Bioinspired Collagen/Hyaluronic Acid/Fibrin-Based Hydrogels for Soft Tissue Engineering: Design, Synthesis, and In Vitro Characterization

Abstract

A major challenge for future drug development comprises finding alternative models for drug screening. The use of animal models in research is highly controversial, with an ongoing debate on their ethical acceptability. Also, animal models are often poorly predictive of therapeutic outcomes due to the differences between animal and human physiological environments. In this study, we aimed to develop a biomimetic hydrogel that replicates the composition of skin for potential use in in vitro modeling within tissue engineering. The hydrogel was fabricated through the crosslinking of collagen type I, hyaluronic acid, four-arm PEG succinimidyl glutarate (4S-StarPEG), and fibrinogen. Various ratios of these components were systematically optimized to achieve a well-interconnected porosity and desirable rheological properties. To evaluate the hydrogel’s cytocompatibility, fibroblasts were embedded within the matrix. The resulting hydrogel exhibited promising properties as a scaffold, also facilitating the growth of and proliferation of the cells. This biomimetic hydrogel holds great potential for tissue engineering applications, particularly in skin regeneration and cancer research. The study used melanoma spheroids fabricated using the 96-round bottom well plate method as a potential application. The results demonstrate that the developed hydrogels allowed the maintenance of spheroid integrity and viability, meaning it has a promising use as a three-dimensional in vitro model of melanoma for both tissue engineering and drug screening applications.

Fabrication and Characterization of Quad-Component Bioinspired Hydrogels to Model Elevated Fibrin Levels in Central Nervous Tissue Scaffolds

“…Similarly, Bindi et al developed a bioinspired hydrogel mimicking skin’s extracellular matrix (ECM) based on collagen type I, hyaluronic acid, 4S-StarPEG, and fibrin. The hydrogel was optimized for porosity and rheological properties, showing improved viscoelasticity and promoting cell growth, presenting a promising biomimetic matrix for diverse soft tissue-engineering applications [ 29 ]. In previous studies, our research team has been able to successfully fabricate and characterize scaffolds containing Col I, HA, and PEGDA into a single hydrogel [ 22 , 23 ].…”