FACTORS INFLUENCING SURVIVAL OF VASCULAR BONE GRAFTS

影响血管骨移植存活的因素

• 批准号: 3155355
• 负责人: ANDREW J WEILAND
• 金额: $ 13.47万
• 依托单位: HOSPITAL FOR SPECIAL SURGERY
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-07-01 至 1991-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3155355
• 关键词: bone transplantation; cyclosporines; densitometry; gender difference; histocompatibility; histology; homologous transplantation; laboratory rat; limb transplantation; monoclonal antibody; musculoskeletal circulation; osteoporosis; radiation immunosuppression

This proposal seeks to: 1. Evaluate prolonging vascularized bone allograft (VBA) survival by methods relatively nontoxic to the host, the material properties of orthotopically placed VBAs, and ultrastructural changes of these grafts. Having determined the roles of classic specific and nonspecific means of immunosuppression, monoclonal antibodies and the use of graft irradiation to prolong graft survival in a heterotopic model will be explored. Grafts will be placed in the orthotopic position, and the duration of classic immunosuppressive therapy regimens will be determined. The material properties of these orthotopically placed grafts will be evaluated, and ultrastructural changes in the graft will be studied in order to discern the focus of the rejection process in these composite grafts. 2 We plan to use a syngeneic vascularized bone transplantation model to study (1) the influences of gender and hormonal milieu on longitudinal skeletal growth and (2) the molecular mechanisms involved in disuse osteoporosis which is typically seen in the transplanted limbs. Limbs will be transplanted form female rats to pre- and post-pubertal male rats and to control females in an attempt to dissect the influences of chondrocyte genotype and hormonal environment on skeletal growth. Hypophysectomized rats at progressive weeks after surgery will be used as donors to evaluate the duration of growth potential and possible mechanisms involved in senescence at the growth plate. To examine disuse osteoporosis, immunohistochemical staining will be used to determine which matrix components are appropriately incorporated into bone; for those components which are not present, in situ hybridization will be used to establish whether this control is at the transcriptional or translational level. 3. Explore the reconstructive potential of the concept previously termed "molded vascularized osteoneogenesis" in which the incorporation of a vascular pedicle with nonvascularized bone grafts in a mold of predetermined size and shape will result in a viable vascularized bone graft. Experiments have been designed to determine if these grafts can be transferred as island or free grafts, the optimum timing for transfer of such grafts, the healing and material properties of these grafts, and the ability of non- host bone substances to become molded vascularized grafts.

这项建议旨在： 1. 评估延长血管化同种异体骨移植物（CABG）的存活率 通过对宿主相对无毒的方法， 原位放置的VBAs，和这些超微结构的变化， 移植物 在确定了经典的具体和 非特异性免疫抑制手段，单克隆抗体， 移植物照射延长移植物存活的应用 将探索异位模型。 移植物将被放置在 原位位置和经典免疫抑制剂的持续时间 将确定治疗方案。 的材料特性 将对这些原位放置的移植物进行评价， 将研究移植物的超微结构变化， 在这些复合材料中辨别拒绝过程的焦点 移植物 2我们计划使用同基因血管化骨移植 模型研究（1）性别和激素环境对 纵向骨骼生长和（2）分子机制 参与废用性骨质疏松症， 移植的肢体 将从雌性大鼠身上移植肢体 对青春期前和青春期后雄性大鼠以及对照雌性大鼠进行了一项 试图剖析软骨细胞基因型的影响， 激素环境对骨骼生长的影响。 垂体切除的大鼠 在手术后的几周内，将用作供体， 评估增长潜力的持续时间和可能的机制 参与生长板的衰老。 审废 骨质疏松症，免疫组织化学染色将用于 确定适当加入的基质组分 骨内;对于那些不存在的成分，原位 杂交将用于确定该对照是否处于 转录或翻译水平。 3. 探索先前概念的重建潜力 称为“模制血管化骨生成”， 血管蒂与非血管化骨结合 在预定尺寸和形状的模具中的移植物将导致 有活力的血管化骨移植物 实验的目的是 确定这些移植物是否可以作为岛状或游离移植 移植物，转移这种移植物的最佳时机，愈合 这些移植物的材料特性，以及非- 宿主骨物质成为模制的血管化移植物。