BRIGE: The Fabrication of a Novel, Full Thickness, Artificial Bone Graft for Bone Tissue Engineering

BRIGE：用于骨组织工程的新型全层人工骨移植物的制造

• 批准号: 0926970
• 负责人: Joseph Freeman
• 金额: $ 17.48万
• 依托单位: Virginia Polytechnic Institute and State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0926970&HistoricalAwards=false
• 关键词: BRIGE; Fabrication; Novel; Full; Thickness

0926970FreemanBone loss due to trauma or disease is prevalent in the U.S. Over 3 million orthopaedic procedures are performed every year; approximately 500,000 of these are bone grafting procedures making bone second only to blood as the most transplanted material. Bone loss is usually treated using autografts or allografts. Although they do have their benefits, each of these materials has a set of drawbacks which limit the extent of their use. With this in mind, the objective of this project is to use tissue engineering to create new scaffolds as practical and functional alternatives for bone replacement and regeneration. The new scaffolds will have a nanofibrous structure and be structurally similar to natural bone, containing both cortical and trabecular areas and microvascularization. To accomplish this task we will complete the following objectives: 1) Perform a finite element analysis to discover the nanofiber orientation necessary for the scaffold to bear the appropriate load. 2) Construct fully mineralized, porous, nanofibrous scaffolds for trabecular bone by combining techniques for nanofiber mineralization, pore creation, and sintering. 3) Creating cortical bone like structures with vascular channels using electrospinning techniques with microfibers and nanofiber mineralization. 4) Creating a full thickness, porous load bearing scaffold by combining the trabecular and cortical scaffolds with sintering techniques. The resulting structure will be engineered from mineralized poly (L-lactic acid) nanofibers and will be designed to withstand the forces experienced in load bearing bones while having enough porosity to allow for full thickness cellular and tissue infiltration. Intellectual Merit: Although many studies have created scaffolds to replace bone, most of these seek to only replace trabecular bone. No currently available scaffold or technique seeks to mimic the structure and properties of both trabecular and cortical bone, including correctly placed vasculature. The creation of this scaffold would also lead to a solution to the problem of cell movement in nanofiber scaffolds. Typically the pores in nanofibrous scaffolds are too small to allow significant cellular infiltration. The method of micro-porous nanofibrous scaffold fabrication described in this project would solve this problem and could be used for the other tissue engineering applications. Broader Impacts: The proposed research will advance the field of tissue engineering through the creation of nanofibrous scaffolds that do not hinder cell motility and the production of a full thickness bone graft. This research will provide an opportunity for many students to gain experience in experimental design, data analysis, engineering, and the ability to work in a group environment. Dr. Freeman is devoted to establishing outreach programs to recruit students from underrepresented groups into engineering and science. Currently, he mentors graduate students from all segments of underrepresentation. Since arriving at Virginia Tech over 2 years ago he has also mentioned 3 undergraduates of underrepresented groups. Dr. Freeman is involved in the Multicultural Academic Opportunities Program (MAOP) and the Center for the Enhancement of Engineering Diversity (CEED) at Virginia Tech. Students will be chosen from these programs to conduct research based on this project. He will use aspects from this project in his presentations to encourage student interest in math, science, and engineering.

0926970弗里曼在美国，由于创伤或疾病导致的骨丢失很普遍。每年进行超过300万例矫形手术;其中约50万例是骨移植手术，使骨成为仅次于血液的最大移植材料。骨丢失通常使用自体移植物或同种异体移植物治疗。虽然它们确实有其优点，但这些材料中的每一种都有一系列限制其使用范围的缺点。考虑到这一点，本项目的目标是使用组织工程来创建新的支架，作为骨替代和再生的实用和功能性替代品。新的支架将具有纳米纤维结构，在结构上与天然骨相似，包含皮质和小梁区域以及微血管化。为了完成这项任务，我们将完成以下目标：1）进行有限元分析，以发现脚手架承受适当载荷所需的方向。2)通过结合骨矿化、造孔和烧结技术，构建完全矿化的多孔纳米纤维骨小梁支架。3)使用微纤维和微矿化的静电纺丝技术创建具有血管通道的皮质骨样结构。4)通过结合骨小梁和皮质支架与烧结技术来创建全厚度多孔承重支架。所得到的结构将由矿化的聚（L-乳酸）纳米纤维设计，并且将被设计为承受承重骨中经历的力，同时具有足够的孔隙率以允许全厚度细胞和组织浸润。智力优势：尽管许多研究已经创造了支架来替代骨，但大多数研究都只寻求替代骨小梁。目前没有可用的支架或技术试图模拟小梁骨和皮质骨的结构和性质，包括正确放置的脉管系统。这种支架的创建也将导致解决细胞在支架中移动的问题。通常，纳米纤维支架中的孔太小而不允许显著的细胞浸润。本计画所描述的微多孔奈米纤维支架制造方法将解决此问题，并可用于其他组织工程的应用。更广泛的影响：这项拟议中的研究将通过创造不阻碍细胞运动的纳米纤维支架和生产全厚度骨移植物来推进组织工程领域。这项研究将为许多学生提供一个机会，以获得经验，实验设计，数据分析，工程，并在一个小组的环境中工作的能力。弗里曼博士致力于建立外展计划，从代表性不足的群体招募学生进入工程和科学。目前，他指导来自代表性不足的各个领域的研究生。自从2年前来到弗吉尼亚理工大学以来，他还提到了3名代表性不足的本科生。弗里曼博士参与了弗吉尼亚理工大学的多元文化学术机会计划（MAOP）和工程多样性增强中心（CEED）。学生将从这些程序中选择进行基于这个项目的研究。 他将在他的演讲中使用这个项目的各个方面，以鼓励学生对数学，科学和工程的兴趣。