Currently there is no ideal restoration method for large volume skeletal muscle loss. Previously investigated solutions include autologous muscle transplants and the use of various cell sources (exogenous myogenic cells, satellite cells, and myoblasts). While these techniques have had some success, they also have drawbacks. Autologous transplantation, for example, leads to morbidity, loss of function, decreased volume at the donor site, and limited effectiveness when transplanted. These problems have made tissue engineering a more popular approach for muscle regeneration. Skeletal muscle cells have been grown on numerous materials including natural substrates, synthetic polymers, and decellularized tissue. These options all develop new muscle, but they do not provide functionality (contraction for movement) until the tissue is regenerated. The system presented here is designed to contract upon implantation to give the patient immediate function as new tissue develops. The proposed project will investigate the potential of combining polymeric, actuating nanofibers with implantable microelectronic stimulators to form contractile scaffolds for skeletal muscle tissue engineering. The nanofibers are designed to behave as ionic polymeric composites that will actuate when placed inside an electric field. As ionic polymeric composites bend, the components of each nanofiber will be arranged to convert bending along the nanofiber length into contraction. Previous work has shown that muscle cell growth and tissue development increase when the muscle cells are stimulated mechanically (through strain) and electrically. The proposed system will take advantage of these phenomena by using the scaffold contraction caused by the electrical stimulation to stimulate the growth and development of muscle cells and new muscle. The electric field that causes the contraction will be induced by an implantable multi-level programmable voltage regulator. The microchip is designed to generate different voltage levels, giving the user the freedom to control the degree of scaffold contraction. The power required for the operation of the microchip will be provided through a wireless link. In addition, the required voltage level can be adjusted remotely. The potential and applicability of the system will be evaluated in vitro and in vivo by its ability to functionally replace and regenerate muscle tissue. The proposed system will be created through completion of the following objectives: Refining nanowire composition-polymer concentration and nanoparticle concentration and evaluating scaffold tissue regenerative capability in vitro; Developing a highly-integrated subcutaneous microchip for the electrical stimulation of nanofibers; Integrating the nanowire scaffold and the stimulation microchip; and Investigating the in vivo capability of the scaffolds to promote tissue healing. The scaffold will be investigated for contractility (strength, speed, degree of contraction). The scaffold will also be investigated for biocompatibility and regenerative ability with both skeletal muscle cells (for muscle regeneration) and vascular cells (for potential vascularization). These tests will be conducted both with and without electrical stimulation. A highly-integrated low power controllable multi-level voltage regulator will be developed using low-drop out topology. The chip will contain a carefully designed induction link that will enable the implantable microsystem to be powered and controlled wirelessly. The chip will be packaged to ensure its biocompatibility. The scaffold and stimulatory microchip will be integrated by sintering (bonding by heating) nanofibers to the wires and around the wires. The complete integrated electric stimulator-actuating scaffold device will be evaluated in vivo in a muscle pocket model. The creation of a wireless, electrically stimulated, contractile scaffold for muscle regeneration will enable the application of ionic polymeric composites for tissue engineering. The proposed system will also enhance the microelectronics field by developing biocompatible low power circuits that can operate reliably in biological media.
|Effective start/end date||8/1/14 → 7/31/17|
- National Science Foundation (NSF)