Periodontal Engineering by Growth Factor Release from Hollow HA Microspheres

描述（由申请人提供）：新型支架的开发及其加工成复杂结构对于组织的修复和再生变得越来越重要，并且是最终临床应用的组织工程进步的关键步骤。该R15提案的假设是，一种将机械支撑与生物活性相结合的生物活性支架可以由空心羟基磷灰石（HA）微球形成。这项工作的重点是探索支架开发的关键步骤，以最终应用于牙周组织工程，但结果预计将在组织工程中有更广泛的应用。我们的初步工作表明，通过硼酸盐玻璃微球在磷酸盐水溶液中反应，可以在接近室温的情况下形成空心透明质酸微球，并且通过改变空心微球壁的孔隙率可以控制微球中封装的蛋白质牛血清白蛋白释放到磷酸盐缓冲盐水（PBS）周围介质中。我们的方法是 (1) 全面表征由硼酸盐玻璃形成的空心 HA 微球的结构和机械性能，(2) 评估生长因子从微球到周围介质的受控释放和生物活性。骨形态发生蛋白 (BMP-2) 被选为生长因子，因为它具有诱导成骨和牙骨质形成（牙周修复涉及的多个过程中的两个）的强大能力。我们的长期目标是制造空心 HA 微球复合支架，使其能够调整机械性能、释放多种生长因子、细胞浸润以及与周围组织的整合，最终应用于牙周和其他组织的工程。目前的 R15 项目将提供有关这些空心 HA 微球的结构和机械性能以及微球在生长因子输送中的价值的重要信息。体外研究预计将产生更大规模的应用（R01），涉及多个校区，其中将在体内深入研究牙周组织工程作为含有空心 HA 微球的复合结构递送生长因子的函数。与该研究相结合的其他目标是（1）让研究生和本科生接触材料科学和生物科学的跨学科研究，这对于开发新型和改进的生物材料至关重要，以及（2）加强密苏里大学罗拉分校当前和未来在生物医学研究和教育方面的努力。牙周病是世界上最常见的传染病之一，几乎在某种程度上影响着所有成年人。一些牙周疾病会导致颅面部主要器官牙齿的丧失，并严重损害生理功能。基于从生物材料支架传递细胞或生长因子的组织工程方法，为牙周组织的完全再生提供了有前途的解决方案。 公共卫生相关性：牙周病是世界上最常见的传染病之一，几乎在某种程度上影响着所有成年人。一些牙周疾病会导致颅面部主要器官牙齿的丧失，并严重损害生理功能。基于从生物材料支架传递细胞或生长因子的组织工程方法，为牙周组织的完全再生提供了有前景的解决方案。

DESCRIPTION (provided by applicant): The development of new scaffolds and their processing into complex structures are becoming increasingly important for the repair and regeneration of tissues and are a key step to tissue engineering advances for ultimate clinical application. The hypothesis of this R15 proposal is that a bioactive scaffold combining mechanical support with biological activity may be formed from hollow hydroxyapatite (HA) microspheres. The focus of the work is to explore key steps in the development of scaffolds for eventual application to tissue engineering of the periodontium, but the results are expected to have additional wider applications to tissue engineering. Our preliminary work showed that hollow HA microspheres can be formed at near room temperature by reacting borate glass microspheres in an aqueous phosphate solution, and that the release of an encapsulated protein, bovine serum albumin, from the microspheres into a surrounding medium of phosphate buffered saline (PBS) is controllable by altering the porosity of the hollow microsphere wall. Our approach will be to (1) comprehensively characterize the structure and mechanical properties of hollow HA microspheres formed from borate glass, and (2) evaluate the controlled release and biological activity of a growth factor from the microspheres into a surrounding medium. Bone morphogenetic protein (BMP-2) is chosen as the growth factor because of its potent ability to induce osteogenesis and cementum formation, two of the multiple processes involved in periodontal repair. Our long-term goal is to fabricate composite scaffolds of hollow HA microspheres which allow tailoring of the mechanical properties, release of multiple growth factors, cellular infiltration, and integration with surrounding tissue, for eventual application to engineering of periodontal and other tissues. The present R15 project will provide important information on the structure and mechanical properties of these hollow HA microspheres and the value of the microspheres for use in the delivery of growth factors. The in vitro studies are anticipated to lead to a larger application (R01), involving multiple campuses, in which engineering of the periodontium will be intensely investigated in vivo as a function of delivery of growth factors from composite constructs containing hollow HA microspheres. Additional goals to be pursued in conjunction with the research are (1) exposure of graduate and undergraduate students to cross-disciplinary research in materials science and biological sciences, which is critical to the development of new and improved biomaterials, and (2) strengthening current and future efforts in biomedical research and education at the University of Missouri-Rolla. Periodontal disease is one of the most common infectious diseases in the world, affecting virtually all adults to some degree. Several periodontal diseases lead to the loss of teeth as a major organ in the craniofacial region, and severe compromise in physiological function. Tissue engineering approaches, based on cell or growth factor delivery from biomaterials scaffolds, offer promising solutions for complete regeneration of the periodontium. PUBLIC HEALTH RELEVANCE: Periodontal disease is one of the most common infectious diseases in the world, affecting virtually all adults to some degree. Several periodontal diseases lead to the loss of teeth as a major organ in the craniofacial region, and severe compromise in physiological function. Tissue engineering approaches, based on cell or growth factor delivery from biomaterials scaffolds, offer promising solutions for complete regeneration of the periodontium.