Investigators: Dennis R. Carter, PhDand Gary S. Beaupré, PhD Project Staff: Elizabeth G. Loboa, MS; R. Lane Smith, PhD; and Stuart B. Goodman, MD, PhD Project Categories: Arthritis / Osteoporosis - 2000 Skeletal regeneration is accomplished by a cascade of biological events that may include differentiation of pluripotential tissue and bone resorption. These processes, which can occur at bone/implant interfaces as well as during fracture healing and distraction osteogenesis, are strongly influenced by the local mechanical loading history. Intermittent musculoskeletal forces impose displacements and cyclic stresses and strains in the bone and regenerating tissue near bone surfaces. Using a theoretical framework for tissue differentiation in conjunction with finite element modeling techniques we have demonstrated that the patterns of tissue differentiation, bone formation, and bone resorption observed at implant interfaces, fracture sites, and distraction osteogenesis environments can be predicted from fundamental mechanobiological concepts. These analyses and other experimental and clinical data indicate that: 1) direct intramembranous bone formation (or implant osseointegration/bony ingrowth) is permitted in areas of low stress and strain; 2) low to moderate magnitudes of hydrostatic tensile stress may further stimulate intramembranous ossification (or implant bony ingrowth); 3) high tensile (or shear) strain is a stimulus for the net production of fibrous tissue (or a fibrous implant interface); 4) tensile (or shear) strain with a superimposed hydrostatic compressive stress will stimulate the development of fibrocartilage (or a fibrocartilage implant interface); 5) although hydrostatic compressive stress is a stimulus for chondrogenesis, excessive hydrostatic compression near bone surfaces will cause bone resorption (associated with implant migration). This work has important clinical relevance related to the design of joint replacements, the design of fracture fixation devices and techniques for fracture stabilization. A significant milestone related to this project is the issuance of a patent for intramedullary prostheses having a novel curvilinear collar. This collar design is expected to perform better than existing collars, leading to longer lasting hip replacements with a reduced incidence of loosening and a decreased rate of revision. Much of the research that established proof of concept and performance characteristics for this invention was done by Jay Mandell (PhD, 1998) as part of his Stanford PhD thesis work on "Load Transfer in Cementless Intramedullary Prostheses" in collaboration with Dr. David Schurman and was accomplished in association with the VA-supported project "Mechanical Regulation of Skeletal Tissue in Normal and Prosthetic Joints," VA Merit Review project A501-2RA. Recent Publications and Presentations: Carter DR, Beaupré GS, Giori NJ, Helms JA: Mechanobiology of skeletal regeneration, Clinical Orthopaedics and Related Research, 355:S41-S55, 1998. Carter DR, Polefka EGL, Beaupré GS: "Mechanical Influences on Skeletal Regeneration and Bone Resporption," In: Bone Engineering, (ed. J. Davies), University of Toronto Press, 2000. Carter DR, Loboa Polefka EG, Beaupré GS: "Mechanical Influences on Skeletal Regeneration," In: Human Life Support Biomechanics, Springer-Verlag, 2000. Loboa Polefka EG, Beaupré GS, Carter DR: Stress and strain distributions are correlated with pseudarthrosis development. Trans Orthop Res Soc 25:861, 2000. Loboa Polefka EG, Beaupré GS, Carter DR: Mechanobiology of pseudarthrosis formation with oblique fractures. Submitted to the Journal of Orthopaedic Research. Funding Source: VA RR&D Merit Review |
