An Elastic Mineralized 3D Electrospun PCL Nanofibrous Scaffold for Drug Release and Bone Tissue Engineering.

Complex shaped and critical-sized bone defects have been a clinical challenge for many years. Scaffold-based strategies such as hydrogels provide localized drug release while filling complex defect shapes, but ultimately possess weaknesses in low mechanical strength alongside a lack of macroporous and collagen-mimicking nanofibrous structures. Thus, there is a demand for mechanically strong, extracellular matrix (ECM) mimicking scaffolds that can robustly fit complex shaped critical sized defects and simultaneously provide localized, sustained, multiple growth factor release. We therefore developed a composite, bi-phasic PCL/hydroxyapatite (HA) 3D nanofibrous (NF) scaffold for bone tissue regeneration by using our innovative electrospun-based thermally induced self-agglomeration (TISA) technique. One intriguing feature of our ECM-mimicking TISA scaffolds is that they are highly elastic and porous even after evenly coated with minerals and can easily be pressed to fit different defect shapes. Furthermore, the bio-mimetic mineral deposition technique allowed us to simultaneously encapsulate different type of drugs, e.g., proteins and small molecules, on TISA scaffolds under physiologically mild conditions. Compared to scaffolds with physically surface-adsorbed phenamil, a BMP2 signaling agonist, incorporated phenamil composite scaffolds indicated less burst release and longer lasting sustained release of phenamil with subsequently improved osteogenic differentiation of cells in vitro. Overall, our study indicated that the innovative press-fit 3D NF composite scaffold may be a robust tool for multiple-drug delivery and bone tissue engineering.

Gelatin-crosslinked pectin nanofiber mats allowing cell infiltration.

Pectin nanofiber mats are promising tissue engineering scaffolds but suffer from poor cell infiltration. In this study, gelatin, a collagen derived cell adhesive protein, was used to crosslink the electrospun nanofibers of periodate oxidized pectin. Cell culture experiment results demonstrated that cells were able to grow into the gelatin-crosslinked pectin nanofiber mats rather than only spread on mat surface. The nanofiber mats showed moderate mechanical strength, with a maximum tensile strength of up to 2.3 MPa, an ultimate tensile strain of up to 15%, and were capable of degrading gradually over 4 weeks or even longer periods in simulated body fluids. Thus, gelatin-crosslinked pectin nanofiber mats hold a great potential for soft tissue regeneration.

Tailoring weight ratio of PCL/PLA in electrospun three-dimensional nanofibrous scaffolds and the effect on osteogenic differentiation of stem cells.

Three-dimensional (3D) scaffolds as artificial ECMs have been extensively studied to mimic the critical features of natural ECMs. To develop more clinically relevant 3D scaffolds, electrospun nanofibrous scaffolds with different weight ratios of PCL/PLA (i.e., 100/0, 60/40, and 20/80) were fabricated via the thermally induced (nanofiber) self-agglomeration (TISA) method. The hypothesis was that, with the weight ratio increase of stiffer and more bioactive PLA in the 3D PCL/PLA blend scaffolds, the osteogenic differentiation of human mesenchymal stem cells (hMSCs) would be enhanced. The results indicated that, all of the 3D scaffolds were elastic/resilient and possessed interconnected and hierarchical pores with sizes from sub-microns to ∼300 µm; therefore, the morphological structures of these scaffolds were similar to those of natural ECMs. The PLA80 scaffolds exhibited the best overall properties in terms of density, porosity, water absorption capacity, mechanical properties, bioactivity, and cell viability. Furthermore, with increasing the PLA weight ratio, the alkaline phosphatase (ALP) activity, calcium content, and gene expression level were also increased, probably due to the improved stiffness/bioactivity of scaffold. Hence, the novel 3D electrospun PLA80 nanofibrous scaffold might be desired/favorable for the osteogenic differentiation of hMSCs.