Nanocomposite Hydrogels and Extracellular Matrix-Advantages and Associated Risks.

Hydrogels can be considered as mimics of the extracellular matrix (ECM). Through integrins, the cytoskeleton is connected to the ECM, and cytoskeleton tension depends on ECM stiffness. A number of age-related diseases depend on cellular processes related to cytoskeleton function. Some examples of cancer initiation and progression and heart disease in relation to ECM stiffness have been analyzed. The incorporation of rigid particles into the ECM can increase ECM stiffness and promote the formation of internal residual stresses. Water migration, changes in water binding energy to biomactomolecules, and changes in the state of water from tightly bound water to free and loosely bound water lead to changes in the stiffness of the ECM. Cardiac tissue engineering, ECM stiffness and cancer, the equivalence of ECM stiffness, oxidative stress, inflammation, multi-layer polyelectrolyte complex hydrogels and bioprinting, residual internal stresses, viscoelastic hydrogels, hydrogel nanocomposites, and the effect of water have been reported. Special attention has been paid to the role of bound water and internal stresses in ECM stiffness. The risks related to rigid particle incorporation into the ECM have been discussed. The potential effect of polyphenols, chitosan, and chitosan oligosaccharide on ECM stiffness and the potential for anti-TNF-α and anti-NF-κB therapies have been discussed.