eCM (Eur Cell Mater / e Cells & Materials) eCM Open Access Scientific Journal
 ISSN:1473-2262         NLM:100973416 (link)         DOI:10.22203/eCM

2013   Volume No 25 – pages 229-247

Title: Cartilage constructs engineered from chondrocytes overexpressing IGF-I improve the repair of osteochondral defects in a rabbit model

Author: H Madry, G Kaul, D Zurakowski, G Vunjak-Novakovic, M Cucchiarini

Address: Centre of Experimental Orthopaedics, Medical Faculty, Building 37, Saarland University, D-66421 Homburg, Germany

E-mail: henning.madry at uks.eu

Key Words: Tissue engineering; gene therapy; articular chondrocytes; bioreactor; insulin-like growth factor I; transplantation; scaffold; osteochondral defects; cartilage repair; osteoarthritis.

Publication date: April 16th 2013

Abstract: Tissue engineering combined with gene therapy is a promising approach for promoting articular cartilage repair. Here, we tested the hypothesis that engineered cartilage with chondrocytes overexpressing a human insulin-like growth factor I (IGF-I) gene can enhance the repair of osteochondral defects, in a manner dependent on the duration of cultivation. Genetically modified chondrocytes were cultured on biodegradable polyglycolic acid scaffolds in dynamic flow rotating bioreactors for either 10 or 28 d. The resulting cartilaginous constructs were implanted into osteochondral defects in rabbit knee joints. After 28 weeks of in vivo implantation, immunoreactivity to ß-gal was detectable in the repair tissue of defects that received lacZ constructs. Engineered cartilaginous constructs based on IGF-I-overexpressing chondrocytes markedly improved osteochondral repair compared with control (lacZ) constructs. Moreover, IGF-I constructs cultivated for 28 d in vitro significantly promoted osteochondral repair vis-à-vis similar constructs cultivated for 10 d, leading to significantly decreased osteoarthritic changes in the cartilage adjacent to the defects. Hence, the combination of spatially defined overexpression of human IGF-I within a tissue-engineered construct and prolonged bioreactor cultivation resulted in most enhanced articular cartilage repair and reduction of osteoarthritic changes in the cartilage adjacent to the defect. Such genetically enhanced tissue engineering provides a versatile tool to evaluate potential therapeutic genes in vivo and to improve our comprehension of the development of the repair tissue within articular cartilage defects. Insights gained with additional exploration using this model may lead to more effective treatment options for acute cartilage defects.

Article download: Pages 229-247 (PDF file)
DOI: 10.22203/eCM.v025a17