Subcutaneous toxicity of a dual ionically cross-linked atelocollagen and sodium hyaluronate gel: Rat in vivo study for biological safety evaluation of the injectable hydrogel

Hydrogels are commonly used in wound dressing, as they retain moisture, accelerate healing, and break down necrotic tissue. This process enhances patient comfort levels while simultaneously reducing pain caused by dead tissue. The purpose of this study was to investigate the in vivo toxicity of a dual hydrogel consisting of type I atelocollagen cross-linked with sodium hyaluronate hydrogel used for wound dressing. Porcine type I atelocollagen was cross-linked with sodium hyaluronate to form the hydrogel. For subcutaneous implantation, 0.5 ml of dual hydrogel was injected into two different sites of twenty rats per group. High density polyethylene rods were implanted subcutaneously to serve as a control material. Hematological assessment, blood biochemistry, histopathological, and histological evaluations were scored and graded after 4 weeks. A bioreactivity rating was used for evaluation of subacute toxicity. Differences observed in blood chemical analysis and hematological analysis between control and test groups were within normal variations and considered unrelated to the test article implantation. No significant implantation-related lesions were observed in any of the major organs of all test animals. The overall histopathological index of the test article implantation sites was evaluated as 0. The bioreactivity rating was evaluated as non-irritant after 4-week subcutaneous implantation. Overall, these results indicate that the dual hydrogel of type I atelocollagen and sodium hyaluronate is biologically and chemically safe for clinical application as a wound dressing.