Synthesis and characterization of methacryl glycol chitosan as a novel functionally advanced thermogel for biomedical applications.

Thermo-responsive hydrogels (thermogels), known for their sol-gel transition capabilities, have garnered significant interest for biomedical applications over recent decades. However, conventional thermogels are hindered by intrinsic physicochemical and functional limitations that impede their broader utility. This study introduces methacryl glycol chitosan (MGC) as a novel thermogel, offering enhanced functionality and addressing these limitations. MGCs, synthesized through N-methacrylation of glycol chitosan, exhibit tunable thermogelling and photo-crosslinking behaviors. The thermo-reversible sol-gel transition of MGCs occurs within a 21-54 °C range, adjustable by polymer concentration and methacryl substitution degree. Photo-crosslinking using UV light further enhances the mechanical properties of MGC thermogels, creating thermo-irreversible, chemically crosslinked hydrogels. MGCs show no cytotoxic effects and effectively support cell encapsulation. In vivo studies demonstrate stable crosslinking with minimal UV-induced skin damage. Due to their unique thermo-sensitivity, multi-functionality, and customizable properties, MGC thermogels are promising novel biomaterials for various biomedical applications, particularly injectable tissue engineering and cell encapsulation, thus overcoming the limitations of conventional thermogels.

Thermo-irreversible glycol chitosan/hyaluronic acid blend hydrogel for injectable tissue engineering.

Thermogels that undergo temperature-dependent sol-gel transition have recently attracted attention as a promising biomaterial for injectable tissue engineering. However, conventional thermogels usually suffer from poor physical properties and low cell binding affinity, limiting their practical applications. Here, a simple approach for developing a new thermogel with enhanced physical properties and cell binding affinity is proposed. This thermogel (AcHA/HGC) was obtained by simple blending of a new class of polysaccharide-based thermogel, N-hexanoyl glycol chitosan (HGC), with a polysaccharide possessing good cell binding affinity, acetylated hyaluronic acid (AcHA). Gelation of AcHA/HGC was initially triggered by the thermosensitive response of HGC and gradually intensified by additional physical crosslinking mechanisms between HGC and AcHA, resulting in thermo-irreversible gelation. Compared to the thermos-reversible HGC hydrogel, the thermo-irreversible AcHA/HGC hydrogel exhibited enhanced physical stability, mechanical properties, cell binding affinity, and tissue compatibility. These results suggest that our thermo-irreversible hydrogel is a promising biomaterial for injectable tissue engineering.

Injectable Polypeptide Thermogel as a Tissue Engineering System for Hepatogenic Differentiation of Tonsil-Derived Mesenchymal Stem Cells.

A poly(ethylene glycol)-b-poly(l-alanine) (PEG-l-PA) hydrogel incorporating tonsil-derived mesenchymal stem cells (TMSCs), tauroursodeoxycholic acid (TUDCA), hepatocyte growth factor (HGF), and fibroblast growth factor 4 (FGF4) was prepared through thermal gelation of an aqueous polymer solution for an injectable tissue engineering application. The thermal gelation accompanied conformational changes of both PA and PEG blocks. The gel modulus at 37 °C was controlled to be 1000 Pa by using a 14.0 wt % aqueous polymer solution. The gel preserved its physical integrity during the 3D culture of the cells. TUDCA, HGF, and FGF4 were released from the PEG-l-PA hydrogel over 21 days of the 3D cell culture period. TMSCs initially exhibited a spherical shape, whereas some fibers protruded from the cells on days 14-21 of 3D culture. The injectable system exhibited pronounced expressions of the hepatic biomarkers at both mRNA and protein levels, which are significantly better than the commercially available hyaluronic acid gel. In particular, the hepatogenically differentiated cells from the TMSCs in the injectable system demonstrated hepatic biofunctions comparable to HepG2 cells for the uptakes of low density lipoproteins (52%) and indocyanine green (76%), and the production of albumin (40%) and urea (52%), which are also significantly better than the 3D-cultured cells in the commercially available hyaluronic acid gel. Our studies suggest that the PEG-l-PA thermogel incorporating TMSCs, TUDCA, and growth factors is highly promising as an in situ forming tissue engineering system.