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Biomaterials

Biomaterials - Poster Session E

Poster O2 - Hydrogel Delivery of Urine Derived Stem Cells (USCs) and USC-derived Extracellular Vesicles to Promote Diabetic Skin Wound Healing

Saturday, October 26, 2024
10:00 AM - 11:00 AM EST
Location: Exhibit Hall E, F & G

Introduction:  Diabetes makes patients more susceptible to formation of chronic, nonhealing skin wounds which, in the worst cases, leads to lower limb amputations. Infection control is the primary focus of clinical care, and pharmacological treatments that promote diabetic wound healing are lacking. While stem cells are a promising alternative to promoting wound repair, chronic wounds are an inhospitable environment characterized by uncontrolled inflammation and overproduction of reactive oxygen species (ROS), limiting the viability and potential benefits of cell therapies.
Here, a nanoparticle (NP) and hyaluronic acid (HA) c2omposite, shear-thinning hydrogel was tested for delivery and protection of stem cells or stem cell-derived extracellular vesicles (EVs) in diabetic skin wounds. The NP component is an ROS scavenging/degradable component, while HA was chosen due to it known bioactive, pro-regenerative function. In one arm, we test the direct delivery of human urine derived stem cells (USCs); this unique cell source is motivated by the potential to noninvasively harvest and therapeutically apply a patient’s autologous stem cells. Because paracrine effects are believed to be the primary source of stem cell bioactivity, another arm tests the delivery of USC-derived EVs. This arm of the study is motivated by the growing evidence for therapeutic potential of cell-derived EVs along with the convenience that a cell-derived product offers in terms of lack of viability concerns and the potential to establish a more universal product.

Materials and

Methods:  The hydrogel was assembled by guest-host chemistry to mediate physical crosslinking between HA and the NPs. The NPs were surface functionalized with adamantane (AD), while the HA was β-grafted with cyclodextrin (HA-CD). The NPs were formulated from a linear ABC triblock co-polymer synthesized in-house to create NPs whose core comprises the ROS-responsive polymer poly(propylene sulfide) (PPS). This hydrogel system was loaded with USCs or USC EVs and tested in vivo for excisional wound healing in transgenic (db/db) diabetic mice.

Results, Conclusions, and Discussions: The NP/HA composite hydrogels delivering USCs and USC-EVs trend toward better wound closure at 14 days post-injury compared to untreated and hydrogel alone treated wounds (Figure 1a) and better overall wound closure than untreated wounds (Figure 1b). Additionally, wounds treated with hydrogels containing USC-EVs saw greater mean perfusion than untreated wounds and wounds treated with USCs alone.
This work shows promise in NP/HA composite shear-thinning hydrogels for delivering therapeutic stem cells and EVs to accelerate repair of diabetic skin wounds. EVs are an especially promising therapy that may be, relative to living cells, simpler and more universal to deploy as a product, while maintaining similar if not better therapeutic function.

Acknowledgements (Optional):