Development of a biodegradable load-bearing DBM carrier

可生物降解承重DBM载体的研制

• 批准号: 6957395
• 负责人: TIEN-MIN G CHU
• 金额: $ 7.38万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6957395
• 关键词: biodegradable product; bioengineering /biomedical engineering; biomaterial development /preparation; biomaterial evaluation; biomechanics; biotechnology; bone density; bone disorder; bone regeneration; calcium phosphate; computed axial tomography; femur; laboratory rat; photon absorptiometry; polymethacrylate; tissue engineering; tissue support frame

Segmental defects in bones often are difficult to manage and require multiple-phase surgery to achieve adequate union and function. Current treatment options including autografts, allografts, and distraction osteogenesis have brought forth successes, yet are still with many limitations. In case of treatment failure, alternative treatment may involve serious consequences such as leg shortening or amputation. To overcome the limitations in these treatment options, we are exploring tissue engineering. Tissue engineering approach uses a biodegradable scaffold to carry biological factors and/or cells to facilitate tissue regeneration. This approach has been successful when scaffold is protected from load bearing. Bone regeneration in scaffolds subjected to loading has been challenging due to the relatively low mechanical properties in scaffolds. In this project, we propose to regenerate bone in large segmental bone defects using a load-bearing, biodegradable carrier carrying demineralized bone matrix (DBM). Unlike traditional porous scaffolds, the degradable carrier can be stabilized by intramedullary pin and participate in load-bearing function in the initial healing phase. After providing biomechanical stability and DBM delivery, the carrier will degrade at a later time. The hypotheses we have for this proposal are: 1. Load-bearing carrier combined with DBM shortens the time required for bone union to take place in rat femoral segmental defects. 2. Load-bearing carrier combined with DBM improves bone formation in rat femoral segmental defects. 3. Load-bearing carrier combined with DBM improves final mechanical properties of the rat femur after segmental defect regeneration. Forty-five Long-Evans rats will be used to test the hypotheses. Biodegradable carriers will be manufactured from poly(caprolacton) trimethacrylate/tricalcium phosphate composites. Low (0.05ml) and high (0.3 ml) dose of putty type DBM (DBX(r), Densply) will be incorporated into the carrier. The carrier will be implanted in a 5 mm segmental defect in rat femurs for 24 weeks. The time for unions to occur will be evaluated with x-ray at week 1, 3, 6, 15 and 24 weeks after implantation. The femurs will be retrieved after 24 weeks of implantation. Five femurs from each group will be evaluated with dual energy X-ray absorptiometry (DXA) for bone mineral content (BMC; g) and with peripheral computed tomography (pQCT) for the bone cross sectionaj area (CSA; mm2), volumetric bone density (vBMD; mg/cm3), and bone mineral content (BMC; mg/cm). The specimens will then be embedded in paraffin, decalcified, sectioned, and stained with McNeals Tetrachrome and Safarin-0 in alternating sections for bone and cartilage. The BMC, CSA, and vBMD of control versus low dose and control versus high dose groups will be compared. Ten femurs from each group will be tested with four-point-bending on a material testing machine for bending strength. The ultimate force (Fu; N), stiffness (S; N/mm) and energy to ultimate force (U; N.mm) will be compared between the control and the DBM treated groups.

骨骼中的节段缺陷通常很难管理，需要多相手术才能实现足够的结合和功能。当前的治疗选择在内，包括自体移植，同种异体移植和分心的成骨作用取得了成功，但仍有许多局限性。在治疗失败的情况下，替代治疗可能涉及严重的后果，例如腿部缩短或截肢。为了克服这些治疗方案的局限性，我们正在探索组织工程。组织工程方法使用可生物降解的支架携带生物学因素和/或细胞来促进组织再生。当保护脚手架免受负载轴承时，这种方法已经成功。由于脚手架的机械性能相对较低，脚手架的骨再生一直具有挑战性。在这个项目中，我们建议使用承载载矿化骨基质（DBM）的承载，可生物降解的载体在大节骨缺损中再生骨骼。与传统的多孔脚手架不​​同，可降解的载体可以通过髓内引脚稳定，并在初始愈合阶段参与负载功能。在提供生物力学稳定性和DBM传递之后，载体将在以后的时间降解。我们对该提案的假设是：1。承载载体与DBM结合缩短骨骼联合发生在大鼠股骨分段缺陷中所需的时间。 2。承载载体与DBM结合，改善了大鼠股骨分段缺陷中的骨形成。 3。承载载体与DBM结合，改善了节段性缺陷再生后大鼠股骨的最终机械性能。四十五只长evans大鼠将用于检验假设。可生物降解的载体将由二甲基丙烯酸酯/磷酸三乙烯酸酯复合材料制造。低（0.05毫升）和高剂量的油腻型DBM（DBX（R），Densply）将掺入载体中。该载体将在大鼠股骨中植入5 mM节段缺陷24周。植入后第1、3、6、15和24周，将使用X射线评估工会的时间。植入24周后，将检索股骨。每组的五个股骨将通过双能X射线吸收法（DXA）进行评估，用于骨矿物质含量（BMC; G），以及用于骨横截面区域（CSA; MM2）的外围计算机断层扫描（PQCT），体积骨密度，VBMD; MG/CM3和BMC/CMC（BMC）（BMC）（MMD; MM2）（VBMD; MM2）。然后，样品将嵌入石蜡中，用麦克尼（McNeals Tetrachrome）脱钙，切片和染色，并在交替的骨骼和软骨中交替切片中。将比较对照与低剂量和对照组与高剂量组的BMC，CSA和VBMD。每组的十个股骨将通过材料测试机上的四点弯曲进行测试，以实现弯曲强度。最终力（FU; n），刚度（S; n/mm）和对最终力的能量（u; n.mm）将在对照组和经DBM处理组之间进行比较。