In situ crosslinking of a biomimetic peptide-PEG hydrogel via thermally triggered activation of factor XIII

There is a medical need for robust, biocompatible hydrogels that can be rapidly crosslinked in situ through the use of gentle and non-toxic triggers, which could be used as a surgical adhesive, a bone-inductive material, or for drug and gene delivery. The complete gelation system described here includes calcium-loaded liposomes, hrFactor XIII, thrombin, and an enzymatic substrate based on a four-armed PEG in which each arm terminates with a 20mer peptide sequence derived from the γ-chain of fibrin. Controlled release of calcium ions for efficient hrFXIII activation was accomplished by thermal triggering of a tailored liposome phase transition at 37°C, which allowed the entire gelation system to be stored in aqueous solution at room temperature without premature gelation. When the system temperature was raised to 37°C (body temperature), the released calcium activates the hrFactor XIII, and gelation was observed to occur within 9 min. Rheological studies performed to quantitatively determine the storage modulus (G′) of the gel during oscillatory shear show that it behaves as a robust, elastic solid. Scanning electron microscopy studies revealed the hydrogel to have a very dense morphology overall, however spherical voids are observed in regions where calcium-loaded liposomes were entrapped during gelation.