Passaged Adult Chondrocytes Can Form Engineered Cartilage with Functional Mechanical Properties: A Canine Model

Abstract

It was hypothesized that previously optimized serum-free culture conditions for juvenile bovine chondrocytes could be adapted to generate engineered cartilage with physiologic mechanical properties in a preclinical, adult canine model. Primary or passaged (using growth factors) adult chondrocytes from three adult dogs were encapsulated in agarose, and cultured in serum-free media with transforming growth factor-beta3. After 28 days in culture, engineered cartilage formed by primary chondrocytes exhibited only small increases in glycosaminoglycan content. However, all passaged chondrocytes on day 28 elaborated a cartilage matrix with compressive properties and glycosaminoglycan content in the range of native adult canine cartilage values. A preliminary biocompatibility study utilizing chondral and osteochondral constructs showed no gross or histological signs of rejection, with all implanted constructs showing excellent integration with surrounding cartilage and subchondral bone. This study demonstrates that adult canine chondrocytes can form a mechanically functional, biocompatible engineered cartilage tissue under optimized culture conditions. The encouraging findings of this work highlight the potential for tissue engineering strategies using adult chondrocytes in the clinical treatment of cartilage defects.

Hydrogels for the Repair of Articular Cartilage Defects

“…203,204 Adult chondrocytes were used successfully to generate cartilage in agarose hydrogels that repaired non-weight-bearing defects in a canine model with good integration with the surrounding tissue. 205 Chondrocytes can also be isolated from a patient's auricular, nasoseptal, and costal cartilages, with cells from each source differing slightly in behavior, response to external forces, and potential to produce new cartilage tissue. For example, nasal and auricular chondrocytes proliferate much faster than articular chondrocytes.…”

Cartilage Matrix Formation by Bovine Mesenchymal Stem Cells in Three-dimensional Culture Is Age-dependent

“…The literature suggests lower proliferation, extracellular matrix (ECM) forming potential, and more senescence in aged human chondrocytes [5,21,31]. Similarly, aged bovine chondrocytes produce less cartilage ECM in threedimensional culture [50], and adult canine chondrocytes generate functional grafts only when expanded in specialized media [39]. Adkisson and coworkers noted that immature human chondrocytes in a scaffold-free system produced cartilage-like ECM superior to adult chondrocytes [1].…”

Bioactive Glass 13-93 as a Subchondral Substrate for Tissue-engineered Osteochondral Constructs: A Pilot Study

“…Additionally, agarose is being used as a copolymer in autologous chondrocyte transplantation (Cartipatch 1 ; Banque de tissues, Mions, France) in Europe [39]. Our previous work demonstrates agarose can support the elaboration of functional cartilage in the chondral layer of bilayered tissue-engineered osteochondral constructs [28,36].…”