Delivery of Active FGF-2 From Mechanically-Stable Biological Nanofibers Accelerates Cell Ingress Into Multifiber Composites

Fibrocartilaginous tissues such as the meniscus and annulus fibrosus serve critical load-bearing roles, relying on arrays of highly organized collagen fibers to resist tensile loads [1]. As these specialized structures are often injured, there exists great demand for engineered tissues for repair or replacement. Cell-laden aligned nanofibrous scaffolds formed from poly(ε-caprolactone) (PCL) have shown promise in achieving tissuelike mechanical and biochemical properties and can direct cellular and matrix organization in vitro [2]. A current limitation of nanofibrous scaffolds, however, is a slow rate of cellular infiltration, particularly in thick scaffolds. To address this, dynamic composite nanofibrous scaffolds have been fabricated via multi-fiber spinning [3], which can offer tunable modes of degradation depending on the polymer sources. For example, water-soluble polyethylene oxide (PEO) fibers can be co-spun with PCL to improve porosity and hasten cell ingress [4]. Incorporation of additional tunable and bioactive polymer sources may add greater versatility to these composite systems. For example, aqueous-based silk fibroin can be used as a slow-degrading, mechanically strong composite fiber component [5] into which active biologic factors (drugs, growth factors) can be incorporated [6]. Variably-degradable silk fibers can be formed by modulating post-spinning treatments, and protein release kinetics can likewise be manipulated by the physical crosslinking method [7]. We hypothesized that incorporation of robust and tunable silk protein-based fibers into a composite of slow-degrading synthetic fibers would provide mechanical function while delivering active biologic factors to expedite cell proliferation and encourage more rapid construct colonization. To test this hypothesis, we characterized the release kinetics of recombinant FGF-2 from silk fibers and its bioactivity in vitro and in a rat subcutaneous implant model.