Abstract
Injectable hydrogels are attractive for therapeutic delivery because they can be locally administered through minimally-invasive routes. Charge-complementary peptide nanofibers provide hydrogels that are suitable for encapsulation of biotherapeutics, such as cells and proteins, because they assemble under physiological temperature, pH, and ionic strength. However, relationships between the sequences of charge-complementary peptides and the physical properties of the hydrogels that they form are not well understood. Here we show that hydrogel viscoelasticity, pore size, and pore structure depend on the pairing of charge-complementary "CATCH(+/-)" peptides. Oscillatory rheology demonstrated that co-assemblies of CATCH(4+/4-), CATCH(4+/6-), CATCH(6+/4-), and CATCH(6+/6-) formed viscoelastic gels that can recover after high-shear and high-strain disruption, although the extent of recovery depends on the peptide pairing. Cryogenic scanning electron microscopy demonstrated that hydrogel pore size and pore wall also depend on peptide pairing, and that these properties change to different extents after injection. In contrast, no obvious correlation was observed between nanofiber charge state, measured with ζ-potential, and hydrogel physical properties. CATCH(4+/6-) hydrogels injected into the subcutaneous space elicited weak, transient inflammation whereas CATCH(6+/4-) hydrogels induced stronger inflammation. No antibodies were raised against the CATCH(4+) or CATCH(6-) peptides following multiple challenges in vehicle or when co-administered with an adjuvant. These results demonstrate that CATCH(+/-) peptides form biocompatible injectable hydrogels with viscoelastic properties that can be tuned by varying peptide sequence, establishing their potential as carriers for localized delivery of therapeutic cargoes.