PROMOTION OF ALVEOLAR SOCKET HEALING WITH BIOPOLYMERS

描述(申请人提供)：本方案的目标是通过植入生物活性的、可生物降解的聚合物支架，促进在临界大小的牙槽窝缺损中形成耐用的骨组织。我们实验室的初步工作表明，兔拔牙槽骨模型的愈合牙槽骨内的成骨作用与特定生长因子定位的增加有关。我们计划通过总结在愈合的亚临界拔牙槽骨缺损中观察到的那些事件，促进临界大小的牙槽窝缺损的骨形成，这种牙槽窝不能自然愈合。我们计划重述的关键步骤是血管生长、祖细胞迁移和骨形成，因为这些事件在骨组织的愈合中最重要。这将通过植入我们实验室开发的可生物降解的聚(富马酸丙二醇酯-乙二醇共聚物)[P(PF-co-EG)]水凝胶支架来实现，该支架也可以作为特定生长因子的受控输送载体。首先，将开发一种仿生P(PF-co-EG)水凝胶支架，在伤口愈合的初始阶段释放成纤维细胞生长因子-2，这是伤口愈合和血管生成的早期因素，以促进缺损处血管的生长和维持。其次，支架的设计将通过加入一种对成骨细胞具有选择性的粘附性骨桥蛋白衍生多肽来鼓励祖细胞迁移到缺损处，同时通过防止软组织入侵来促进伤口愈合组织基质的形成。第三，支架将释放转化生长因子-β1，一种有效的分化因子，通过在缺损处向成骨细胞分化来促进骨形成。将通过光学显微镜、免疫组织化学染色切片的组织形态计量学和微型计算机断层分析来评估骨形成的数量和新形成的骨的质量。该项目将提供有关新的组织诱导牙科生物材料的临床有价值的信息，用于恢复口腔功能和美学，为患有临界大小牙槽窝缺陷的患者提供帮助。

DESCRIPTION (provided by applicant): The objective of this proposal is to promote the formation of durable bone tissue in critical size alveolar socket defects by the implantation of a biologically active, biodegradable polymer scaffold. Preliminary work in our laboratory has shown that osteogenesis within the healing alveolar bone of a rabbit tooth extraction socket model, a subcritical size defect, correlates with an increase in specific growth factor localizations. We plan to promote bone formation in a critical size alveolar socket defect, which does not heal naturally, by recapitulating those events observed in the healing, subcritical extraction socket defect. The key steps we plan to recapitulate are vascular growth, progenitor cell migration, and bone formation, as these events are most significant in the healing of bone tissue. This will be achieved by implanting a biodegradable poly(propylene fumarate-co-ethylene glycol) [P(PF-co-EG)] based hydrogel scaffold, developed in our laboratory, that also serves as a carrier for the controlled delivery of specific growth factors. First, a biomimetic P(PF-co-EG) hydrogel scaffold will be developed to release fibroblastic growth factor-2, an early factor in wound healing and angiogenesis, during the initial stages of healing to promote vascular growth and maintenance within the defect site. Second, the scaffold will be designed to encourage progenitor cell migration into the defect site by the incorporation of an adhesive osteopontin-derived peptide selective for osteoblastic cells, while enhancing the formation of a wound healing tissue matrix by preventing soft tissue invasion. Third, the scaffold will release transforming growth factor-beta1, a potent differentiating factor, to encourage bone formation by osteoblastic differentiation of progenitor cells within the defect site. The amount of bone formation and quality of the newly formed bone will be assessed by light microscopy, histomorphometry of immunohistochemically stained sections, and micro-computed tomography analysis. This project will provide clinically valuable information regarding new tissue-inducing dental biomaterials for restoring oral function and esthetics to individuals who are afflicted with critical size alveolar socket defects.