Review of Bioprinting in Regenerative Medicine: Naturally Derived Bioinks and Stem Cells

Abstract

Regenerative medicine offers the potential to repair or substitute defective tissues by constructing active tissues to address the scarcity and demands for transplantation. The method of forming 3D constructs made up of biomaterials, cells, and biomolecules is called bioprinting. Bioprinting of stem cells provides the ability to reliably recreate tissues, organs, and microenvironments to be used in regenerative medicine. 3D bioprinting is a technique that uses several biomaterials and cells to tailor a structure with clinically relevant geometries and sizes. This technique's promise is demonstrated by 3D bioprinted tissues, including skin, bone, cartilage, and cardiovascular, corneal, hepatic, and adipose tissues. Several bioprinting methods have been combined with stem cells to effectively produce tissue models, including adult stem cells, embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and differentiation techniques. In this review, technological challenges of printed stem cells using prevalent naturally derived bioinks (e.g., carbohydrate polymers and protein-based polymers, peptides, and decellularized extracellular matrix), recent advancements, leading companies, and clinical trials in the field of 3D bioprinting are delineated.

A Guide to Polysaccharide-Based Hydrogel Bioinks for 3D Bioprinting Applications

“…Indeed, Ca 2+ -alginate hydrogels are one of the most studied systems in the field of 3D bioprinting ( Table 1 ) due to their excellent tunability and printability, as reflected and documented in the dedicated literature reviews about the main progress in the domain of alginate-based bioinks since 2016 [ 29 , 33 , 37 , 38 ]. Despite its widely recognized and explored advantages, some recent research efforts on the development of alginate-based bioinks are still focused on tackling the biological and mechanical limitations of alginate hydrogels.…”

“…The developments in the field of bioinks for 3D bioprinting applications have been the theme of several appraisals [ 18 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 ]. Specifically, the progress over the last two decades was reviewed by Pedroza-Gonzalez et al [ 39 ], who provided a systematic analysis of more than 390 original papers from 2000 to 2019.…”

“…Specifically, the progress over the last two decades was reviewed by Pedroza-Gonzalez et al [ 39 ], who provided a systematic analysis of more than 390 original papers from 2000 to 2019. From a materials perspective, many of these revisions gave special emphasis to hydrogel bioinks [ 18 , 35 , 36 , 50 , 52 , 53 ] and to natural materials-based bioinks [ 33 , 38 ]. Moreover, recent reviews have also focused on the use of specific polysaccharides to produce bioinks, namely alginate [ 29 , 33 , 37 , 38 ], (nano)cellulose [ 32 , 35 , 40 , 41 , 46 , 47 , 49 ], chitosan [ 44 ], and hyaluronic acid [ 31 ].…”

“…From a materials perspective, many of these revisions gave special emphasis to hydrogel bioinks [ 18 , 35 , 36 , 50 , 52 , 53 ] and to natural materials-based bioinks [ 33 , 38 ]. Moreover, recent reviews have also focused on the use of specific polysaccharides to produce bioinks, namely alginate [ 29 , 33 , 37 , 38 ], (nano)cellulose [ 32 , 35 , 40 , 41 , 46 , 47 , 49 ], chitosan [ 44 ], and hyaluronic acid [ 31 ]. Most recently, Mahendiran et al [ 37 ] provided an overview of 3D printing technologies and the use of different plant-based bioinks in tissue engineering, focusing on plant polysaccharides of terrestrial (starch, nanocellulose, and pectin) and marine (ulvan, sodium alginate (commonly referred as alginate), fucoidan, agarose, and carrageenan) origins [ 37 ].…”

3D bioprinting of multi-layered segments of a vessel-like structure with ECM and novel derived bioink

“…To overcome these main drawbacks, 3D bioprinting technique have been recently exploited, as it provides incomparable advantages (Gao et al, 2019). This new technology enables to obtain of 3D cellularized constructs with distinct layers in a single fabrication step, thus replicating the hierarchical complex structure of vascular tissue (Moghaddam et al, 2021) (Schwab et al, 2020). Among the many bioprinting strategies, pneumatic extrusion-based bioprinting seems the most promising to produce large vessels characterized by cell layers of centimeter-size tubular architectures.…”