Abstract
The fibrotic response plays an important role in the performance and longevity of implantable devices. Thus, development of effective anti-inflammatory and anti-fibrosis biomaterial implants has become an urgent task. In this work, we developed a novel supramolecular polymer hydrogel through the copolymerization of N-acryloyl glycinamide (NAGA) and carboxybetaine acrylamide (CBAA) in the absence of any chemical crosslinker, which the mechanical properties being tunable through changing the monomer concentration and the monomer ratio over a broad scope. The hydrogel possessed the superior mechanical performances: high tensile strength (~1.13 MPa), large stretchability (~1200%), and excellent compressive strength (~9 MPa) at high monomer concentration and NAGA/CBAA ratio. Introduction of CBAA could promote the self-healability, thermoplasticity of suparmolecular polymer hydrogels at lower temperatures, meanwhile dramatically improving anti-fouling property. Histological analysis and in vitro cytotoxicity assays testified the excellent biocompatibility of the hydrogel. This high strength supramolecular polymer hydrogel with integrated multiple functions holds promising potentials as a scaffold biomaterial for treating degenerated soft supporting tissues.
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Lutolf M P, Lauer-Fields J L, Schmoekel H G, et al. Synthetic matrix metalloproteinase-sensitive hydrogels for the conduction of tissue regeneration: Engineering cell-invasion characteristics. Proc Natl Acad Sci USA, 2003, 100: 5413–5418
Benoit D S W, Schwartz M P, Durney A R, et al. Small functional groups for controlled differentiation of hydrogel-encapsulated human mesenchymal stem cells. Nat Mater, 2008, 7: 816–823
Peppas N A, Keys K B, Torres-Lugo M, et al. Poly(ethylene glycol)-containing hydrogels in drug delivery. J Control Release, 1999, 62: 81–87
Annabi N, Tamayol A, Uquillas J A, et al. 25th anniversary article: Rational design and applications of hydrogels in regenerative medicine. Adv Mater, 2014, 26: 85–124
Wang W, Sun L, Zhang P, et al. An anti-inflammatory cell-free collagen/ resveratrol scaffold for repairing osteochondral defects in rabbits. Acta Biomater, 2014, 10: 4983–4995
Qiu Y, Park K. Environment-sensitive hydrogels for drug delivery. Adv Drug Deliver Rev, 2001, 53: 321–339
Xu Z, Liu W. Poly(N-acryloyl glycinamide): a fascinating polymer that exhibits a range of properties from UCST to high-strength hydrogels. Chem Commun, 2018, 54: 10540–10553
Jiang Z C, Xiao Y Y, Kang Y, et al. Shape memory polymers based on supramolecular interactions. ACS Appl Mater Interfaces, 2017, 9: 20276–20293
Le X, Lu W, Zheng J, et al. Stretchable supramolecular hydrogels with triple shape memory effect. Chem Sci, 2016, 7: 6715–6720
Lu W, Le X, Zhang J, et al. Supramolecular shape memory hydrogels: A new bridge between stimuli-responsive polymers and supramolecular chemistry. Chem Soc Rev, 2017, 46: 1284–1294
Avula M N, Rao A N, McGill L D, et al. Modulation of the foreign body response to implanted sensor models through device-based delivery of the tyrosine kinase inhibitor, masitinib. Biomaterials, 2013, 34: 9737–9746
Nichols S P, Koh A, Brown N L, et al. The effect of nitric oxide surface flux on the foreign body response to subcutaneous implants. Biomaterials, 2012, 33: 6305–6312
Ward W K, Slobodzian E P, Tiekotter K L, et al. The effect of microgeometry, implant thickness and polyurethane chemistry on the foreign body response to subcutaneous implants. Biomaterials, 2002, 23: 4185–4192
Langer R. Perspectives and challenges in tissue engineering and regenerative medicine. Adv Mater, 2009, 21: 3235–3236
Grainger D W. All charged up about implanted biomaterials. Nat Biotechnol, 2013, 31: 507–509
Williams D F. On the mechanisms of biocompatibility. Biomaterials, 2008, 29: 2941–2953
Ye Q, Harmsen M C, van Luyn M J A, et al. The relationship between collagen scaffold cross-linking agents and neutrophils in the foreign body reaction. Biomaterials, 2010, 31: 9192–9201
Kenneth Ward W. A review of the foreign-body response to subcutaneously-implanted devices: The role of macrophages and cytokines in biofouling and fibrosis. J Diabetes Sci Technol, 2008, 2: 768–777
Swartzlander M D, Barnes C A, Blakney A K, et al. Linking the foreign body response and protein adsorption to PEG-based hydrogels using proteomics. Biomaterials, 2015, 41: 26–36
Zhang L, Cao Z, Bai T, et al. Zwitterionic hydrogels implanted in mice resist the foreign-body reaction. Nat Biotechnol, 2014, 31: 553–556
Ratner B D. Reducing capsular thickness and enhancing angiogenesis around implant drug release systems. J Control Release, 2002, 78: 211–218
Zhang Y, An D, Pardo Y, et al. High-water-content and resilient PEGcontaining hydrogels with low fibrotic response. Acta Biomater, 2017, 53: 100–108
Dai X, Zhang Y, Gao L, et al. A mechanically strong, highly stable, thermoplastic, and self-Healable supramolecular polymer hydrogel. Adv Mater, 2015, 27: 3566–3571
Yang W, Bai T, Carr L R, et al. The effect of lightly crosslinked poly (carboxybetaine) hydrogel coating on the performance of sensors in whole blood. Biomaterials, 2012, 33: 7945–7951
Yang W, Zhang L, Wang S, et al. Functionalizable and ultra stable nanoparticles coated with zwitterionic poly(carboxybetaine) in undiluted blood serum. Biomaterials, 2009, 30: 5617–5621
Carr L R, Xue H, Jiang S. Functionalizable and nonfouling zwitterionic carboxybetaine hydrogels with a carboxybetaine dimethacrylate crosslinker. Biomaterials, 2011, 32: 961–968
Chou Y N, Sun F, Hung H C, et al. Ultra-low fouling and high antibody loading zwitterionic hydrogel coatings for sensing and detection in complex media. Acta Biomater, 2016, 40: 31–37
Huang T, Liu H, Liu P, et al. Zwitterionic copolymers bearing phosphonate or phosphonic motifs as novel metal-anchorable antifouling coatings. J Mater Chem B, 2017, 5: 5380–5389
Bai T, Liu S, Sun F, et al. Zwitterionic fusion in hydrogels and spontaneous and time-independent self-healing under physiological conditions. Biomaterials, 2014, 35: 3926–3933
Rodriguez-Emmenegger C, Schmidt B V K J, Sedlakova Z, et al. Low temperature aqueous living/controlled (RAFT) polymerization of carboxybetaine methacrylamide up to high molecular weights. Macromol Rapid Commun, 2011, 32: 958–965
Wang H, Wu Y, Cui C, et al. Antifouling super water absorbent supramolecular polymer hydrogel as an artificial vitreous body. Adv Sci, 2018, 2: 1800711
Wang H, Zhu H, Fu W, et al. A high strength self-healable antibacterial and anti-inflammatory supramolecular polymer hydrogel. Macromol Rapid Commun, 2017, 38: 1600695
Bossard F, Aubry T, Gotzamanis G, et al. pH-tunable rheological properties of a telechelic cationic polyelectrolyte reversible hydrogel. Soft Matter, 2006, 2: 510–516
Xu D, Bhatnagar D, Gersappe D, et al. Rheology of Poly(N-isopropylacrylamide)-clay nanocomposite hydrogels. Macromolecules, 2015, 48: 840–846
Ren Y, Zhang Y, Sun W, et al. Methyl matters: An autonomic rapid self-healing supramolecular poly(N-methacryloyl glycinamide) hydrogel. Polymer, 2017, 126: 1–8
Roberts M, Hanson M, Massey A, et al. Dynamically restructuring hydrogel networks formed with reversible covalent crosslinks. Adv Mater, 2007, 19: 2503–2507
Song G, Zhao Z, Peng X, et al. Rheological behavior of tough PVP-in situ-PAAm hydrogels physically cross-linked by cooperative hydrogen bonding. Macromolecules, 2016, 49: 8265–8273
Gao F, Zhang Y, Li Y, et al. Sea cucumber-inspired autolytic hydrogels exhibiting tunable high mechanical performances, repairability, and reusability. ACS Appl Mater Interfaces, 2016, 8: 8956–8966
Wei Z, He J, Liang T, et al. Autonomous self-healing of poly(acrylic acid) hydrogels induced by the migration of ferric ions. Polym Chem, 2013, 4: 4601–4605
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Wang, H., Li, H., Wu, Y. et al. A high strength, anti-fouling, self-healable, and thermoplastic supramolecular polymer hydrogel with low fibrotic response. Sci. China Technol. Sci. 62, 569–577 (2019). https://doi.org/10.1007/s11431-018-9371-0
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DOI: https://doi.org/10.1007/s11431-018-9371-0