Enhancing Fracture Healing with 3D Bioprinted Hif1a‐Overexpressing BMSCs Hydrogel: A Novel Approach to Accelerated Bone Repair
Jiajia Lu, Xiaojian Shi, Zhibin Zhou, N. Lu, Guangxin Chu, Hai Jin, Lei Zhu, Aimin Chen
Abstract
Addressing the urgent need for effective fracture treatments, this study investigates the efficacy of a 3D bioprinted biomimetic hydrogel, enriched with bone marrow mesenchymal stem cells (BMSCs) and targeted hypoxia-inducible factor 1 alpha (Hif1a) gene activation, in enhancing fracture healing. A photocross-linkable bioink, gelatin methacryloyl bone matrix anhydride (GBMA) is developed, and selected its 5% concentration for bioink formulation. Rat BMSCs are isolated and combined with GBMA to create the GBMA@BMSCs bioink. This bioink is then used in 3D bioprinting to fabricate a hydrogel for application in a rat femoral fracture model. Through transcriptome sequencing, WGCNA, and Venn analysis, the hypoxia-inducible factor Hif1a is identified as a critical gene in the fracture healing process. In vitro studies showed that Hif1a promoted BMSC proliferation, chondrogenic differentiation, and cartilage matrix stability. The in vivo application of the GBMA@BMSCs hydrogel with Hif1a overexpression significantly accelerated fracture healing, evidenced by early and enhanced cartilage callus formation. The study demonstrates that 3D bioprinting of GBMA@BMSCs hydrogel, particularly with Hif1a-enhanced BMSCs, offers a promising approach for rapid and effective fracture repair.