Plant-Based Bioinks for Tissue Engineering

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The scarcity of fully functional materials for bioprinting is one of the main factors that limit rapid progress in this field. Thus, the manufacture and characterization of new bioinks are always in focus, resulting in the continuous evolution of new strategies to develop and modify materials to be used in bioink formulations for bioprinting. The selection of biomaterials used in bioinks is essential, since it is where the cells will be incorporated and used for printing. The formulation of bioinks must include cells in different environments and shapes, such as individual cells, cells aggregated in spheroids or organoids. [1,2]

In the recent decades, plant (and algae)-based bioinks have taken precedence over synthetic and animal-based materials in bioprinting due to their desirable attributes such as their abundance, low cost, biocompatibility, and medicinal properties. Several plant proteins have cell attachment sites and allow the crosslinking of polymers for the formulation of bioinks. Also, secondary metabolites present in plants can accelerate cellular processes and induce collagen secretion and cell differentiation [3].

Figure 1: Plant-derived bioinks and their potential in 3D bioprinting [3].

Agar, alginate, cellulose and starch are polysaccharides widely used in plant-based bioprinting techniques. Alginate, in addition to having a low cost, which guarantees it a high appeal for use in 3D bioprinting approaches, is also biocompatible and biodegradable and can be processed in a hydrogel [4]. Daly et al. presented a new strategy for engineering whole bones from developmentally inspired hypertrophic cartilage templates, that were engineered in vitro using stem cells within a supporting gamma-irradiated alginate bioink incorporating Arg-Gly-Asp adhesion peptides. With this approach, the researchers developed a cartilaginous template mimicking the geometry of a vertebral body and incorporating a functional vasculature, trabecular-like bone, and a supporting medullary cavity. The method is a promising technique for orthopedic and craniofacial medicine [5].

Using agarose as the basis for a plant-based bioink, Nadernezhad and his team engineered a nanocomposite material with custom properties using 2D nanosilicate additives, which were used to adjust the flow behavior of agarose solutions. The proper selection of the concentration of nanosilicate resulted in extrusion 3D printed structures with high fidelity of form and structural integrity. The incorporation of the nanomaterial resulted in an improvement in the metabolic activity of the encapsulated cells. The results suggest that designed agarose-nanosilicate bioinks can be of great potential to be used as bioactive and printable 3D bioinks for tissue engineering applications [6].

Figure 2: Optical photos of the pure (a) and nanocomposite (b) agarose gels during 3D printing [6].


1. Groll, J. et al. A definition of bioinks and their distinction from biomaterial inks. Biofabrication 11, 013001 (2018).

2. Indurkar, A., Pandit, A., Jain, R. & Dandekar, P. Plant-based biomaterials in tissue engineering. Bioprinting 21, e00127 (2021).

3. Jovic, T. H., Kungwengwe, G., Mills, A. C. & Whitaker, I. S. Plant-Derived Biomaterials: A Review of 3D Bioprinting and Biomedical Applications. Front. Mech. Eng. Chin. 5, 19 (2019).

4. Ching, S. H., Bansal, N. & Bhandari, B. Alginate gel particles–A review of production techniques and physical properties. Crit. Rev. Food Sci. Nutr. 57, 1133–1152 (2017).

5. Daly, A. C. et al. 3D Bioprinting: 3D Bioprinting of Developmentally Inspired Templates for Whole Bone Organ Engineering (Adv. Healthcare Mater. 18/2016). Advanced Healthcare Materials vol. 5 2352–2352 (2016).

6. Nadernezhad, A. et al. Nanocomposite Bioinks Based on Agarose and 2D Nanosilicates with Tunable Flow Properties and Bioactivity for 3D Bioprinting. ACS Appl. Bio Mater. 2, 796–806 (2019).

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