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Open AccessArticle

Dedifferentiated Human Articular Chondrocytes Redifferentiate to a Cartilage-Like Tissue Phenotype in a Poly(ε-Caprolactone)/Self-Assembling Peptide Composite Scaffold

1
Tissue Engineering Laboratory, Bioengineering Department, IQS School of Engineering, Ramon Llull University, Via Augusta 390, Barcelona 08017, Spain
2
Cytex Therapeutics Inc., Durham, NC 27705, USA
3
Department of Orthopaedic Surgery, Washington University and Shriners Hospitals for Children—St. Louis, St. Louis, MO 63110, USA
4
Analytical Chemistry Department, Institut Químic de Sarrià, Ramon Llull University, Via Augusta 390, Barcelona 08017, Spain
*
Author to whom correspondence should be addressed.
Academic Editor: Peter Dubruel
Materials 2016, 9(6), 472; https://doi.org/10.3390/ma9060472
Received: 27 April 2016 / Revised: 29 May 2016 / Accepted: 3 June 2016 / Published: 17 June 2016
(This article belongs to the Special Issue Smart Hydrogels for (Bio)printing Applications)
Adult articular cartilage has a limited capacity for growth and regeneration and, with injury, new cellular or biomaterial-based therapeutic platforms are required to promote repair. Tissue engineering aims to produce cartilage-like tissues that recreate the complex mechanical and biological properties found in vivo. In this study, a unique composite scaffold was developed by infiltrating a three-dimensional (3D) woven microfiber poly (ε-caprolactone) (PCL) scaffold with the RAD16-I self-assembling nanofibers to obtain multi-scale functional and biomimetic tissue-engineered constructs. The scaffold was seeded with expanded dedifferentiated human articular chondrocytes and cultured for four weeks in control and chondrogenic growth conditions. The composite constructs were compared to control constructs obtained by culturing cells with 3D woven PCL scaffolds or RAD16-I independently. High viability and homogeneous cell distribution were observed in all three scaffolds used during the term of the culture. Moreover, gene and protein expression profiles revealed that chondrogenic markers were favored in the presence of RAD16-I peptide (PCL/RAD composite or alone) under chondrogenic induction conditions. Further, constructs displayed positive staining for toluidine blue, indicating the presence of synthesized proteoglycans. Finally, mechanical testing showed that constructs containing the PCL scaffold maintained the initial shape and viscoelastic behavior throughout the culture period, while constructs with RAD16-I scaffold alone contracted during culture time into a stiffer and compacted structure. Altogether, these results suggest that this new composite scaffold provides important mechanical requirements for a cartilage replacement, while providing a biomimetic microenvironment to re-establish the chondrogenic phenotype of human expanded articular chondrocytes. View Full-Text
Keywords: cartilage tissue engineering; 3D cell culture; human chondrocytes; cell differentiation; biomimetic materials cartilage tissue engineering; 3D cell culture; human chondrocytes; cell differentiation; biomimetic materials
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MDPI and ACS Style

Recha-Sancho, L.; Moutos, F.T.; Abellà, J.; Guilak, F.; Semino, C.E. Dedifferentiated Human Articular Chondrocytes Redifferentiate to a Cartilage-Like Tissue Phenotype in a Poly(ε-Caprolactone)/Self-Assembling Peptide Composite Scaffold. Materials 2016, 9, 472.

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