StarPEG/heparin-hydrogel based in vivo engineering of stable bizonal cartilage with a calcified bottom layer

• Verfasst von: Kunisch, Elke [VerfasserIn]
• Verfasst von: Knauf, Anne-Kathrin [VerfasserIn]
• Verfasst von: Hesse, Eliane [VerfasserIn]
• Verfasst von: Bothe, Friederike [VerfasserIn]
• Verfasst von: Diederichs, Solvig [VerfasserIn]
• Verfasst von: Richter, Wiltrud [VerfasserIn]
• Titel: StarPEG/heparin-hydrogel based in vivo engineering of stable bizonal cartilage with a calcified bottom layer
• Verf.angabe: Elke Kunisch, Anne-Kathrin Knauf, Eliane Hesse, Uwe Freudenberg, Carsten Werner, Friederike Bothe, Solvig Diederichs, and Wiltrud Richter
• Jahr: 2019
• Jahr des Originals: 2018
• Fussnoten: Published 30 October 2018 ; Gesehen am 31.07.2019
• Titel Quelle: Enthalten in: Biofabrication
• Ort Quelle: Bristol : IOP Publ., 2009
• Jahr Quelle: 2019
• Band/Heft Quelle: 11(2019,1) Artikel-Nummer 015001, ? Seiten
• ISSN Quelle: 1758-5090
• DOI: doi:10.1088/1758-5090/aae75a
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1670325660

Abstract

Repaired cartilage tissue lacks the typical zonal structure of healthy native cartilage needed for appropriate function. Current grafts for treatment of full thickness cartilage defects focus primarily on a nonzonal design and this may be a reason why inferior nonzonal regeneration tissue developed in vivo. No biomaterial-based solutions have been developed so far to induce a proper zonal architecture into a non-mineralized and a calcified cartilage layer. The objective was to grow bizonal cartilage with a calcified cartilage bottom zone wherein main tissue development is occurring in vivo. We hypothesized that starPEG/heparin-hydrogel owing to the glycosaminoglycan heparin contained as a building-block would prevent mineralization of the upper cartilage zone and be beneficial in inhibiting long-term progression of calcified cartilage into bone. MSCs were pre-cultured as self-assembling non-mineralized cell discs before a chondrocyte-seeded fibrin- or starPEG/heparin-hydrogel layer was cast on top directly before ectopic implantation. Bizonal cartilage with a calcified bottom-layer developed in vivo showing stronger mineralization compared to in vitro samples, but the hydrogel strongly determined outcome. Zonal fibrin-constructs lost volume and allowed non-organized expansion of collagen type X, ALP-activity and mineralization from the bottom-layer into upper regions, whereas zonal starPEG/heparin-constructs were of stable architecture. While non-zonal MSCs-derived discs formed bone over 12 weeks, the starPEG/heparin-chondrocyte layer prevented further progression of calcified cartilage into bone tissue. Conclusively, starPEG/heparin-hydrogel-controlled and cell-type mediated spatiotemporal regulation allowed in vivo growth of bizonal cartilage with a stable calcified cartilage layer. Altogether our work is an important milestone encouraging direct in vivo growth of organized cartilage after biofabrication.