Electrospun Polycaprolactone 3D Nanofibrous Scaffold with Interconnected and Hierarchically Structured Pores for Bone Tissue Engineering.

Ultrathin fibers (with diameters from tens to hundreds of nanometers, commonly known as electrospun nanofibers) prepared via the electrospinning method are of great interests for tissue engineering applications, because electrospun nanofibers have diameters similar to those of fibrous structures in natural extracellular matrix (ECM).  The major limitation of electrospun scaffolds is owing to their morphological structure of overlaid nanofiber mats with apparent/equivalent pore sizes in sub-micrometers; in other words, electrospun nanofibrous mats lack the needed macropores (with sizes from tens to hundreds of micrometers) for cell growth and tissue formation.

In the reported studies, novel electrospun three-dimensional (3D) nanofibrous scaffold has been developed by an innovative and convenient approach (i.e., thermally induced nanofiber self-agglomeration followed by freeze drying) from a biopolymer of polycaprolactone (PCL) for the first time, and the scaffold possesses interconnected and hierarchically structured pores (in specific, the macropores with sizes in hundreds of micrometers would maintain the structural stability of scaffold, support cell proliferation, ECM deposition, and tissue formation; the medium pores with sizes in tens of micrometers or smaller would facilitate the diffusion of nutrients and promote the formation of vascularization, while the small pores with sizes in micrometers or smaller would have impacts on some cell behaviors such as seeding and genes expressions).  The novel polycaprolactone 3D scaffold is soft and elastic with very high porosity of ~96.4%, thus it is morphologically/structurally similar to natural ECM and well-suited for cell functions (e.g., adhesion, proliferation, migration, and differentiation) and tissue formation.

The in vitro studies reveal that the novel scaffold can lead to high cell viability; more importantly, it is able to promote more potent bone morphogenetic protein 2 (BMP2) induced chondrogenic (rather than osteogenic) differentiation of mouse bone marrow mesenchymal stem cells (mBMSCs).  Consistent to the in vitro findings, the in vivo results indicate that electrospun polycaprolactone 3D scaffold acts as a favorable synthetic ECM for functional bone regeneration through the physiological endochondral ossification process (i.e., through formation of cartilage intermediate), which is a new strategy of “developmental tissue engineering” to mimic natural endochondral bone repair process.  Hence, it is envisioned that the developed electrospun polycaprolactone 3D nanofibrous scaffold would be very promising for tissue engineering applications including the regenerations of bone, cartilage, and their composite tissue of osteochondral (an especially challenged tissue repair in clinics).