The role that biophysical forces play in regenerative medicine is expanding, with increased interest in the use of intrinsic electrical forces (via regulation of cell membrane channels) and externally applied electric fields (via bioreactor environments) as important control points. Despite significant potential of electrical signals for regenerative medicine, they have not yet been integrated into the design of tissue engineering systems. We propose a radically new strategy to improve connective tissue regeneration by electrotherapeutic control of cell function, through the integrated use of molecular and electrical control of cell function and tissue formation. Our hypothesis is that the synergistic application of molecular control of transmembrane ion flux and externally applied electric fields will improve the quality of cartilage and bone regeneration and accelerate their integration in vivo. We will rigorously test this hypothesis by studying the regeneration of composite bone/cartilage grafts. The regulation of cell function and tissue regeneration will be first studied in vitro using controlled bioreactor environments, and then in vivo in an orthotropic animal model of cartilage and bone regeneration.
Three specific aims will be pursued: (a) Biophysical regulation of chondrogenesis and osteogenesis in adult human stem cells, (b) Electrotherapeutic bioreactor models for regeneration of cartilage/bone tissues, and (c) Animal studies of cartilage/bone regeneration. The anticipated scientific impact will be in significant new insights into the biophysical control of connective tissue repair by modulation of electrical regulatory signals. The main technological impact will be in improved regeneration of cartilage/bone tissues, and the new generation of electrotherapeutic medical devices termed BioDomes.

Public Health Relevance

Radically new approaches are necessary for advancing the integration and healing of musculoskeletal tissues. The proposed studies are designed to enable in-depth understanding of the effects and mechanisms of electrical cellular control on connective tissue healing and regeneration. The scientific findings will be translated into the development of novel electrotherapeutic devices, BioDomes, for potential application in a range of regenerative medicine scenarios.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR061988-02
Application #
8319344
Study Section
Special Emphasis Panel (ZRG1-BST-M (02))
Program Officer
Wang, Fei
Project Start
2011-08-01
Project End
2016-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
2
Fiscal Year
2012
Total Cost
$645,728
Indirect Cost
$107,289
Name
Tufts University
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
073134835
City
Medford
State
MA
Country
United States
Zip Code
02155
White, James D; Wang, Siran; Weiss, Anthony S et al. (2015) Silk-tropoelastin protein films for nerve guidance. Acta Biomater 14:10-Jan
Spiller, Kara L; Freytes, Donald O; Vunjak-Novakovic, Gordana (2015) Macrophages modulate engineered human tissues for enhanced vascularization and healing. Ann Biomed Eng 43:616-27
Spiller, Kara L; Nassiri, Sina; Witherel, Claire E et al. (2015) Sequential delivery of immunomodulatory cytokines to facilitate the M1-to-M2 transition of macrophages and enhance vascularization of bone scaffolds. Biomaterials 37:194-207
Elia, Roberto; Michelson, Courtney D; Perera, Austin L et al. (2015) Electrodeposited silk coatings for bone implants. J Biomed Mater Res B Appl Biomater 103:1602-9
Hernández-Díaz, Sonia; Levin, Michael (2014) Alteration of bioelectrically-controlled processes in the embryo: a teratogenic mechanism for anticonvulsants. Reprod Toxicol 47:111-4
Wang, Qin; Xia, Xiaoxia; Huang, Wenwen et al. (2014) High Throughput Screening of Dynamic Silk-Elastin-Like Protein Biomaterials. Adv Funct Mater 24:4303-4310
Bhumiratana, Sarindr; Eton, Ryan E; Oungoulian, Sevan R et al. (2014) Large, stratified, and mechanically functional human cartilage grown in vitro by mesenchymal condensation. Proc Natl Acad Sci U S A 111:6940-5
Blasioli, Dominick J; Matthews, Gloria L; Kaplan, David L (2014) The degradation of chondrogenic pellets using cocultures of synovial fibroblasts and U937 cells. Biomaterials 35:1185-91
Yuan, Xiaoning; Arkonac, Derya E; Chao, Pen-hsiu Grace et al. (2014) Electrical stimulation enhances cell migration and integrative repair in the meniscus. Sci Rep 4:3674
Tang-Schomer, Min D; Hu, Xiao; Tupaj, Marie et al. (2014) Film-based Implants for Supporting Neuron-Electrode Integrated Interfaces for The Brain. Adv Funct Mater 24:1938-1948

Showing the most recent 10 out of 24 publications