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

Keywords:

3D bioprinting, Poly-L-lactic acid, Bone marrow mesenchymal stem cells, Osteoarthritis, Cartilage defect.


Published online: Oct 08 2026

https://doi.org/10.52628/92.3.15610

LIU T.1, ZHANG S.2, WANG B.3, MEI Z.4, XIAO G.5, HE H.4, ZHAO Y.2, WU S.-Y.6, YANG Z.7, DU K.8, LIU P.9,10

1School of Biomedicine and Nursing (Shandong Institute of Petroleum and Chemical Technology), Dongying, 257097, PR China
2School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China
3Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai 264200, China
4Guangzhou Punoshi Biotechnology Co., Ltd., Guangzhou, China
5Department of Ecommerce, School of Information Science and Technology, Sanda University, Shanghai 201209, China
6Shanghai Sanda University Department of Student Affairs, Shanghai 201209, China
7DaLi Bai Autonomous Prefecture People’s Hospital, Dali 671000, China
8Department of Orthopedics, Shidong Hospital Affiliated to University of Shanghai for Science and Technology, Shanghai 200438, China
9Department of Computer, School of Information Science and Technology, Sanda University, Shanghai 201209, China
10Department of science and education, Dongying People’s Hospital (Dongying Hospital of Shandong Provincial Hospital Group), Dongying 257091, China

Abstract

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.