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bioRxiv · 10.1101/2025.04.01.646472

Photocrosslinkable and biodegradable hydrogels for the controlled delivery of exosomes

Ayala-Mar, S.·Jeon, O.·Chacon-Ponce, P.·Gonzalez-Valdez, J.·Alsberg, E. A.
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Abstract

Local and controlled delivery of exosomes using hydrogels can improve the efficacy of exosome-based therapeutics. Hydrogels based on oxidized and methacrylated alginate (OMA) can be produced through photocrosslinking and exhibit controllable degradability. The degradation properties of OMA hydrogels can be tailored by varying the alginate oxidation degree, which is advantageous for exploring new therapeutic strategies. Here, we prepared photocrosslinkable, biodegradable, cytocompatible, and tunable alginate hydrogels for exosome delivery. We synthesized OMA with different degrees of alginate oxidation to generate OMA hydrogels that undergo both rapid and slow degradation. The degradation rate, swelling ratio and mechanical stability of the OMA hydrogels were investigated. Likewise, we examined exosome release rate and kinetics. The cytocompatibility and functionality of these systems were confirmed. Increasing the alginate oxidation degree greatly enhanced the degradation of OMA hydrogels. Rapid degradation correlated with accelerated exosome release, while slow degradation correlated with enhanced exosome retention. Physicochemical properties including the rheological behavior and swelling also influenced the exosome release rate. Kinetic equation fits showed that the Korsmeyer-Peppas model can be used to describe the release process. These findings demonstrate that OMA hydrogels are suitable delivery carriers for the controlled release of exosomes and highlight the potential use of this technology in applications that depend on either rapid or slow exosome delivery and the temporary presence of the hydrogel, including tissue engineering, wound healing and localized and targeted drug delivery.

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Ayala-Mar, S., Jeon, O., Chacon-Ponce, P., Gonzalez-Valdez, J., Alsberg, E. A.. 2025-04-08. Photocrosslinkable and biodegradable hydrogels for the controlled delivery of exosomes. https://doi.org/10.1101/2025.04.01.646472

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