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Hyaluronic Acid-based Bioink Composition Enabling 3D Bioprinting and Improving Quality of Deposited Cartilaginous Extracellular Matrix

Tuesday (17.03.2020)
15:50 - 16:10
Part of:

Hyaluronic acid (HA) represents a main component of the human extracellular matrix (ECM) and is, hence, a desirable material in biofabrication. For cartilage regeneration, in principle, HA is an attractive bioink, however, homogeneous ECM distribution can represent a major challenge due to high polymer contents enabling bioprinting. Therefore, in this study, HA-based bioink formulations were investigated that allowed for reduction of polymer content, and ECM development was evaluated after chondrogenic differentiation of human mesenchymal stromal cells (MSC).

In order to form a range of stable hydrogels, thiol-modified HA (HA-SH) was UV-crosslinked with allyl-modified polyglycidol employing different concentrations of both components. MSC-laden constructs were cultured in chondrogenic medium for 21 days. Decreasing total polymer content from 15 wt.% to 3 wt.% increased construct quality by improved distribution of MSC-derived ECM within the construct, while quantitative analysis of ECM components revealed no significant differences. In order to enable PCL-supported 3D bioprinting, bioink viscosity was increased by further supplementation with 1 wt.% unmodified high molecular weight HA (hmHA). Strikingly, addition of hmHA resulted in completely homogeneous ECM distribution throughout the hydrogels with 3 wt.% polymer content, which was demonstrated histologically, immunohistochemically, and by histomorphometric quantification of key ECM components such as aggrecan and collagen II. This homogeneous ECM distribution led to the stiffest hydrogels with a 170-fold increase in Young’s modulus over time. In contrast, higher concentrated constructs showed only pericellular matrix deposition resulting in lower construct stiffness. Furthermore, GPC measurements of the supernatant revealed 40% release of unbound hmHA from the low concentrated constructs, but only 5% from high concentrated ones, suggesting that release of hmHA generated porous constructs facilitating ECM distribution throughout the gels. The study contributes to rational and effective bioink development, demonstrating dual function of a supplement enabling bioprinting and at the same time improving biological properties of the resulting constructs.

Julia Hauptstein
University of Würzburg
Additional Authors:
  • Michael Bartolf-Kopp
    University of Würzburg
  • Leonard Forster
    University of Würzburg
  • Dr. Rainer Detsch
    Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU)
  • Dr. Tomasz Jüngst
    University of Würzburg
  • Prof. Dr. Jürgen Groll
    University of Würzburg
  • Dr. Jörg Teßmar
    University of Würzburg
  • Prof. Dr. Torsten Blunk
    University of Würzburg