Fine-tuning Dynamic Cross-linking for Enhanced 3D Bioprinting of Hyaluronic Acid Hydrogels

3D bioprinting of stem cells shows promise for medical applications, but the development of an efficient bioink remains a challenge. Recently, the emergence of dynamically cross-linked hydrogels has advanced this field to obtain self-healing materials. However, more advanced bioinks are needed that display optimum gelling kinetics, viscoelasticity, shear-thinning property, structural fidelity, and hold the printed structures sufficiently long enough that allow maturation of the new tissue. Here, a novel extracellular matrix-based bioink for human mesenchymal stem cells (hMSCs) is presented. Hyaluronic acid (HA) is modified with cysteine and aldehyde functional groups, creating hydrogels with dual cross-linking of disulfide and thiazolidine products. The investigation demonstrates that this cross-linking significantly improves hydrogel stability and biological properties. The bioink exhibits fast gelation kinetics, shear-thinning, shape-maintaining properties, high cell survival after printing with >2-fold increase in stemness marker (OCT3/4 and NANOG), and supports cell proliferation and migration. Disulfide cross-linking contributes to self-healing and cell migration, while thiazolidine cross-linking reduces gelation time, enhances long-term stability, and supports cell proliferation. Overall, the HA-based bioink fulfills the requirements for successful 3D printing of stem cells, providing a promising solution for cell therapy and regenerative medicine.

Krishnan, NithiyanandanUppsala universitet,Makromolekylär kemi(Swepub:uu)nitkr373 (author)
Mokhtari, HamidrezaUppsala universitet,Makromolekylär kemi(Swepub:uu)hammo663 (author)
Oommen, Oommen P.Tampere Univ, Fac Med & Hlth Technol, Bioengn & Nanomed Grp, Tampere 33720, Finland.;BioMediTech Inst, Tampere 33720, Finland. (author)
Varghese, Oommen P.,1977-Uppsala universitet,Makromolekylär kemi(Swepub:uu)oopva021 (author)
Uppsala universitetMakromolekylär kemi (creator_code:org_t)

In:Advanced Functional Materials: Wiley-VCH Verlagsgesellschaft34:41616-301X1616-3028

By the author/editor: Tavakoli, Shima; Krishnan, Nithiy ...; Mokhtari, Hamidr ...; Oommen, Oommen P ...; Varghese, Oommen ...

About the subject

NATURAL SCIENCES: NATURAL SCIENCES; and Chemical Science ...; and Polymer Chemistr ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Cell and Molecul ...

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