An anisotropic nanofiber/microsphere composite with controlled release of biomolecules for fibrous tissue engineering

Aligned nanofibrous scaffolds can recapitulate the structural hierarchy of fiber-reinforced tissues of the musculoskeletal system. While these electrospun fibrous scaffolds provide physical cues that can direct tissue formation when seeded with cells, the ability to chemically guide a population of cells, without disrupting scaffold mechanical properties, would improve the maturation of such constructs and add additional functionality to the system both in vitro and in vivo. In this study, we developed a fabrication technique to entrap drug-delivering microspheres within nanofibrous scaffolds. We hypothesized that entrapping microspheres between fibers would have a less adverse impact on mechanical properties than placing microspheres within the fibers themselves, and that the composite would exhibit sustained release of multiple model compounds. Our results show that microspheres ranging from 10 - 20 microns in diameter could be electrospun in a dose-dependent manner to form nanofibrous composites. When delivered in a sacrificial PEO fiber population, microspheres remained securely entrapped between slow-degrading PCL fibers after removal of the sacrificial delivery component. Stiffness and modulus of the composite decreased with increasing microsphere density for composites in which microspheres were entrapped within each fiber, while stiffness did not change when microspheres were entrapped between fibers. The release profiles of the composite structures were similar to free microspheres, with an initial burst release followed by a sustained release of the model molecules over 4 weeks. Further, multiple model molecules were released from a single scaffold composite, demonstrating the capacity for multi-factor controlled release ideal for complex growth factor delivery from these structures.