Bioreactor Based Bone Tissue Engineering

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A multidisciplinary project is to develop novel polymer and polymer-ceramic based matrices for bone tissue engineering. Using principles from chemical, mechanical, and materials engineering as well as cell and molecular biology, the goal is to create and study structural replacements that provide an environment appropriate for new bone formation. The development of a matrix of this sort combined with novel tissue culture technology provides opportunities for studying polymer-cell interactions, polymer matrix effects on cellular response, and effects of transport on cellular response in matrix based systems. Moreover these matrices may find clinical applications in grafting of non-unions, surgical arthrodeses, cranio-facial defects, and prosthetic implants and/or implant coatings. The researchers recently described the development of novel degradable microsphere-based matrices for bone tissue engineering. In preliminary studies these three-dimensional matrices have been shown to support the growth and maturation of osteoblast cells in vitro, and support the formation of bone in vivo. In the panned project these systems would be developed further and optimized these systems by performing innovative experiments aimed at understanding and enhancing bone formation using three dimensional matrices. The matrix would be exposed to fluid and nutrient flux via placement in a dynamic cell culturing environment. The researchers have hypothesized that in conditions where transport is enhanced, the quality of bone formation will ultimately be enhanced in such matrix systems. Additionally, a more fundamental understanding of the manner in which cells interact with these degradable polymeric matrices is to be sought. Therefore studies are proposed to evaluate cell surface receptor expression of osteoblasts seeded onto these biomimetic devices. Finally, in vivo studies will be performed, examining the ability of these tissue engineered bioreactor cultured matrices to heal non-union bone defects. Careful attention will be given to the mechanical strength of the healing defect and the short- and long-term histology and histomorphometry at the defect site. The studies to be performed in a four year time-frame should yield important new fundamental information broadly applicable in tissue engineering.The planned investigation builds on the foundation of 3-D polymer scaffolds from polymer microspheres developed by the PI in previously funded NSF studies.The major direct benefit from a successful project would be the nearly 1 million patients each year who have surgeries that require some form of bone grafting. Presently there is no consensus on the optimized scaffold design parameters, e.g. mechanical strength, pore volume, pore size, and degradation rate. All of these issues are to be addressed in the project.