NSF/DMR-BSF: Nanoparticle-Stabilized PolyHIPEs that Promote Integrin-Mediated Osteogenesis

NSF/DMR-BSF：促进整合素介导的成骨的纳米颗粒稳定的 PolyHIPE

• 批准号: 1822196
• 负责人: Elizabeth Cosgriff-Hernandez
• 金额: $ 40万
• 依托单位: University of Texas at Austin
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1822196&HistoricalAwards=false
• 关键词: NSF; DMR; BSF; Nanoparticle; Stabilized

NON-TECHNICAL: Over one million surgical procedures are performed each year to treat bone injury and defects with an associated medical cost of over 5 billion dollars. Current procedures are fraught with problems that limit clinical success. One important approach for the treatment of bone fractures and defects is in the use of injectable fillers or cements. However, current bone cements do not adequately support bone healing, and may lead to poor clinical outcomes. This project utilizes a novel method in preparing polymers to generate an injectable bone filler that cures within the body, and forming a rigid and strong foam implant. This specially prepared polymer composite is expected to promote bone regeneration and growth by stimulating cells around the polymer. In addition to improving care for patients that suffer from traumatic bone injuries, these studies will provide exceptional training of future scientists in materials research. Educational and outreach activities will focus on strategies that enhance recruitment and retention of women and minorities in science and engineering areas in addressing the national needs to increase the participation of underrepresented groups in the scientific and engineering workforce. Finally, this Israeli-US partnership provides opportunities to train students to compete globally through a summer internship exchanges at the partnering laboratories.TECHNICAL: Current injectable bone cements used for bone fracture and repairs are of limited value because of lack of cement porosity, limited biodegradability, prolonged recovery time and lack of significant stabilization and support of the damaged bones. In addition, these synthetic scaffolds lack cellular cues to promote bone repair and regeneration, without the addition of growth factors in the injectable cements, and these involve high costs and safety concerns. To address these issues, this project will develop a novel high internal phase emulsion graft polymers (polyHIPE) using an emulsion-templating method. The graft polymers prepared will be used to generate injectable bone fillers that cure within the body to form rigid foams that are: 1) surface-modified with collagen-mimetic proteins to induce osteogenic differentiation of mesenchymal stem cells; and 2) prepared without surfactants to minimize concerns with respect to biocompatibility of leached breakdown products from these surfactants. Additionally, bioactive nanoparticles with different size, distribution, and hydrophobicity will be incorporated in these graft polymers, and these nanoparticles are expected to migrate spontaneously to the pore surface of the foam during curing process in the body. This migration of nanoparticle not only strengthen the cured polymer cement but is also expected to promote enhanced bone regeneration by stimulating cells in the polymer pores. Overall, these studies are designed such that fundamental advances will be made in synthesis and application of novel materials for the integrin-mediated osteogenesis for injectable bone grafts. Although this work is focused on bone repair and regeneration, the knowledge gained has potential to be applied to a variety of other applications such as development of membranes with well-defined pore size in battery and for water purification. Students participating in the research will receive rigorous training in material science and tissue engineering that will prepare them for careers in biomedical engineering. This collaboration with Israeli scientists would also provide opportunities in training students through a summer internship exchange at the partnering laboratory and prepare these students to compete globally. An integrated educational platform will focus on strategies that enhance recruitment and retention of women and minorities in engineering to address the national need to increase the participation of underrepresented groups in the scientific and engineering workforce.

非技术性：每年进行超过一百万次外科手术来治疗骨损伤和骨缺损，相关的医疗费用超过50亿美元。目前的手术充满了限制临床成功的问题。治疗骨折和骨缺损的一种重要方法是使用可注射的填充剂或粘固剂。然而，目前的骨水泥不能充分支持骨愈合，并可能导致不良的临床结果。该项目利用一种新的方法制备聚合物，以产生可在体内固化的可注射骨填充物，并形成刚性和坚固的泡沫植入物。这种特殊制备的聚合物复合材料有望通过刺激聚合物周围的细胞来促进骨再生和生长。除了改善对创伤性骨损伤患者的护理外，这些研究还将为未来的材料研究科学家提供特殊的培训。教育和外联活动将侧重于加强科学和工程领域征聘和留住妇女和少数群体的战略，以满足国家增加科学和工程工作队伍中代表性不足群体的参与的需要。最后，以色列和美国的合作伙伴关系通过在合作实验室进行暑期实习交流，为培养学生在全球范围内竞争提供了机会。技术：目前用于骨折和修复的可注射骨水泥价值有限，因为缺乏水泥孔隙率，生物降解性有限，恢复时间长，缺乏对受损骨骼的显著稳定和支持。此外，这些合成支架缺乏促进骨修复和再生的细胞因子，在可注射骨水泥中没有添加生长因子，并且这些涉及高成本和安全性问题。为了解决这些问题，本项目将使用乳液模板法开发新型高内相乳液接枝聚合物（polyHIPE）。所制备的接枝聚合物将用于产生可注射的骨填充物，其在体内固化以形成硬质泡沫，所述硬质泡沫：1）用胶原模拟蛋白进行表面改性以诱导间充质干细胞的成骨分化;和2）在没有表面活性剂的情况下制备，以最大限度地减少关于来自这些表面活性剂的沥滤分解产物的生物相容性的担忧。此外，具有不同尺寸、分布和疏水性的生物活性纳米颗粒将被掺入这些接枝聚合物中，并且这些纳米颗粒预期在体内固化过程中自发地迁移到泡沫的孔表面。纳米颗粒的这种迁移不仅增强了固化的聚合物水泥，而且还有望通过刺激聚合物孔中的细胞来促进增强的骨再生。总体而言，这些研究的设计，使根本性的进展，将在合成和应用的新材料的整合素介导的成骨注射骨移植。虽然这项工作的重点是骨修复和再生，但所获得的知识有可能应用于各种其他应用，如电池和水净化中具有明确孔径的膜的开发。参与研究的学生将接受材料科学和组织工程方面的严格培训，为他们在生物医学工程领域的职业生涯做好准备。与以色列科学家的合作还将提供机会，通过在合作实验室进行暑期实习交流来培训学生，并使这些学生为参与全球竞争做好准备。一个综合教育平台将侧重于加强工程领域妇女和少数民族的招聘和保留的战略，以满足国家增加科学和工程劳动力中代表性不足群体的参与的需要。