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

非技术性：每年进行100多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。目前的程序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物或粘固剂。然而，目前的骨水泥不足以支持骨愈合，并可能导致较差的临床结果。该项目利用一种新的方法来制备聚合物，以产生可注射的骨填充物，在体内治愈，并形成坚硬而坚固的泡沫植入物。这种特制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。除了改善对遭受创伤性骨损伤的患者的护理外，这些研究还将为未来的科学家提供材料研究方面的特殊培训。教育和外联活动将侧重于加强招聘和留住科学和工程领域的妇女和少数群体的战略，以满足国家增加科学和工程劳动力中任职人数不足的群体的需要。最后，这种以色列和美国的合作关系提供了机会，通过在合作实验室的暑期实习交流来培训学生参加全球竞争。技术：目前用于骨折和修复的可注射骨水泥价值有限，因为缺乏骨水泥孔隙率，有限的生物降解性，恢复时间延长，以及对受损骨骼缺乏显著的稳定和支持。此外，这些合成支架缺乏促进骨修复和再生的细胞信号，在可注射骨水泥中没有添加生长因子，这涉及到高成本和安全问题。为了解决这些问题，本项目将使用乳液模板方法开发一种新型的高内相乳液接枝聚合物(PolyHIPE)。制备的接枝聚合物将用于产生可注射的骨填充物，在体内固化以形成硬质泡沫，这些泡沫是：1)用类胶原蛋白进行表面修饰，以诱导间充质干细胞成骨分化；以及2)不使用表面活性剂制备，以最大限度地减少对这些表面活性剂浸出的分解产物的生物兼容性的担忧。此外，不同大小、分布和疏水性的生物活性纳米颗粒将被整合到这些接枝聚合物中，这些纳米颗粒有望在体内固化过程中自发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，还有望通过刺激聚合物孔中的细胞来促进骨再生。总体而言，这些研究的设计将使整合素介导的可注射骨移植成骨新材料的合成和应用取得根本性进展。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其他各种应用，如开发电池中具有明确孔径的膜和水净化。参与这项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通过在Partnering实验室的暑期实习交流为学生提供培训机会，并为这些学生在全球竞争做好准备。综合教育平台将侧重于加强招聘和留住工程学领域妇女和少数群体的战略，以满足国家需要增加科学和工程学劳动力中任职人数不足的群体的参与。

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.