Development of Bioerodible Polymer Matrices for Osteoblast Growth and Maturation

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Laurencin, Cato T. BES 970786 An interdisciplinary approach is taken for the development of systems for the regeneration of bone using polymeric materials, ceramics and cells. Possible clinical applications of these proposed cell-polymer matrices would be in areas of grafting for atrophic non-unions of bone, for surgical arthrodeses, for healing cranio-facial defects, and for use as prosthetic implants or coatings. This is a renewal proposal of our grant (first funded in July,. 1990 and renewed in July, 1993). After successfully fulfilling the objectives of our 1990 funded grant in which we developed and fully characterized cultures of bone cells using cell culture techniques, constructed and characterized 2-dimensional matrices of biocompatible, degradable polymers, and studied cell-polymer interactive phenomena via cell attachment, spread, growth and DNA expression experiments, we moved on to the design of 3-dimensional matrices for bone cell support. Through our 1993 funded grant we have made remarkable progress toward achieving our overall goals. A new 3-dmensional matrix system was formulated and by biomechanical analyses and electron microscopic studies, found to be similar to cancellous bone. Bone cells were successfully seeded onto these matrices and demonstrated not only their ability to attach and grow, but when placed under suitable environments, demonstrated the ability to lay down a mineral matrix. Finally novel methods were designed to evaluate cellular growth and phenotype in these opaque mineralizing matrices. In this grant proposal the optimization of these 3-dimensional bone bioerodible polymer systems is performed by further study of the nature of the mineral matrix formed in vitro using material science techniques, and the further study of the nature of the bone cell response to op timized 3-dimensional matrices using confocal and immunofluorescence cell characterization technology we developed during the previous grant. Finally, a series of experiments will be undertaken to evaluate the ability of these materials to effect healing of bony defects alone and with bone cells. ***