Developmentally Engineered Callus Organoid Bioassemblies Exhibit Predictive In Vivo Long Bone Healing.

Autor: Nilsson Hall G; Prometheus Division of Skeletal Tissue Engineering Skeletal Biology and Engineering Research Center Department of Development and Regeneration KU Leuven O&N1, Herestraat 49, PB 813 3000 Leuven Belgium., Mendes LF; Prometheus Division of Skeletal Tissue Engineering Skeletal Biology and Engineering Research Center Department of Development and Regeneration KU Leuven O&N1, Herestraat 49, PB 813 3000 Leuven Belgium., Gklava C; Prometheus Division of Skeletal Tissue Engineering Skeletal Biology and Engineering Research Center Department of Development and Regeneration KU Leuven O&N1, Herestraat 49, PB 813 3000 Leuven Belgium., Geris L; Prometheus Division of Skeletal Tissue Engineering KU Leuven O&N1, Herestraat 49, PB 813 3000 Leuven Belgium.; GIGA In Silico Medicine Université de Liège Avenue de l'Hôpital 11-BAT 34 4000 Liège 1 Belgium.; Biomechanics Section KU Leuven Celestijnenlaan 300C, PB 2419 3001 Leuven Belgium., Luyten FP; Prometheus Division of Skeletal Tissue Engineering Skeletal Biology and Engineering Research Center Department of Development and Regeneration KU Leuven O&N1, Herestraat 49, PB 813 3000 Leuven Belgium., Papantoniou I; Prometheus Division of Skeletal Tissue Engineering Skeletal Biology and Engineering Research Center Department of Development and Regeneration KU Leuven O&N1, Herestraat 49, PB 813 3000 Leuven Belgium.; Present address: Institute of Chemical Engineering Sciences (ICE-HT) Foundation for Research and Technology Hellas (FORTH) Stadiou St. Platani 26504 Patras Greece.
Jazyk: angličtina
Zdroj: Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2019 Dec 10; Vol. 7 (2), pp. 1902295. Date of Electronic Publication: 2019 Dec 10 (Print Publication: 2020).
DOI: 10.1002/advs.201902295
Abstrakt: Clinical translation of cell-based products is hampered by their limited predictive in vivo performance. To overcome this hurdle, engineering strategies advocate to fabricate tissue products through processes that mimic development and regeneration, a strategy applicable for the healing of large bone defects, an unmet medical need. Natural fracture healing occurs through the formation of a cartilage intermediate, termed "soft callus," which is transformed into bone following a process that recapitulates developmental events. The main contributors to the soft callus are cells derived from the periosteum, containing potent skeletal stem cells. Herein, cells derived from human periosteum are used for the scalable production of microspheroids that are differentiated into callus organoids. The organoids attain autonomy and exhibit the capacity to form ectopic bone microorgans in vivo. This potency is linked to specific gene signatures mimicking those found in developing and healing long bones. Furthermore, callus organoids spontaneously bioassemble in vitro into large engineered tissues able to heal murine critical-sized long bone defects. The regenerated bone exhibits similar morphological properties to those of native tibia. These callus organoids can be viewed as a living "bio-ink" allowing bottom-up manufacturing of multimodular tissues with complex geometric features and inbuilt quality attributes.
Competing Interests: The authors declare no conflict of interest.
(© 2019 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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