A Collagen-Mimetic Organic-Inorganic Hydrogel for Cartilage Engineering

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.

Degradation-Dependent Stress Relaxing Semi-Interpenetrating Networks of Hydroxyethyl Cellulose in Gelatin-PEG Hydrogel with Good Mechanical Stability and Reversibility

“…Various types (natural, synthetic or hybrid) and forms (films, sponge, microsphere) of scaffolding materials can be used for the in vitro regeneration of cartilage tissue [ 7 ]. Among them, hydrogel—a highly hydrated polymeric crosslinked three-dimensional (3D) network—has attracted ample interest as a scaffolding material due to some of its exceptional properties such as high-water content, stability, flexibility, biocompatibility, degradability, similarity to natural tissue, tunability in physical, chemical and mechanical properties, as well as porosity required to impart a chondrosupportive and/or chondroinductive milieu [ 8 ]. Over the past few decades, semi-IPN networks of hydrogels were widely used for cartilage tissue engineering [ 9 , 10 , 11 , 12 ].…”

A Beginner’s Guide to the Characterization of Hydrogel Microarchitecture for Cellular Applications

“…The fast freezing step preserves biological structures with a higher fidelity than conventional SEM, rendering the Cryo-SEM imaging more factual in order to evaluate the hydrogel pore size [ 95 ], porosity [ 99 ], and fiber diameter ( Figure 2 ) [ 98 , 99 ]. The presence of cells can also be detected [ 100 , 101 ]. As in SEM, most limitations of Cryo-SEM arise during the sample preparation stage.…”

Silylated biomolecules: Versatile components for bioinks

“…Silylated collagen-mimetic peptides containing the repeated triplet Pro-Hyp-Gly are so far the only reported peptides that were used as main network components ( Figure 4 ). ( Echalier et al, 2017b ; Valot et al, 2021 ) They formed hydrogels at 6–10 wt% in physiological media depending on the number of Pro-Hyp-Gly repeats and provided a chondroconductive environment to embedded mesenchymal stromal cells when cultured in chondroinductive medium. Interestingly, mixing mono-silylated peptides with bifunctional ones allowed fine-tuning mechanical properties towards more elastic hydrogels.…”