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

主要研究者：Mei Wei提案ID：1347130在美国，每年进行超过130万例骨修复手术，这构成了社会医疗费用的很大一部分。尽管对骨移植材料的需求巨大，但目前许多可用的移植材料仍表现出较差的骨再生效率。因此，迫切需要开发旨在更快和更好的骨再生的新移植材料。在本研究中，我们提出制造具有良好的生物降解性，良好的骨传导性和骨诱导性，并能够诱导原位直流电刺激的自供电支架。该研究的具体目的是：（1）制造能够产生具有受控电流方向的原位直流电场的可生物降解支架;以及（2）评估体外细胞-纳米电池-支架相互作用，并确定刺激细胞活性而不导致毒性作用的最佳纳米电池负载。拟议中的研究在组织工程、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，它探索了一种全新的方法，可以更好更快地修复和再生骨骼。它的智能优势可以概括为以下两个方面：（1）原位产生直流电场以刺激骨祖细胞活性的自供电支架的制造：（2）通过介电泳在磷灰石/胶原支架中排列纳米电池;（3）采用四维成像平台实时观察纳米电池与GFP之间的相互作用。标记的细胞，以阐明电刺激对成骨细胞的机制。这是第一次将自供电电刺激与组织工程支架结合使用，以产生早期和高质量的新骨形成。更广泛的影响：拟议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。该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，缺乏骨诱导性，骨愈合缓慢。该方法也可能为老年、糖尿病、骨质疏松等条件性患者的骨不连和延迟愈合提供有效的解决方案。因此，所提出的研究将对组织工程领域具有重要意义和变革性，因为它将产生新一代的组织工程支架，其不仅是骨传导性的，而且是骨诱导性的，具有在限定区域刺激新骨形成的能力。这里建立的策略也可以用来刺激其他细胞的组织修复和再生骨以外，如血管，神经，软骨等，预计新的方法将大大缩短患者的康复时间，从而大大降低医疗费用与住院，医疗保健等社会。因此，拟议项目的社会和经济影响是非常宝贵的。此外，该项目还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，同时使他们接触多学科研究环境。将努力通过将我们的研究活动与部门和机构一级现有的招聘工作相结合，招聘女性和少数民族学生。制定了一项计划，参加各种专业协会为代表人数不足的少数群体组织的活动。此外，K- 12外展也将针对高中生，特别是女性和代表性不足的少数民族，对再生工程感到兴奋。从该项目获得的成果将通过在科学期刊上发表、在会议上介绍和在公众网站上公布而广泛传播。

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.