The purpose of this research is to test the global hypothesis that the incorporation and function of a tissue engineered construct for bone regeneration is significantly influenced by the transmission of physical forces through its extracellular matrix. Utilizing a series of in vivo rat models, the investigators will test for the synergistic affects of device mediated mechanical forces and local delivery of biologic factors in stimulating the repair and incorporation of tissue engineered bone substitutes. The models in both a cranial-facial and long bone site utilize specifically designed external fixators which enable the implementation of experimentally controlled mechanical loading conditions across surgically created osteotomy gaps. Local biologic factors will be produced by placing DNA-delivering matrices within these fracture gaps. The effects of the mechanical and biologic factors on tissue repair and regeneration will be assayed by documenting the spatial patterns of gene expression, matrix synthesis, and bone morphology as a function of time and anatomic location. This information is fundamental to the development of strategies to replace or augment bony defects in the cranial-facial or appendicular skeleton. Identification of factors which influences the incorporation and remodeling of tissue engineered transplants will lead to significantly improved and more reliable biomimetic therapies.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Project (R01)
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Special Emphasis Panel (ZHL1-CSR-F (M2))
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Kousvelari, Eleni
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University of Michigan Ann Arbor
Schools of Medicine
Ann Arbor
United States
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Rhee, Samuel T; El-Bassiony, Loai; Buchman, Steven R (2006) Extracellular signal-related kinase and bone morphogenetic protein expression during distraction osteogenesis of the mandible: in vivo evidence of a mechanotransduction mechanism for differentiation and osteogenesis by mesenchymal precursor cells. Plast Reconstr Surg 117:2243-9
Rhee, Samuel T; Buchman, Steven R (2005) Colocalization of c-Src (pp60src) and bone morphogenetic protein 2/4 expression during mandibular distraction osteogenesis: in vivo evidence of their role within an integrin-mediated mechanotransduction pathway. Ann Plast Surg 55:207-15
Smith-Adaline, E A; Volkman, S K; Ignelzi Jr, M A et al. (2004) Mechanical environment alters tissue formation patterns during fracture repair. J Orthop Res 22:1079-85
Tong, Lawrence; Buchman, Steven R; Ignelzi Jr, Michael A et al. (2003) Focal adhesion kinase expression during mandibular distraction osteogenesis: evidence for mechanotransduction. Plast Reconstr Surg 111:211-22; discussion 223-4
Buchman, Steven R; Ignelzi Jr, Michael A; Radu, Caius et al. (2002) Unique rodent model of distraction osteogenesis of the mandible. Ann Plast Surg 49:511-9
Guilak, F; Butler, D L; Goldstein, S A (2001) Functional tissue engineering: the role of biomechanics in articular cartilage repair. Clin Orthop Relat Res :S295-305