Development of a Self-Expandable Injectable Hydrogel Foam for Non-Compressible Hemorrhage

Abstract

Background: According to reports, annually, around 1.5 million deaths are reported due to uncontrolled hemorrhage from traumatic injury globally, accounting for over 85%-90% of deaths on the battlefield and 30%-40% of deaths in the civilian setting. The first hour after trauma (golden hour), is largely responsible for the survival outcome. Existing hemostatic gauze, powder, bandages, fibrin sealants etc. have their limitations when applied to irregular or deep bleeding sites and may require cold storage, limiting prehospital first-aid management. More advanced approaches, such as XStat, ResQFoam show promising results but need trained professionals to remove these from the injured site, which is not convenient for first aid rescue. Therefore, the development of biomaterial for non-compressible hemorrhage management remains a major focus of ongoing research. Objectives: The present study is focusing on the development of biocompatible, injectable self-expandable hydrogel foam that is easily deployable and capable of forming a strong mechanical plug at the injured site without adhering to the surrounding tissue, allowing for safe and easy removal. Methods: The compositions of hydrogel foam are optimized by varying the concentration of gelatin, chitosan, glutaraldehyde and effervescent agents. Precursor solutions are mixed in a specific ratio during extrusion to make the hydrogel foam in situ. Gelation time, curing time, precursor solution preparation time were optimized. Shape retention, swelling behaviour, and percentage of expansion of hydrogel foam have been assessed so far. Cell viability was evaluated through MTT assay (ISO 10993). Further characterization involved, FTIR validation and ex vivo efficacy establishment. Results: Two formulations, prepared by varying the concentration of chitosan have been shortlisted. Both have shown rapid gelation within 27-30 seconds and expands around 340% (v/v) w.r.t polymer solution. The entrapped CO2 gas bubbles remained stable without collapse. Additionally, the cytocompatibility of the material improved a little bit and has shown the potential to act as a good mechanical plug for the temporary management of non-compressible hemorrhage. Further optimization in formulation is required to enhance cytocompatibility and hemostatic performance to support its potential for uncontrolled hemorrhage management.