Oxygen release by chondrocytes-laden hydrogels obtained via catalyst-free click chemistry for tissue engineering

The development of smart biomaterials requires optimized properties leading to integrative platforms with surrounding tissues and cells in injured regions. Engineering hydrogels through click chemistry offers a sustainable and efficient method for tailoring their properties. Another crucial challenge in tissue engineering is extended oxygen supply, particularly in three-dimensional (3D) networks as hydrogels used for in vitro cell culture. In this regard, a novel hydrogel combining chondroitin sulfate (CS) and polyethylene glycol (PEG) was synthesized using a catalyst-free click reaction, resulting in self-standing, crosslinked hydrogels with tunable rheological and mechanical properties. To address the oxygen supply, oxygen-generating microparticles were obtained by calcium peroxide (CPO) encapsulation via electrospray technology, so incorporated into chondrocyte-laden hydrogels via inverse electron demand Diels-Alder (iEDDA) click reaction. These biomaterials provided sustained oxygen release, fostering chondrocyte viability and differentiation, as confirmed through gene expression analysis. The CPO was synthesized from calcium nitrate and chloride using methanol and ethanol as solvents, CPO particles exhibited controlled size, charge, and morphology, ensuring prolonged oxygen release upon contact with water. Characterization via DLS, XRD, DSC, and SEM/EDS validated the encapsulation and oxygen-supplying capability of these structures. The optimal formulation, TCS-8A-PEG (40 KD), demonstrated enhanced wound healing by promoting blood perfusion, vessel formation, and collagen deposition, highlighting its potential for skin tissue engineering. The integration of click chemistry-engineered hydrogels with oxygen-releasing microparticles presents a promising avenue for advanced tissue engineering applications.