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

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一部分。尽管对植骨材料的需求量很大，但目前许多可用的植骨材料在骨再生方面的效率仍然很低。因此，迫切需要开发新的植骨材料，以实现更快更好的骨再生。在本研究中，我们提出制造具有良好生物降解性、优异的骨导电性和骨诱导性的自供电支架，并能够诱导原位直流电刺激。本研究的具体目标是：(1)制备能够产生可控电流方向的原位直流电场的可生物降解支架；(2)评估体外细胞-纳米电池-支架的相互作用，并确定在不产生毒性作用的情况下刺激细胞活性的最佳纳米电池负载。智力优势：该研究在组织工程、纳米技术、电化学、发育生物学和骨科等领域具有高度创新性，探索了一种更好、更快的骨修复和再生的全新方法。其智力优势可以概括为以下两个方面：(1)原位产生直流电场刺激骨祖细胞活性的自供电支架的制造；(2)通过介质电泳对纳米电池在磷灰石/胶原支架中的定位；(3)利用4d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，阐明电刺激成骨细胞的机制。这是首次将自供电电刺激与组织工程支架结合使用，实现早期高质量的新骨形成。更广泛的影响：提出的应用探索了一种全新的方法，将原位直流电刺激应用于骨组织工程。本研究的成功实施将直接解决骨组织工程支架存在的骨导电性差、骨诱导能力不足、骨愈合缓慢等问题。该方法也可为老年人、糖尿病患者、骨质疏松患者等有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，本文提出的研究将对组织工程领域具有重要的变革意义，因为它将产生新一代的组织工程支架，它不仅具有骨导电性，而且具有骨诱导能力，能够在特定区域刺激新骨的形成。这里建立的策略也可以用于刺激除骨以外的其他细胞进行组织修复和再生，如血管、细胞、软骨等。预计这种新方法将大大缩短患者的康复时间，从而大大降低社会与住院、保健等相关的医疗费用。因此，拟议项目的社会和经济影响是无价的。此外，该项目将培养两名组织工程和电化学领域的研究生和一些本科生，同时使他们接触到多学科的研究环境。我们将把我们的研究活动与系级和院校一级现有的招聘工作结合起来，努力招收女性和少数民族学生。制定了一项计划，参加各种专门为代表性不足的少数民族组织的活动。此外，K- 12的外展也将针对高中学生，特别是女性和少数族裔，对再生工程感兴趣。项目取得的成果将通过在科学杂志上发表、在会议上发表和在一般公共网站上宣传等方式广泛传播。

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.