Modulating the Release of Therapeutic Agents from PLGA Coated Cancellous Allografts

Bone grafts are used in 2 million annual surgeries with that statistic expected to rise due to the increasing elderly population as well as sports related injuries. At a certain size bone fracture or defect, the body is unable to heal spontaneously, and a bone graft must be implanted into the defect site. Allografts are used as bone grafts due to their availability and elimination of donor site morbidity, however they show poor bioactivity and bone regeneration. This study utilizes a degradable poly(lactic-co-glycolide) (PLGA) polymer coating applied to cancellous allografts, loaded with a variety of therapeutic agents aimed to improve the bioactivity of the allografts. Bone morphogenetic protein-2 (BMP-2) was physically encapsulated in the polymer coating, the antibiotic gentamicin was physically encapsulated and surface adsorbed, and previous studies surface adsorbed the growth factor vascular endothelial growth factor (VEGF), attempting to mimic the natural healing process. Results show that encapsulated proteins followed the trend of a moderate burst release within the first day of release, followed by sustained release for the 6 week time period that followed. Surface adsorbed tests additionally show a larger burst release in the first day, followed by a less gradual, faster release of 100% of protein. Qualitative results of an in vivo study using cortical allografts with dual coating of encapsulated BMP-2 and surface adsorbed VEGF showed enhanced bone callus formation in the combined group compared to BMP-2 alone, with X-Ray and MicroCT imaging showing a near bony union by 8 weeks in the combined group.