3D打印智能材料Li-Cu-n-HA/ColⅠ协同SDF1-CXCR4调控干细胞归巢治疗ONFH研究

The pathogenesis of osteonecrosis of femoral head (ONFH) has been reported to be associated with suppression of mesenchymal stem cells (MSCs) and osteoblast in the bone marrow, which inhibits angiogenesis and bone repair of local necrotic lesion. In recent years the SDF-1α/CXCR4 pathway has been widely studied and evidence demonstrates that the SDF-1α–CXCR4 signaling pathway was involved in mobilization and recruitment of MSCs and endothelial progenitor cells (EPCs) after tissue injury. Our previous studies also found that local application of lithium could accelerate bone regeneration by Wnt signal-mediated osteoblastogenesis through regulating proliferation and differentiation of local MSCs. Additionally, the recent researches have revealed that copper can promote vascularization of vascular endothelial cells or EPCs through HIF-1/PHD/VEGF signaling pathway, thus contributing to formation of new bones in necrotic zones. With rapid advances in 3D printed bone tissue engineering scaffolds, smart biomaterials have increasingly become the focus of research in recent years. Based on the synergism of stem cell biologiy and smart biomaterials and lithium- copper mediated neo-angiogenesis and osteogenesis, it reasonable to assume that a new promising smart biomaterials, consisting of 3D printed lithium- copper –doped nano hydroxyapaptite/collagen bone tissue engineering scaffolds composite with controlled-release SDF-1α microspheres, could be designed to rebuild biomechanical support of necrotic lesion in femoral head, and therefore prevent the collapse of femoral head, by pro-angiogenic and pro-osteogenic repair effects resulting from mobilization and recruitment of MSCs and EPCs, activation of canonical Wnt signaling pathway and excellent osteoconduction of 3D printed bone engineering tissue engineering scaffolds.

股骨头坏死发生发展与局部bMSCs和成骨细胞数量减少、活性下降导致血管生成、骨修复停滞相关。SDF-1α-CXCR4生物轴调控体内干细胞向组织损伤处迁移、归巢，锂调控经典Wnt信号通路促进MSCs/HCPs成骨，铜调控HIF-1/ PHD/VEGF信号通路促进内皮细胞成血管分化；具有生物活性的智能生物材料是骨组织工程研究的热点和方向。基于干细胞与新型智能生物材料的协同以及前期锂促进成骨研究成果，将锂、铜掺入n-HA/ColⅠ并通过3D打印设计具有生物活性的智能材料Li-Cu/n-HA/ColⅠ，并携载SDF-1α缓释微球，动员、诱导MSCs/HCPs定向迁移、归巢至植入材料部位，智能生物材料所具有的持久、有效的生物物理信号调控归巢的MSCs/HCPs成骨、成血管，修复死骨清除后的骨缺损、重建股骨头力学性能，避免股骨头塌陷，为早期股骨头坏死的保头治疗提供新的、有效地治疗方法。

股骨头坏死发生发展与局部bMSCs和成骨细胞数量减少、活性下降导致血管生成、骨修复停滞相关。SDF-1α-CXCR4生物轴调控体内干细胞向组织损伤处迁移、归巢，锂调控经典Wnt信号通路促进MSCs/HCPs成骨，铜调控HIF-1/ PHD/VEGF信号通路促进内皮细胞成血管分化，并且铜具有上调SDF-1α表达从而发挥调控细胞归巢的潜能；具有生物活性的智能生物材料是骨组织工程研究的热点和方向。基于干细胞与新型智能生物材料的协同以及前期锂促进成骨研究成果，将锂、铜掺入n-HA并设计具有生物活性的智能材料Li-Cu/n-HA支架，探讨了Cu动员、诱导MSCs/HCPs定向迁移、归巢至植入材料部位，智能生物材料所具有的持久、有效的生物物理信号调控归巢的MSCs/HCPs成骨、成血管，修复清除死骨后的骨缺损、重建股骨头力学性能，避免股骨头塌陷，为早期ONFH的保头治疗提供新的、有效地治疗方法。