posted on 2016-08-08, 00:00authored byAndreina Parisi-Amon, David D. Lo, Daniel T. Montoro, Ruby E. Dewi, Michael T. Longaker, Sarah C. Heilshorn
Recently,
supramolecular hydrogels assembled through nonspecific interactions
between polymers and nanoparticles (termed PNP systems) were reported
to have rapid shear-thinning and self-healing properties amenable
for cell-delivery applications in regenerative medicine. Here, we
introduce protein engineering concepts into the design of a new family
of PNP hydrogels to enable direct control over the polymer–nanoparticle
interactions using peptide-based molecular recognition motifs. Specifically,
we have designed a bifunctional peptide that induces supramolecular
hydrogel assembly between hydroxy apatite nanoparticles and an engineered,
recombinant protein. We demonstrate that this supramolecular assembly
critically requires molecular recognition, as no assembly is observed
in the presence of control peptides with a scrambled amino acid sequence.
Titration of the bifunctional peptide enables direct control over
the number of physical cross-links within the system and hence the
resulting hydrogel mechanical properties. As with previous PNP systems,
these materials are rapidly shear-thinning and self-healing. As proof-of-concept,
we demonstrate that these materials are suitable for therapeutic cell
delivery applications in a preclinical murine calvarial defect model.