Development of an Implantable Electrical Stimulation Device for Bone Regeneration

Abstract

Electrical stimulation modulates cellular process in a form of ionic current through regulating cell membrane potential. Electrical stimulation has effects of up-regulation of cell proliferation rate and cell viability. As a good osteoinductive tool, electrical stimulation has effects of differentiation to bone cell, acceleration of ossification and calcium induction that improve bone regeneration. Although implantable electrical stimulation devices for bone regeneration were commercialized, there was limitation for applying to bone graft transplantation due to the shape of the device and stimulation delivery. In the present dissertation, implantable bone regeneration device using electrical stimulation is demonstrated. The device can deliver a concentrated electrical stimulation to three-dimensional bone graft. The evaluation of bone regeneration targeting animal bone defect model using the designed device is demonstrated. As a preliminary step for developing bone regeneration device, a bioreactor device which allows intracorporeal cell culture using electrical stimulation was designed. Using this device, human mesenchymal stromal cell was cultured intracorporeally with electrical stimulation. The cell proliferation of the electrical stimulated stem cell was increased by 23% compared to the unstimulated stem cell. Also in the electrically stimulated group, stem cell had more stable adhesion to the collagen sponge and better extracellular matrix formation compare to the control group. Through improvement of the bioreactor device, bone regeneration experiment targeting a rabbit mandible was executed by transplantation of stem cell graft and electrical stimulation device into the defect site. Polyimide electrode was designed to be suited the defect of animal and electrical current generator was packaged with silicone. The electrical stimulated group showed a higher bone volume by 260% compared with unstimulated group. Also electrical stimulated group showed better new bone formation results in various bone parameters. Then LCP-based bone regeneration device was designed with a built-in electrical current generator and wireless power receiver device. LCP has good hermeticity and good osseo-integration property. This device performs a graft containment system and electrical stimulation device simultaneously. From these results, bone regeneration treatment using implantable bone regeneration device which can apply electrical stimulation to defect site directly can be an effective and new methods for bone defect recovery. Furthermore, it can be expected that development of implantable bone regeneration device using LCP and development of combined treatment of intracorporeal stem cell culture and electrical stimulation.