Microengineered Osteon-Mimetic Composite

这项由材料研究部的生物材料项目授予南卡罗来纳大学的热切奖项是开发模仿致密骨基本结构单元的新型细胞种子结构。这项拟议的研究将制造一套由可生物降解的纳米纤维制成的粘合微管，这些微管与载细胞的水凝胶复合材料层叠，以模仿天然骨基质中存在的骨离子的结构。这些构建物有望为骨生长提供结构支持，促进营养物质的运输，并为细胞外基质的均质生产提供环境。以前用植入物重建大型骨缺损的努力受到营养交换不足和机械强度不足的限制。这个项目的智力价值在于，仿骨生物材料的设计和支架的制造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：1)水凝胶/磷灰石复合材料，具有可控的物理化学和生物学特性，作为组织结构的软相，用于均匀的细胞种植；2)仿骨纤维增强的层状微管，用于向所种植的细胞提供营养；以及3)由一组粘合的细胞负载的微管组成的组织结构，以保证结构的稳定性。更广泛的影响在于将仿生生物材料的概念应用于其他领域，如心脏瓣膜置换、靶向给药和干细胞治疗。这项拟议的研究有望为学生提供一个独特的多学科环境，将材料科学与工程、生物化学和生物学结合在一起，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建立的项目来招募和培训少数族裔学生，这些学生将在研究活动中接受培训，以合成和测试用于再生医学潜在尖端生物医学应用的新型生物材料。在美国，每年有100多万个骨折需要干预，其中许多是以植骨手术的形式进行的。这些需求包括肿瘤切除、创伤或感染导致的骨丢失、与年龄相关的骨折和先天性骨骼畸形。尽管骨科和颌面外科对植骨的临床需求一直很高，但骨量有限、发病率高、恢复时间长、手术费用高等问题一直困扰着这一过程。这些植入物材料的使用受到其结构不稳定以及这些植入物中央缺乏血液供应以及时生长的限制。这些缺陷可能导致较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，灵感来自于致密骨的自然微结构，并克服目前使用的骨移植材料的一些局限性，如机械不稳定、缺乏营养物质的运输和及时供氧来促进骨的成熟。该项目为学生的教学和培训创造了一个独特的多学科环境。利用校园正在进行的计划，该项目将从南卡罗来纳州招募代表人数不足的学生，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，暑期期间，南卡罗来纳州的高中生将参加生物材料研究活动，鼓励他们投身科学和工程事业。

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.