Programmable stiffness and stress-relaxation of cross-linked self-assembling peptide hydrogels

The use of self-assembling peptide (SAPs) biomaterials is a promising therapeutic strategy to repair soft tissues as spinal cord, brain, liver, and pancreas. However, these latter have storage moduli, stress resistance, and stress relaxation that change depending on the anatomic region. The SAP molecules relying only on noncovalent interactions struggle to cope with such a wide range of mechanical properties. Hence, we report the design of supramolecular hydrogels based on LKLK12 SAP and SM(PEG)(24) cross-linker to precisely tune hydrogel stiffness over the range of 5-60 kPa. We found that G' increases by similar to 12 kPa, and stress resistance by similar to 1 kPa for each additional 1.35 mM of SM(PEG)(24). Furthermore, the cross-linked SAPs self-assemble into supramolecular beta-sheet-containing nanofibers with stress relaxation ranging from 90 to 150 s. Lastly, post-treatment of cross-linked hydrogel with acetonitrile to unfold SM(PEG)(24) linker significantly improved its strain failure, reaching a breakage strain of 4612%, unprecedented for this class of SAP-based biomaterials. This work provides a new strategy to fine tune the mechanical properties of SAP-based hydrogels to be helpful for soft tissues regeneration.