Bioengineered 3D living fibers as in vitro human tissue models of tendon physiology and pathology

• Published in: Advanced healthcare materials 2022-08, Vol.11 (15), p.e2102863-n/a
• Main Authors: Calejo, Isabel, Labrador-Rached, Claudia J., Gomez-Florit, Manuel, Docheva, Denitsa, Reis, R. L., Domingues, Rui Miguel Andrade, Gomes, Manuela E.
• Format: Article
• Language: English
• Subjects: 3D multiplex models; Bioengineering; Biomedical Engineering; Cell Differentiation; composite living fibers; Cytoskeleton; Drug development; Drug screening; Electrospun microfibers; Elongation; Fibers; Human tissues; Humans; in vitro models; Markers; Microfibers; Science & Technology; Tendon; Tendons; Tendons - metabolism; Three dimensional models; Tissue Engineering; Tissue models
• ISSN: 2192-2640; 2192-2659
• DOI: 10.1002/adhm.202102863

Clinically relevant in vitro models of human tissue's health and disease are urgently needed for a better understanding of biological mechanisms essential for the development of novel therapies. Herein, physiological (healthy) and pathological (disease) tendon states are bioengineered by coupling the biological signaling of platelet lysate components with controlled 3D architectures of electrospun microfibers to drive the fate of human tendon cells in different composite living fibers (CLFs). In the CLFs-healthy model, tendon cells adopt a high cytoskeleton alignment and elongation, express tendon-related markers (scleraxis, tenomodulin, and mohawk) and deposit a dense tenogenic matrix. In contrast, cell crowding with low preferential orientation, high matrix deposition, and phenotypic drift leading to increased expression of nontendon related and fibrotic markers, are characteristics of the CLFs-diseased model. This diseased-like profile, also reflected in the increase of COL3/COL1 ratio, is further evident by the imbalance between matrix remodeling and degradation effectors, characteristic of tendinopathy. In summary, microengineered 3D in vitro models of human tendon healthy and diseased states are successfully fabricated. Most importantly, these innovative and versatile microphysiological models offer major advantages over currently used systems, holding promise for drugs screening and development of new therapies. Work developed under the framework of the Cooperation Agreement established with the Serviço de Imuno-Hemoterapia do Centro Hospitalar de S. João, EPE. The authors would like to thank the Plastic Surgery Department of Hospital da Prelada (Porto, Portugal) for providing tendon tissue samples. Authors acknowledge the financial support from the ERC Grant CoG MagTendon No. 772817; FCT– Fundação para a Ciência e a Tecnologia for the Ph.D. grant of IC (PD/BD/128088/2016) and CL (PD/BD/150515/2019); for the contract to M.G.F. (CEECIND/01375/2017); and for project SmarTendon (PTDC/NAN-MAT/30595/2017) and Achilles (Grant no. 810850). After ini tial online publication, the present address for D.D. was added to the af filiations section on August 3, 2022.