An official website of the United States government
Abstract Chronic wounds present significant therapeutic challenges due to prolonged inflammation and bacterial infections, impeding healing. Conventional medicinal dressings typically deliver a single drug with a fixed release profile and lack responsiveness to variations in wound size, nature, or severity. This study introduces an innovative microneedle (MN) patch designed with different microneedle geometries and capable of dual‐drug delivery to address irregular wounds and complex therapeutic requirements. Utilizing CO₂ laser lithography, microneedle molds are fabricated with diverse geometries by precisely controlling laser parameters such as speed, power, and focus, achieving needle heights ranging from 162 ± 30 µm to 1570 ± 40 µm. The patch facilitates simultaneous delivery of simvastatin (SIM) for anti‐inflammatory and tetracycline hydrochloride (TH) for antibacterial properties, targeting different skin depths. In vitro diffusion studies confirm geometry‐dependent drug release profiles, with SIM achieving controlled release over three days and TH exhibiting sustained release over four days. Biocompatibility assays confirmed safety and enhanced fibroblast migration is noted in wound‐healing studies. Antimicrobial testing reveals a 99.9% reduction in bacterial viability. This cost‐effective and scalable approach enables precise, localized delivery and customization of MN arrays to match various wound geometries, offering a versatile platform for personalized medicine and improved chronic wound management.
more »
« less
A Wirelessly Controlled Smart Bandage with 3D‐Printed Miniaturized Needle Arrays
Abstract Chronic wounds are one of the most devastating complications of diabetes and are the leading cause of nontraumatic limb amputation. Despite the progress in identifying factors and promising in vitro results for the treatment of chronic wounds, their clinical translation is limited. Given the range of disruptive processes necessary for wound healing, different pharmacological agents are needed at different stages of tissue regeneration. This requires the development of wearable devices that can deliver agents to critical layers of the wound bed in a minimally invasive fashion. Here, for the first time, a programmable platform is engineered that is capable of actively delivering a variety of drugs with independent temporal profiles through miniaturized needles into deeper layers of the wound bed. The delivery of vascular endothelial growth factor (VEGF) through the miniaturized needle arrays demonstrates that, in addition to the selection of suitable therapeutics, the delivery method and their spatial distribution within the wound bed is equally important. Administration of VEGF to chronic dermal wounds of diabetic mice using the programmable platform shows a significant increase in wound closure, re‐epithelialization, angiogenesis, and hair growth when compared to standard topical delivery of therapeutics.
more »
« less
- Award ID(s):
- 1826135
- PAR ID:
- 10457747
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Functional Materials
- Volume:
- 30
- Issue:
- 13
- ISSN:
- 1616-301X
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Remick, Daniel (Ed.)ABSTRACT Infection of wounds delays healing, increases treatment costs, and leads to major complications. Current methods to manage such infections include antibiotic ointments and antimicrobial wound dressings, both of which have significant drawbacks, including frequent reapplication and contribution to antimicrobial resistance. In this work, we developed wound dressings fabricated with a medical-grade polyurethane coating composed of natural plant secondary metabolites, cinnamaldehyde, and alpha-terpineol. Our wound dressings are easy to change and do not adhere to the wound bed. They kill gram-positive and -negative microbes in infected wounds due to the Food and Drug Administration–approved for human consumption components. The wound dressings were fabricated by dip coating. Antimicrobial efficacy was determined by quantifying the bacteria colonies after a 24 h of immersion. Wound healing and bacterial reduction were assessed in anin vivofull-thickness porcine burn model. Our antimicrobial wound dressings showed a > 5-log reduction (99.999%) of different gram-positive and gram-negative bacteria, while maintaining absorbency. In thein vivoporcine burn model, our wound dressings were superior to bacitracin in decreasing bacterial burden during daily changes, without interfering with wound healing. Additionally, the dressings had a significantly lower adhesion to the wound bed. Our antimicrobial wound dressings reduced the burden of clinically relevant bacteria more than commercial antimicrobial wound dressings. In anin vivoinfected burn wound model, our coatings performed as well or better than bacitracin. We anticipate that our wound dressings would be useful for the treatment of various types of acute and chronic wounds.more » « less
-
Chronic wounds are a major health problem because of delayed healing, causing hardships for the patient. The infection present in these wounds plays a role in delayed wound healing. Silver wound dressings have been used for decades, beginning in the 1960s with silver sulfadiazine for infection prevention for burn wounds. Since that time, there has been a large number of commercial silver dressings that have obtained FDA clearance. In this review, we examine the literature involving in vitro and in vivo (both animal and human clinical) studies with commercial silver dressings and attempt to glean the important characteristics of these dressings in treating infected wounds. The primary presentation of the literature is in the form of detailed tables. The narrative part of the review focuses on the different types of silver dressings, including the supporting matrix, the release characteristics of the silver into the surroundings, and their toxicity. Though there are many clinical studies of chronic and burn wounds using silver dressings that we discuss, it is difficult to compare the performances of the dressings directly because of the differences in the study protocols. We conclude that silver dressings can assist in wound healing, although it is difficult to provide general treatment guidelines. From a wound dressing point of view, future studies will need to focus on new delivery systems for silver, as well as the type of matrix in which the silver is deposited. Clearly, adding other actives to enhance the antimicrobial activity, including the disruption of mature biofilms is of interest. From a clinical point of view, the focus needs to be on the wound healing characteristics, and thus randomized control trials will provide more confidence in the results. The application of different wound dressings for specific wounds needs to be clarified, along with the application protocols. It is most likely that no single silver-based dressing can be used for all wounds.more » « less
-
Abstract Chronic wounds remain a substantial source of morbidity worldwide. An emergent approach that may be well‐suited to induce the complex, multicellular processes such as angiogenesis that are required for wound repair is the use of extracellular vesicles (EVs). EVs contain a wide variety of proteins and nucleic acids that enable multifactorial signaling. Here, the capability of EVs is leveraged to be engineered via producer cell modification to investigate the therapeutic potential of EVs from mesenchymal stem/stromal cells (MSCs) transfected to overexpress long non‐coding RNA HOX transcript antisense RNA (HOTAIR). HOTAIR is previously shown by the authors' group to be critical in mediating angiogenic effects of endothelial cell EVs, and MSCs are chosen as EV producer cells for this study due to their widely reported intrinsic angiogenic properties. The results indicate that MSCs overexpressing HOTAIR (HOTAIR‐MSCs) produce EVs with increased HOTAIR content that promote angiogenesis and wound healing in diabetic (db/db) mice. Further, endothelial cells exposed to HOTAIR‐MSC EVs exhibit increased HOTAIR content correlated with upregulation of the angiogenic protein vascular endothelial growth factor. Thus, this study supports EV‐mediated HOTAIR delivery as a strategy for further exploration toward healing of chronic wounds.more » « less
-
Abstract Butyrate is a key bacterial metabolite that plays an important and complex role in modulation of immunity and maintenance of epithelial barriers. Its translation to clinic is limited by poor bioavailability, pungent smell, and the need for high doses, and effective delivery strategies have yet to realize clinical potential. Here, a novel polymeric delivery platform for tunable and sustainable release of butyrate consisting of a methacrylamide backbone with butyryl ester or phenyl ester side chains as well as mannosyl side chains, which is also applicable to other therapeutically relevant metabolites is reported. This platform's utility in the treatment of non‐healing diabetic wounds is explored. This butyrate‐containing material modulated immune cell activation in vitro and induced striking changes in the milieu of soluble cytokine and chemokine signals present within the diabetic wound microenvironment in vivo. This novel therapy shows efficacy in the treatment of non‐healing wounds through the modulation of the soluble signals present within the wound, and importantly accommodates the critical temporal regulation associated with the wound healing process. Currently, the few therapies to address non‐healing wounds demonstrate limited efficacy. This novel platform is positioned to address this large unmet clinical need and improve the closure of otherwise non‐healing wounds.more » « less
