Coaxially fabricated polylactic acid electrospun nanofibrous scaffold for sequential release of tauroursodeoxycholic acid and bone morphogenic protein2 to stimulate angiogenesis and bone regeneration

Angiogenesis and bone formation are closely related process in skeletal development and fracture healing. Angiogenic growth factors are predominantly expressed during the early phase in bone regeneration. Recently, chemical chaperone tauroursodeoxycholic acid (TUDCA) has been shown to potentiate vascular induction. The aim of this study was to investigate whether the sequential release of TUDCA and bone morphogenic protein2 (BMP2) from the coaxially electrospun fibers could enhance bone formation or not. We first coaxially fabricated the electrospun fibers using a polylactic acid (PLA)/BMP 2 composite solution as the core fluid and PLA/TUDCA solution as the sheath fluid. Morphological analysis showed that optimum sheath/core ratio (3.5/3.5) scaffold fibers were uniformed with a diameter of 631 +/- 158 nm. Incorporation of drugs into scaffolds also increased hydrophilicity without compromising its thermal stability and tensile strength besides drug release performance. Initial burst release was similar to 65% of TUDCA within the first 12 h, and similar to 75% cumulative release was observed up till 72 h. In case of FITC-BSA, as protein model for BMP2, similar to 28% of protein release was observed up till 72 h without any initial burst release, sequentially. In vitro results showed that TUDCA/BMP2 coaxial fiber scaffold promoted angiogenic and osteogenic differentiation in endothelial cell and mesenchymal stem cells, respectively. In addition, in in vivo rabbit calvarial defect model, implantation of TUDCA/BMP2 coaxial fibers scaffold enhanced new blood vessel formation and bone regeneration as confirmed by micro-computed tomography and histological staining, respectively. These results indicate that TUDCA and BMP2 loaded coaxial scaffold might be useful to promote bone regeneration with enhancing angiogenesis.