Vascularization in Bioartificial Parenchymal Tissue: Bioink and Bioprinting Strategies

Abstract

Among advanced therapy medicinal products, tissue-engineered products have the potential to address the current critical shortage of donor organs and provide future alternative options in organ replacement therapy. The clinically available tissue-engineered products comprise bradytrophic tissue such as skin, cornea, and cartilage. A sufficient macro- and microvascular network to support the viability and function of effector cells has been identified as one of the main challenges in developing bioartificial parenchymal tissue. Three-dimensional bioprinting is an emerging technology that might overcome this challenge by precise spatial bioink deposition for the generation of a predefined architecture. Bioinks are printing substrates that may contain cells, matrix compounds, and signaling molecules within support materials such as hydrogels. Bioinks can provide cues to promote vascularization, including proangiogenic signaling molecules and cocultured cells. Both of these strategies are reported to enhance vascularization. We review pre-, intra-, and postprinting strategies such as bioink composition, bioprinting platforms, and material deposition strategies for building vascularized tissue. In addition, bioconvergence approaches such as computer simulation and artificial intelligence can support current experimental designs. Imaging-derived vascular trees can serve as blueprints. While acknowledging that a lack of structured evidence inhibits further meta-analysis, this review discusses an end-to-end process for the fabrication of vascularized, parenchymal tissue.

Biocompatibility evaluation of antioxidant cocktail loaded gelatin methacrylamide as bioink for extrusion-based 3D bioprinting

“…Some of the limitations of conventional tissue engineering can be overcome using 3D bioprinting. The advantage of 3D bioprinting is its ability to spatially distribute cells within the construct and to design the vasculature within the construct [30]. To achieve the highest level of functional performance in bioprinted constructs, it is necessary to mimic the cell arrangement and microenvironment of the native tissues.…”

Recent Advancements of Bioinks for 3D Bioprinting of Human Tissues and Organs

“…Currently, there are two main ways to promote blood vessel formation: (1) adding pro-angiogenic signaling molecules to the bioink and (2) encapsulating cells that promote blood vessel formation in specific bioinks. 149 The most prominent signaling molecule integrated into bioinks for promoting angiogenesis is vascular endothelial growth factor (VEGF). The optimal dosage of this pro-angiogenic signaling molecule is influenced by various factors, such as the composition of the bioink, cell density, and culture conditions.…”

“…In addition, the extracellular matrix components and binding motifs contained in bioinks can also influence blood vessel formation. 149 For example, research has shown that incorporating the arginine−glycine− aspartic acid (RGD) sequence can promote endothelial cell adhesion and proliferation. This sequence is naturally present in hydrogel materials, such as collagen, fibronectin, and hyaluronic acid.…”

“…Ultimately, the bioprinted constructs implanted in the body need to support vascularization as the long-term viability of any bioprinted tissue construct relies on vascularization. Currently, there are two main ways to promote blood vessel formation: (1) adding pro-angiogenic signaling molecules to the bioink and (2) encapsulating cells that promote blood vessel formation in specific bioinks . The most prominent signaling molecule integrated into bioinks for promoting angiogenesis is vascular endothelial growth factor (VEGF).…”

“…According to recent reports, the pores and surface geometry formed after the gelation of different bioink materials can promote and accelerate the formation of vascular networks. In addition, the extracellular matrix components and binding motifs contained in bioinks can also influence blood vessel formation . For example, research has shown that incorporating the arginine–glycine–aspartic acid (RGD) sequence can promote endothelial cell adhesion and proliferation.…”