Biomimetic Cell-Laden MeHA Hydrogels for the Regeneration of Cartilage Tissue.

Evgenia Tsanaktsidou,Costas Kiparissides,Olga Kammona,Norina Labude,Sabine Neuss,Melanie Krüger,Linda Kock

doi:10.3390/polym12071598

Abstract

Methacrylated hyaluronic acid (MeHA) and chondroitin sulfate (CS)-biofunctionalized MeHA (CS-MeHA), were crosslinked in the presence of a matrix metalloproteinase 7 (MMP7)-sensitive peptide. The synthesized hydrogels were embedded with either human mesenchymal stem cells (hMSCs) or chondrocytes, at low concentrations, and subsequently cultured in a stem cell medium (SCM) or chondrogenic induction medium (CiM). The pivotal role of the synthesized hydrogels in promoting the expression of cartilage-related genes and the formation of neocartilage tissue despite the low concentration of encapsulated cells was assessed. It was found that hMSC-laden MeHA hydrogels cultured in an expansion medium exhibited a significant increase in the expression of chondrogenic markers compared to hMSCs cultured on a tissue culture polystyrene plate (TCPS). This favorable outcome was further enhanced for hMSC-laden CS-MeHA hydrogels, indicating the positive effect of the glycosaminoglycan binding peptide on the differentiation of hMSCs towards a chondrogenic phenotype. However, it was shown that an induction medium is necessary to achieve full span chondrogenesis. Finally, the histological analysis of chondrocyte-laden MeHA hydrogels cultured on an ex vivo osteochondral platform revealed the deposition of glycosaminoglycans (GAGs) and the arrangement of chondrocyte clusters in isogenous groups, which is characteristic of hyaline cartilage morphology.

Highlights

Glass-like, avascular and aneural articular cartilage tissue, lining the ends of articulating bones, is characterized for its minimal friction and ability to tolerate heavy loads, facilitating the movement of one bone against another
The developed methacrylated hyaluronic acid (MeHA) and chondroitin sulfate (CS)-MeHA hydrogels were found to create a proper environment for the growth and proliferation of human mesenchymal stem cells (hMSCs) and to promote their differentiation towards a chondrogenic phenotype, even when cultured in an expansion medium (SCM)
This was more pronounced in the case of chondroitin sulfate-methacrylated hyaluronic acid (CS-MeHA) hydrogels, indicating the positive effect of the CS-binding peptide on the expression of chondrogenic markers

Summary

Introduction

Glass-like, avascular and aneural articular cartilage tissue, lining the ends of articulating bones, is characterized for its minimal friction and ability to tolerate heavy loads, facilitating the movement of one bone against another. Articular cartilage consists of water (65–80 wt%) and solids comprising mainly collagens (50–75 dry wt%) and proteoglycans (15–30 dry wt%), as well as protein molecules and chondrocytes [1,2]. Polymers 2020, 12, 1598 proliferative activity, and high extracellular matrix protein density, the intrinsic healing ability of the native cartilage tissue is limited and no tissue regeneration can be observed following cartilage injuries like chondral defects, microfractures, etc. Two common operative procedures (i.e., the autologous chondrocyte implantation, ACI, and the matrix-associated autologous chondrocyte implantation, MACI) used for cartilage repair exhibit limitations with regard to the cartilage defect size and geometry [1,3,4,5,6,7]. Non-invasive topical administration via the injection of in situ forming cell-laden hydrogels could offer a promising alternative to the above operative procedures [8]

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Conclusion