Injectable Thermosensitive Chitosan-Collagen Hydrogel as A Delivery System for Marine Polysaccharide Fucoidan

Abstract

Fucoidans, sulfated polysaccharides from brown algae, possess multiple bioactivities in regard to osteogenesis, angiogenesis, and inflammation, all representing key molecular processes for successful bone regeneration. To utilize fucoidans in regenerative medicine, a delivery system is needed which temporarily immobilizes the polysaccharide at the injured site. Hydrogels have become increasingly interesting biomaterials for the support of bone regeneration. Their structural resemblance with the extracellular matrix, their flexible shape, and capacity to deliver bioactive compounds or stem cells into the affected tissue make them promising materials for the support of healing processes. Especially injectable hydrogels stand out due to their minimal invasive application. In the current study, we developed an injectable thermosensitive hydrogel for the delivery of fucoidan based on chitosan, collagen, and β-glycerophosphate (β-GP). Physicochemical parameters such as gelation time, gelation temperature, swelling capacity, pH, and internal microstructure were studied. Further, human bone-derived mesenchymal stem cells (MSC) and human outgrowth endothelial cells (OEC) were cultured on top (2D) or inside the hydrogels (3D) to assess the biocompatibility. We found that the sol-gel transition occurred after approximately 1 min at 37 °C. Fucoidan integration into the hydrogel had no or only a minor impact on the mentioned physicochemical parameters compared to hydrogels which did not contain fucoidan. Release assays showed that 60% and 80% of the fucoidan was released from the hydrogel after two and six days, respectively. The hydrogel was biocompatible with MSC and OEC with a limitation for OEC encapsulation. This study demonstrates the potential of thermosensitive chitosan-collagen hydrogels as a delivery system for fucoidan and MSC for the use in regenerative medicine.

Formulation and Evaluation of Chitosan-Gelatin Thermosensitive Hydrogels Containing 5FU-Alginate Nanoparticles for Skin Delivery

“…Chitosan a positive charge polymer interacts electrostatically with gelatin and form hydrogels. Gelatin temperature of hydrogels is determined by several factors including GP content, chitosan concentration, polymers molecular weight and its degree of deacetylation [ 41 ]. The elastic modulus ( G ′) of the prepared hydrogel increase gradually after 30 °C, which confirms the thermosensitive behavior of the prepared hydrogels.…”

“…The hydrogel components were mixed in a glass sample vial and incubated at 37 °C using water bath immediately after mixing and inverted every minute. The gelation time refers to the time required for “no flow” to be observed for hydrogel formulation [ 41 ].…”

Fucoidan-Incorporated Composite Scaffold Stimulates Osteogenic Differentiation of Mesenchymal Stem Cells for Bone Tissue Engineering

“…Biodegradation is a necessary feature for bone scaffolds, which play a critical role in the bone tissue regeneration process. The biodegradation of scaffolds happens simultaneously with the new bone tissue formation [ 48 , 49 ]. Figure 5 D represents the biodegradation of the developed composites.…”

“…Recently, a study investigated the thermosensitive delivery system for fucoidan composed of collagen, chitosan, and β-glycerophosphate. The study reports that 60% was released in two days and 80% in the next six days [ 49 ]. Thus, the crosslinked multi-material scaffold-loaded fucoidan served to deliver an extended release.…”

Unveiling the secrets of marine—derived fucoidan for bone tissue engineering—A review

“…FIGURE 10The anti-angiogenic potential of fucoidan. [Reproduced with permission from Ref(Ohmes et al, 2022b) under Creative Commons Attribution License (CC BY)].…”