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）：一种实现骨修复的新颖而有前途的方法，尤其是用于大骨缺损的方法是移植人骨髓基质细胞或间质干细胞（HMSC）。在多孔羟基磷灰石（HAP）或磷酸三钙（TCP）陶瓷载体上移植到免疫受损的受体小鼠中，培养的HMSC已表现出显着的成骨潜力。由于其直接的骨粘结能力，这种陶瓷被称为生物活性。但是，由于其固有的机械性能固有的较低的机械性能，这些陶瓷对于没有次级硬件的载荷轴承的移植物没有指示。 在绵羊模型中，新的一类新的多孔皮层结构化陶瓷（CSC）显示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HMSC的响应，分化和扩散是什么？ 在第1阶段计划中，将通过优化CSC移植物的孔隙率和孔径来解决这个问题，以实现强度和HMSC加载/输送。将确定生物力学特性，并评估CSC移植/HMSC复合材料的体外HMSC附着和增殖。建立良好的和公开的方案将用于确定使用免疫强化的裸鼠在下二型部位中这些移植物-HMSC复合材料的成骨潜力。标准HAP/TCP移植物将用作对照。定性和定量的组织密码学都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的控制和先前的结果进行比较，我们将建立新型CSC Graft-HMSC复合材料作为负载轴承，生物活性，生物模仿型脚手架的优点和可行性，以增强骨质修复。