Microgels of Levan Polysaccharide and Their Use for the Controlled Release of CBD

ABSTRACT

Hydrogels are widely investigated as tissue engineering scaffolds due to their structural similarity to the extracellular matrix and their ability to support cell growth and controlled drug delivery. In this study, levan‐based microgels were developed as injectable scaffolds capable of filling amorphous and hard‐to‐reach soft tissue defects while enabling controlled release of cannabidiol (CBD). A cytocompatible and immuno‐neutral levan hydrogel with a porous architecture and high water uptake was successfully synthesized. The physicochemical, rheological, and biological properties of the hydrogel were systematically evaluated in different physical forms (oven‐dried, lyophilized, bulk, ground, and injectable). The hydrogel exhibited a high swelling capacity (approximately 15–18 g g ⁻¹ ) and a well‐developed porous structure throughout both surface and cross‐sectional regions. Cytocompatibility was confirmed with adipocytes, gingival mesenchymal stem cells (GMSC), human osteoblasts (HOB), and human fibroblasts (PCS‐201‐012). ELISA results demonstrated stable interleukin‐6 (IL‐6) and tumor necrosis factor‐α (TNF‐α) secretion levels in GMSC cultures, indicating an immuno‐neutral response. Furthermore, the hydrogel enabled a low and sustained release of CBD. Collectively, these findings highlight the potential of levan‐based hydrogels as injectable, wound‐healing‐oriented drug delivery systems for soft tissue engineering applications.