Load Bearing Bio-Active Bone Grafts

承重生物活性骨移植物

• 批准号: 6742835
• 负责人: ASHOK C KHANDKAR
• 金额: $ 9.89万
• 依托单位: SINTX TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2005-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6742835
• 关键词: aluminum; athymic mouse; bioengineering /biomedical engineering; biomaterial development /preparation; biomechanics; biomimetics; bone regeneration; cell adhesion; cell differentiation; cell growth regulation; cell proliferation; ceramics; histology; medical implant science; mesenchyme; morphometry; musculoskeletal disorder therapy; musculoskeletal injury; nonhuman therapy evaluation; osteogenesis; physical property; pluripotent stem cells; stem cell transplantation; tissue engineering; zirconium

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.

描述（由申请人提供）：一种实现骨修复（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，移植到多孔羟基磷灰石 (HAP) 或磷酸三钙 (TCP) 陶瓷载体上的免疫功能低下的受体小鼠中，已显示出显着的成骨潜力。由于其直接骨粘合能力，此类陶瓷被称为生物活性陶瓷。然而，由于这些陶瓷固有的机械性能较低，因此不适用于没有辅助硬件的承重移植物。 一种新型多孔皮质松质结构陶瓷（CSC）在绵羊模型中表现出足够的强度和高生物活性/向内生长。关键问题是：CSC 移植物周围和内部的 hMSC 的反应、分化和增殖是什么？ 在第一阶段计划中，这个问题将通过优化 CSC 移植物的孔隙率和孔径大小来回答，以提高强度和 hMSC 装载/输送。将确定生物力学特性，并评估 CSC 移植物/hMSC 复合材料的体外 hMSC 附着和增殖。完善且已发布的方案将用于使用免疫受损的裸鼠确定这些移植物-hMSC 复合材料在皮下部位的成骨潜力。标准 HAP/TCP 移植物将用作对照。定性和定量组织形态计量学将用于全面评估这些新型移植物的骨形成。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结果进行比较，我们将确定新型 CSC 移植物-hMSC 复合材料作为增强骨的承载、生物活性、仿生支架的优点和可行性维修。