Polymer oxidation: A strategy for the controlled degradation of injectable cryogels

Cryogels, an advanced subclass of hydrogels, are widely used in biomedical applications such as tissue engineering, drug delivery, and immunotherapy. Biopolymers, like hyaluronic acid (HA), are key building blocks for cryogel fabrication due to their intrinsic biological properties, biocompatibility, and biodegradability. HA undergoes biodegradation through hydrolysis, enzymatic degradation, and oxidation, but becomes less susceptible to degradation once chemically modified. This modification is necessary for producing HA-based cryogels with unique properties, including an open macroporous network, mechanical resilience, shape memory, and syringe injectability. Endowing cryogels with resorbable features is essential for meeting regulatory requirements and improving treatment outcomes. To this end, HA was oxidized with sodium periodate (HA_ox) and chemically modified with glycidyl methacrylate (HA_oxGM) to create HA_oxGM cryogels with controlled degradation. Oxidation of HA increased the susceptibility of the polymer backbone to breakdown through various mechanisms, including oxidative cleavage and alkaline hydrolysis. Compared to their poorly degradable counterparts, HA_oxGM cryogels retained their advantageous properties despite reduced compressive strength. HA_oxGM cryogels were highly cytocompatible, biocompatible, and tunable in degradation. When injected subcutaneously into mice, the HA_oxGM cryogels were biocompatible and resorbed within two weeks. To validate the beneficial effect of controlled biodegradation in a relevant <i>in vivo</i> setting, we demonstrated that the degradation of HA_oxGM cryogels accelerates ovalbumin release and enhances its uptake and response by immune cells in mice. This versatile oxidation strategy can be applied to a wide range of polymers, allowing better control over cryogel degradation, and advancing their potential for biomedical applications and clinical translation.