EAGER: Fabrication of self-powered scaffolds for enhanced bone repair

在美国，每年进行的骨修复手术超过130万例，占社会医疗费用的很大比例。尽管对骨移植材料的需求量很大，但现有的许多移植材料在骨再生方面仍然表现出较低的效率。因此，迫切需要开发新的移植材料，以期更快、更好地再生骨。在这项研究中，我们建议制备具有良好的生物降解性、良好的骨传导性和骨诱导性以及能够诱导原位直流电刺激的自给能支架。这项研究的具体目的是：(1)构建可原位产生直流电场的可生物降解支架，并控制电流方向；(2)评估体外细胞-纳米电池复合支架-支架的相互作用，确定刺激细胞活动而不会导致毒性影响的最佳纳米电池负载。智力优势：该研究跨越组织工程、纳米技术、电化学、发育生物学和骨科领域，具有很高的创新性，为更好、更快地修复和再生骨探索了一条全新的途径。它的智能优势可以概括为以下两个方面：(1)自供电支架的制备，以原位产生直流电场来刺激成骨细胞的活性；(2)通过介电泳法在磷灰石/胶原支架中对准纳米球；(3)利用4-D成像平台实时观察纳米电池与GFP标记细胞之间的相互作用，以阐明电刺激成骨细胞的机制。首次将自力式电刺激与组织工程支架相结合，产生早期高质量的新骨形成。广泛影响：该应用探索了一种将原位直流电刺激应用于骨组织工程的全新方法。这项研究的成功实施将直接解决骨组织工程支架存在的问题，如骨传导性差、缺乏骨诱导能力、骨愈合缓慢等。它的方法也可能为老年、糖尿病、骨质疏松症等条件患者的骨修复不愈合和延迟愈合提供有效的解决方案。因此，这项研究对组织工程领域具有重要的意义和变革意义，因为它将产生新一代组织工程支架，它不仅具有骨传导性，而且具有骨诱导性，能够在一定范围内刺激新骨形成。这里建立的策略也可以用来刺激骨以外的其他细胞进行组织修复和再生，如血管、神经、软骨等。预计这种新方法将大大缩短患者的康复时间，从而大幅降低与住院、医疗保健等相关的社会医疗成本。因此，拟议项目的社会和经济影响是不可估量的。此外，该项目将在组织工程和电化学领域培训两名研究生和一些本科生，同时将他们暴露在多学科的研究环境中。我们将努力通过将我们的研究活动与现有的部门和机构一级的招聘工作结合起来，努力招募女性和少数族裔学生。制定了一项计划，参加各种专业协会为代表不足的少数群体组织的活动。此外，还将开展K-12外联活动，目标是对再生工程感到兴奋的高中生，特别是女性和代表性不足的少数族裔。该项目所取得的成果将通过在科学期刊上发表、在会议上发表以及在一般公众网站上进行宣传来广泛传播。

PI: Mei WeiProposal ID: 1347130More than 1.3 million bone-repair procedures are conducted every year in the USA, which constitutes a large proportion of the medical bills of the society. Despite of the huge demand in bone grafting materials, many currently available grafting materials still exhibit poor efficiency in bone regeneration. Thus, there is a pressing need for the development of new grafting materials aimed at faster and better bone regeneration. In this study, we propose to fabricate self-powered scaffolds with good biodegradability, excellent osteoconductivitiy and osteoinductivitiy, and capable of inducing in-situ DC electric stimulation. The specific aims of the study are:(1) Fabrication of biodegradable scaffolds capable of generating in-situ DC electric field with controlled electric current direction; and (2) Evaluations of the in vitro cell-nanobattery incorporated-scaffolds interactions, and determine the optimum nanobattery loading for stimulating cell activities without resulting in toxic effects.Intellectual Merit: The proposed research is highly innovative across fields of tissue engineering, nanotechnology, electrochemistry, developmental biology, and orthopedics, which explores a completely new approach for better and faster bone repair and regeneration. Its intellectual merits can be summarized into the following two aspects: (1) The fabrication of self-powered scaffolds for in situ generation of DC electric field to stimulate osteoprogenitor activities; (2) Alignment of nanobatteries in the apatite/collagen scaffold via dielectrophoresis; (3) The employment of a 4-D imaging platform for real-time observation of the interactions between nanobattery and GFP-labeled cells to elucidate mechanisms of electric stimulation on osteoblastic cells. It is for the first time that self-powered electrical stimulation is used in conjunction with tissue engineering scaffold to produce early and high-quality new bone formation.Broader Impacts: The proposed application explores a completely new approach to apply in situ DC electric stimulation to bone tissue engineering. The successful implementation of the proposed study will address directly the existing problems of bone tissue engineering scaffolds, such as poor osteoconductivity, lack of osteoinductivity, and slow bone healing. Its approach may also provide an effective solution to non-union and delayed union of bone repair in conditioned patients, such as aging, diabetics, osteoporosis patients. Thus, the proposed research will be significant and transformative to the tissue engineering field as it will result in a new generation of tissue engineering scaffold which is not only osteoconductive, but also osteoinductive with the capability of stimulating new bone formation in define areas. The strategies established here can also be used to stimulate other cells for tissue repair and regeneration other than bone, such as blood vessel, never, cartilage, etc. It is expected that the novel approach will greatly shorten the rehabilitation time of patients and thereby substantially lower medical costs associated with hospitalization, health care, etc for the society. Thus, the social and economic impact of the proposed project is invaluable. Also, this project will result in the training of two graduate students and a number of undergraduate students in areas of tissue engineering and electrochemistry, while exposing them to a multidisciplinary research environment. Efforts will be made to recruit females and minority students by integrating our research activities with existing recruiting efforts at the Departmental as well as Institutional levels. A plan is made to participate in activities organized by various professional societies dedicated to underrepresented minorities. In addition, K- 12 outreach will also be carried out to target high school students, especially females and underrepresented minorities, excited about regenerative engineering. The results obtained from the project will be disseminated broadly via publishing in scientific journals, presenting in conferences and publicizing to general public web site.