(358d) Investigation of the Effect of BMP-2 Release Kinetics on Craniomaxillofacial Bone Regeneration Using Layer-By-Layer Films

Craniomaxillofacial bone defects can be difficult to treat due to their proximity to important organ systems and unique shape and size of the defects and can have a significant impact on patient quality of life. The current gold standard treatment, bone grafts, suffer from some disadvantages including risk of donor site morbidity and high complication and failure rates. An alternative treatment strategy is to utilize synthetic scaffolds augmented with growth factors to direct and improve bone repair. A major delivery challenge of growth factor delivery is short in vivo half-life, which makes it difficult to maintain dose in the defect site for a sufficient time to induce bone growth while keeping concentration low enough to mitigate risk of side effects. Thus far, the optimal delivery window of a safe BMP-2 dose has yet to be determined. This project aims to investigate the question of optimal BMP-2 delivery window by leveraging layer-by-layer assembly to create conformal coatings on synthetic degradable implants with various release kinetics of BMP-2. Layer-by-layer technology allows for a variety of surfaces to be coated with therapeutics in a high weight percent while protecting the bioactivity of the drugs due to the mild assembly conditions. With careful engineering of film components and assembly conditions, release kinetics of the therapeutics can be tuned. In this work, we created BMP-2-containing layer-by-layer films with different release kinetics ranging from days to weeks through use of diffusional barrier tools. Specifically, we leveraged the barrier properties of laponite clay nanoplatelets to create diffusional barriers on and within layer-by-layer films, mitigating interlayer diffusion as well as diffusion-based release of BMP-2 in physiological conditions. We fabricated these films on cell-free, biodegradable poly(lactic-co-glycolic acid) implants and tested these formulations in vivo in rat critically-sized calvarial defects in a pilot study. Bone growth was measured weekly using microCT imaging. Preliminary results indicate that BMP-2 release kinetics from the implant may influence bone growth. We plan to carry out a large scale animal study upon resumption of normal campus activities. In addition to weekly tracking of bone growth via microCT, the study will be followed with histology and mechanical testing of calvarial explants to determine maturity, quality, and strength of new bone and osseointegration of new bone with native bone.