<p>3D bioprinting offers excellent control over the placement of biomaterials and stem cells for the fabrication of tissue scaffolds. When supplied with the appropriate biochemical and mechanical cues, scaffold-resident stem cells can differentiate into discrete tissue-specific lineages which work synergistically to form de novo tissues. However, a major impediment to the more broad-scale clinical acceptance of bioprinted scaffolds for tissue regeneration applications, is the potential risk of immune response to the biomaterials from which the scaffolds are fabricated. Conventional bioprinted tissue scaffolds are composed of synthetic, or biologically derived polymers which are deposited and crosslinked into complex, implantable hierarchical structures. However, many printable biomaterials, such as gelatin methacryloyl (GelMA) and methacrylated collagen (ColMA) offer excellent cytocompatibility and cell adhesion, but have been shown to elicit foreign body responses when implanted. Conversely, biocompatible polymers such as poly(ethylene glycol) diacrylate are not known to confer immunological responses upon implantation, but also do not promote favorable cellular adhesion. To address the lack of printable biomaterials which offer favorable cell adhesion and biocompatibility, while minimizing immunogenicity, we have developed a novel, blood plasma-based bioink composed of purified blood plasma and PEGDA. Blood plasma is rich in the proteins albumin and fibrinogen, which can support nutrient uptake and cell adhesion, respectively. The addition of PEGDA to the plasma-based bioink allows for easy modulation of the mechanical properties of the scaffolds, such as their compressive modulus and swelling behaviors. As a general proof-of-concept study to assess the regenerative potential of the plasma-based scaffolds, round porous tissue scaffold matrices were fabricated using our custom-made stereolithography (SLA) bioprinter, and an optimized mixture of purified bovine blood plasma and PEGDA. Upon printing, the plasma-based scaffolds were seeded with a co-culture of human adipose-derived stem cells (ADSCs) and human umbilical vein endothelial cells (HUVECs). Our data reveals that even with the addition of 5% (w/v) PEGDA to the ink formulation, the plasma-based scaffolds notably enhanced cell adhesion and proliferation with respect to the PEGDA control scaffolds. Cell viability and proliferation analysis demonstrates that &gt;90% of the co-cultured cells were viable and proliferating 24hrs post seeding. The introduction of neural differentiation media to the co-culture caused the ADSCs to selectively differentiate towards neuronal phenotypes. Immunohistochemical staining against the mature neuronal lineage marker MAP2 revealed enhanced neural differentiation and maturation on the plasma-based scaffolds with respect to the PEGDA control scaffolds. The enhanced neural differentiation of ADSCs together with the HUVEC-derived capillary sprouts observed growing on the surface of the Plasma-ink scaffolds resulted in a distinct preliminary vascularized neural tissue after 2 weeks of culturing.</p>

Development of a Novel 3d Bioprintable Blood Plasma-Based Bioink for Complex Tissue Regeneration

Paper Proceedings: https://asmedigitalcollection.asme.org/IMECE/IMECE2021/volume/85543

ASME 2021 International Mechanical Engineering Congress and Exposition (IMECE2021)

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