A Collagen-Mimetic Organic-Inorganic Hydrogel for Cartilage Engineering.

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.

Inorganic Sol-Gel Polymerization for Hydrogel Bioprinting.

An inorganic sol-gel polymerization process was used as a cross-linking reaction during three-dimensional (3D) bioprinting of cell-containing hydrogel scaffolds. Hybrid hydroxypropyl methyl cellulose (HPMC), with a controlled ratio of silylation, was prepared and isolated as a 3D-network precursor. When dissolved in a biological buffer containing human mesenchymal stem cells, it yields a bioink that can be printed during polymerization by extrusion. It is worth noting that the sol-gel process proceeded at pH 7.4 using biocompatible mode of catalysis (NaF and glycine). The printing window was determined by rheology and viscosity measurements. The physicochemical properties of hydrogels were studied. Covalent functionalization of the network can be easily performed by adding a triethoxysilyl-containing molecule; a fluorescent hybrid molecule was used as a proof of concept.

Chemical insights into bioinks for 3D printing.

3D printing has triggered the acceleration of numerous research areas in health sciences, which traditionally used cells as starting materials, in particular tissue engineering, regenerative medicine and also in the design of more relevant bioassays for drug discovery and development. While cells can be successfully printed in 2D layers without the help of any supporting biomaterial, the obtainment of more complex 3D architectures requires a specific bioink, i.e. a material in which the cells are embedded during and after the printing process helping to support them while they are arranged in superimposed layers. The bioink plays a critical role in bioprinting: first, it must be adapted to the 3D printing technology; then, it must fulfil the physicochemical and mechanical characteristics of the target construct (e.g. stiffness, elasticity, robustness, transparency); finally it should guarantee cell viability and eventually induce a desired behaviour. This review focuses on the nature of bioink components of natural or synthetic origin, and highlights the chemistry required for the establishment of the 3D network in conditions compatible with the selected 3D printing technique and cell survival.

Biocompatible Glycine-Assisted Catalysis of the Sol-Gel Process: Development of Cell-Embedded Hydrogels.

The sol-gel process can be used for hydrogel cross-linking, thus opening an attractive route for the design of biocompatible hydrogels under soft conditions. The sol-gel process can be catalysed at basic or acidic pH values, under neutral conditions with the addition of a nucleophile. Therefore, working around pH 7 unlocks the possibility of direct cell embedment and the preparation of bioinks. We aimed to propose a generic method for sol-gel 3D bioprinting, and first screened different nucleophilic catalysts using bis-silylated polyethylene glycol (PEG) as a model hydrogel. A synergistic effect of glycine and NaF, used in low concentrations to avoid any toxicity, was observed. Biocompatibility of the approach was demonstrated by embedding primary mouse mesenchymal stem cells. The measure of viscosity as a function of time showed the impact of reaction parameters, such as temperature, complexity of the medium, pH and cell addition, on the kinetics of the sol-gel process, and allowed prediction of the gelation time.