Generation of Human Bioartificial Tissues Using Agarose-Derived Biomaterials

Agarose is a thermoreversible, highly biocompatible polysaccharide increasingly used in tissue engineering (TE). Its molecular architecture, optical clarity, tunable mechanics, and chemical inertness make agarose hydrogels attractive scaffolds for generating bioartificial tissues by TE. This review summarizes current knowledge on agarose extraction, purification, structural variants, and physicochemical properties regarding gelation behavior, stiffness, porosity, and bioactivity. We discuss how agarose type and concentration critically determine hydrogel biomechanical and optical performance, influencing cell behavior and in vivo suitability. Although biologically inert, agarose can be functionalized or combined with fibrin, collagen, chitosan, and other biomaterials to enhance cell adhesion, proliferation, and differentiation. Diverse biofabrication approaches-including micromolding, bead production, 3D bioprinting, and de novo assembly of cells, biomaterials and bioactive factors-have enabled the generation of microtissues, organoids, and complex multilayered constructs. Agarose-based biomaterials allowed for the successful generation of bioartificial substitutes of cartilage, bone, adipose tissue, skin, cornea, oral mucosa, and the peripheral nerve, with several fibrin-agarose advanced therapy medicinal products (ATMP) already reaching clinical application, including the skin substitute UGRSKIN, the artificial cornea NANOULCOR and the palate mucosa BIOCLEFT. Together, current evidence positions agarose as a versatile and translationally relevant biomaterial for next-generation TE, warranting further exploration of its potential in additional therapeutic contexts.