Soft and flexible bioelectronic micro-systems for electronically controlled drug delivery

The concept of targeted and controlled drug delivery, which directs treatment to precise anatomical sites, offers benefits such as fewer side effects, reduced toxicity, optimized dosages, and quicker responses. However, challenges remain to engineer dependable systems and materials that can modulate host tissue interactions and overcome biological barriers. To stay aligned with advancements in healthcare and precision medicine, novel approaches and materials are imperative to improve effectiveness, biocompatibility, and tissue compliance. Electronically controlled drug delivery (ECDD) has recently emerged as a promising approach to calibrated drug delivery with spatial and temporal precision. This article covers recent breakthroughs in soft, flexible, and adaptable bioelectronic micro-systems designed for ECDD. It overviews the most widely reported operational modes, materials engineering strategies, electronic interfaces, and characterization techniques associated with ECDD systems. Further, it delves into the pivotal applications of ECDD in wearable, ingestible, and implantable medical devices. Finally, the discourse extends to future prospects and challenges for ECDD

Laser-processed parchment paper for fabrication of chronic wound dressings with selective oxygenation

Chronic non-healing wounds (e.g., diabetic foot ulcers and bed sores) impact over 6.5 million Americans per year, costs in excess of $25 billion to treat on an annual basis, and are on the rise due to increasing levels of obesity and diabetes compounded by an aging population. A major inhibitor of healing is suboptimal oxygenation of the wound bed. Unlike acute injuries that receive sufficient oxygen via a functional blood vessel network, chronic wounds often suffer from the lack of a proper vascular network; thus being incapable of providing sufficient oxygen for tissue growth. Typical medical treatment of hypoxic chronic wounds typically employs hyperbaric oxygen therapy, which requires bulky equipment and often exposes large areas of the body to unnecessarily elevated oxygen concentrations that can damage healthy tissue. A more recent and convenient approach is topical oxygen therapy (TOT), in which the dressing itself can generate and deliver the required oxygen; various such systems exist commercially, but they are not economical, they do not provide selective delivery to only hypoxic regions, and their design does not permit further expansion for other wound-healing therapies on the same platform. A more practical implementation of such dressings would comprise an inexpensive dressing platform for adaptive oxygen therapy which is capable of delivering appropriate oxygen gas where and when it is needed. This work presents a low-cost alternative for continuous oxygen delivery comprising of an inexpensive, paper-based, biocompatible, flexible platform for locally generating and delivering oxygen to selected hypoxic regions. The platform takes advantage of recent developments in the fabrication of flexible microsystems including the incorporation of paper as a substrate and the use of inexpensive laser machining. The use of paper simultaneously provides structural strength, flexibility, mammalian cell biocompatibility, as well as selective filtering functionality, i.e., it allows for oxygen to pass through while preventing aqueous solutions to reach the tissue. The laser machining enables the precise definition of oxygen generating regions that match the hypoxic wound profile. Together these two technologies enable the development of a low-cost patch/wound-dressing with customized, wound-specific oxygen generating regions

Hydrogel dressings for advanced wound management

The published manuscript is available at EurekaSelect via http://www.eurekaselect.com/openurl/content.php?genre=article&doi=10.2174/0929867324666170920161246Composed in a large extent of water and due to their non-adhesiveness, hydrogels found their way to the wound dressing market as materials that provide a moisture environment for healing while being comfortable to the patient. Hydrogels’ exploitation is constantly increasing after evidences of their even broader therapeutic potential due to resemblance to dermal tissue and ability to induce partial skin regeneration. The innovation in advanced wound care is further directed to the development of so-called active dressings, where hydrogels are combined with components that enhance the primary purpose of providing a beneficial environment for wound healing. The aim of this mini-review is to concisely describe the relevance of hydrogel dressings as platforms for delivery of active molecules for improved management of difficult-to-treat wounds. The emphasis is on the most recent advances in development of stimuli-responsive hydrogels, which allow for control over wound healing efficiency in response to different external modalities. Novel strategies for monitoring of the wound status and healing progress based on incorporation of sensor molecules into the hydrogel platforms are also discussed.Peer ReviewedPostprint (author's final draft

Smart Bandaid Integrated with Fully Textile OECT for Uric Acid Real-Time Monitoring in Wound Exudate

: Hard-to-heal wounds (i.e., severe and/or chronic) are typically associated with particular pathologies or afflictions such as diabetes, immunodeficiencies, compression traumas in bedridden people, skin grafts, or third-degree burns. In this situation, it is critical to constantly monitor the healing stages and the overall wound conditions to allow for better-targeted therapies and faster patient recovery. At the moment, this operation is performed by removing the bandages and visually inspecting the wound, putting the patient at risk of infection and disturbing the healing stages. Recently, new devices have been developed to address these issues by monitoring important biomarkers related to the wound health status, such as pH, moisture, etc. In this contribution, we present a novel textile chemical sensor exploiting an organic electrochemical transistor (OECT) configuration based on poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) for uric acid (UA)-selective monitoring in wound exudate. The combination of special medical-grade textile materials provides a passive sampling system that enables the real-time and non-invasive analysis of wound fluid: UA was detected as a benchmark analyte to monitor the health status of wounds since it represents a relevant biomarker associated with infections or necrotization processes in human tissues. The sensors proved to reliably and reversibly detect UA concentration in synthetic wound exudate in the biologically relevant range of 220-750 μM, operating in flow conditions for better mimicking the real wound bed. This forerunner device paves the way for smart bandages integrated with real-time monitoring OECT-based sensors for wound-healing evaluation

WOUND HEALING CONCEPTS: CONTEMPORARY PRACTICES AND FUTURE PERSPECTIVES

The advancements in the development of wound dressings have seen tremendous growth in the past few decades. Wound healing approach has majorly shifted from dry healing to moist healing. There has been a significant advancement in our understanding of the underlying physiology involved in wound healing and the associated systemic factors having a direct or indirect influence on the healing. This has resulted in the development of wound dressings designed to treat specific types of wounds. The present review discusses the physiology of wound healing, followed by different factors that contribute to healing. The advancements in wound dressings with their merits and limitations, newer approaches in wound care i.e., hyperbaric oxygen, negative pressure therapy, skin substitutes and role of growth factors in wound healing, have been highlighted. In addition, more recent approaches for effective wound care like smart devices with sensing, reporting and responding functions are discussed

Correlating the Effect of Dynamic Variability in the Sensor Environment on Sensor Design

This dissertation studies the effect of biofluid dynamics on the electrochemical response of a wearable sensor for monitoring of chronic wounds. The research investigates various dynamic in vivo parameters and correlates them with experimentally measured behavior with wound monitoring as a use case. Wearable electrochemical biosensors suffer from several unaddressed challenges, like stability and sensitivity, that need to be resolved for obtaining accurate data. One of the major challenges in the use of these sensors is continuous variation in biofluid composition. Wound healing is a dynamic process with wound composition changing continuously. This dissertation investigates the effects of several in vivo biochemical and environmental parameters on the sensor response to establish actionable correlations. Real-time assessment of wound healing was carried out through longitudinal monitoring of uric acid and other wound fluid characteristics. A textile sensor was designed using a simple fabrication approach combining conductive inks with a polymeric substrate, for conformal contact with the wound bed. A −1 cm−2, establishing the applicability of the sensor for measurements in the physiologically relevant range. The sensor was also found to be stable for a period of 3 days when subjected to physiological and elevated temperatures (37oC and 40oC) confirming its relevance for long-term monitoring. A direct correlation between sensor response and the dynamic parameters was seen, with the results showing a ~20% deviation from the accurate UA reading. The results confirmed that as a consequence of these parameters temporally changing in the wound environment, the sensor response will be altered. The work develops mathematical models correlating this effect on sensor response to allow for real-time sensor calibration. The clinical validation studies established the feasibility of UA measurement by the developed electrochemical sensor and derive correlations between the wound chronicity and UA levels. The protocols developed in this work for the design, fabrication, and calibration of the sensor to correct for the dynamic in vivo behavior can be extended to any wearable sensor for improved accuracy

Antibacterial hydrogel dressings and their applications in wound treatment

Antimicrobial hydrogels, both in semi-stiff sheets and amorphous form, have been extensively studied for wound management mainly owing to their high-water content, lower wound adherence, promoted autolysis debridement, epithelial migration, and granulation growth. Benefiting from the recent advances in materials science, biotechnology, and a growing understanding of wound microbiology, an extensive variety of antimicrobial hydrogels have been developed. These novel antimicrobial hydrogels can prevent and control microbial infection. In addition, they possess wound healing functions for improved wound management. This chapter will provide a comprehensive summary of the current studied antimicrobial hydrogels in literature and available hydrogel dressings in the market, including their design, fabrication method, and wound management efficacy in vitro or in vivo. The detailed and critical discussion of the advantages and disadvantages of each type of hydrogel dressing will provide insights into the future design of antimicrobial hydrogels for better management of wounds in clinical application

Smart dressings based on bacterial cellulose for chronic wounds healing and monitoring

In recent years, there has been an upward trend for novel biomass based green materials for dressing chronic wounds, which can assist in wound healing and monitoring. This research focuses on candidate components for smart chronic wound dressings based on bacterial cellulose (BC), which is comprised of two parts: antimicrobial BC nanocomposites for wound dressing, and a BC-derived pH sensor for monitoring chronic wounds. This research demonstrates a novel ability to utilise BC and BC-derived nanocomposites in potential applications for smart wound dressings. In the chapter regarding BC production, samples grown in static from four different Acetobacter bacterial strains are characterized and compared for the first time. SEM and BET results demonstrate a large surface area (>100 m2/g) and XRD analysis reveals high crystallinity (>60%). In vitro cell tests indicate potential biocompatibility. In the BC based pH sensor chapter, a pyrolyzed BC (p-BC) aerogel was incorporated with polyaniline (PANI) and polydimethylsiloxane (PDMS), exhibiting near-Nernst pH sensitivity (50.4 mV/pH). In the chapter on antimicrobial BC nanocomposites, the inorganic BC/silver nanoparticle (BC/AgNP) and organic BC/lysozyme, BC/eggshell membrane (BC/ESM), BC/methylglyoxal (BC/MGO) nanocomposites were fabricated and characterized, with BC/ESM and BC/MGO nanocomposites proposed for the first time. The antimicrobial properties were tested via a disk diffusion method, with BC/MGO exhibiting the greatest antimicrobial activity, with diameters of inhibition zone (DIZ) up to 17.1 ± 0.6 mm against S. aureus and 15.5 ± 0.5 mm against E. coli. Tensile tests show the nanocomposites still retain the high tensile strength of plain BC (>2 MPa). These results indicate that BC and BC-derived nanocomposites are promising candidate materials for smart wound dressings. The future work will focus on more detailed in vitro biocompatibility tests and in vivo wound healing assays

A manufacturable smart dressing with oxygen delivery and sensing capability for chronic wound management

Chronic non-healing wounds, impact over 6.5 million Americans, costs in excess of $25 billion to treat on an annual basis and its incidence is predicted to rise due to the prevalence of obesity and type-2 diabetes. One of the primary complications often associated with chronic wounds is the improper functionality of the peripheral vasculature to deliver O2-rich blood to the tissue which leads to wound hypoxia. Although hyperbaric oxygen therapy are widely used and accepted as an effective approach to bolster tissue O2 levels in hypoxic chronic wounds, most of such treatments require bulky equipment and often expose large areas of the body to unnecessarily elevated oxygen concentrations that can damage healthy tissue. In this paper, we present a smart low-cost wound dressing with integrated oxygen sensor and delivery for locally generating and delivering oxygen to selected hypoxic regions on the wound. The dressing is fabricated on a biocompatible water resistant/hydrophobic paper-based substrate with printed optical oxygen sensors and patterned catalytic oxygen generating regions that are connected to a flexible microfluidic systems. Oxygen generation occurs by flowing H2O2 through the channels and chemical decomposition at the catalyst printed regions on the paper substrate. The hydrophobic paper provides structural stability and flexibility while simultaneously offering printability, selective gaseous filtering, and physical/chemical protection. The fabrication process take advantage of scalable manufacturing technologies including laser processing, inkjet printing, and lamination

A Wirelessly Controlled Smart Bandage with 3D-Printed Miniaturized Needle Arrays

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