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.
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- Award ID(s):
- 2011854
- PAR ID:
- 10507523
- Publisher / Repository:
- Wiley
- Date Published:
- Journal Name:
- Advanced Healthcare Materials
- Volume:
- 12
- Issue:
- 26
- ISSN:
- 2192-2640
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract Impaired wound healing is a common complication for diabetic patients and effective diabetic wound management remains a clinical challenge. Furthermore, a significant problem that contributes to patient morbidity is the suboptimal quality of healed skin, which often leads to reoccurring chronic skin wounds. Herein, a novel compound and biomaterial building block, panthenol citrate (PC), is developed. It has interesting fluorescence and absorbance properties, and it is shown that PC can be used in soluble form as a wash solution and as a hydrogel dressing to address impaired wound healing in diabetes. PC exhibits antioxidant, antibacterial, anti‐inflammatory, and pro‐angiogenic properties, and promotes keratinocyte and dermal fibroblast migration and proliferation. When applied in a splinted excisional wound diabetic rodent model, PC improves re‐epithelialization, granulation tissue formation, and neovascularization. It also reduces inflammation and oxidative stress in the wound environment. Most importantly, it improves the regenerated tissue quality with enhanced mechanical strength and electrical properties. Therefore, PC could potentially improve wound care management for diabetic patients and play a beneficial role in other tissue regeneration applications.
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Wound healing presents a unique challenge for patients with diabetes. Gas therapies have gained significant attention in the wound-healing community. Carbon monoxide (CO) is a small molecule that is well known for its immune-modulating properties when administered at sublethal concentrations. CO is currently in clinical trials for lung disease, sickle cell anemia, and organ transplantation. Here, we investigated the effects of CO in an in vitro wound-healing model and subsequently developed and tested CO gas-entrapping materials (CO-GEMs) for topical application on wounds to promote healing. In this study, we report the efficacy of CO-GEMs in treating full-thickness wounds and pressure ulcers in diabetic mouse models. Collectively, our findings demonstrate that these novel gas entrapping materials could serve as an alternative therapy to both protect the wound bed and promote healing and replace bulky hyperbaric chambers, standard gauze wound dressings, or expensive skin grafts.more » « less
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Abstract Impaired wound healing after trauma, disorders, and surgeries impact millions of people globally every year. Dysregulation in orchestrated healing mechanisms and underlying medical complications make chronic wound management extremely challenging. Besides standard‐of‐care treatments including broad spectrum antibiotics and wound‐debridement, novel adjuvant therapies are clinically tested and commercialized. These include topical agents, skin substitutes, growth factor delivery, and stem cell therapies. With a goal to overcome factors playing pivotal role in delayed wound healing, researchers are exploring novel approaches to elicit desirable healing outcomes in chronic wounds. Although recent innovations in wound care products, therapies, and devices are extensively reviewed in past, a comprehensive review summarizing their clinical outcomes is surprisingly lacking. Herein, this work reviews the commercially available wound care products and their performance in clinical trials to provide a statistically comprehensive understanding of their safety and efficacy. The performance and suitability of various commercial wound care platforms, including xenogeneic and allogenic products, wound care devices, and novel biomaterials, are discussed for chronic wounds. The current clinical evaluation will provide a comprehensive understanding of the benefits and drawbacks of the most‐recent approaches and will enable researchers and healthcare providers to develop next‐generation technologies for chronic wound management.
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Wound healing is one of the most complex processes in the human body, supported by many cellular events that are tightly coordinated to repair the wound efficiently. Chronic wounds have potentially life-threatening consequences. Traditional wound dressings come in direct contact with wounds to help them heal and avoid further complications. However, traditional wound dressings have some limitations. These dressings do not provide real-time information on wound conditions, leading clinicians to miss the best time for adjusting treatment. Moreover, the current diagnosis of wounds is relatively subjective. Wearable electronics have become a unique platform to potentially monitor wound conditions in a continuous manner accurately and even to serve as accelerated healing vehicles. In this review, we briefly discuss the wound status with some objective parameters/biomarkers influencing wound healing, followed by the presentation of various novel wearable devices used for monitoring wounds and accelerating wound healing. We further summarize the associated device working principles. This review concludes by highlighting some major challenges in wearable devices toward wound healing that need to be addressed by the research community.more » « less
- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1002/adhm.202300515
