Enhancement of Chondrogenic Differentiation of Human Articular Chondrocytes by Biodegradable Polymers

Abstract

Biodegradable polymers are attractive candidates for chondrocyte embedding and transplantation in cartilage tissue engineering. In an attempt to determine the effects of a variety of biodegradable materials on cartilage proliferation and extracellular matrix production, poly-L-lactic acid (PLLA) with a molecular weight of 5,000, polyglycolic acid (PGA) with a molecular weight of 3,000, and copolymer of poly(L-lactic acid-glycolic acid) 50:50 (PLGA) with a molecular weight of 5,000, were dissolved in DMSO and added into the medium for 4 weeks in in vitro high-density micromass culture of multiplied human articular chondrocytes (HAC). PLLA with a molecular weight of 270,000 (PLAO3) was used as thin film. Cell proliferation and differentiation in these biomaterials were compared with tissue culture polystyrene (TCPS) as a control. Alamar blue and alcian blue staining were carried out to determine the chondrocyte proliferation and differentiation, respectively. Samples exposed to these biomaterials promoted cell proliferation in the range of 86-105% of the control proliferation, and a slight but significant increase in cell proliferation was noted only in the culture exposed to PLGA. The sample exposed to PGA elicited a significant 3.7-fold higher (p < 0.01) cell differentiation than controls and was significantly higher than that of the samples exposed to PLLA, PLAO3, and PLGA. After 4 weeks of culture, the cell differentiation from most to least was in the following order PGA > PLAO3 > PLGA = PLLA > Cont. = DMSO. Chondrocyte differentiation of the samples exposed to various biomaterials were significantly higher compared with controls. Thus, serially passage chondrocytes are competent for cell growth and quantifiable matrix production, and biodegradable polymers, especially PGA, hold promise as suitable substrates for scaffolding materials for human cartilage tissue engineering.

Pellet culture elicits superior chondrogenic redifferentiation than alginate‐based systems

“…7 Coming from the observation of mesenchymal condensation in the developing limb bud, pellet culture systems had been established to differentiate mesenchymal stem cells 13,14 and dedifferentiated chondrocytes 15,16 into hyaline cartilage pellets. Although the micro mass system is performing excellently in terms of chondrogenic differentiation, its application for clinical use in tissue engineering is in doubt, mainly due to the limited size and instability of the constructs in vivo.…”

Prediction of the Optimal Mechanical Properties for a Scaffold Used in Osteochondral Defect Repair

“…Besides ensuring the obvious need for biocompatibility, significant effort has also gone into developing scaffolds that are both highly porous and permeable, facilitating a homogenous cell seeding, increased cell attachment and diffusion of nutrients and growth factors to the cells throughout the scaffold. Scaffolds fabricated from synthetic biodegradable polymers such as poly-L-lactic acid (PLA), polyglycolic acid (PGA) [1,2] and copolymer poly(L-lactic acid-glycolic acid) (PLGA) [3], as well as gels such as collagen [4], alginate [5] and agarose [6] possess many of these properties and have been shown to support, to differing degrees, the chondrogenic phenotype and proliferation in vitro, and the synthesis of collagen type II and proteoglycan. Furthermore when used to treat osteochondral defects in vivo, such cell seeded scaffolds have improved the quality of the repair tissue compared to untreated controls [7,8,9,10,11].…”

Markedly different effects of hyaluronic acid and chondroitin sulfate‐A on the differentiation of human articular chondrocytes in micromass and 3‐D honeycomb rotation cultures

“…38 The assay reveals the metabolic activity of cells by detecting mitochondrial activity. Alamar blue used as an indicator dye is incorporated into the cells, reduced, and excreted as a fluorescent product.…”