Loading of viral vectors in synthetic
polymers is a promising strategy for overcoming hurdles associated with viral gene delivery. For enhanced gene expression at a specific site, gene transfer by using
hydrogels represents a versatile approach. In this study, adeno-associated virus serotype 2 containing the
green fluorescent protein gene (rAAV2-GFP) were loaded into poly(
ethylene glycol) (PEG)
hydrogels, with and without incorporation of poly-L-hisditine (polyHis). Inclusion of polyHis created pH responsive
hydrogels in a physiological range of tissues, containing the damaged vasculature and activated phagocytosis. The fraction of polyHis used controlled the degree of swelling, water uptake and subsequent degradation of the
hydrogels and release rate of rAAV2-GFP. The swelling ratio of the PEG-polyHis
hydrogels increased inversely with environment pH. As pH declined from 7.4 to 6.0, PEG-polyHis
hydrogel swelling ratio and degradation rate increased 875% and 135%, respectively. As a result, release and transduction efficiency of the rAAV2-GFP from PEG-polyHis
hydrogel in human HT-1080
fibrosarcoma cells increased significantly compared to a PEG
hydrogel. Transduction rate can be controlled by the
hydrogels' polyHis concentration and is sensitive to localized decreases in pH consistent with
inflammation. This is relevant to optimizing parameters for
wound care and regenerative medicine applications.