Jiahuan You

Effective reprogramming of chronic wound healing remains challenging due to the limited drug delivery efficacy hindered by physiological barriers, as well as the inappropriate dosing timing in distinct healing stages. Herein, a core-shell structured microneedle array patch with programmed functions (PF-MNs) is designed to dynamically modulate the wound immune microenvironment according to the varied healing phases. Specifically, PF-MNs combat multidrug-resistant bacterial biofilm at the early stage via generating reactive oxygen species (ROS) under laser irradiation. Subsequently, the ROS-sensitive MN shell gradually degrades to expose the MN core component, which neutralizes various inflammatory factors and promotes the phase transition from inflammation to proliferation. In addition, the released verteporfin inhibits scar formation by blocking Engrailed-1 (En1) activation in fibroblasts. Our experiments demonstrate that PF-MNs promote scarless wound repair in mouse models of both acute and chronic wounds, and inhibit the formation of hypertrophic scar in rabbit ear models.

Angiogenesis is a prominent component during the highly regulated process of wound healing. The application of exogenous vascular endothelial growth factor (VEGF) has shown considerable potential in facilitating angiogenesis. However, its effectiveness is often curtailed due to chronic inflammation and severe oxidative stress in diabetic wounds. Herein, an inflammation-responsive hydrogel incorporating Prussian blue nanoparticles (PBNPs) is designed to augment the angiogenic efficacy of VEGF. Specifically, the rapid release of PBNPs from the hydrogel under inflammatory conditions effectively alleviates the oxidative stress of the wound, therefore reprogramming the immune microenvironment to preserve the bioactivity of VEGF for enhanced angiogenesis. In vitro and in vivo studies reveal that the PBNPs and VEGF co-loaded hydrogel is biocompatible and possesses effective anti-inflammatory properties, thereby facilitating angiogenesis to accelerate the wound healing process in a type 2 diabetic mouse model.

Abstract Subcutaneous (SC) injection is a common administration route for rapid and efficient delivery of biotherapeutics. However, syringe‐based injections usually require professional assistance and are associated with pain and potential risks of infections, thus leading to undesired patient compliance and poor life quality. Herein, this work presents an ultrarapid‐acting microneedle (URA‐MN) patch for immediate transdermal delivery of therapeutics in a minimally invasive manner. Effervescent agents are incorporated into the tip of URA‐MN for rapid generation of CO 2 bubbles upon insertion into the skin, immediately powering the biotherapeutics release within a few minutes. The release kinetics of diverse agents including liraglutide (LRT), insulin, and heparin from the URA‐MN patches are evaluated in three different mouse models, and the rapid release of biotherapeutics and potent therapeutic effects are achieved with only 5 min administration. Noteworthily, attributed to the short application duration and negligible residuals of MN matrix remaining in the skin, the URA‐MN patch shows desirable biocompatibility after six‐week administration.

The maintenance of stable plasma drug concentrations within a therapeutic window can be critical for drug efficacy. Here, we developed a wearable osmotic microneedle (OMN) patch to support sustained drug dosing for at least 24 hours without the use of electronic components. The OMN patch uses an osmotic pressure driving force to deliver drug solution into the skin through three hollow microneedles with diameters of less than 200 micrometers. The rate of drug release was related to the composition and concentration of the osmogen and drug and to the physical properties of the semipermeable membrane separating the low- and high-solute compartments. The OMN patch released the peptide drug exenatide in rats and mice for 24 hours, whereas subcutaneous injection resulted in a burst release and rapid decline in the plasma drug concentration. OMN release of exenatide improved glycemic control in a diabetic mouse model consistent with a sustained effective plasma concentration of the drug. Continuous release of the small-molecule chemotherapeutic drug cytarabine reduced the progression of acute myeloid leukemia in mice more effectively than subcutaneous injection. Further evaluation of the OMN patch in canines demonstrated continuous dosing of cytarabine up to 225 milligrams for 24 hours, satisfying clinical requirements (150 to 300 milligrams daily). OMN patches were well tolerated in human participants with minimal pain or irritation of the skin and a stated preference over other administration routes. This wearable drug delivery system could provide a platform for stable high-dose drug release with convenience and safety.