Development of a biodegradable load-bearing DBM carrier

可生物降解承重DBM载体的研制

基本信息

项目摘要

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.
骨骼的节段性缺损通常难以处理,需要进行多阶段手术才能实现足够的愈合和功能。目前的治疗方案包括自体移植、同种异体移植和牵引成骨,已经取得了成功,但仍然存在许多局限性。如果治疗失败,替代治疗可能会带来严重后果,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来携带生物因子和/或细胞以促进组织再生。当脚手架免受承重保护时,这种方法是成功的。由于支架的机械性能相对较低,承受负载的支架中的骨再生一直具有挑战性。在这个项目中,我们建议使用承载脱矿骨基质(DBM)的承重、可生物降解载体来再生大节段骨缺损中的骨。与传统的多孔支架不同,可降解载体可以通过髓内钉稳定,并在初始愈合阶段参与承重功能。在提供生物力学稳定性和 DBM 输送后,载体将在稍后降解。我们对此提案的假设是: 1. 承载载体结合 DBM 缩短了大鼠股骨节段缺损骨愈合所需的时间。 2.承载载体联合DBM改善大鼠股骨节段缺损骨形成。 3.承载载体结合DBM提高了节段性缺损再生后大鼠股骨的最终力学性能。四十五只朗-埃文斯大鼠将被用来测试这些假设。可生物降解的载体将由聚(己内酯)三甲基丙烯酸酯/磷酸三钙复合材料制成。低剂量(0.05ml)和高剂量(0.3ml)腻子型DBM(DBX(r),Densply)将被掺入载体中。载体将被植入大鼠股骨 5 毫米的节段缺损中,持续 24 周。将在植入后第 1、3、6、15 和 24 周通过 X 射线评估愈合时间。股骨将在植入 24 周后取出。将使用双能 X 射线吸收测定法 (DXA) 评估每组的 5 个股骨的骨矿物质含量 (BMC; g),并使用外周计算机断层扫描 (pQCT) 评估骨横截面积 (CSA; mm2)、体积骨密度(vBMD;mg/cm3)和骨矿物质含量(BMC;mg/cm3)。然后将标本包埋在石蜡中、脱钙、切片,并在骨和软骨的交替切片中用 McNeals Tetrachrome 和 Safarin-0 染色。将比较对照组与低剂量组以及对照组与高剂量组的 BMC、CSA 和 vBMD。每组的 10 根股骨将在材料试验机上进行四点弯曲测试,以检测弯曲强度。将比较对照组和 DBM 处理组之间的极限力 (Fu; N)、刚度 (S; N/mm) 和极限力能量 (U; N.mm)。

项目成果

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TIEN-MIN G CHU其他文献

TIEN-MIN G CHU的其他文献

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{{ truncateString('TIEN-MIN G CHU', 18)}}的其他基金

Development of a biodegradable load-bearing DBM carrier
可生物降解承重DBM载体的研制
  • 批准号:
    7118573
  • 财政年份:
    2005
  • 资助金额:
    $ 7.38万
  • 项目类别:

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