Abstract

Promising strategies for cartilage regeneration rely on the encapsulation of mesenchymal stromal cells (MSCs) in a hydrogel followed by an injection into the injured joint. Preclinical and clinical data using MSCs embedded in a collagen gel have demonstrated improvements in patients with focal lesions and osteoarthritis. However, an improvement is often observed in the short or medium term due to the loss of the chondrocyte capacity to produce the correct extracellular matrix and to respond to mechanical stimulation. Developing novel biomimetic materials with better chondroconductive and mechanical properties is still a challenge for cartilage engineering. Herein, we have designed a biomimetic chemical hydrogel based on silylated collagen-mimetic synthetic peptides having the ability to encapsulate MSCs using a biorthogonal sol-gel cross-linking reaction. By tuning the hydrogel composition using both mono- and bi-functional peptides, we succeeded in improving its mechanical properties, yielding a more elastic scaffold and achieving the survival of embedded MSCs for 21 days as well as the up-regulation of chondrocyte markers. This biomimetic long-standing hybrid hydrogel is of interest as a synthetic and modular scaffold for cartilage tissue engineering.

Highlights

  • Human mesenchymal stem or stromal cells (MSCs) encapsulated within these novel hydrogels stayed alive for 21 days and expressed chondrocyte markers when induced to differentiate in a chondrogenic medium

  • Collagen hydrogels have been widely used for tissue engineering approaches for diverse applications

  • As far as cartilage engineering is concerned, the encapsulation of MSCs requires a hydrogel, which has to be stiffer than collagen hydrogels to attain a matrix elasticity consistent with the MSC commitment towards chondrocyte differentiation

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Summary

A Collagen-Mimetic Organic-Inorganic Hydrogel for Cartilage Engineering

Laurine Valot 1,2,† , Marie Maumus 3,4,† , Luc Brunel 1 , Jean Martinez 1 , Muriel Amblard 1 , Danièle Noël 3, * , Ahmad Mehdi 2, * and Gilles Subra 1, *.

Introduction
Synthesis and Characterization of the Hybrid Peptides
Structural and Mechanical Characterization of the Hydrogels
Biological Evaluation of the Hydrogels for Cell Encapsulation
Conclusions
Peptide Silylation on the Lysine Side Chains
Circular Dichroism Analyses
Preparation of the Hybrid Hydrogels
Cryo-SEM Images
Indentation Measurements
Swelling Studies
Full Text
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