title: Injectable biocompatible and biodegradable pH-responsive hollow particle gels containing poly(acrylic acid): the effect of copolymer composition on gel properties.
abstract: The potential of various pH-responsive alkyl (meth)acrylate ester- and (meth)acrylic acid-based copolymers, including poly(methyl methacrylate-co-acrylic acid) (PMMA-AA) and poly(n-butyl acrylate-co-methacrylic acid) (PBA-MAA), to form pH-sensitive biocompatible and biodegradable hollow particle gel scaffolds for use in non-load-bearing soft tissue regeneration have been explored. The optimal copolymer design criteria for preparation of these materials have been established. Physical gels which are both pH- and redox-sensitive were formed only from PMMA-AA copolymers. MMA is the optimal hydrophobic monomer, whereas the use of various COOH-containing monomers, e.g., MAA and AA, will always induce a pH-triggered physical gelation. The PMMA-AA gels were prepared at physiological pH range from concentrated dispersions of swollen, hollow, polymer-based particles cross-linked with either cystamine (CYS) or 3,3'-dithiodipropionic acid dihydrazide (DTP). A linear relationship between particle swelling ratios, gel elasticity, and ductility was observed. The PMMA-AA gels with lower AA contents feature lower swelling ratios, mechanical strengths, and ductilities. Increasing the swelling ratio (e.g., through increasing AA content) decreased the intraparticle elasticity; however, intershell contact and gel elasticity were found to increase. The mechanical properties and performance of the gels were tuneable upon varying the copolymers' compositions and the structure of the cross-linker. Compared to PMMA-AA/CYS, the PMMA-AA/DTP gels were more elastic and ductile. The biodegradability and cytotoxicity of the new hollow particle gels were tested for the first time and related to their composition, mechanical properties, and morphology. The new PMMA-AA/CYS and PMMA-AA/DTP gels have shown good biocompatibility, biodegradability, strength, and interconnected porosity and therefore have good potential as a tissue repair agent.
authors.affiliation: Institute for Materials Research and Innovation, University of Bolton , Deane Road, Bolton, Greater Manchester, BL3 5AB, United Kingdom.
authors.forename: Silvia S
authors.initials: SS
authors.lastname: Halacheva
authors.forename: Daman J
authors.initials: DJ
authors.lastname: Adlam
authors.forename: Eseelle K
authors.initials: EK
authors.lastname: Hendow
authors.forename: Tony J
authors.initials: TJ
authors.lastname: Freemont
authors.forename: Judith
authors.initials: J
authors.lastname: Hoyland
authors.forename: Brian R
authors.initials: BR
authors.lastname: Saunders
mesh_terms: D000180:Acrylic Resins / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005782:Gels / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008968:Molecular Conformation; D010316:Particle Size; D016062:Porosity; D013329:Structure-Activity Relationship; D013499:Surface Properties
chemical_list: D000180:Acrylic Resins; D001672:Biocompatible Materials; D005782:Gels; C006903:carbopol 940