Synthesis and Characterization of Biocompatible Methacrylated Kefiran Hydrogels: Towards Tissue Engineering Applications

Abstract

Hydrogel application feasibility is still limited mainly due to their low mechanical strength and fragile nature. Therefore, several physical and chemical cross-linking modifications are being used to improve their properties. In this research, methacrylated Kefiran was synthesized by reacting Kefiran with methacrylic anhydride (MA). The developed MA-Kefiran was physicochemically characterized, and its biological properties evaluated by different techniques. Chemical modification of MA-Kefiran was confirmed by 1H-NMR and FTIR and GPC-SEC showed an average Mw of 793 kDa (PDI 1.3). The mechanical data obtained revealed MA-Kefiran to be a pseudoplastic fluid with an extrusion force of 11.21 ± 2.87 N. Moreover, MA-Kefiran 3D cryogels were successfully developed and fully characterized. Through micro-CT and SEM, the scaffolds revealed high porosity (85.53 ± 0.15%) and pore size (33.67 ± 3.13 μm), thick pore walls (11.92 ± 0.44 μm) and a homogeneous structure. Finally, MA-Kefiran revealed to be biocompatible by presenting no hemolytic activity and an improved cellular function of L929 cells observed through the AlamarBlue® assay. By incorporating methacrylate groups in the Kefiran polysaccharide chain, a MA-Kefiran product was developed with remarkable physical, mechanical, and biological properties, resulting in a promising hydrogel to be used in tissue engineering and regenerative medicine applications.

Impact of Kefiran Exopolysaccharide Extraction on Its Applicability for Tissue Engineering and Regenerative Medicine

“…For E1 (Figure 4A), a power law region can be observed through the full range of the measured shear rate; this typically describes shear thinning behavior, also known as pseudoplastic flow, which is the most common type of non-Newtonian behavior where fluid viscosity decreases, and shear stress rises with increasing shear rate. Most polymer solutions exhibit shear thinning behavior and these results are in accordance with those previously described for kefiran extracted through the same procedure and analyzed in 1% and 10% (w/v) solutions at 37 • C [9,15], and others [18][19][20][21][22][23]51,52]. However, for E2 and E3 (Figure 4B,C), this shear thinning behavior is only observed for lower shear rates, showing a shift to an apparent Newtonian behavior that is not observed for E1 in the same shear rate range.…”

“…The applicability of the kefiran polysaccharide for tissue engineering and regenerative medicine has been previously explored by Radhouani et al [9,[15][16][17], and others [11,[18][19][20][21][22][23] as viscosupplementation, films and scaffolds, coatings, drug delivery systems, among other TERM applications. However, distinct kefiran extraction methods are usually performed which are reported to differently affect the obtained results [24].…”

Development of Conjugated Kefiran-Chondroitin Sulphate Cryogels with Enhanced Properties for Biomedical Applications

“…In this pioneering study, a carbodiimide-based modification was performed involving kefiran and chondroitin sulfate. Previous studies on the chemical modification of kefiran were carried out by methacrylating kefiran with methacrylic anhydride, resulting in a higher degree of substitution (about 48%) [ 24 ] compared to the new kefiran-CS conjugate. More recently, kefiran was esterified with octenyl succinic anhydride, resulting in a shallow degree of substitution (about 0.041%) [ 25 ].…”

Recent Advances in Chemically-Modified and Hybrid Carrageenan-Based Platforms for Drug Delivery, Wound Healing, and Tissue Engineering

“…According to Figure 1 A, by substituting the hydroxyl groups on κ-carrageenan with methacrylate groups, the methacrylation process occurred. The extent of the substitution of hydroxyl groups was considered equivalent to the degree of methacrylation [ 11 , 51 , 52 ]. Compared to other modification approaches, the methacrylation process provides the ability to be photocrosslinked in the presence of a chemical photoinitiator, including Irgacure 2959 [ 11 , 12 , 13 , 53 , 54 ], eosin Y [ 14 , 50 ], α-ketoglutaric acid [ 55 ], and LAP [ 56 ], under ultraviolet (UV) light [ 57 ] or even visible light [ 14 ].…”