In Situ Forming, Silanized Hyaluronic Acid Hydrogels with Fine Control Over Mechanical Properties and In Vivo Degradation for Tissue Engineering Applications

Abstract

In situ forming hydrogels that can be injected into tissues in a minimally-invasive fashion are appealing as delivery vehicles for tissue engineering applications. Ideally, these hydrogels should have mechanical properties matching those of the host tissue, and a rate of degradation adapted for neo-tissue formation. Here, the development of in situ forming hyaluronic acid hydrogels based on the pH-triggered condensation of silicon alkoxide precursors into siloxanes is reported. Upon solubilization and pH adjustment, the low-viscosity precursor solutions are easily injectable through fine-gauge needles prior to in situ gelation. Tunable mechanical properties (stiffness from 1 to 40 kPa) and associated tunable degradability (from 4 days to more than 3 weeks in vivo) are obtained by varying the degree of silanization (from 4.3% to 57.7%) and molecular weight (120 and 267 kDa) of the hyaluronic acid component. Following cell encapsulation, high cell viability (> 80%) is obtained for at least 7 days. Finally, the in vivo biocompatibility of silanized hyaluronic acid gels is verified in a subcutaneous mouse model and a relationship between the inflammatory response and the crosslink density is observed. Silanized hyaluronic acid hydrogels constitute a tunable hydrogel platform for material-assisted cell therapies and tissue engineering applications.

A Carboxymethyl Chitosan‐Based Double‐Crosslinking Hydrogel with Enhanced Antibacterial Properties for Accelerated Wound Healing

“…Silane serves as a covalent crosslinker and forms covalent bonds between the polymers, maintaining the stability of the overall hydrogel network. [ 27 ] AgNPs are incorporated to introduce the antibacterial activity to the hydrogel. Meanwhile, the carboxyl groups on the polymer chain ionically crosslink with Ca 2+ to form a double‐crosslinking matrix (Figure S1, Supporting Information).…”

A Tissue Engineering Acoustophoretic (TEA) Set-up for the Enhanced Osteogenic Differentiation of Murine Mesenchymal Stromal Cells (mMSCs)

“…In closing, the TEA set-up has the potential to be adapted for in situ applications during surgical procedures, where gel components containing cells and/or biofactors can be injected directly into a deteriorated organ site and organized via acoustic fields in the required pattern. Injectable smart materials with tunable mechanical properties [ 72 , 73 ] and non-invasive technologies, such as TEA, are of critical importance for this indispensable advancement in personalized medicine.…”

Bioink Formulation and Machine Learning-Empowered Bioprinting Optimization

“…HA naturally acts as a signaling molecule for cell migration and proliferation ( Lee et al, 2021 ), owing to its extensive use in hydrogel formulation. In situ -forming, silanized hyaluronic acid hydrogels with tunable mechanical properties were able to sustain cell viabilities of over 80% after 7 days of culture ( Flegeau et al, 2020 ).…”