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 gamma-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 degrees 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 degrees 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.