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Improved Chondrogenic Capacity of Collagen Hydrogel-Expanded Chondrocytes: In Vitro and in Vivo Analyses

Sanz-Ramos, Patricia PhD; Duart, Julio MD, PhD; Rodríguez-Goñi, María Victoria MD; Vicente-Pascual, Mikel PhD; Dotor, Javier PhD; Mora, Gonzalo MD, PhD; Izal-Azcárate, Iñigo PhD

Journal of Bone & Joint Surgery - American Volume: 2 July 2014 - Volume 96 - Issue 13 - p 1109–1117
doi: 10.2106/JBJS.M.00271
Scientific Articles

Background: The use of autologous chondrocytes in cartilage repair is limited because of loss of the cartilage phenotype during expansion. The mechanosensing capacity of chondrocytes suggests evaluating the use of soft substrates for in vitro expansion. Our aim was to test the expansion of chondrocytes on collagen hydrogels to improve their capacity for chondrogenesis after a number of passages.

Methods: Rat cartilage cells were expanded on collagen hydrogels and on plastic, and the preservation of their chondrogenic capacity was tested both in vitro and in vivo. The expression of relevant markers during expansion on each surface was measured by real-time PCR (polymerase chain reaction). Expanded cells were then implanted in focal lesions in the medial femoral condyle of healthy sheep, and the newly formed tissue was analyzed by histomorphometry.

Results: Compared with cells cultured on plastic, cells cultured on hydrogels had better maintenance of the expression of the Sox9, Col2 (type-II collagen), FGFR3, and Alk-5 genes and decreased expression of Alk-1 and BMP-2. Pellets also showed increased expression of the cartilage marker genes aggrecan, Sox9, and Col2, and decreased expression of Col1 and Col10 (type-I and type-X collagen). ELISA (enzyme-linked immunosorbent assay) also showed a higher ratio of type-II to type-I collagen in pellets formed from cells expanded on hydrogels. When sheep chondrocytes were expanded and implanted in cartilage lesions in the femoral condyle of healthy sheep, hydrogel-expanded cells produced histologically better tissue compared with plastic-expanded cells.

Conclusions: The expansion of chondrocytes on collagen hydrogels yielded cells with an improved chondrogenic capacity compared with cells expanded on plastic.

Clinical Relevance: The study results favor the use of hydrogel-expanded cells over the traditional plastic-expanded cells for autologous chondrocyte implantation.

1Laboratory for Orthopaedic Research, School of Medicine, Ed. Los Castaños, University of Navarra, Irunlarrea 1, 31008 Pamplona, Navarra, Spain. E-mail address for I. Izal-Azcárate:

2Trauma and Orthopaedic Surgery, Servicio Navarro de Salud, Irunlarrea 3, 31008 Pamplona, Navarra, Spain

3DIGNA Biotech, Pio XII 22, 31008 Pamplona, Navarra, Spain

Copyright 2014 by The Journal of Bone and Joint Surgery, Incorporated
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