Genetically Designed Materials for Cartilage Repair

描述（由申请人提供）： 已经研究了用于椎间盘修复或再生的基于生物学的策略，包括生长因子或蛋白酶抑制剂的蛋白质或基因递送，使用干细胞、自体细胞或同种异体细胞的细胞补充，以及生物材料补充，包括使用原位固化或交联的聚（乙烯基）醇、聚（环氧乙烷）和聚（氨基甲酸酯）。在该补充申请中，我们提出开发一种原位交叉生物基材料，其可以是生物诱导的，并且在植入髓核后充当功能支架。在正在进行的关于母基金“用于软骨修复的遗传设计材料”的工作中，该实验室合成并评估了一种可用于关节软骨缺损填充应用的原位交叉弹性蛋白多肽。拟议的工作的目的是开发这些多肽的修改版本，将层粘连蛋白肽序列，我们认为可能是适当的支持椎间盘修复成熟或受损组织。这个补充项目将为莱曼W博士提供一年的研究经验。惠特拉奇，神经外科住院医师，三年级。惠特拉奇博士拥有博士学位。在生理学和有兴趣追求的职业生涯作为一个临床研究者集中在脊柱后，完成他的居住。拟议的研究包括基因设计，重组蛋白合成，生物材料表征，细胞和分子生物学，生物化学和组织化学相关的椎间盘生物学技术。这些研究将推动Whitlatch博士朝着他的目标发展，即开发一个转化研究项目，重点是设计和开发治疗椎间盘疾病的新策略。

DESCRIPTION (provided by applicant): Biologically-based strategies for intervertebral disc repair or regeneration have been investigated including protein or gene delivery of growth factors or protease inhibitors, cell supplementation using stem, autologous cells or allogenic cells, and biomaterial supplementation including the use of in situ curing or cross-linking poly(vinyl) alcohols, poly(ethylene oxide), and poly(urethane)s. In this supplemental application, we propose to develop an in situ cross-linkable biologically-based material that may be bioinductive and act as a functional scaffold after implantation in the nucleus pulposus. In work ongoing on the parent grant, Genetically Designed Materials for Cartilage Repair", the laboratory has synthesized and evaluated an in situ cross-linkable elastin-based polypeptide useful for defect-filling applications in articular cartilage. The purpose of the proposed work is to develop modified versions of these polypeptides incorporating laminin peptide sequences that we believe may be appropriate for supporting intervertebral disc repair in mature or damaged tissues. This supplemental project will provide support for a one-year research experience for Dr. Lyman W. Whitlatch, a third-year neurosurgery resident. Dr. Whitlatch holds a Ph.D. in physiology and is interested in pursuing a career as a clinical investigator focused in spine upon completion of his residency. The proposed studies incorporate techniques of gene design, recombinant protein synthesis, biomaterial characterization, cell and molecular biology, biochemistry and histochemistry relevant to intervertebral disc biology. These studies will move Dr. Whitlatch towards his goal of developing a translational research program focused on the design and development of novel strategies for treatment of disc disorders.