Molecularly cleavable bioinks facilitate high-performance digital light processing-based bioprinting of functional volumetric soft tissues

Abstract

Digital light processing bioprinting favors biofabrication of tissues with improved structural complexity. However, soft-tissue fabrication with this method remains a challenge to balance the physical performances of the bioinks for high-fidelity bioprinting and suitable microenvironments for the encapsulated cells to thrive. Here, we propose a molecular cleavage approach, where hyaluronic acid methacrylate (HAMA) is mixed with gelatin methacryloyl to achieve high-performance bioprinting, followed by selectively enzymatic digestion of HAMA, resulting in tissue-matching mechanical properties without losing the structural complexity and fidelity. Our method allows cellular morphological and functional improvements across multiple bioprinted tissue types featuring a wide range of mechanical stiffness, from the muscles to the brain, the softest organ of the human body. This platform endows us to biofabricate mechanically precisely tunable constructs to meet the biological function requirements of target tissues, potentially paving the way for broad applications in tissue and tissue model engineering.

Poly(ethylene glycol)–Norbornene as a Photoclick Bioink for Digital Light Processing 3D Bioprinting

“…The high cross-linking density is generally desired for high printing fidelity but at the expense of tissue-mimetic matrix stiffness and cell viability. In this regard, Wang et al developed a selective enzymatic degradation approach to modulate the stiffness of DLP-printed hyaluronic acid–gelatin hybrid hydrogels for matching mechanical properties of various tissues . During enzyme-mediated degradation, high molecular weight of HA led to a higher degree of cell spreading and function and no cell proliferation was observed in the HA/gelatin hybrid hydrogel due to the stiffness.…”

“…In this regard, Wang et al developed a selective enzymatic degradation approach to modulate the stiffness of DLP-printed hyaluronic acid−gelatin hybrid hydrogels for matching mechanical properties of various tissues. 55 During enzyme-mediated degradation, high molecular weight of HA led to a higher degree of cell spreading and function and no cell proliferation was observed in the HA/ gelatin hybrid hydrogel due to the stiffness. While in this work, we achieved a reasonably high initial cell viability (>70%) in the DLP-printed hydrogels, the current hydrogels did not contain any bioactive motifs, such as cell-binding ligands or MMP degradable sequences.…”

3D printing of bone and cartilage with polymer materials

“…A variety of polymer synthesis brackets can have more selectivity in the needs of their spatial structure design and physical and chemical properties. Wang et al (2022b) develops a dual-factor-oriented porous structure of bionic cartilage. Made of sugar and sodium hyaluronate, prepared by collagen, chitosan, and sequin protein, the transition layer of the microtubule array structure is ready.…”

Bioprinting microporous functional living materials from protein-based core-shell microgels

“…Bioprinting microbes has also seen increased applications in recent years, as it furthers our understanding of dynamic bacterial communities 26 and affords insights for bioprocessing enhancement 3–6 . However, current bioprinting routines often trade off suitability to cells for improved material manufacturability, as the inherent mechanical and rheological properties of the bioink cannot be properly decoupled from cellular microenvironments 27,28 . Moreover, it remains a challenge to construct arbitrary macroscopic material morphologies with well-defined cell niches to establish robust interactions among different cell communities 20,21,29 .…”