Current approaches in developing porous 3D scaffolds face various challenges, such as failure of mimicking extracellular matrix (ECM) native building blocks, non-sustainable scaffold fabrication techniques, and lack of functionality. Polysaccharides and proteins are sustainable, inexpensive, biodegradable, and biocompatible, with structural similarities to the ECM. As a result, 3D-structured cellulose (e.g., cellulose nanofibrils, nanocrystals and bacterial nanocellulose)-based aerogels with high porosity and interconnected pores are ideal materials for biomedical applications. Such 3D scaffolds can be prepared using a green, scalable, and cost-effective freeze-drying technique. The physicochemical, mechanical, and biological characteristics of the cellulose can be improved by incorporation of proteins and other polysaccharides. This review will focus on recent developments related to the cellulose-based 3D aerogels prepared by sustainable freeze-drying methods for tissue engineering applications. We will also provide an overview of the scaffold development criteria; parameters that influenced the aerogel production by freeze-drying; and in vitro and in vivo studies of the cellulose-based porous 3D aerogel scaffolds. These efforts could potentially help to expand the role of cellulose-based 3D scaffolds as next-generation biomaterials.

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