A dual-active biological scaffold with in situ loaded Abaloparatide and bone marrow-derived mesenchymal stem cells synergistically regulatory T cell to promote bone regeneration

Bone defect repair remains a significant challenge faced in clinical practice. Bone tissue engineering has emerged as an effective approach for bone defect repair due to its ample donor source and remarkable repair efficacy. In this study, we combined Abaloparatide (ABL) with bone marrow-derived mesenchymal stem cells (BMSCs) and utilized methacrylated gelatin (GelMA) as a matrix to successfully develop a bio-scaffold with dual activity (ABL@GelMA/BMSCs). BMSCs regulate the bone microenvironment by secreting cytokines, which promote bone repair through a paracrine mechanism. The addition of ABL not only facilitated the osteogenic differentiation and paracrine function of BMSCs but also significantly enhanced the bone induction capability of the scaffold, as evidenced by the marked upregulation of osteogenic markers (ALP, RUNX2, OCN). Furthermore, this bio-scaffold was able to upregulate the Foxp3 gene, inducing Foxp3+ regulatory T cells, thereby modulating the local immune microenvironment to promote bone formation. After implantation of this bio-scaffold into a critical-sized cranial defect model, histological results demonstrated a higher bone mineral density (BMD), and CT reconstruction indicated good healing of the defect. In summary, this bio-scaffold exhibits a powerful capacity for bone defect repair while improving the bone microenvironment through the synergistic modulation of regulatory T cells, providing a new strategy for bone defect repair.