Biodegradable hydrogels composed of oxime crosslinked poly(ethylene glycol), hyaluronic acid and collagen: a tunable platform for soft tissue engineering

In situ crosslinking hydrogels are attractive for application as injectable hydrogel-based tissue scaffolds that adapt to fill patient-specific cavities. Oxime click chemistry was used to crosslink hydrogels that were biodegradable, soft and supportive of cell adhesion. Linear poly(ethylene glycol)s (PEGs, Mn 2 or 4kDa) terminated at both ends with aminooxy moieties and hyaluronic acid (HA, Mn 2 MDa) derivatives displaying aldehydes were non-toxic towards primary Schwann cells. The PEG and HA derivatives form oxime crosslinked hydrogels with mechanical and swelling properties that were tunable based on the composition of the hydrogels to values analogous to soft tissues such as those found in the central or peripheral nervous system. Gels incorporating collagen-1 supported the adhesion of human mesenchymal stem cells. Such chemistry has the potential to generate clinically relevant injectable hydrogels for minimally invasive personalized medical procedures in the central or peripheral nervous systems.