In vitroandin vivoco-culture of chondrocytes and bone marrow stem cells in photocrosslinked PCL-PEG-PCL hydrogels enhances cartilage formation

Abstract

Chondrocytes (CH) and bone marrow stem cells (BMSCs) are sources that can be used in cartilage tissue engineering. Co-culture of CHs and BMSCs is a promising strategy for promoting chondrogenic differentiation. In this study, articular CHs and BMSCs were encapsulated in PCL-PEG-PCL photocrosslinked hydrogels for 4 weeks. Various ratios of CH:BMSC co-cultures were investigated to identify the optimal ratio for cartilage formation. The results thus obtained revealed that co-culturing CHs and BMSCs in hydrogels provides an appropriate in vitro microenvironment for chondrogenic differentiation and cartilage matrix production. Co-culture with a 1:4 CH:BMSC ratio significantly increased the synthesis of GAGs and collagen. In vivo cartilage regeneration was evaluated using a co-culture system in rabbit models. The co-culture system exhibited a hyaline chondrocyte phenotype with excellent regeneration, resembling the morphology of native cartilage. This finding suggests that the co-culture of these two cell types promotes cartilage regeneration and that the system, including the hydrogel scaffold, has potential in cartilage tissue engineering. Copyright © 2013 John Wiley & Sons, Ltd.

Cell-laden hydrogels for osteochondral and cartilage tissue engineering

“…Although a variety of hydrogels have been developed and used as artificial ECM for cell delivery and 3D culture, only limited cell types such as chondrocytes, preosteoblasts/osteoblasts, MSCs, induced pluripotent stem cells (iPSCs), ESCs, and peripheral blood mononuclear cells (PBMSCs), have the potential of chondrogenic and/or osteogenic differentiation to regenerate cartilage and osteochondral tissues (Table 1) [183, 196–201]. Autologous chondrocyte implantation has been successfully used as a clinical method to treat cartilage defects.…”

“…In vitro studies have demonstrated that chondrocytes could spread and proliferate well in 3D hydrogel matrices, showing enhanced expressions of cartilage-related proteins/genes with well-maintained cell morphology and phenotype [38, 39, 42, 45, 48, 49, 196]. However, hydrogel matrices made from different polymers behaved differently in directing chondrogenesis of chondrocytes.…”

“…2C) [51]. In vivo evaluations further indicated that chondrocytes encapsulated in hydrogels could regenerate hyaline cartilage tissues with structure remodeling [44, 73, 183, 196]. Although chondrocyte-based therapy shows promising potentials in regenerating cartilage tissues, notable limitations exist.…”

“…Chondrocytes and MSCs were encapsulated with different population ratios (1:0, 1:1, 1:2, 1:3, and 1:4) in PCL-PEG composite hydrogels, which were cultured in chondrogenic medium and implanted in rabbits in a full-thickness articular cartilage defect model (Fig. 4A) [196]. In vitro results at 4 weeks indicated that co-culture of articular chondrocytes and MSCs facilitated expression of chondrogenic phenotype and production of cartilaginous ECM.…”

“…(iii) Histological results showing in vivo cartilage formation. Reproduced with permission [196] Copyright © 2013 John Wiley & Sons, Inc. (B) A structured bilayered co-culture of chondrocytes and MSCs in agarose hydrogels for chondrogenesis and endochondral ossification. Alcian blue and Alizarin red staining are used to characterize cartilage ECM formation.…”