Health care and medicine were revolutionized in recent years by the development of biomaterials, such as stents, implants, personalized drug delivery systems, engineered grafts, cell sheets, and other transplantable materials. These materials not only support the growth of cells before transplantation but also serve as replacements for damaged tissues in vivo. Among the various biomaterials available, those made from natural biological sources such as extracellular proteins (collagen, fibronectin, laminin) have shown significant benefits, and thus are widely used. However, routine biomaterial-based research requires copious quantities of proteins and the use of pure and intact extracellular proteins could be highly cost ineffective. Gelatin is a molecular derivative of collagen obtained through the irreversible denaturation of collagen proteins. Gelatin shares a very close molecular structure and function with collagen and thus is often used in cell and tissue culture to replace collagen for biomaterial purposes. Recent technological advancements such as additive manufacturing, rapid prototyping, and three-dimensional printing, in general, have resulted in great strides toward the generation of functional gelatin-based materials for medical purposes. In this review, the structural and molecular similarities of gelatin to other extracellular matrix proteins are compared and analyzed. Current strategies for gelatin crosslinking and production are described and recent applications of gelatin-based biomaterials in cell culture and tissue regeneration are discussed. Finally, recent improvements in gelatin-based biomaterials for medical applications and future directions are elaborated.

Understanding the biophysical relationships between stem cells and applied biomaterials can facilitate the ability to control the functions and behaviors of stem cells. However, the role of 3D microenvironment in stem cell biology remains largely unexplored, compared with that of 2D cell‐culture environment. Here, a new strategy that improves the efficacy of Yamanaka's four‐factor‐induced cellular reprogramming into induced pluripotent stem cells (iPSCs) by incorporating cues derived from the 3D microenvironment and biophysical ligands is reported. Among the various 3D hydrogel systems tested, methacrylated hyaluronic acid (HA) hydrogel significantly improves cellular reprogramming into iPSCs. Additionally, the initial upregulation of CD44 in encapsulated cells in low‐level methacrylated soft HA hydrogel accelerates the reprogramming. In conclusion, the reported HA hydrogel with low modulus accelerates reprogramming into iPSCs and thus offers potential advantages for translational applications.

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