(from the application): The purpose of this proposal is to study the transplantation of laser-perforated and partially demineralized cortical bone allografts in the management of patients with skeletal defects as a result of tumor resection. Conventional fresh frozen bone allografts now in use show promise, but clinical complications including fractures, non-unions, and infections remain. A new processing technique consisting of controlled partial demineralization and laser-perforation has been developed in our laboratory with the objective of improving incorporation of cortical bone allografts into the host's own bone. Study of the incorporation of these new types of grafts in humans by imaging, histological and immunohistochemical studies, investigation of immune response in their recipients and a comparative analysis of causes of complications with data from an existing historical control group of patients, who received fresh frozen bone allografts, form the basis for the aims of this proposal. 1.To investigate clinical results and outcome with the use partially demineralized and laser-drilled cortical bone allografts when applied in the reconstruction of long bone defects after massive resection of diaphyseal bone tumors. The results of this clinical series will be documented and reviewed with use of a standardized rating system for limb sparing procedures. The incorporation process will be assessed by means of radiographic evaluation of healing at the host-bone graft junction sites and evidence of bone resorption and new bone formation along the transplant diaphysis using plain radiographs, MRI and CAT scans. Additionally, histological and immunohistochemical examination of tissue specimens from revision surgeries or tissue donations will be performed to assess for bone resorption and new bone formation. 2.To analyze development of a donor specific immune response in human recipients of partially demineralized and laser-perforated cortical bone allografts. 3.To correlate radiographic, histological and other clinical outcome data with immunological data and to compare results with those of the historical control group in which fresh frozen control allografts were used in order to determine whether the incorporation process of partially demineralized and laser-perforated cortical bone allografts is dependent on donor specific allostimulation. An estimated 250,000 orthopaedic allotransplants are now being used annually in the United States for a variety of disorders involving loss of skeletal structures, and there are currently no satisfactory alternatives for such grafts, particularly in young people, the population most affected by these conditions. Information gained by achievement of these aims is expected to significantly contribute to the understanding of the incorporation of cortical bone allografts. This pilot study in orthopaedic oncologic patients is expected to form the basis for a future R01 or R29 application aiming at broadening of the application of laser-perforated and partially demineralized bone allografts to other orthopaedic applications such as the treatment of osteolysis and traumatic loss.
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