3D bioprinted porous PLLA implants with dual gene modified BMSCs for osteoarthritis cartilage repair

This study evaluated whether three-dimensional (3D) bioprinted spherical, porous poly-L-lactic acid (PLLA) drug- loaded implants, combined with bone marrow mesenchymal stem cells (BMSCs) overexpressing transforming growth factor-β1 (TGF-β1) and interleukin-10 (IL-10), can enhance the repair of osteoarthritis (OA)-related cartilage defects. Rat BMSCs were transduced with lentiviral vectors to achieve dual overexpression of TGF-β1 and IL-10, induced toward chondrogenic differentiation, and assessed for chondrogenic marker expression (COL2A1, SOX-9, and aggrecan). Spherical porous PLLA drug-loaded implants were fabricated by 3D bioprinting and characterized for drug loading, porosity, cytocompatibility, skin sensitization, biodegradation, and in vivo release behavior. Histology, micro-computed tomography (micro-CT), and molecular assays evaluated cartilage repair and subchondral bone remodeling. Dual-gene transduction markedly promoted BMSC chondrogenic differentiation with significant up-regulation of COL2A1, SOX-9, and aggrecan. The PLLA scaffolds exhibited high porosity (88.88 ± 2.87%), meeting biomaterial requirements, showed no evident cytotoxicity or skin sensitization, and achieved a 12-week mass-loss (biodegradation) of 42.65%. In vivo, the combined treatment group displayed superior cartilage regeneration and subchondral bone repair compared with controls, accompanied by increased BMP2 and type II collagen (COL-2) expression. 3D-bioprinted porous PLLA drug-loaded implants combined with TGF-β1/IL-10 dual-gene-transduced BMSCs effectively promote repair of OA cartilage defects, indicating satisfactory biocompatibility and potential for clinical translation.