Biodegradable Implant with TGF-beta Delivery for Enhanced Healing of Bone Tissue: A Computational Model
Eckes, Kevin; Post, David; Sutermaster, Bryan; Villarreal, Sarah
In most common fractures, bone is able to heal itself over a six week time period. Catastrophic fractures, however, may require that shards of bone be removed surgically, leaving critical size defects in fracture areas that are unable to heal in a reasonable amount of time. For this reason, bone is frequently targeted by tissue engineering and drug delivery strategies aiming to encourage bone regeneration. Often, such strategies involve scaffolds or implants in combination with cells and/or growth factors. One major design requirement in growth factor delivery from such an implant is that it must exhibit controlled growth factor release, defined by relatively constant flux over time. Additionally, the growth factor must remain in the tissue at an effective concentration over the time required for healing. We report on a computational model and analysis of the release of Transforming Growth Factor beta (TGF-beta) from a spherical, collagen-based implant with biodegradable polymer-coated layers containing varying concentrations of TGF-beta. This model, created using COMSOL Multiphysics software, allows for rational design of a biodegradable, drug-eluting implant for tissue regeneration. Using such a model, it is easily possible to simulate a variety of conditions (such as different numbers of layers or different initial concentrations of drug within each layer) in order to achieve relatively constant flux and sustain a physiologically effective concentration of the growth factor over time. The following simulations were run: non-layered construct with uniform growth factor concentration throughout; five-layered sphere with radially increasing concentrations; five-layered sphere with radially decreasing concentrations; ten-layered sphere with radially increasing concentrations; ten-layered sphere with uniform concentration; ten-layered sphere with radially decreasing concentrations. We observed that spheres with more layers exhibited a quasi-linear drug release profile, and that radially increasing initial growth factor concentration in the layers, such that the highest concentration is at the center, results in relatively constant flux. We also show that over time, an implant with radially increasing initial TGF-beta concentration exhibits sustained release within the range of the effective concentration of TGF-beta in hyaline cartilage. Our model is important because it can be used to design drug delivery devices rationally before costly and time-consuming wet-lab experiments are done. Furthermore, our model can be extended to a variety of other drug delivery situations which require construct degradation coupled with controlled release.
BEE 4530 Project
Biodegradable Implant; TGF-Beta