EARLY CORTICAL BONE GRAFT-HOST INTERACTIONS

尽管骨移植广泛用于创伤重建， 总关节手术，生理和生物学事件， 这对合并过程和控制机制至关重要 这些行为只是表面上的理解。 已知的是 合并需要接受者之间的合作互动， 部位和骨移植，每一个都提供独特的和不可或缺的 捐款. 新鲜的自体或同系移植物被认为是 “金本位”;他们早血运重建，刺激有序新生 骨形成，并成为原始骨和新骨的完整混合物。 我们以前的体内研究表明，冷冻移植物和 移植物免疫原性对移植过程是有害的 合并。 移植细胞不能在冷冻中存活： 同系移植物使血运重建延迟数月， 早期新骨形成。 同种异体移植物的血运重建很差， 刺激组织不良的新编织骨形成， 原始骨和新骨的完整混合物。 四个星期后， 手术，新鲜同基因移植物和冷冻或 同种异体移植已经很明显了 这些体内研究结果表明 宿主和移植物之间发生了关键的相互作用， 植入后的头几周。 因此，我们提出假设，早期的相互作用之间的 骨移植物的细胞和宿主炎症/伤口的细胞 愈合/免疫反应决定最终的血管再生， 皮质移植物的结合和替代。 最佳 血管重建，合并和替代发生时，正常的 炎症反应是在缺乏特异性免疫的情况下引起的， 反应和细胞的反应与活细胞的相互作用 骨移植 单核细胞/巨噬细胞、淋巴细胞和骨细胞均 合成、释放和应答白细胞介素1（IL-1），转化 生长因子β（TGF-β）、肿瘤坏死因子α（TNF-α）和 前列腺素E2（PGE 2）。 我们推测， 这些介质调节愈合、血管再生、免疫应答 和骨骼生理学。 我们提出的体内笼模型， 用于研究正常炎症和伤口愈合的标准模型， 将移植物隔离在真实的环境中， 相互作用以及细胞和流体的顺序采样 移植物周围 我们将通过定义宿主来检验我们的假设 对新鲜同系移植物的反应，然后将反应与 同种异体移植物和冷冻移植物与新鲜的同系移植物相比。 我们预测同种异体和冷冻移植的反应会有所不同 与新鲜同系移植物引起的那些显著不同。 知识 宿主与移植物相互作用的早期序列， 阳性结果（新鲜同基因移植物）和变异澄清 在导致延迟或不良结果的序列中（冻结或 同种异体移植物）可以允许移植物中的治疗性细胞因子干预 合并。

Despite the widespread use of bone grafts in reconstructive trauma and total joint surgery, the physiological and biological events that are crucial to the process of incorporation and the mechanisms that control these actions are only superficially understood. It is known that incorporation requires cooperative interactions between the recipient site and the bone graft, each providing unique and indispensable contributions. Fresh autogenous or syngeneic grafts are considered the "gold standard"; they are revascularized early, stimulate orderly new bone formation, and become integrated mixtures of original and new bone. Our previous in vivo work has shown that both the freezing of a graft and immunogenicity of a graft are deleterious to the process of graft incorporation. Graft cells do not survive freezing: freezing of syngeneic grafts retards revascularization by several months and delays early new bone formation. Allogeneic grafts are poorly revascularized, stimulate poorly organized new woven bone formation, and never become integrated mixtures of original and new bone. By four weeks after surgery, the differences between fresh syngeneic grafts and frozen or allogeneic grafts are already apparent. These in vivo findings imply that critical interactions occur between the host and the graft during the first few weeks following implantation. Therefore, we propose the hypothesis that early interactions between the cells of a bone graft and the cells of the host inflammatory/wound healing/immune response determine the ultimate revascularization, incorporation and substitution of a cortical graft. The optimum revascularization, incorporation and substitution occur when a normal inflammatory response is invoked in the absence of a specific immune response and the cells of that response interact with living cells of the bone graft. Monocytes/macrophages, lymphocytes, and bone cells all synthesize, release and respond to interleukin 1 (IL-1), transforming growth factor beta (TGF-B), tumor necrosis factor alpha (TNF-A), and prostaglandin E2 (PGE2). We speculate that bidirectional actions of these mediators modulate healing, revascularization, immune responses, and bone physiology. Our proposed in vivo cage model, which is a standard model for the study of normal inflammation and wound healing, isolates the graft in a realistic environment which allows host-graft interactions as well as sequential sampling of the cells and fluid surrounding the graft. We will test our hypothesis by defining the host response to fresh syngeneic grafts and then comparing the response to allogeneic grafts and to frozen grafts to that of fresh syngeneic grafts. We predict that the responses to allogeneic and frozen grafts will differ significantly from those elicited by fresh syngeneic grafts. Knowledge of the early sequence of host-graft interactions that leads to a known positive outcome (fresh syngeneic graft) and clarification of variations in the sequence that lead to delayed or poor outcome (frozen or allogeneic grafts) may permit therapeutic cytokine intervention in graft incorporation.