Biodegradable and Implantable Microbots to Accelerate Bone Regeneration
Objectives: Bone loss (e.g. alveolar bone) is a common medical condition. Current methods of remedying bone loss and/or regenerating bone have various limitations. For example, bone morphogenetic protein 2 (BMP2) that is applied clinically for spinal fusion can cause undesirable bone growth in places outside of the defect area. Parathyroid hormone (PTH) is a hormone with varying effects on bone. When delivered intermittently, PTH increases bone formation, while continuous delivery cause net bone loss. In this work, we developed a unique biodegradable and implantable microbot that delivers PTH in an intermittent manner under the control of magnetic stimulation to accelerate bone regeneration. Methods: The microbot was designed using a CAD and slicing software and printed using a 3D printer. Inside the microbot, a micro-spring is attached to the lid and applies a constant force to the back of the plunger, which is stopped by the wedges. Whenever a dose of PTH is required, an external magnetic stimulation exerts a force to the micro-spring to causes the wedge to be pulled back and release one dose of PTH. Continuing this process leads to the delivery of PTH in a precisely time-controlled intermittent manner. The biocompatibility and controlled drug delivery of the microbot, and in vitro cellular experiments were examined. Results: Poly(lactic acid)-based microbots with various sizes (millimeters to centimeters) were fabricated using a 3D printer. Under the stimulation of magnetic field, the microbot precisely released the drug solution (n=6, p<0.05) once a dose for many times in a time-controlled manner (hours, days, and weeks). SEM (n=3) and confocal images (n=3) and CCK8 assay (n=6) show the microbot was biocompatible and supported the adhesion and growth of bone marrow stem cells. Conclusions: The biodegradable and implantable microbot precisely controls drug delivery in an intermittent manner and has a potential for bone regeneration.