Magnesium (Mg) and its alloys have attracted much research interest as degradable implant materials. Mg ions may enhance phenotype of chondrocytes at optimal concentrations. In this study, we investigated the effects of fluctuant concentrations of Mg ion released from in vitro degradation of pure Mg microspheres on the phenotype of chondrocytes. The chondrocytes were cultured with 250 μg/mL, 500 μg/mL, and 1000 μg/mL of Mg microspheres (75–150 μm) either on tissue culture plates or within alginate hydrogels, with 5, 10, and 20 mM of MgCl₂ solution set as the control group. Concentrations of Mg ions and pH values of the culture medium were measured at 3 days' interval. Cytotoxicity was evaluated while glycosaminoglycan (GAG) content and gene expression of collagen type I/II/X, aggrecan were quantified. Results showed that peak concentrations of Mg ion reached 10, 20, 30 mM, respectively, at day 3 in groups containing Mg-250 μg/mL, Mg-500 μg/mL, and Mg-1000 μg/mL, respectively, whereas pH values increased mildly to approximately 8 in all experimental groups. No significant cytotoxic effects were found at day 1 and day 3 in all experimental groups. GAG content increased 6% at day 14 in Mg-250 μg/mL group in tissue culture plate, but not in the hydrogel culture. Gene expression of collagen type I/II/X and aggrecan in Mg-1000 μg/mL group decreased significantly when chondrocytes were cultured in cell culture plates. Increase of gene expression of collagen type X in Mg-250 μg/mL group at day 7 was observed. However, gene expressions of collagen type I/II/X and aggrecan in Mg groups increased significantly at day 7 when chondrocytes were cultured in hydrogels. It was concluded that the phenotype of chondrocytes was regulated with dynamic concentration of Mg ions and pH values in a dose- and time-dependant manners. Fine-tuned degradation of Mg microspheres could be used to facilitate layered structures of articular cartilage. Furthermore, it would be cautious to extrapolate from results from 2D chondrocyte cultures. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 4455–4463, 2014.

The injury and degeneration of articular cartilage and associated arthritis are leading causes of disability worldwide. Cartilage tissue engineering as a treatment modality for cartilage defects has been investigated for over 20 years. Various scaffold materials have been developed for this purpose, but has yet to achieve feasibility and effectiveness for widespread clinical use. Currently, the regeneration of articular cartilage remains a formidable challenge, due to the complex physiology of cartilage tissue and its poor healing capacity. Although intensive research has been focused on the developmental biology and regeneration of cartilage tissue and a diverse plethora of biomaterials have been developed for this purpose, cartilage regeneration is still suboptimal, such as lacking a layered structure, mechanical mismatch with native cartilage and inadequate integration between native tissue and implanted scaffold. The ideal scaffold material should have versatile properties that actively contribute to cartilage regeneration. Functional scaffold materials may overcome the various challenges faced in cartilage tissue engineering by providing essential biological, mechanical, and physical/chemical signaling cues through innovative design. This review thus focuses on the complex structure of native articular cartilage, the critical properties of scaffolds required for cartilage regeneration, present strategies for scaffold design, and future directions for cartilage regeneration with functional scaffold materials. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 100A: 2526–2536, 2012.