Composite Hydrogel Containting Collagen-Modified Polylactic Acid-hydroxylactic acid Copolymer Microspheres Loaded with Tetramethylpyrazine Promotes Articular Cartilage Repair.

Abstract

Articular cartilage defects pose a significant challenge due to the limited self-healing ability of cartilage. However, traditional techniques face limitations including autologous chondrocyte expansion issues. This study aims to investigate the effects of collagen-surface modified polylactic acid-glycolic acid (PLGA) microspheres (CPLGA) loaded with tetramethylpyrazine (TMP) on two cell types and the regeneration potential of articular cartilage. PLGA microspheres are fabricated using an emulsification-solvent evaporation method, followed by surface grafting of type II collagen through the Steglich reaction. Microsphere identification is performed using FTIR, XPS, and fluorescence labeling. Additionally, the protein-grafting rate, physical properties, drug loading, and drug release curves of microspheres are characterized. We evaluated the effects of TMP-loaded microspheres on the proliferation and migration of HUVEC, and examined the antioxidant capacity, angiogenesis, and apoptosis related gene expression of HUVEC, and evaluated the compatibility of blank microspheres with bone marrow mesenchymal stem cells and their potential to promote cartilage differentiation. We evaluate the compatibility of microspheres with BMSCs and their potential to promote chondrogenic differentiation. Subcutaneous implant immune tests and cartilage defect treatment are conducted to assess biocompatibility and cartilage repair potential. The results highlight the efficacy of CPLGA microspheres in promoting tissue regeneration, attributed to improved hydrophilicity and collagen-induced mitigation of degradation. Under hypoxic conditions, both CPLGA and PLGA TMP-loaded microspheres exhibit inhibitory effects on HUVEC proliferation, migration, and angiogenesis. Notably, CPLGA microspheres show enhanced compatibility with BMSCs, facilitating chondrogenic differentiation. Moreover, the CPLGA microsphere-composite hydrogel exhibits potential for cartilage repair by modulating angiogenesis and promoting BMSC differentiation. This article is protected by copyright. All rights reserved.