Injectable delivery vehicles in tissue engineering are often required for successful tissue formation in a minimally invasive manner. Shear-reversibly crosslinked hydrogels, which can recover gel structures from shear-induced breakdown, can be useful as an injectable, because gels can flow as a liquid when injected but re-gel once placed in the body. In this study, injectable and shear-reversible alginate hydrogels were prepared by combination crosslinking using cell-crosslinking and ionic crosslinking techniques. The addition of a small quantity of calcium ions decreased the number of cells that were required to form cell-crosslinked hydrogels without changing the shear reversibility of the system. The physical properties and gelation behavior of the gels were dependent on the concentration of both the cells and the calcium ions. We found that gels crosslinked by combination crosslinking methods were effective to engineer cartilage tissues in vivo. Using both ionic and cell-crosslinking methods to control the gelation behavior may allow the design of novel injectable systems that can be used to deliver cells and other therapeutics for minimally invasive therapy, including tissue engineering.
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