Challenges for Natural Hydrogels in Tissue Engineering

Protein-based biopolymers derived from natural tissues possess a hierarchical structure in their native state. Strongly solvating, reducing and stabilizing agents, as well as heat, pressure, and enzymes are used to isolate protein-based biopolymers from their natural tissue, solubilize them in aqueous solution and convert them into injectable or preformed hydrogels for applications in tissue engineering and regenerative medicine. This review aims to highlight the need to investigate the nano-/micro-structure of hydrogels derived from the extracellular matrix proteins of natural tissues. Future work should focus on identifying the nature of secondary, tertiary, and higher order structure formation in protein-based hydrogels derived from natural tissues, quantifying their composition, and characterizing their binding pockets with cell surface receptors. These advances promise to lead to wide-spread use of protein-based hydrogels derived from natural tissues as injectable or preformed matrices for cell delivery in tissue engineering and regenerative medicine.