PROMOTION OF ALVEOLAR SOCKET HEALING WITH BIOPOLYMERS

描述（由申请人提供）：本提案的目的是通过植入生物活性、可生物降解的聚合物支架，促进关键尺寸牙槽窝缺损中耐久骨组织的形成。我们实验室的初步工作表明，兔拔牙窝模型（亚临界尺寸缺损）愈合牙槽骨内的成骨与特定生长因子定位的增加相关。我们计划通过重现在愈合的亚临界拔牙窝缺损中观察到的那些事件来促进不能自然愈合的临界尺寸牙槽窝缺损中的骨形成。我们计划概括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（丙二醇酯-共-乙二醇）[P（PF-co-EG）]水凝胶支架来实现，该支架也可作为特定生长因子受控递送的载体。首先，将开发仿生P（PF-co-EG）水凝胶支架，以在愈合的初始阶段释放成纤维细胞生长因子-2（伤口愈合和血管生成的早期因子），以促进缺损部位内的血管生长和维持。第二，支架将被设计为通过掺入对成骨细胞具有选择性的粘附性骨桥蛋白衍生肽来促进祖细胞迁移到缺损部位，同时通过防止软组织侵入来增强伤口愈合组织基质的形成。第三，支架将释放转化生长因子-β 1，一种有效的分化因子，通过缺损部位内祖细胞的成骨细胞分化促进骨形成。将通过光学显微镜、化学染色切片的组织形态计量学和显微计算机断层扫描分析评估骨形成量和新形成骨的质量。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的个人谁是患有临界尺寸的牙槽窝缺损。

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.