Load Bearing Bio-Active Bone Grafts

描述（由申请人提供）：一种用于实现骨修复（尤其是大骨缺损）的新颖且有前景的方法是移植人骨髓基质细胞或间充质干细胞（hMSC）。培养扩增的hMSCs，移植到免疫受损的受体小鼠的多孔羟基磷灰石（HAP）或磷酸三钙（TCP）陶瓷载体，已显示出显着的成骨潜力。由于它们的直接骨结合能力，这种陶瓷被称为生物活性的。然而，由于这些陶瓷固有的低机械性能，它们不适用于没有辅助硬件的承重移植物。 一类新型多孔皮质-松质骨结构陶瓷（CSC）在绵羊模型中显示出足够的强度和高生物活性/长入。关键问题是：CSC移植物周围和内部的hMSCs的反应、分化和增殖是什么？ 在第1阶段项目中，将通过优化CSC移植物的孔隙率和孔径以获得强度和hMSC加载/递送来回答这个问题。将测定生物力学性质，并将评估CSC移植物/hMSC复合物的体外hMSC附着和增殖。将使用完善的和已发表的方案来确定这些移植物-hMSC复合物在免疫受损裸鼠皮下部位的成骨潜力。标准HAP/TCP移植物将用作对照。定性和定量的组织形态测量学将用于全面评估这些新型移植物中的骨形成。通过将CSC移植物中新骨形成的质量和程度与陶瓷载体上的对照和先前的结果进行比较，我们将建立新型CSC移植物-hMSC复合物作为用于增强骨修复的承重、生物活性、仿生支架的优点和可行性。

DESCRIPTION (provided by applicant): A novel and promising approach for achieving bony repair especially for large bone defects is to transplant human bone marrow stromal cells or mesenchymal stem cells (hMSCs). Culture expanded hMSCs, transplanted into immuno-compromised recipient mice on porous Hydroxyapatite (HAP) or Tri-calcium phosphate (TCP) ceramic carriers, have demonstrated significant osteogenic potential. Owing to their direct bone bonding capability, such ceramics are known as bioactive. However, these ceramics are not indicated for load bearing grafts without secondary hardware, owing to their inherently low mechanical properties. A new class of porous cortico-cancellous structured ceramics (CSC) have shown adequate strength and high bioactivity/ingrowth in a sheep model. The key question is: What is the response and differentiation and proliferation of hMSCs around and within the CSC grafts? In the Phase 1 program, this question will be answered by optimizing the porosity and pore size of the CSC grafts for strength and hMSC loading/delivery. The biomechanical properties will be determined and in-vitro hMSC attachment and proliferation of CSC graft/hMSC composites will be assessed. Well-established and published protocols, will be used to determine the osteogenic potential of these graft-hMSC composites in a sub-cutaneous site using immuno-compromised nude mice. Standard HAP/TCP grafts will be used as a control. Both qualitative and quantitative histo-morphometry will be used to comprehensively assess the bone formation in these novel grafts. By comparing the quality and extent of new bone formation in the CSC grafts with the control and previous results on ceramic carriers, we will establish the merit and feasibility of the novel CSC graft-hMSC composites as load bearing, bioactive, biomimetic scaffolds for enhanced bony repair.