Periodontal Engineering by Growth Factor Release from Hollow HA Microspheres

描述(申请人提供)：新支架的开发及其加工成复杂结构对于组织的修复和再生正变得越来越重要，并且是最终临床应用的组织工程学进步的关键步骤。R15建议的假设是，由中空的羟基磷灰石(HA)微球可以形成一种结合了机械支撑和生物活性的生物活性支架。这项工作的重点是探索支架开发的关键步骤，最终应用于牙周组织工程，但结果有望在组织工程中得到更广泛的应用。我们的初步工作表明，通过在磷酸盐水溶液中与硼酸盐玻璃微球反应，可以在近室温下形成中空HA微球，并且通过改变中空微球壁的孔隙率，可以控制微球中包裹的蛋白质牛血清白蛋白进入磷酸盐缓冲盐水(PBS)的周围介质中。我们的方法将是(1)综合表征由硼酸盐玻璃形成的中空HA微球的结构和力学性能，以及(2)评估微球中的生长因子在周围介质中的控制释放和生物活性。骨形态发生蛋白(BMP-2)被选为生长因子，因为它具有强大的诱导成骨和牙骨质形成的能力，这两个过程涉及牙周修复。我们的长期目标是构建中空HA微球的复合支架，使其能够定制力学性能，释放多种生长因子，细胞渗透，并与周围组织整合，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中空HA微球的结构和机械性能以及用于输送生长因子的微球的价值的重要信息。体外研究预计将导致更大的应用(R01)，涉及多个校园，其中牙周组织工程将作为从含有中空HA微球的复合结构中输送生长因子的功能在体内进行密集研究。与这项研究一起追求的其他目标是：(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，这对开发新的和改进的生物材料至关重要，以及(2)加强密苏里-罗拉大学目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，在某种程度上影响着几乎所有的成年人。几种牙周病导致作为头面部主要器官的牙齿丧失，并严重损害生理功能。基于生物材料支架的细胞或生长因子输送的组织工程方法，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，在某种程度上影响着几乎所有的成年人。几种牙周病导致作为头面部主要器官的牙齿丧失，并严重损害生理功能。基于生物材料支架的细胞或生长因子输送的组织工程方法，为牙周组织的完全再生提供了有前途的解决方案。

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.