pH controlled release of extracellular vesicles from a hydrogel scaffold for therapeutic applications.

Abstract

Cell-based therapies are gaining attention as a promising approach for repairing damaged tissues and organs, offering alternatives to invasive treatments like organ transplants and powerful medications. Recent research has shifted towards extracellular vesicles (EVs), membrane-bound particles that can carry therapeutic compounds like DNA, RNA, and proteins, which may offer advantages over cell-based therapies, such as higher potency and reduced immune reactions. A key challenge in EV therapy is ensuring that the vesicles reach their intended target tissues. While EVs are often delivered via injection, systemic administration can result in off-target effects. To address this, we highlight the microfluidic encapsulation of EVs in hydrogel microcapsules that include a CD9 binding peptide (CD9BP), allowing for controlled EV release in response to a shift in environmental pH. By encapsulating CD9+ EVs in CD9BP hydrogel capsules, we demonstrate the release of their contents in acidified environments typical of damaged tissues. This method allows for targeted, localized EV delivery. The approach promises more effective tissue regeneration while reducing the need for broad, non-specific drug delivery.