Massive frozen osteochondral allografts are currently being used for reconstructive orthopaedic surgery following limb-sparing en bloc tumor resections, segmental skeletal losses resulting from trauma and for replacement of arthritic joint surfaces. While initial clinical impressions are encouraging, the ultimate success of this approach depends upon identification of biologic, immunologic and biomechanical parameters most compatible with individual recipient needs and a system of banking safe and efficacious allografts of sufficient variety and quantity to support the clinical program. Sensitive and objective histomorphometric techniques will be used to evaluate the biology of repair and incorporation as reflected in cortical and cancellous test aliquots of bone implanted at the time of primary reconstructive surgery and available for retrieval 12 weeks later in patients being treated at the collaborating institutions. The massive grafts (and test aliquots) will be dispensed from a uniform multi-institution banking program with tissues being chosen on the basis of biomechanical considerations alone, particularly fit at the articular surfaces. Tissue typing (A, B and DR) of donors and recipients will be determined but not be intentionally matched. Post-operative antibody screens for anti-HLA responses will be conducted at 3 month intervals during at least the first 2 years of follow-up. Clinical success will be measured by evaluating function, x-rays and technetium scans. Correlation of clinical success with biological changes (histomorphometric analysis), biochemical consideration (joint congruity and stable fixation) and immunological responses will identify those parameters predictive of clinical success and provide a basis for determining appropriate tissue matches, banking methods and transplantation techniques on a prospective basis in the future.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA032968-04
Application #
3170858
Study Section
(SSS)
Project Start
1982-07-01
Project End
1987-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
4
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Yale University
Department
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
Friedlaender, G E; Strong, D M; Tomford, W W et al. (1999) Long-term follow-up of patients with osteochondral allografts. A correlation between immunologic responses and clinical outcome. Orthop Clin North Am 30:583-8
Berrey Jr, B H; Lord, C F; Gebhardt, M C et al. (1990) Fractures of allografts. Frequency, treatment, and end-results. J Bone Joint Surg Am 72:825-33
Jofe, M H; Gebhardt, M C; Tomford, W W et al. (1988) Reconstruction for defects of the proximal part of the femur using allograft arthroplasty. J Bone Joint Surg Am 70:507-16
Lord, C F; Gebhardt, M C; Tomford, W W et al. (1988) Infection in bone allografts. Incidence, nature, and treatment. J Bone Joint Surg Am 70:369-76
Mankin, H J; Gebhardt, M C; Tomford, W W (1987) The use of frozen cadaveric allografts in the management of patients with bone tumors of the extremities. Orthop Clin North Am 18:275-89
Friedlaender, G E (1987) Bone grafts. The basic science rationale for clinical applications. J Bone Joint Surg Am 69:786-90
Horowitz, M C; Friedlaender, G E (1987) Immunologic aspects of bone transplantation. A rationale for future studies. Orthop Clin North Am 18:227-33
Friedlaender, G E (1987) Bone banking. In support of reconstructive surgery of the hip. Clin Orthop Relat Res :17-21
Trumble, T E; Friedlaender, G E (1987) Allogeneic bone in the treatment of tumors, trauma, and congenital anomalies of the hand. Orthop Clin North Am 18:301-10
Tomford, W W; Mankin, H J; Friedlaender, G E et al. (1987) Methods of banking bone and cartilage for allograft transplantation. Orthop Clin North Am 18:241-7

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