DEVELOPMENT OF PICKERING EMULSIONS AS INJECTABLE BONE GRAFTS

描述（由申请人提供）：肌肉骨骼损伤对生活质量有巨大影响，仍然是患者寻求医疗护理的主要原因之一。当传统的移植无法获得或失败时，工程组织移植物具有修复受损组织的潜力。我们的实验室已经开发了一种新的乳液模板方法来生成用于骨再生的微孔聚合物支架。我们实验室的一个重大进展是通过开发可注射的高孔隙度骨移植物将该技术转化为组织工程。原位固化的可注射支架可以填充不规则形状的缺陷，改善支架与周围组织之间的接触，并消除对昂贵的成型技术的需要。13，14乳液模板具有优于目前孔隙率低和生物降解性差的可注射材料的几个优点（例如，骨水泥）或不能承受生理负荷（例如，水凝胶）。在目前的提案中，我们将开发第二代聚HIPE，其利用羟基磷灰石（HA）纳米颗粒赋予骨移植物骨诱导特性。我们还将研究在固化前HIPE中细胞包封的潜力，作为在缺损部位递送和保留MSC的手段。具体目标1：在含有HA纳米颗粒的聚HIPE支架上开发和表征成骨细胞分化特定目标2：评价可注射聚HIPE支架的关键部署变量和包封后hMSC的活力。在成功完成该R21项目后，通过提供高度多孔的支架，所提出的移植物将是骨移植程序的重大进步，该支架1）空间填充不规则形状的缺损以促进上级组织整合; 2）固化至合适的机械强度; 3）将hMSC直接递送至缺损部位;以及4）为这些hMSC的成骨分化提供必要的线索。R 01中的后续研究将检查这些骨诱导移植物增强临界尺寸骨缺损再生的潜力，并提供大骨移植物中骨生成和血管化的扩展机制研究。

DESCRIPTION (provided by applicant): Musculoskeletal injuries have an enormous impact on quality of life and remain one of the leading reasons that patients seek medical care. Engineered tissue grafts have the potential to repair damaged tissues when traditional transplants are unavailable or fail. Our laboratory has developed a novel emulsion templating methodology to generate microcellular polymer scaffolds for bone regeneration. A significant advance by our laboratory is the translation of this technology to tissue engineering through the development of injectable, high porosity bone grafts. Injectable scaffolds that cure in situ can fil irregular shaped defects, improve contact between the scaffold and surrounding tissue, and eliminate the need for costly molding techniques.13,14 Emulsion templating has several advantages over current injectable materials that suffer from low porosity and biodegradability (e.g., bone cements) or inability to withstand physiological loading (e.g., hydrogels). In the current proposal, we will develop a second generation polyHIPE that utilize hydroxyapatite (HA) nanoparticles to impart osteoiductive character to the bone graft. We will also investigate the potential of cell encapsulation in the HIPEs prior to cure as a means to deliver and retain MSCs at the defect site. Specific Aim 1: Develop and characterize osteoblastic differentiation on polyHIPE scaffolds containing HA nanoparticles Specific Aim 2: Evaluate key deployment variables of injectable polyHIPE scaffolds and viability of hMSCs after encapsulation. Following successful completion of this R21 project, the proposed grafts will be a significant advance in bone grafting procedures by providing a highly porous scaffold that 1) space-fills irregular shaped defects to promote superior tissue integration; 2) cures to suitable mechanical strength; 3) delivers hMSCs directly to the defect site; and 4) provides the necessary cues for osteogenic differentiation of those hMSCs. Subsequent investigation in an R01 will examine the potential of these osteoinductive grafts to enhance regeneration in critical size bone defects and provide expanded mechanistic studies of osteogenesis and vascularization in large bone grafts.