Methods to achieve tissue-mimetic physicochemical properties in hydrogels for regenerative medicine and tissue engineering

Hydrogels are water-swollen polymeric matrices with properties that are remarkably similar in function to the extracellular matrix. For example, the polymer matrix provides structural support and adhesion sites for cells in much of the same way as the fibers of the extracellular matrix. In addition, depending on the polymer used, bioactive sites on the polymer may provide signals to initiate certain cell behavior. However, despite their potential as biomaterials for tissue engineering and regenerative medicine applications, fabricating hydrogels that truly mimic the physicochemical properties of the extracellular matrix to physiologically-relevant values is a challenge. Recent efforts in the field have sought to improve the physicochemical properties of hydrogels using advanced materials science and engineering methods. In this review, we highlight some of the most promising methods, including crosslinking strategies and manufacturing approaches such as 3D bioprinting and granular hydrogels. We also provide a brief perspective on the future outlook of this field and how these methods may lead to the clinical translation of hydrogel biomaterials for tissue engineering and regenerative medicine applications.