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

在美国，由于创伤或疾病导致的自由骨丢失很普遍。每年有300多万例整形外科手术；其中约500,000例是骨移植手术，使骨成为仅次于血液的最多移植材料。骨丢失通常采用自体或同种异体骨移植治疗。尽管它们确实有它们的好处，但每一种材料都有一系列限制其使用范围的缺点。考虑到这一点，该项目的目标是利用组织工程学创造新的支架，作为骨替代和再生的实用和功能替代材料。新的支架将具有纳米纤维结构，在结构上类似于自然骨，包括皮质和小梁区以及微血管形成。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，以确定支架承受适当载荷所需的纳米纤维取向。2)结合纳米纤维矿化、造孔和烧结技术，构建完全矿化的、多孔的、纳米纤维的松质骨支架。3)利用微纤维和纳米纤维矿化的静电纺丝技术创造具有血管通道的皮质骨样结构。4)将骨小梁和皮质支架与烧结技术相结合，形成全厚度、多孔的承重支架。最终的结构将由矿化的聚(L-乳酸)纳米纤维制成，设计成能够承受承重骨所受的力，同时具有足够的孔隙度，允许全层细胞和组织渗透。智力价值：尽管许多研究已经创造了支架来替代骨骼，但大多数都只是寻求替代骨小梁。目前还没有可用的支架或技术试图模拟骨小梁和皮质骨的结构和特性，包括正确放置的血管系统。这种支架的建立也将导致纳米纤维支架中细胞运动问题的解决。通常情况下，纳米纤维支架中的孔太小，无法进行显著的细胞渗透。本项目所描述的微孔纳米纤维支架的制备方法将解决这一问题，并可用于其他组织工程应用。更广泛的影响：拟议的研究将通过创建不阻碍细胞移动的纳米纤维支架和生产全厚度骨移植来推动组织工程领域的发展。这项研究将为许多学生提供一个在实验设计、数据分析、工程设计和在团队环境中工作的能力方面获得经验的机会。弗里曼博士致力于建立外展项目，从代表性不足的群体中招收工程和科学专业的学生。目前，他指导所有代表性不足领域的研究生。自从两年多前来到弗吉尼亚理工大学以来，他还提到了3名代表不足群体的本科生。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)和加强工程多样性中心(CEED)。学生将从这些项目中被挑选出来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来鼓励学生对数学、科学和工程的兴趣。

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.