Comparative Potential of Juvenile and Adult Human Articular Chondrocytes for Cartilage Tissue Formation in Three-Dimensional Biomimetic Hydrogels

Abstract

Regeneration of human articular cartilage is inherently limited and extensive efforts have focused on engineering the cartilage tissue. Various cellular sources have been studied for cartilage tissue engineering including adult chondrocytes, and embryonic or adult stem cells. Juvenile chondrocytes (from donors below 13 years of age) have recently been reported to be a promising cell source for cartilage regeneration. Previous studies have compared the potential of adult and juvenile chondrocytes or adult and osteoarthritic (OA) chondrocytes. To comprehensively characterize the comparative potential of young, old, and diseased chondrocytes, here we examined cartilage formation by juvenile, adult, and OA chondrocytes in three-dimensional (3D) biomimetic hydrogels composed of poly(ethylene glycol) and chondroitin sulfate. All three human articular chondrocytes were encapsulated in the 3D biomimetic hydrogels and cultured for 3 or 6 weeks to allow maturation and extracellular matrix formation. Outcomes were analyzed using quantitative gene expression, immunofluorescence staining, biochemical assays, and mechanical testing. After 3 and 6 weeks, juvenile chondrocytes showed a greater upregulation of chondrogenic gene expression than adult chondrocytes, while OA chondrocytes showed a downregulation. Aggrecan and type II collagen deposition and glycosaminoglycan accumulation were high for juvenile and adult chondrocytes but not for OA chondrocytes. Similar trend was observed in the compressive moduli of the cartilage constructs generated by the three different chondrocytes. In conclusion, the juvenile, adult and OA chondrocytes showed differential responses in the 3D biomimetic hydrogels. The 3D culture model described here may also provide a useful tool to further study the molecular differences among chondrocytes from different stages, which can help elucidate the mechanisms for age-related decline in the intrinsic capacity for cartilage repair.

What Is the Effect of Matrices on Cartilage Repair? A Systematic Review

“…The manufacturer of DeNovo-Natural Tissue combined allograft particulated juvenile cartilage with fibrin adhesive to create a product that got regulatory approval as a minimally processed allograft in the United States [9,27]. As a cell source, DeNovo-Natural Tissue offers significant theoretical benefits with increased replicative and matrix synthetic ability compared with adult chondrocytes [1,22,38]. Similarly, other companies are producing minimally processed allograft tissue matrices.…”

Stem Cell Therapy for Cartilage Defects

“…However, harvesting human ESCs (HESCs) is surrounded by considerable ethical, moral and religious dilemmas and barriers. There is evidence that younger cells, such as chondrocytes, are a more promising cell source for cartilage regeneration (Smeriglio et al 2014).…”

Establishment and Simulation of the Articular Cartilage Two Phase Model Based on the Hyperelastic Solid Phase

“…Complex organic matter mainly includes collagen and proteoglycan. Interstitial fluid contains mostly water, the flow of the fluid not only has an important influence on cartilage mechanical properties, also has a close relationship with the vascular tissue nutrient transport [1]. At the same time, articular cartilage has a very low coefficient of friction, which plays a good role in lubrication [2].…”

“…The following finite element analysis procedure is carried out within a time step 1 t  , supposing that 1 1 0 1s t t t     , time integral parameter 0.6   , each time step reflects the changing process of load at this moment, the relationship between stress and velocity was calculated, as shown in Fig.2 (b). The simulation results are compared with the results that used the penalty finite element method, and the experimental data obtained by the Spilker and Holmes et al in Rensselaer Polytechnic Institute [14], the contrast curves are shown in Fig.2 (b).…”