Biocompatibility Evaluation of Ionic‐ and Photo‐Crosslinked Methacrylated Gellan Gum Hydrogels: In Vitro and In Vivo Study

Abstract

In this study, the stability and biocompatibility of methacrylated gellan gum hydrogels, obtained either by ionic- (iGG-MA) or photo-crosslinking (phGG-MA), were evaluated in vitro and in vivo. Size exclusion chromatography analysis of the methacrylated gellan gum (GG-MA) powder revealed that molecular weight is lower as compared to the non-modified material, i.e., low acyl gellan gum. The water uptake and swelling of iGG-MA and phGG-MA hydrogels were investigated in phosphate-buffered saline solution (pH 7.4). The biocompatibility of the hydrogels was firstly evaluated by producing cell-laden hydrogels. The in vitro cells encapsulation study showed that lung fibroblast cells (L929 cells) and human intervertebral disc (hIVD) cells are viable when cultured within both hydrogels, up to 21 days of culturing. The iGG-MA and phGG-MA hydrogels were also subcutaneously implanted in Lewis rats for 10 and 18 days. Tissue response to the hydrogels implantation was determined by histological analysis (haematoxylin-eosin staining). A thin fibrous capsule was observed around the implanted hydrogels. No necrosis, calcification, and acute inflammatory reaction were observed. The results presented in this study demonstrate that iGG-MA and phGG-MA hydrogels are stable in vitro and in vivo, support L929 and hIVD cells' encapsulation and viability, and were found to be well-tolerated and non-toxic in vivo.

Cell-laden hydrogels for osteochondral and cartilage tissue engineering

“…Chemical modification of gellan gum has also been demonstrated by the incorporation of methacrylate groups for improved structural stability and mechanical properties with retaining the biocompatibility [139, 154–156]. A Young’s modulus of 148 kPa was achieved for methacrylated gellan gum hydrogels [139].…”

“…A Young’s modulus of 148 kPa was achieved for methacrylated gellan gum hydrogels [139]. The in vitro and in vivo studies showed that such hydrogels supported cell encapsulation with good viability and cytocompatibility [155, 156]. Chemically modified gellan gum hydrogels have shown decreased gelation temperature, improved mechanical properties, and better in vivo stability that are crucial as injectable biomaterials for OTE and CTE applications.…”

Biomimetic Strategies to Engineer Mineralized Human Tissues

“…Our group is a pioneer in processing hydrogels based on a polysaccharide gellan gum, obtained from Sphingomonas elodea, for tissue engineering applications [28][29][30]. Methacrylated gellan gum hydrogels were produced through chemical modification by means of methacrylation of low-acyl gellan gum.…”

Gellan Gum‐based Hydrogels for Tissue Engineering Applications

“…In this study, the authors showed that is possible to fine-tune the hydrogel mechanical properties without compromising the viability of encapsulated rabbit NP cells. In addition, an in vivo study showed a promising biological performance for the GG-based hydrogels [71]. The use of anti-angiogenic materials or drugs, peptides or growth factors with the ability to control of innervation and blood vessel infiltration during IVD repair has been attracting great deal of attention.…”