A high strength, anti-fouling, self-healable, and thermoplastic supramolecular polymer hydrogel with low fibrotic response
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摘要
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.
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.
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.
引文
1 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
2 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
3 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
4 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
5 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
6 Qiu Y,Park K.Environment-sensitive hydrogels for drug delivery.Adv Drug Deliver Rev,2001,53:321-339
7 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
8 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
9 Le X,Lu W,Zheng J,et al.Stretchable supramolecular hydrogels with triple shape memory effect.Chem Sci,2016,7:6715-6720
10 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
11 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
12 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
13 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
14 Langer R.Perspectives and challenges in tissue engineering and regenerative medicine.Adv Mater,2009,21:3235-3236
15 Grainger D W.All charged up about implanted biomaterials.Nat Biotechnol,2013,31:507-509
16 Williams D F.On the mechanisms of biocompatibility.Biomaterials,2008,29:2941-2953
17 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
18 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
19 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
20 Zhang L,Cao Z,Bai T,et al.Zwitterionic hydrogels implanted in mice resist the foreign-body reaction.Nat Biotechnol,2014,31:553-556
21 Ratner B D.Reducing capsular thickness and enhancing angiogenesis around implant drug release systems.J Control Release,2002,78:211-218
22 Zhang Y,An D,Pardo Y,et al.High-water-content and resilient PEG-containing hydrogels with low fibrotic response.Acta Biomater,2017,53:100-108
23 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
24 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
25 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
26 Carr L R,Xue H,Jiang S.Functionalizable and nonfouling zwitterionic carboxybetaine hydrogels with a carboxybetaine dimethacrylate crosslinker.Biomaterials,2011,32:961-968
27 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
28 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
29 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
30 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
31 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
32 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
33 Bossard F,Aubry T,Gotzamanis G,et al.p H-tunable rheological properties of a telechelic cationic polyelectrolyte reversible hydrogel.Soft Matter,2006,2:510-516
34 Xu D,Bhatnagar D,Gersappe D,et al.Rheology of Poly(N-isopropylacrylamide)-clay nanocomposite hydrogels.Macromolecules,2015,48:840-846
35 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
36 Roberts M,Hanson M,Massey A,et al.Dynamically restructuring hydrogel networks formed with reversible covalent crosslinks.Adv Mater,2007,19:2503-2507
37 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
38 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
39 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
2 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
3 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
4 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
5 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
6 Qiu Y,Park K.Environment-sensitive hydrogels for drug delivery.Adv Drug Deliver Rev,2001,53:321-339
7 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
8 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
9 Le X,Lu W,Zheng J,et al.Stretchable supramolecular hydrogels with triple shape memory effect.Chem Sci,2016,7:6715-6720
10 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
11 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
12 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
13 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
14 Langer R.Perspectives and challenges in tissue engineering and regenerative medicine.Adv Mater,2009,21:3235-3236
15 Grainger D W.All charged up about implanted biomaterials.Nat Biotechnol,2013,31:507-509
16 Williams D F.On the mechanisms of biocompatibility.Biomaterials,2008,29:2941-2953
17 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
18 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
19 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
20 Zhang L,Cao Z,Bai T,et al.Zwitterionic hydrogels implanted in mice resist the foreign-body reaction.Nat Biotechnol,2014,31:553-556
21 Ratner B D.Reducing capsular thickness and enhancing angiogenesis around implant drug release systems.J Control Release,2002,78:211-218
22 Zhang Y,An D,Pardo Y,et al.High-water-content and resilient PEG-containing hydrogels with low fibrotic response.Acta Biomater,2017,53:100-108
23 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
24 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
25 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
26 Carr L R,Xue H,Jiang S.Functionalizable and nonfouling zwitterionic carboxybetaine hydrogels with a carboxybetaine dimethacrylate crosslinker.Biomaterials,2011,32:961-968
27 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
28 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
29 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
30 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
31 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
32 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
33 Bossard F,Aubry T,Gotzamanis G,et al.p H-tunable rheological properties of a telechelic cationic polyelectrolyte reversible hydrogel.Soft Matter,2006,2:510-516
34 Xu D,Bhatnagar D,Gersappe D,et al.Rheology of Poly(N-isopropylacrylamide)-clay nanocomposite hydrogels.Macromolecules,2015,48:840-846
35 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
36 Roberts M,Hanson M,Massey A,et al.Dynamically restructuring hydrogel networks formed with reversible covalent crosslinks.Adv Mater,2007,19:2503-2507
37 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
38 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
39 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