OPTIMIZED BIODEGRADABLE FIBRIN HYDROGELS AS IN VITRO MODELS OF WOUND HEALING

Abstract

Skin is the largest organ of the body. Its integrity plays a crucial role in maintaining physiological homeostasis, protects against mechanical forces and infections, fluid imbalance, and thermal dysregulation. Numerous pathological states, such as diabetes mellitus, peripheral vascular disease, thermal injuries, or degloving lead to inadequate wound healing, necessitating medical intervention. Established wound healing techniques such as autologous and allogeneic skin grafts are inefficient due to the limited availability of donor tissues or probable immunogenic reactions. Current research in the field of tissue engineering aims to facilitate wound healing and restore skin functionality, focusing on key aspects of wound healing, such as extracellular matrix (ECM) reorganization, cell growth, and collagen synthesis/deposition. The research aims at developing and characterizing an in-vitro fibrin gel culture model system that stimulates the process of wound healing. The specific goal of this research is to investigate how the varied chemical composition of fibrin hydrogels can enhance fibroblast proliferation and promote accelerated collagen matrix formation, which is a significant step in tissue repair and regeneration.The fibrin gels are optimized by modulating the primary gel constituents (i.e. the concentrations of fibrin and thrombin). The ensuing hydrogels are characterized using Scanning Electron Microscope and compression testing to test for fiber size, porosity, elasticity, and mechanical properties. Cultured fibroblasts are used to investigate the effects of varying fibrin concentrations on cell-biomaterial interactions, including cell proliferation, cellular infiltration, and network formation. Furthermore, matrix formation and maturation as a function of fibrinogen concentration as defined by collagen matrix deposition, are also studied. Increasing the fibrinogen concentration, lead to an increase in elasticity and Young’s modulus, while a decrease in thrombin concentration generated a stronger fiber structure. Additionally, a decrease in fibrinogen concentration resulted in an increased proliferation rate of fibroblast cells, suggesting better cell adhesion and network formation within the gel substrate. These results were consistent and confirmed by quantifying a mature collagen matrix deposited by fibroblasts when subjected to ascorbic acid. In summary, this research investigates how the varied chemical composition of fibrin hydrogels can enhance fibroblast proliferation and promote accelerated collagen matrix formation, which is a significant step in tissue repair and regeneration.