(277d) Modulation of Inflammatory Response for Accelerated Tissue Vascularization and Bone Regeneration

There is a profound need for bone regeneration strategies due to trauma and various musculoskeletal diseases. Tissue engineering offer alternative approaches to regenerate tissues. The transfer of tissue engineering from the lab to the clinic is limited by the failure to adequately vascularize scaffolds and control immune response. The goal of this study is to harness the wound healing potential of macrophages and human mesenchymal stem cells (hMSCs) to enhance directed angiogenesis and bone formation. We explored the use of resveratrol, a natural compound commonly used in complementary medicine, to mediate M1 to M2 macrophage plasticity, impart natural release of angiogenic factors by macrophages and enhance osteogenic differentiation of hMSCs. To this end, we mapped the time-dependent response of macrophage gene expression as well as hMSC osteogenic differentiation to varying doses of resveratrol in 2D and 3D biomaterial environments. The results demonstrated that macrophages adopted a pro-healing phenotype in the presence of resveratrol, as confirmed by the expression of IL-6 and TNF-α. This effect was coupled with higher expression of anti-inflammatory markers VEGF and IL-10. In addition, hMSCs exposed to resveratrol demonstrated a higher level of calcium deposition and alkaline phosphatase activity. Our results altogether delineate the potential to synergistically accelerate angiogenic factor release and upregulate osteogenic signaling pathways by â??dialingâ? the appropriate degree of resveratrol release.