title: Photo-cross-linked hydrogels from thermoresponsive PEGMEMA-PPGMA-EGDMA copolymers containing multiple methacrylate groups: mechanical property, swelling, protein release, and cytotoxicity.
abstract: Photo-cross-linked hydrogels from thermoresponsive polymers can be used as advanced injectable biomaterials via a combination of physical interaction (in situ thermal gelation) and covalent cross-links (in situ photopolymerization). This can lead to gels with significantly enhanced mechanical properties compared to non-photo-cross-linked thermoresponsive hydrogels. Moreover, the thermally phase-separated gels have attractive advantages over non-thermoresponsive gels because thermal gelation upon injection allows easy handling and holds the shape of the gels prior to photopolymerization. In this study, water-soluble thermoresponsive copolymers containing multiple methacrylate groups were synthesized via one-step deactivation enhanced atom transfer radical polymerization (ATRP) of poly(ethylene glycol) methyl ether methacrylate (PEGMEMA, M(n) = 475), poly(propylene glycol) methacrylate (PPGMA, M(n) = 375), and ethylene glycol dimethacrylate (EGDMA) and were used to form covalent cross-linked hydrogels by photopolymerization. The cross-linking density was found to have a significant influence on the mechanical and swelling properties of the photo-cross-linked gels. Release studies using lysozyme as a model protein demonstrated a sustained release profile that varied dependent on the copolymer composition, cross-linking density, and the temperature. Mouse C2C12 myoblast cells were cultured in the presence of the copolymers at concentrations up to 1 mg/mL. It was found that the majority of the cells remained viable, as assessed by Alamar Blue, lactate dehydrogenase (LDH), and Live/Dead cell viability/cytotoxicity assays. These studies demonstrate that thermoresponsive PEGMEMA-PPGMA-EGDMA copolymers offer potential as in situ photopolymerizable materials for tissue engineering and drug delivery applications through a combination of facile synthesis, enhanced mechanical properties, tunable cross-linking density, low cytotoxicity, and accessible functionality for further structure modifications.
authors.affiliation: School of Chemistry, Bangor University, Bangor, United Kingdom. h.tai@bangor.ac.uk
authors.forename: Hongyun
authors.initials: H
authors.lastname: Tai
authors.forename: Daniel
authors.initials: D
authors.lastname: Howard
authors.forename: Seiji
authors.initials: S
authors.lastname: Takae
authors.forename: Wenxin
authors.initials: W
authors.lastname: Wang
authors.forename: Tina
authors.initials: T
authors.lastname: Vermonden
authors.forename: Wim E
authors.initials: WE
authors.lastname: Hennink
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Stayton
authors.forename: Allan S
authors.initials: AS
authors.lastname: Hoffman
authors.forename: Andreas
authors.initials: A
authors.lastname: Endruweit
authors.forename: Cameron
authors.initials: C
authors.lastname: Alexander
authors.forename: Steven M
authors.initials: SM
authors.lastname: Howdle
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Shakesheff
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry*; D008689:Methacrylates / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D010777:Photochemistry; D011506:Proteins / Q000737:chemistry*; D012212:Rheology; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000180:Acrylic Resins; D020100:Hydrogels; D008689:Methacrylates; D011506:Proteins; C542326:poly(ethylene glycol) methyl ether methacrylate-co-poly(propylene glycol) methacrylate-co-poly(ethylene glycol dimethacrylate)