More 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.
