Development of Bioerodible Polymer Matrices for Osteoblast Growth and Maturation

Laurencin, Cato T. BES 970786采用跨学科的方法来开发使用聚合物材料，陶瓷和细胞的骨再生系统。这些提出的细胞-聚合物基质可能的临床应用将在骨骼萎缩性不连的移植、手术关节、修复颅面缺陷以及用作假体植入物或涂层等领域。这是我们拨款的续期提案（第一次拨款是在七月）。1990年，1993年7月续订)。在成功完成了我们1990年资助的目标之后，我们利用细胞培养技术开发并充分表征了骨细胞培养，构建并表征了生物相容性可降解聚合物的二维基质，并通过细胞附着、扩散、生长和DNA表达实验研究了细胞-聚合物相互作用现象。我们继续设计用于骨细胞支持的三维基质。通过1993年的资助赠款，我们在实现总体目标方面取得了显著进展。通过生物力学分析和电镜研究，发现一个新的三维基质系统与松质骨相似。骨细胞被成功地植入到这些基质上，不仅证明了它们附着和生长的能力，而且当放置在合适的环境中时，还证明了它们形成矿物基质的能力。最后，设计了新的方法来评估这些不透明矿化基质中的细胞生长和表型。在这项拨款申请中，通过使用材料科学技术进一步研究体外形成的矿物基质的性质，以及使用我们在之前的拨款中开发的共聚焦和免疫荧光细胞表征技术进一步研究骨细胞对优化三维基质的反应的性质，来优化这些三维骨生物可降解聚合物系统。最后，我们将进行一系列的实验来评估这些材料单独或与骨细胞一起修复骨缺损的能力。＊＊＊

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. ***