Nano-structuring and Micro-structuring of Novel Composite Hydrogels Loaded with Hemostatic Agents and Fibers for Bioadhesive and Sealant Applications

Background: The use of bioadhesives and sealants for wound closure and sealing applications is becoming widespread due to their many advantages. However, the currently available surgical adhesives do not combine high strength with biocompatibility and other desired properties. Therefore, novel tissue adhesives based on natural polymers which behave as hydrogels, were recently developed and studied by our research group. The objective of the current research was to further develop these novel formulations and investigate the new concept of "composite bioadhesives", i.e. bioadhesives loaded with combination of various functional fillers that can enhance their function.

Methods: A bioadhesive formulation based on a combination of gelatin and alginate, crosslinked with carbodiimide was used as basic formulation. In addition, two hemostatic agents (montmorillonite and kaolin) and cellulose fibers were incorporated in the bioadhesive to enhance its function in a hemorrhagic environment and improve its sealing ability and bulk properties. Two types of mechanical tests were selected for mechanical evaluation of the novel composite bioadhesive, on the basis of relevant standards. The combination of these methods enables the establishment of a thorough understanding of the bioadhesive’s function.

Results: While montmorillonite significantly affected the burst strength and bulk properties, kaolin showed only slight effect of these properties. Incorporation of cellulose fibers significantly improved all mechanical properties, due to enhanced cohesion strength. In addition, our composite formulations showed high biocompatibility in in-vitro tests on fibroblast cells.

Conclusion: The incorporation of fibers with hemoststic agents into the gelatin-alginate bioadhesive reinforced the hydrogel and resulted in superior mechanical properties.