Clickable Dynamic Bioinks Enable Post‐Printing Modifications of Construct Composition and Mechanical Properties Controlled over Time and Space

Abstract

Bioprinting is a booming technology, with numerous applications in tissue engineering and regenerative medicine. However, most biomaterials designed for bioprinting depend on the use of sacrificial baths and/or non‐physiological stimuli. Printable biomaterials also often lack tunability in terms of their composition and mechanical properties. To address these challenges, the authors introduce a new biomaterial concept that they have termed “clickable dynamic bioinks”. These bioinks use dynamic hydrogels that can be printed, as well as chemically modified via click reactions to fine‐tune the physical and biochemical properties of printed objects after printing. Specifically, using hyaluronic acid (HA) as a polymer of interest, the authors investigate the use of a boronate ester‐based crosslinking reaction to produce dynamic hydrogels that are printable and cytocompatible, allowing for bioprinting. The resulting dynamic bioinks are chemically modified with bioorthogonal click moieties to allow for a variety of post‐printing modifications with molecules carrying the complementary click function. As proofs of concept, the authors perform various post‐printing modifications, including adjusting polymer composition (e.g., HA, chondroitin sulfate, and gelatin) and stiffness, and promoting cell adhesion via adhesive peptide immobilization (i.e., RGD peptide). The results also demonstrate that these modifications can be controlled over time and space, paving the way for 4D bioprinting applications.

Smart responsive in situ hydrogel systems applied in bone tissue engineering

“…In addition, countless biomaterials (e.g., collagen, HA, alginate, dextran, chitosan, gelatin, silk, etc.) are modified by chemical bonds to achieve in situ click chemical crosslinking in physical conditions ( Lao et al, 2023 ; Morrison and Gramlich, 2023 ; Rizwan et al, 2023 ; Tournier et al, 2023 ). For example, to prolong the degradation time of HA in vivo , Park et al (2020) .…”

Boronate Ester Hydrogels for Biomedical Applications: Challenges and Opportunities

“…Recently, we investigated the use of a new class of BE hydrogels that shows long-term stability 54 as potential biomaterial inks for 3D extrusion-based printing ( Figure 5 ). 191 Using o -AM-PBA/glucamine cross-linking, we optimized two HA-based hydrogel formulations with a G ′ 1 Hz of 200 and 2000 Pa, respectively, that could be printed but did not readily collapse under their own weight. The preformed hydrogels prevented cell sedimentation in the cartridge and, thus, ensured homogeneous cell distribution.…”

“…(d) ASC adhesion with or without addition of RGD-N 3 , showing a significant increase in cell adhesion on the top of the hydrogel with clickable RGD. (e) Schematic and pictures of nonclickable and clickable dynamic hydrogels printed side-by-side, before and after 24-h incubation with CF647-HA-N 3 (purple), demonstrating the possibility of spatial control over the postprinting modifications (adapted with permission from Tournier et al 191 ). Copyright [2023] [John Wiley & Sons].…”

Bioprinting of aptamer-based programmable bioinks to modulate multiscale microvascular morphogenesis in 4D

“…Recent progress in bioprinting technology has focused on augmenting resolution and printing speed, greatly broadening our capability to fabricate engineered tissues. [12,13] Most bioinks have been engineered with an emphasis on printability and mimicking the dynamic viscoelastic behavior of living tissues, [14][15][16] yet they frequently overlook the dynamic availability of angiogenic factors during vascular morphogenesis in vivo. While several studies have effectively showcased the formation of patterned, perfusable vasculature within 3D-bioprinted constructs, [3][4][5][6]17,18] many methodologies inadequately address the dynamic remodeling of vasculature over time.…”