title: An anti-inflammatory cell-free collagen/resveratrol scaffold for repairing osteochondral defects in rabbits.
abstract: Inflammatory factor overexpression is the major cause of cartilage and osteochondral damage. Resveratrol (Res) is known for its anti-inflammatory, antioxidant and immunmodulatory properties. However, these effects are hampered by its water insolubility and rapid metabolism in vivo. To optimize its therapeutic efficacy in this study, Res was grafted to polyacrylic acid (PAA, 1000Da) to obtain a macromolecular drug, PAA-Res, which was then incorporated into atelocollagen (Coll) hydrogels to fabricate anti-inflammatory cell-free (Coll/Res) scaffolds with improved mechanical strengths. The Coll/Res scaffolds demonstrated the ability to capture diphenylpicrylhydrazyl free radicals. Both pure Coll and Coll/Res scaffolds could maintain their original shape for 6weeks in phosphate buffered saline. The scaffolds were degraded by collagenase over several days, and the degradation rate was slowed down by Res loading. The Coll and Coll/Res scaffolds with excellent cytocompatibility were shown to promote the proliferation and maintain the normal phenotype of the seeded chondrocytes and bone marrow stromal stem cells (BMSCs). In addition, the Coll/Res scaffold exhibited the capacity to protect the chondrocytes and BMSCs against reactive oxygen species. The acellular Coll/Res scaffolds were transplanted into the rabbit osteochondral defects. After implantation for 2, 4 and 6weeks, the samples were retrieved for quantitative real-time polymerase chain reaction, and the inflammatory related genes interleukin-1β, matrix metalloproteinases-13, COX-2 and bone and cartilage related genes SOX-9, aggrecan, Coll II and Coll I were determined. Compared with the untreated defects, the inflammatory related genes were down-regulated and those bone and cartilage related genes were up-regulated by filling the defect with an anti-inflammatory scaffold. After 12weeks, the osteochondral defects were completely repaired by the Coll/Res scaffold, and the neo-cartilage integrated well with its surrounding tissue and subchondral bone. Immunohistochemical and glycosaminoglycan staining confirmed the distribution of Coll II and glycosaminoglycans in the regenerated cartilage. The anti-inflammatory acellular Coll/Res scaffolds are convenient to administer in vivo, holding a greater potential for future clinical applications.
authors.affiliation: School of Materials Science and Engineering, Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin 300072, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: School of Materials Science and Engineering, Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin 300072, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Sun
authors.affiliation: School of Materials Science and Engineering, Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin 300072, PR China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Zhang
authors.affiliation: School of Materials Science and Engineering, Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin 300072, PR China.
authors.forename: Junfei
authors.initials: J
authors.lastname: Song
authors.affiliation: School of Materials Science and Engineering, Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin 300072, PR China. Electronic address: wgliu@tju.edu.cn.
authors.forename: Wenguang
authors.initials: W
authors.lastname: Liu
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry; D002357:Cartilage Diseases / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy*; D002474:Cell-Free System; D003131:Combined Modality Therapy / Q000295:instrumentation / Q000379:methods; D004343:Drug Implants / Q000008:administration & dosage* / Q000737:chemistry; D004867:Equipment Design; D019544:Equipment Failure Analysis; D048091:Guided Tissue Regeneration / Q000295:instrumentation*; D008422:Materials Testing; D011817:Rabbits; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage*; D054457:Tissue Scaffolds; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004343:Drug Implants; D013267:Stilbenes; D000077185:Resveratrol
keywords: Acellular; Anti-inflammation; Collagen; Osteochondral damage; Resveratrol