang H-J (2005) Poly (2-hydroxyethyl methacrylate) wound dressing containing ciprofloxacin and its drug release studies. J Mater Sci: Mater Med 16(2):95–100
Li H, Yang J, Hu X, Liang J, Fan Y, Zhang X (2011) Superabsorbent polysaccharide hydrogels based on pullulan derivate as antibacterial release wound dressing. J Biomed Mater Res Part A 98(1):31–39
Peng K-T, Chen C-F, Chu I-M, Li Y-M, Hsu W-H, Hsu RW-W, Chang P-J (2010) Treatment of osteomyelitis with teicoplanin-encapsulated biodegradable thermosensitive hydrogel nanoparticles. Biomaterials 31(19):5227–5236
Chang C-H, Lin Y-H, Yeh C-L, Chen Y-C, Chiou S-F, Hsu Y-M, Chen Y-S, Wang C-C (2009) Nanoparticles incorporated in pH-sensitive hydrogels as amoxicillin delivery for eradication of Helicobacter pylori. Biomacromol 11(1):133–142
Jiang B, Larson JC, Drapala PW, Pérez-Luna VH, Kang-Mieler JJ, Brey EM (2012) Investigation of lysine acrylate containing poly (N-isopropylacrylamide) hydrogels as wound dressings in normal and infected wounds. J Biomed Mater Res Part B 100(3):668–676
Laverty G, Gorman SP, Gilmore BF (2012) Antimicrobial peptide incorporated poly (2-hydroxyethyl methacrylate) hydrogels for the prevention of Staphylococcus epidermidis-associated biomaterial infections. J Biomed Mater Res Part A 100(7):1803–1814
Hudson SP, Langer R, Fink GR, Kohane DS (2010) Injectable in situ cross-linking hydrogels for local antifungal therapy. Biomaterials 31(6):1444–1452
Halpenny GM, Steinhardt RC, Okialda KA, Mascharak PK (2009) Characterization of pHEMA-based hydrogels that exhibit light-induced bactericidal effect via release of NO. J Mater Sci: Mater Med 20(11):2353
Huang L, Li R, Liu W, Dai J, Du Z, Wang X, Ma J, Zhao J (2014) Dynamic culture of a thermosensitive collagen hydrogel as an extracellular matrix improves the construction of tissue-engineered peripheral nerve. Neural Regener Res 9(14):1371
Cheng G, Xue H, Li G, Jiang S (2010) Integrated antimicrobial and nonfouling hydrogels to inhibit the growth of planktonic bacterial cells and keep the surface clean. Langmuir 26(13):10425–10428
Fallows SJ, Garland MJ, Cassidy CM, Tunney MM, Singh TRR, Donnelly RF (2012) Electrically-responsive anti-adherent hydrogels for photodynamic antimicrobial chemotherapy. J Photochem Photobiol B 114:61–72
Peppas N, Bures P, Leobandung W, Ichikawa H (2000) Hydrogels in pharmaceutical formulations. Eur J Pharm Biopharm 50(1):27–46
Kashyap N, Kumar N, Kumar MR (2005) Hydrogels for pharmaceutical and biomedical applications. Crit Rev Ther Drug Carr Syst 22(2):107–150
Young S, Wong M, Tabata Y, Mikos AG (2005) Gelatin as a delivery vehicle for the controlled release of bioactive molecules. J Control Rel 109(1–3):256–274
Einerson NJ, Stevens KR, Kao WJ (2003) Synthesis and physicochemical analysis of gelatin-based hydrogels for drug carrier matrices. Biomaterials 24(3):509–523
Jin C, Song W, Liu T, Xin J, Hiscox WC, Zhang J, Liu G, Kong Z (2018) Temperature and pH responsive hydrogels using methacrylated lignosulfonate cross-linker: synthesis, characterization, and properties. ACS Sust Chem Eng 6(2):1763–1771
Liu C, Zhang Z, Liu X, Ni X, Li J (2013) Gelatin-based hydrogels with β-cyclodextrin as a dual functional component for enhanced drug loading and controlled release. RSC Adv 3(47):25041–25049
Buhus G, Peptu C, Popa M, Desbrieres J (2009) Controlled release of water soluble antibiotics by carboxymethylcellulose-and gelatin-based hydrogels crosslinked with epichlorohydrin. Cellul Chem Technol 43(4):141
Hasan A, Khattab A, Islam MA, Hweij KA, Zeitouny J, Waters R, Sayegh M, Hossain MM, Paul A (2015) Injectable hydrogels for cardiac tissue repair after myocardial infarction. Adv Sci 2(11):1500122
Langer R (2007) Tissue engineering: perspectives, challenges, and future directions. J Tissue Eng 13(1):1–2
El-Sherbiny IM, Yacoub MH (2013) Hydrogel scaffolds for tissue engineering: progress and challenges. Glob Cardiol Sci Pract 3:38
Ovsianikov A, Deiwick A, Van Vlierberghe S, Dubruel P, Möller L, Dräger G, Chichkov B (2011) Laser fabrication of three-dimensional CAD scaffolds from photosensitive gelatin for applications in tissue engineering. Biomacromol 12(4):851–858
Winter GD (1962) Formation of the scab and the rate of epithelization of superficial wounds in the skin of the young domestic pig. Nature 193(4812):293–294
Barnett S, Irving S (1991) Studies of wound healing and the effect of dressings. In: High performance biomaterials. pp 583–620
Quinn K, Courtney JM, Evans J, Gaylor J, Reid W (1985) Principles of burn dressings. Biomaterials 6(6):369–377
Choi YS, Hong SR, Lee YM, Song KW, Park MH, Nam YS (1999) Studies on gelatin-containing artificial skin: II. Preparation and characterization of cross-linked gelatin-hyaluronate sponge. J Biomed Mater Res 48(5):631–639
Balakrishnan B, Mohanty M, Umashankar P, Jayakrishnan A (2005) Evaluation of an in situ forming hydrogel wound dressing based on oxidized alginate and gelatin. Biomaterials 26(32):6335–6342
Acknowledgements
The authors are highly thankful to Higher Education Commission of Pakistan for financial support under the NRPU Project No: 7309.
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Khan, S.A., Shah, L.A., Shah, M. et al. Engineering of 3D polymer network hydrogels for biomedical applications: a review. Polym. Bull. 79, 2685–2705 (2022). https://doi.org/10.1007/s00289-021-03638-5
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00289-021-03638-5