Optimization of Injectable Thermosensitive Scaffolds with Enhanced Mechanical Properties for Cell Therapy

Abstract

Strong injectable chitosan thermosensitive hydrogels can be created, without chemical modification, by combining sodium hydrogen carbonate (SHC) with another weak base, namely beta-glycerophosphate (BGP) or phosphate buffer. Here we studied the influence of gelation agent concentration on the mechanical properties, gelation kinetics, osmolality, swelling and compatibility for cell encapulation, in order to find This is the peer reviewed version of the article published in final form at http://doi.org/10.1002/mabi.201600435. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.2 the most optimal formulations and demonstrate their potential for cell therapy and tissue engineering.The new formulations present up to a 50 fold increase of the Young's modulus after gelation compared with conventional chitosan-BGP hydrogels, while reducing the ionic strength to the level of iso-osmolality. Increasing PB concentration accelerates gelation but reduces the mechanical properties. Increasing BGP also has this effect, but to a lesser extent. Cells can be easily encapsulated by mixing the cell suspension within the hydrogel solution at room temperature, prior to rapid gelation at body temperature.After encapsulation, L929 mouse fibroblasts were homogeneously distributed within scaffolds and presented a strongly increased viability and growth compared with conventional chitosan-BGP hydrogels. Two particularly promising formulations were evaluated with human mesenchymal stem cells. Their viability and metabolic activity were maintained over 7 days in vitro.

Development of Injectable Thermosensitive Chitosan-Based Hydrogels for Cell Encapsulation

“…The tested hydrogel formulations presented a similar degradation profile, showing a faster weight loss percentage in the first 24 h, without any further increase up to 4 days. The maximum weight loss settled in the range of 25-30%, in agreement with other studies [44]. Samples with SHC+BGP without ARG, however, presented weight loss after 48 h of 28.5 ± 1.2% significantly higher than those of other two hydrogel formulations, indicating the possibility of tuning the degradation profile according to the need, by simply varying the GA solution components.…”

“…Conversely, the presence of ARG does not change the hydrogel mechanical properties in compression mode even if a stabilizing effect has been underlined by swelling test. Interestingly, the three hydrogel formulations provide different Young values in compression at low strain values according to the GA composition but always in the range of most of "soft" biological tissues, i.e., 1-10 KPa [41][42][43][44][45][46].…”

Polysaccharide Based Scaffolds for Soft Tissue Engineering Applications

“…Biomacromolecules (polysaccharides and proteins), derived from both animal and plants, are receiving wider interest in scaffold development [44,45]. Indeed, scaffold research has advanced in recent years due to polysaccharides, such as chitosan [46,47], alginate [43,48], dextran [49,50,51], and hyaluronic acid [41,52]. They readily form loose viscoelastic gel in aqueous vehicles via non-covalent interactions.…”

Can we Achieve the Perfect Injectable Scaffold for Cell Therapy?

“…Injectable, cell-encapsulating interpenetrating polymer networks, composed of two polymer networks that can independently and simultaneously crosslink to form hydrogels in a cell-friendly manner, have been developed [ 15 , 16 ]. Thermosensitive hydrogels, which undergo a sol-gel transition upon heating to body temperature, can now achieve high mechanical properties in situ thanks to the use of new gelling agents combinations [ 17 ]. Self-healing hydrogels, crosslinked by unsteady bonds which form and break continuously, are also promising injectable scaffolds.…”