Neural Tissue Engineering with Rat Adipose-Derived Mesenchymal Stem Cells: The Role of an Injectable, Resorbable Hydrogel Scaffold Derived from Oxidized Alginate and Gelatin.

The central nervous system has limited regeneration potential. The multipotency of adipose-derived mesenchymal stem cells (ADMSC) makes them an ideal autologous cell source for the regeneration of neural tissues. However, the likelihood of their differentiation into unwanted cell lineages when transplanted into a hostile injury environment is a serious disadvantage. Transplanting predifferentiated cells via an injectable carrier may aid in site-specific delivery for better survival of cells. Here, we focus on identifying an appropriate injectable hydrogel system that favors stem/progenitor cell attachment and differentiation for neural tissue engineering. An injectable composition of the hydrogel, derived from alginate dialdehyde (ADA) and gelatin, was formulated for this purpose. This hydrogel promoted proliferation/differentiation of ADMSCs to neural progenitors, visualized from the generation of prominent neurospheres and stage-specific expression of a neural progenitor marker (nestin, day 4), an intermittent neuronal marker (ß-III tub, day 5), and a mature neuronal marker (MAP-2, day 8) with neural branching and networking (>85%). The differentiated cells also expressed the functional marker synaptophysin. There was no negative impact on stem/progenitor cell survival (>95%) or differentiation (∼90%) as compared to two-dimensional (2D) culture. Addition of appropriate quantities of asiatic acid specific for neural niche supported cell growth and differentiation without affecting cell survival (>90%) and improved neural branching and elongation. Optimized interconnected porous hydrogel niche exhibited rapid gelation (3 min) and self-healing properties mimicking native neural tissue. Both ADA-gelatin hydrogel by itself and that incorporated with asiatic acid were found to support stem/neural progenitor cell growth and differentiation and have potential applications as antioxidants and growth promoters upon release at the cell transplantation site. In short, the matrix itself or incorporated with phytomoieties could serve as a potential minimally invasive injectable cell delivery vehicle for cell-based therapies of neural diseases.

Injectable self-crosslinking hydrogels for meniscal repair: A study with oxidized alginate and gelatin.

Injectable in situ gelling hydrogels are viable treatment options for meniscal injuries occurring in athletes. The present study aims to develop an injectable hydrogel via borax complexation of oxidized alginate, followed by a self-crosslinking reaction with gelatin through a Schiff's base reaction. Gelation kinetics and degree of crosslinking could be controlled by changing the concentration of components and the formation of Schiff ;'s base formation was confirmed by Raman spectroscopy. The injectable alginate dialdehyde-gelatin (15ADA20G) hydrogel showed 423 ±â€¯20 % water uptake, had an average pore size of 48 µm and compressive strength 295 ±â€¯32 kPa. Phase contrast images, scanning electron micrographs and actin staining depicted adhesion, profuse proliferation, and distribution of fibrochondrocytes on the hydrogel demonstrating its cytocompatibility. Application of hydrogel at the pig meniscal tear ex vivo showed good integration with the host meniscal tissue. Further, the histology of 15ADA20G hydrogel filled meniscus showed retention of hydrogel in the close proximity of meniscal tear even after 3days in culture. The self-crosslinking injectable hydrogel offers a niche for the growth of fibrochondrocytes.