Abstract
Rapid advancements in 3D bioprinting have enabled the design of functionalized bioinks to create scaffolds with robust adhesive properties. These constructs are of great interest in cardiac tissue engineering, where the integration of grafted patch with the host myocardium, through sutures, staples, or adhesives, faces risks such as bleeding, cytotoxicity, and infection. We introduce the first generation of functional adhesive bioinks that can be bioprinted through various modalities to fabricate patch structures with intrinsic adhesive properties. A dopamine-modified hyaluronic acid methacrylate (HAMA-Dopa) and gelatin methacrylate (gelMA) composite bioink is used to create the patch via air and embedded bioprinting. Constructs are crosslinked onto a collagen sheet substrate simulating the host cardiac tissue ( Figure 1A-C ). We developed novel in vitro methods to assess adhesion properties of printed patch under shear, tension, or dynamic loading ( Figure 1C ). Our approach allowed for steady and precise application of stress to the adhesion interface. Embedded-printed HAMA-Dopa/gelMA scaffold showed significantly enhanced adhesion strength (1025 Pa) compared to gelMA (495 Pa) and HAMA (477 Pa) control groups under tension, and under shear (548 Pa vs. 234 and 239 Pa). The adhesion strength of air-printed HAMA-Dopa/gelMA constructs was markedly higher (10,128 Pa) than the embedded ones, possibly due to the more effective, in-situ crosslinking. We also investigated the dynamic adhesive properties in aqueous environment using an ex vivo beating heart model. Air-printed HAMA-Dopa/gelMA showed the greatest adhesion under wet conditions, tolerating 345,600 cycles. We further characterized printing fidelity, mechanical properties, swelling, and biocompatibility of HAMA-Dopa/gelMA constructs, demonstrating adequate functionality of this bioprinted adhesive scaffold for cardiac tissue engineering applications. Figure 1 . Summary of workflow to develop bioprinted adhesive scaffolds. A: Embedded (top) or air (bottom) bioprinting was used to create 3D patch geometries. B: Printing fidelity assessment and optimization. C: Different adhesion mechanisms were assessed using novel customized tools and approaches to apply tensile ( C-i ), shear ( C-ii ), and dynamic ( C-iii ) loading.
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