Targeting extracellular vesicle delivery to the lungs by microgel encapsulation.

Extracellular vesicles (EVs) secreted by stem and progenitor cells have significant potential as cell-free 'cellular' therapeutics. Yet, small EVs (<200 nm) are rapidly cleared after systemic administration, mainly by the liver, presenting challenges targeting EVs to a specific organ or tissue. Microencapsulation using natural nano-porous hydrogels (microgels) has been shown to enhance engraftment and increase the survival of transplanted cells.

Encapsulating therapeutic cells in RGD-modified agarose microcapsules.

Current cell-based strategies for repairing damaged tissue often show limited efficacy due to low cell retention at the site of injury. Encapsulation of cells within hydrogel microcapsules demonstrably increases cell retention but benefits can be limited due to premature cell escape from the hydrogel microcapsules and subsequent clearance from the targeted tissue. We propose a method of encapsulating cells in agarose microcapsules that have been modified to increase cell retention by providing cell attachment domains within the agarose hydrogel allowing cells to adhere to the microcapsules.

Deterministic paracrine repair of injured myocardium using microfluidic-based cocooning of heart explant-derived cells.

While encapsulation of cells within protective nanoporous gel cocoons increases cell retention and pro-survival integrin signaling, the influence of cocoon size and intra-capsular cell-cell interactions on therapeutic repair are unknown. Here, we employ a microfluidic platform to dissect the impact of cocoon size and intracapsular cell number on the regenerative potential of transplanted heart explant-derived cells. Deterministic increases in cocoon size boosted the proportion of multicellular aggregates within cocoons, reduced vascular clearance of transplanted cells and enhanced stimulation of endogenous repair.

Strategies for controlling egress of therapeutic cells from hydrogel microcapsules.

Endothelial progenitor cells and human mesenchymal stem cells (hMSCs) have shown great regenerative potential to repair damaged tissue; however, their injection in vivo results in low retention and poor cell survival. Early clinical research has focussed on cell encapsulation to improve viability and integration of delivered cells. However, this strategy has been limited by the inability to reproduce large volumes of standardized microcapsules and the lack of information on cell-specific egress and timed release from hydrogel microcapsules.