Efficacy of collagen and alginate hydrogels for the prevention of rat chondrocyte dedifferentiation

Abstract

Dedifferentiation of chondrocytes remains a major problem in cartilage tissue engineering. The development of hydrogels that can preserve chondrogenic phenotype and prevent chondrocyte dedifferentiation is a meaningful strategy to solve dedifferentiation problem of chondrocytes. In the present study, three gels were prepared (alginate gel (Alg gel), type I collagen gel (Col gel), and their combination gel (Alg/Col gel)), and the in vitro efficacy of chondrocytes culture while preserving their phenotypes was investigated. While Col gel became substantially contracted with time, the cells encapsulated in Alg gel preserved the shape over the culture period of 14 days. The mechanical and cell-associated contraction behaviors of Alg/Col gel were similar to those of Alg. The cells in Alg and Alg/Col gels exhibited round morphology, whereas those in Col gel became elongated (i.e. fibroblast-like) during cultures. The cells proliferated with time in all gels with the highest proliferation being attained in Col gel. The expression of chondrogenic genes, including SOX9, type II collagen, and aggrecan, was significantly up-regulated in Alg/Col gel and Col gel, particularly in Col gel. However, the chondrocyte dedifferentiation markers, type I collagen and alkaline phosphatase (ALP), were also expressed at significant levels in Col gel, which being contrasted with the events in Alg and Alg/Col gels. The current results suggest the cells cultured in hydrogels can express chondrocyte dedifferentiation markers as well as chondrocyte markers, which draws attention to choose proper hydrogels for chondrocyte-based cartilage tissue engineering.

Dedifferentiation: inspiration for devising engineering strategies for regenerative medicine

“…The sulfation of alginate, which mimics proteoglycans in cartilage, promotes in vitro bovine chondrocyte proliferation, increase cartilage matrix deposition, and inhibits the expression of dedifferentiation markers. A blended gel composed of alginate and collagen also provided a preferable gel matrix environment for the suppression of rat chondrocyte dedifferentiation in vitro 113 . More interestingly, Ding and colleagues 114 concentrated on the effects of external nanoscale features on the dedifferentiation of in vitro cultured primary rat chondrocytes.…”

Production of Injectable Marine Collagen-Based Hydrogel for the Maintenance of Differentiated Chondrocytes in Tissue Engineering Applications

“…NCs were seeded, respectively, within the RTCh and MCh and their behavior was monitored over time. It is known that NCs possess the ability to remodel RTCh [46].…”

Modulating Alginate Hydrogels for Improved Biological Performance as Cellular 3D Microenvironments

“…In biomedical applications, alginate and their hydrogels have been explored, either alone or in combination with other materials, mainly in drug delivery (Nair et al, 2014 ; Garcia-Astrain and Averous, 2018 ; Rossi et al, 2018 ; Shtenberg et al, 2018 ), tissue regeneration and wound healing (Bidarra et al, 2014 ; Liu Q. et al, 2017 ; Luo Z. et al, 2018 ; Zeyang et al, 2018 ; Campiglio et al, 2020 ), three dimensional (3D)-printing (Liu H. et al, 2017 ; Luo Y. et al, 2018 ; Wang et al, 2018 ) and in vitro modeling (Cavo et al, 2018 ; Chu et al, 2018 ). For tissue engineering, in particular, alginate-based biomaterials have been applied in the repair of both soft and hard tissues, including skin (Han et al, 2017 ), heart (Sapir et al, 2011 ; Hayoun-Neeman et al, 2019 ), bone (Maia et al, 2014a , c ), cartilage (Lee H. P. et al, 2017 ; Liao et al, 2017 ; Jin and Kim, 2018 ) and vascular tissue (Bidarra et al, 2011 ; Torres et al, 2018 , 2020 ), among others. In these fields, chemical modification of polymer-based biomaterials is a frequently used strategy to improve not only their structural and mechanical properties but also their biological activity.…”