Morin‐Loaded Chitosan‐Poloxamer Hydrogel as an Osteoinductive Delivery System for Endodontic Applications

Considering the search for new biocompatible intracanal medicaments that can preserve remaining cells and stimulate bone tissue repair in the periapical region, this study aimed to synthesize and characterize the physicochemical properties of morin-loaded chitosan-poloxamer hydrogel (MCP) as well as to evaluate its osteogenic potential. Morin hydrate (M) was loaded into chitosan-poloxamer (CP) hydrogel and the resulting particles were characterized by infrared spectroscopy (FTIR), UV-vis spectrophotometer and scanning electron microscopy. Biological assays evaluated the metabolic activity, cell morphology and alkaline phosphatase (ALP) activity of human bone marrow stem cells (HBMSC) in three different settings, such as the exposure to dissolved morin, hydrogel's leachates and assembled particles by indirect contact. Cells cultured in standard culture conditions were used as control. The effect of CP and MCP particles on the formation of collagenous and mineralized tissues was also assessed within the organotypic model of segmented embryonic chick femora. Datasets were assessed for one-way analysis of variance (ANOVA), followed by Tukey's post hoc test (p < 0.05). Morin at 50 μg/mL was cytocompatible and increased ALP activity. CP and MCP particles showed stability, and morin was entrapped in the hydrogel matrix without changing its chemical structure. Cultures treated with 30-min CP and MCP hydrogel leachates presented significantly higher metabolic activity compared to control. By indirect contact, CP particles increased metabolic activity, but only MCP particles induced an upregulation of ALP activity in comparison to control. The amount of collagenous tissue and mineralized area on the fractured embryonic chick femora was greater in MCP particles compared to CP counterparts. Chitosan-poloxamer platforms are suitable systems to delivery morin, enhancing cell proliferation and bone mineralization, which upholds its application as intracanal medication for endodontic purposes.