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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.

 

A Correction to this paper has been published: https://doi.org/10.1038/s41467-020-20857-y 

Abstract Bioresorbable electronic stimulators are of rapidly growing interest as unusual therapeutic platforms, i.e., bioelectronic medicines, for treating disease states, accelerating wound healing processes and eliminating infections. Here, we present advanced materials that support operation in these systems over clinically relevant timeframes, ultimately bioresorbing harmlessly to benign products without residues, to eliminate the need for surgical extraction. Our findings overcome key challenges of bioresorbable electronic devices by realizing lifetimes that match clinical needs. The devices exploit a bioresorbable dynamic covalent polymer that facilitates tight bonding to itself and other surfaces, as a soft, elastic substrate and encapsulation coating for wireless electronic components. We describe the underlying features and chemical design considerations for this polymer, and the biocompatibility of its constituent materials. In devices with optimized, wireless designs, these polymers enable stable, long-lived operation as distal stimulators in a rat model of peripheral nerve injuries, thereby demonstrating the potential of programmable long-term electrical stimulation for maintaining muscle receptivity and enhancing functional recovery. 

Objective and Impact Statement . Real-time monitoring of the temperatures of regional tissue microenvironments can serve as the diagnostic basis for treating various health conditions and diseases. Introduction . Traditional thermal sensors allow measurements at surfaces or at near-surface regions of the skin or of certain body cavities. Evaluations at depth require implanted devices connected to external readout electronics via physical interfaces that lead to risks for infection and movement constraints for the patient. Also, surgical extraction procedures after a period of need can introduce additional risks and costs. Methods . Here, we report a wireless, bioresorbable class of temperature sensor that exploits multilayer photonic cavities, for continuous optical measurements of regional, deep-tissue microenvironments over a timeframe of interest followed by complete clearance via natural body processes. Results . The designs decouple the influence of detection angle from temperature on the reflection spectra, to enable high accuracy in sensing, as supported by in vitro experiments and optical simulations. Studies with devices implanted into subcutaneous tissues of both awake, freely moving and asleep animal models illustrate the applicability of this technology for in vivo measurements. Conclusion . The results demonstrate the use of bioresorbable materials in advanced photonic structures with unique capabilities in tracking of thermal signatures of tissue microenvironments, with potential relevance to human healthcare. 

3D‐printed hydrogel scaffolds functionalized with conductive polymers have demonstrated significant potential in regenerative applications for their structural tunability, physiochemical compatibility, and electroactivity. Controllably generating conductive hydrogels with fine features, however, has proven challenging. Here, micro‐continuous liquid interface production (μCLIP) method is utilized to 3D print poly(2‐hydroxyethyl methacrylate) (pHEMA) hydrogels. With a unique in‐situ polymerization approach, a sulfonated monomer is first incorporated into the hydrogel matrix and subsequently polymerized into a conjugated polyelectrolyte, poly(4‐(2,3‐dihydro‐thieno[3,4‐b][1,4]dioxin‐2‐ylmethoxy)‐butane‐1 sulfonic acid sodium salt (PEDOT‐S). Rod structures are fabricated at different crosslinking levels to investigate PEDOT‐S incorporation and its effect on bulk hydrogel electronic and mechanical properties. After demonstrating that PEDOT‐S does not significantly compromise the structures of the bulk material, pHEMA scaffolds are fabricated via μCLIP with features smaller than 100 µm. Scaffold characterization confirms PEDOT‐S incorporation bolstered conductivity while lowering overall modulus. Finally, C2C12 myoblasts are seeded on PEDOT‐pHEMA structures to verify cytocompatibility and the potential of this material in future regenerative applications. PEDOT‐pHEMA scaffolds promote increased cell viability relative to their non‐conductive counterparts and differentially influence cell organization. Taken together, this study presents a promising new approach for fabricating complex conductive hydrogel structures for regenerative applications.

 

Diabetic foot ulcers are chronic wounds that affect millions and increase the risk of amputation and mortality, highlighting the critical need for their early detection. Recent demonstrations of wearable sensors enable real‐time wound assessment, but they rely on bulky electronics, making them difficult to interface with wounds. Herein, a miniaturized, wireless, battery‐free wound monitor that measures lactate in real‐time and seamlessly integrates with bandages for conformal attachment to the wound bed is introduced. Lactate is selected due to its multifaceted role in initiating healing. Studies in healthy and diabetic mice reveal distinct lactate profiles for normal and impaired healing wounds. A mathematical model based on the sensor data predicts wound closure rate within the first 3 days post‐injury with ≈76% accuracy, which increases to ≈83% when pH is included. These studies underscore the significance of monitoring biomarkers during the inflammation phase, which can offer several benefits, including short‐term use of wound monitors and their easy removal, resulting in lower risks of injury and infection at the wound site. Improvements in prediction accuracy can be achieved by designing mathematical models that build on multiple wound parameters such as pro‐inflammatory and metabolic markers. Achieving this goal will require designing multi‐analyte wound monitors.