This invention relates to a method of making live autogenous skeletal replacement parts. More particularly, the present invention is concerned with the manufacture of live autogenous skeletal replacement parts through muscle flap molding and osteoinduction.
Bony defects, whether from degenerative, traumatic or cancerous etiologies, pose a formidable challenge to the reconstructive surgeon. Although many types of bone grafts and numerous biocompatible materials have been used clinically, they all suffer from shortcomings or potential long term complications. See, for example, Urist, "Bone transplants and implants" in Fundamental and Clinical Bone Physiology, Chapter 11, Lippincott, Philadelphia, Pa., 1980, pp. 331-368; Habal and Reddi, "An update on bone grafting and bone substitutes in reconstructive surgery" in Advances in Plastic and Reconstructive Surgery, Year Book Medical Publishers, Chicago, Ill., 1987, pp. 147-209.
The search for an off-the-shelf substitute for the conventional autogenous cancellous bone grafts used in orthopedic and maxillofacial surgery has led to considerable research efforts spent towards the isolation and manufacture of osteoinductive factors, e.g., demineralized bone matrix (DBM) and bone morphogenetic protein (BMP) [Urist et al., "Bone Cell Differentiation and Growth Factors," Science 220, 680-686 (1984), and Reddi et al., "Biologic Principles of Bone Induction," Orthop. Clin. of North Am. 18, 207 (1987)].
Current experimental therapeutic approaches with osteoinduction consist of administering the osteoinductive factors locally at the site of bone deficiency with the expectation that bony transformation of the adjacent tissues around the defect will reconstitute the missing bone [Urist and Dawson, "Intertransverse Process Fusion with the Aid of Chemostrelized Autolyzed Antigen Extracted Allogenic (AAA) Bone," Clin. Orthop. Relat. Res. 154, 97 (1981); Hollinger et al., "Calvarial Bone Regeneration Using Osteogenin," J. Oral Maxillofac. Surg. 47, 1182 (1989); and Mulliken et al., "Induced Osteogenesis-the Biological Principle and Clinical Applications," J. Sur. Res. 37, 487 (1984)]. This obvious and simple clinical application of osteoinduction can only achieve limited popularity for the following reasons:
First, in most clinical situations, and by the nature of the original problem itself, bone defects are associated with adjacent soft tissue deficiencies. The remaining surrounding tissues are usually either atrophic, or densely scarred from trauma, inflammation, infection, or radiation; factors that markedly reduce their osteoinductive potential. With poor responsiveness in addition to tissue deficiency, the amount of bone formed is suboptimal for functional skeletal reconstructions.
Second, osteoinductive factors applied freely within the defect site can cause an indiscriminate bony transformation of the few remaining functional muscles. Furthermore, the many vital structures in the area such as nerves, tendons and ligaments are also subject to ossification. The result can reproduce the dreadful pathologic condition known as myositis ossificans, which causes total loss of function in the affected part of the body.
Third, without any architectural constraints, the simple application of osteoinductive factors at the defect site cannot be expected to result in a piece of bone with the exact three dimensional shape necessary to reconstruct complex skeletal defects such as femoral heads, mandibles, carpal bones, etc.
Further background information on demineralized bone matrix-induced osteogenesis and bone morphogenetic protein (BMP) can be had by reference to the review paper by Harakas, "Demineralized Bone-Matrix-Induced Osteogenesis" in Clin. Orthopaedics and Related Res. No. 188, September 1984, pp. 239-251; the research article by Wozney et al., "Novel Regulators of Bone Formation: Molecular Clones and Activities," Science 242, 1528-1534 (1988); and U.S. Pat. Nos. 4,294,753; 4,440,750; 4,455,256; 4,485,097; 4,526,489; 4,563,489; 4,619,989; 4,761,471; 4,789,732; 4,795,804; and 4,857,456.
USPTO Backgrounds
USPTO Backgrounds