Nanofiber-mediated release of retinoic acid and brain-derived neurotrophic factor for enhanced neuronal differentiation of neural progenitor cells

The treatment of an injured central nervous system using stem-cell-based regenerative medicine still faces considerable hurdles that need to be overcome. Chief among which is the lack of efficient strategies to generate functional neurons from stem cells. The sustained delivery of biochemical cues and synergistic topographical signaling from electrospun nanofibrous scaffolds may be a potential strategy to enhance neuronal differentiation of stem cells for therapeutic purposes. In this study, retinoic acid (RA) and brain-derived neurotrophic factor (BDNF) were encapsulated into a copolymer of ε-caprolactone and ethyl ethylene phosphate to form a multifunctional, electrospun nanofibrous scaffold. Sustained release of RA and BDNF was achieved for at least 7 and 14 days, respectively. Despite lower cumulative release of drugs as compared to bolus delivery to plain nanofibers (at least 2× and 50× lower for RA and BDNF, respectively), nanofiber-mediated delivery of RA and/or BDNF resulted in similar capacity for neuronal differentiation of mouse neural progenitor cells (NPCs). In addition, nanofiber topography significantly increased neuronal differentiation (with BDNF, 47.4 % Map2+ cells on 2D vs. 53.4 to 56.5 % on nanofibers, p < 0.05) and reduced glial cell differentiation. BDNF was a more potent inducer of neuronal differentiation than RA. RA supplementation alone resulted in minimal effect on NPC differentiation, and dual supplementation of RA and BDNF did not further enhance the neuronal differentiation of NPCs. Collectively, the results suggest that synergistic effects of nanofiber topography and sustained delivery of RA and/or BDNF may contribute towards the design of a multifunctional artificial stem cell niche for NPC neuronal differentiation.NMRC (Natl Medical Research Council, S’pore

Hydrogels for directed stem cell differentiation and tissue repair

Thanks to their tunable physical and biochemical properties, hydrogels are an attractive tool for tissue engineering applications. This review highlights the design parameters that have been shown to influence stem cell behaviour when cultured on or within hydrogels and presents the various types of materials and crosslinking methods currently used to produce hydrogels suitable for stem cell-based tissue engineering. We also focus on new generations of hydrogels with spatially and dynamically controllable physical and biochemical properties, which open up new perspectives in the study of stem cell behaviour and in the development of therapeutic solutions in regenerative medicine. In line with the current need for more tunable and dynamic properties, polyrotaxane hydrogels can be used to create spatially flexible structures at the molecular scale and are therefore emerging as a new player in the field of tissue engineering

Tissue engineering of the peripheral nervous system

The structure and function of peripheral nerves can be affected by a range of conditions with severe consequences in these patients. Currently, there are several surgical techniques available to treat peripheral nerve defects. Direct repair is the preferred treatment for short nerve gaps, and nerve autografting is the gold standard in critical nerve defects. The autografting is not always available, and the use of allograft, decellularized allograft and nerve conduits are often used with variable success. During the recent years, several outcomes were achieved in peripheral nerve tissue engineering. Promising experimental results have been demonstrated with this novel generation of nerve conduits, mainly composed by biodegradable materials in combination with intraluminal fillers, growth factors and different cell sources