Microengineered Osteon-Mimetic Composite

南卡罗来纳州大学材料研究部生物材料项目的EAGER奖旨在开发新型细胞种植结构，模拟密质骨的基本结构单元。拟议的研究将制作一组由可生物降解的纳米纤维制成的粘合微管，这些纳米纤维与载有细胞的水凝胶复合材料层压在一起，以模仿天然骨基质中存在的骨单位的结构。预期这些构建体提供结构支持，促进营养物质的运输，并提供用于骨生长的细胞外基质的均匀产生的环境。以前用种植体重建大骨缺损的努力受到营养交换不足和缺乏机械强度的限制。该项目的智力价值在于模拟骨生物材料设计和支架制造的概念，这将克服早期骨骼再生研究的一些基本限制。该项目的三个主要任务是制备：1）具有受控理化和生物学特性的水凝胶/磷灰石复合材料，作为组织结构的软相，用于均匀的细胞接种; 2）骨模拟纤维增强层压微管，用于向接种的细胞提供营养; 3）由一组粘合的载有细胞的微管组成的组织结构，用于结构稳定性。更广泛的影响在于将仿生生物材料概念应用于其他领域，如心脏瓣膜置换、靶向药物递送和干细胞治疗。拟议的研究预计将为学生提供一个独特的多学科环境，整合材料科学与工程，生物化学和生物学，以设计和测试用于组织再生的新型生物材料。此外，该项目将利用校园内的既定项目招募和培训少数族裔学生，这些学生将接受研究活动培训，以合成和测试新型生物材料，用于再生医学中潜在的尖端生物医学应用。 在美国，每年有超过一百万例骨折需要干预，其中许多是以骨移植手术的形式。这些需求包括肿瘤切除、创伤或感染引起的骨丢失、年龄相关性骨折和先天性骨骼畸形。尽管在骨科和颌面外科中对骨移植物的临床需求是恒定的，但该过程受到骨供应有限、发病率、恢复时间长和手术成本的困扰。这些植入物材料的使用受到其结构不稳定性以及这些植入物的中心部分缺乏血液供应以供其及时生长的限制。这些缺点可能导致长的恢复时间和这些植入物在体内的整合。该项目的目的是开发新型复合材料，其灵感来自于密质骨的天然微结构，并克服目前使用的骨移植材料的一些局限性，例如它们的机械不稳定性和缺乏及时成熟骨的营养和氧气供应的运输。该项目为教学和培训学生创造了一个独特的多学科环境。该项目将利用校园正在进行的项目，从南卡罗来纳州招募代表性不足的学生，并培训他们在再生生物医学应用的生物材料方面的尖端研究技术。此外，在夏季，来自南卡罗来纳州的高中生将参加生物材料研究活动，以鼓励他们追求科学和工程事业。

This EAGER award by the Biomaterials program in the Division of Materials Research to University of South Carolina is to develop novel cell-seeded constructs that mimick the basic structural unit of the compact bone. The proposed study will fabricate a set of bonded microtubes fabricated from biodegradable nanofibers that are laminated with a cell-laden hydrogel composite to mimic the structure of osteons that are present in the natural bone matrix. These constructs are expected to provide structural support, facilitate transport nutrients and provide an environment for the homogenous production of extracellular matrix for the bone growth. Previous efforts to reconstruct large bone defects with implants were limited by insufficient exchange of nutrients and lack of mechanical strength. The intellectual merit of this project is in the concept that osteon-mimetic biomaterial design and fabrication of scaffolds that would overcome some of the fundamental limitations of the earlier skeletal regeneration studies. The three main tasks of the project are to prepare: 1) a hydrogel/apatite composite with controlled physiochemical and biological properties as the soft phase of the tissue construct for uniform cell seeding; 2) osteon-mimetic fiber-reinforced laminated microtubes for the nutrient supply to the seeded cells; and 3) a tissue construct that is comprised of a set of bonded cell-laden microtubes for structural stability. The broader impact lies in the application of biomimetic biomaterial concept to other areas such as heart valve replacement, targeted drug delivery and stem cell therapy. The proposed research is expected to provide students with a unique multidisciplinary environment that integrates materials science and engineering, biochemistry, and biology to design and test novel biomaterials for tissue regeneration. Additionally, the project will utilize the established programs in the campus for the recruitment and training of minority students and these students will be trained in research activities to synthesize and test novel biomaterials for potential cutting-edge biomedical applications in regenerative medicine. More than one million fractures each year in the US require intervention, many in the form of bone graft procedures. These include the needs arising from resection of tumors, bone loss due to trauma or infection, age-related fractures, and congenital skeletal deformities. Despite the constant clinical need for bone graft in orthopedic and maxillofacial surgery, the process is beleaguered by the limited supply of bone, morbidity, long recovery time, and cost of the operation. The use of these implant materials is limited by their structural instability and lack of blood supply in the central part of these implants for their timely growth. These drawbacks could lead to long recovery times and integration of these implants in the body. The aim of this project is to develop novel composite materials that are inspired by the natural microstructure of the compact bone, and to overcome some of the limitations of currently used bone graft materials such as their mechanical instability and lack of transport of nutrients and oxygen supply for the maturation of bone in a timely manner. This project creates a unique multidisciplinary environment for teaching and training students. With the use of ongoing program at the campus, this project will recruit underrepresented students from South Carolina, and train them in cutting-edge research techniques in biomaterials for regenerative biomedical applications. In addition, during the summer time, high school students from South Carolina will participate in the biomaterials research activities to encourage them to pursue careers in science and engineering.