Tuning hydrogel affinity to control the release of antibodies

This is the authors' abstract. We don't add key points for this paper.

The discovery of specific affinity interactions has paved the way for the development of functional hydrogel systems that enable tunable protein release via non-covalent interactions. This study explores, for the first time, the controlled release of antibody-based therapeutics via affinity interactions with specific fragment crystallizable domain peptide ligands (FcLs) immobilized within a hydrogel system. As a proof of concept, a dual-antibody delivery strategy was designed to stimulate retinal stem cells in the adult mammalian eye, co-releasing Fc-Noggin (targeting bone morphogenic proteins) and anti-sFRP2 (targeting secreted frizzle related protein-2). An FcL capable of binding to both Fc-Noggin and anti-sFRP2 with comparable affinity (10 -8 M) was functionalized onto a hyaluronan-based hydrogel that leverages oxime chemistry for network crosslinking and inverse electron demand Diels-Alder for FcL conjugation. In vitro, FcL1-functionalized hydrogels exhibited affinity-mediated retention of these therapeutics, reducing burst release and preserving protein stability. In vivo, a single intravitreal injection of the hydrogel formulation activated retinal stem cells, in adult CD1 mice, over four days to a similar extent as 3 repeated bolus injections of Fc-Noggin and anti-sFRP2 in saline, demonstrating the advantage of hydrogel-based delivery over bolus administration. This platform technology holds significant potential for broader application to other antibody-based therapies and offers a promising approach for local delivery in the eye.