DEVELOPMENT OF PICKERING EMULSIONS AS INJECTABLE BONE GRAFTS

作为可注射骨移植物的 Pickering 乳液的开发

• 批准号: 8581393
• 负责人: Elizabeth Marie Cosgriff-Hernandez
• 金额: $ 21.06万
• 依托单位: TEXAS ENGINEERING EXPERIMENT STATION
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8581393
• 关键词: Architecture; Body Temperature; Bone Cements; Bone Growth; Bone Regeneration; Bone Transplantation; Caring; Cell Differentiation process; Cells; Characteristics; Chemistry; Clinical; Cues; Defect; Development; Emulsions; Encapsulated; Excision; Fracture; Generations; Grant; Growth Factor; Hydrogels; Hydrophobicity; Hydroxyapatites; In Situ; Injectable; Injury; Inpatients; Investigation; Laboratories; Location; Mechanics; Medical; Mesenchymal Stem Cells; Methodology; Methods; Molds; Natural regeneration; Operative Surgical Procedures; Organ Transplantation; Osteogenesis; Patients; Phase; Physiological; Polymers; Porosity; Property; Quality of life; Research; Safety; Shapes; Site; Surface; Technology; Time; Tissue Engineering; Tissue Grafts; Tissues; Translations; Transplantation; Vascularization; Viscosity; Work; bone; bone morphogenetic protein 2; cost; improved; in vivo; musculoskeletal injury; nanoparticle; novel; osteoblast differentiation; osteogenic; polymerization; public health relevance; reconstruction; repaired; scaffold; self assembly; statistics; tissue regeneration

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.

描述（由申请人提供）：肌肉骨骼损伤对生活质量有巨大影响，并且仍然是患者寻求医疗护理的主要原因之一。当传统移植无法实现或失败时，工程组织移植具有修复受损组织的潜力。我们的实验室开发了一种新的乳液模板方法来生成用于骨再生的微细胞聚合物支架。我们实验室的一项重大进展是通过开发可注射的高孔隙度骨移植物，将这项技术转化为组织工程。原位固化的可注射支架可以填补不规则形状的缺陷，改善支架与周围组织之间的接触，并且消除了昂贵的成型技术的需要与目前的低孔隙度和可生物降解性（如骨水泥）或无法承受生理负荷（如水凝胶）的注射材料相比，乳液模板有几个优点。在目前的建议中，我们将开发第二代polyHIPE，利用羟基磷灰石（HA）纳米颗粒赋予骨移植物骨的诱导特性。我们还将研究在治愈前在HIPEs中进行细胞包封的潜力，作为在缺陷部位传递和保留MSCs的一种手段。具体目标1：开发和表征含HA纳米颗粒的聚hipe支架的成骨细胞分化。具体目标2：评估可注射聚hipe支架的关键部署变量和包封后hMSCs的活力。在R21项目成功完成后，所提出的移植物将是骨移植手术的重大进步，它提供了一个高度多孔的支架，1)空间填充不规则形状的缺陷，促进更好的组织整合；2)固化到合适的机械强度；3)将hMSCs直接输送到缺陷部位；4)为这些hMSCs的成骨分化提供了必要的线索。R01的后续研究将检验这些骨诱导移植物在促进临界尺寸骨缺损再生方面的潜力，并提供大型骨移植物成骨和血管形成的扩展机制研究。