Treatment of Epidermolysis Bullosa and Future Directions: A Review.

Epidermolysis bullosa (EB) comprises rare genetic disorders characterized by skin and mucosal membrane blistering induced by mechanical trauma. Molecularly, pathogenic variants affect genes encoding proteins crucial for epidermal-dermal adhesion and stability. Management of severe EB is multidisciplinary, focusing on wound healing support, ensuring that patients thrive, and complication treatment. Despite extensive research over 30 years, novel therapeutic approaches face challenges. Gene therapy and protein therapy struggle with efficacy, while regenerative cell-based therapies show limited effects. Drug repurposing to target various pathogenic mechanisms has gained attention, as has in vivo gene therapy with drugs for dystrophic and junctional EB that were recently approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA). However, their high cost limits global accessibility. This review examines therapeutic advancements made over the past 5 years, exploiting a systematic literature review and clinical trial data.

Reusable and Porous Skin Patches with Thermopneumatic Adhesion Control Capability and High Water Vapor Permeability.

We present a reusable and porous skin patch (RPS patch) capable of controlling adhesion force with a thermal-pneumatic method for repetitive use as well as improving moisture permeability for long-term use without skin troubles. Previous skin patches cause skin troubles due to high adhesion force (∼30 kPa) and low moisture permeability (∼382 g/m2/day), hindering them from repeatable and long-term use. We control the skin adhesion force of the RPS patch using thermopneumatic pressure generated by an embedded heater on multiple chamber arrays. The RPS patch controls the adhesion force ranging from 8 to 29 kPa on both dry and wet skin while keeping the stable adhesion force for 48 h. It shows repeatable adhesion up to 100 times, and the adhesion force is restored after the RPS patch is washed with water, thus enabling repetitive skin adhesion. We improve the moisture permeability of the RPS patch to 733 g/m2/day while maintaining the adhesion force by making the RPS patch with porous materials. The RPS patch shows no skin troubles for 7 days of attachment, thereby being available for long-term skin attachment. The RPS patch, having adhesion control capability and high moisture permeability, shows potential for use in daily life in biomedical applications, including wearable sensors, medical adhesives, and rehabilitation robots.

Wearable Liquid Metal Composite with Skin-Adhesive Chitosan-Alginate-Chitosan Hydrogel for Stable Electromyogram Signal Monitoring.

In wearable bioelectronics, various studies have focused on enhancing prosthetic control accuracy by improving the quality of physiological signals. The fabrication of conductive composites through the addition of metal fillers is one way to achieve stretchability, conductivity, and biocompatibility. However, it is difficult to measure stable biological signals using these soft electronics during physical activities because of the slipping issues of the devices, which results in the inaccurate placement of the device at the target part of the body. To address these limitations, it is necessary to reduce the stiffness of the conductive materials and enhance the adhesion between the device and the skin. In this study, we measured the electromyography (EMG) signals by applying a three-layered hydrogel structure composed of chitosan-alginate-chitosan (CAC) to a stretchable electrode fabricated using a composite of styrene-ethylene-butylene-styrene and eutectic gallium-indium. We observed stable adhesion of the CAC hydrogel to the skin, which aided in keeping the electrode attached to the skin during the subject movement. Finally, we fabricated a multichannel array of CAC-coated composite electrodes (CACCE) to demonstrate the accurate classification of the EMG signals based on hand movements and channel placement, which was followed by the movement of the robot arm.

Bioinspired poly(aspartic acid) based hydrogel with ROS scavenging ability as mEGF carrier for wound repairing applications.

Poly(amino acid) based self-healing hydrogels have important application in biomedications. In this research, the catechol pendant groups were imported to poly(aspartic acid) based self-healing hydrogel to improved skin adhesion and ROS scavenging performance. The poly(succinimide) (PSI) was reacted with 3,4-dihydroxyphenylalanine (DA) and then hydraziolyzed to import catechol group and hydrazide group respectively, which are responsible for mussel inspired tissue adhesion and dynamic coupling reactivity. The dopamine modified poly(aspartic hydrazide) (PDAH) was reacted with PEO90 dialdehyde (PEO90 DA) to prepare hydrogels, and the resultant hydrogel showed good biocompatibility both in vitro and in vivo. The skin adhesion strength of the mussel inspired hydrogel increased notably with enhanced radical scavenging efficiency fit for in vivo wound repairing applications. The PDAH/PEO90 DA hydrogel also showed sustained albumin release profile and the in vivo wound repairing experiment proved the mouse Epidermal Growth Factor (mEGF) loaded hydrogel as wound dressing material accelerated the wound repairing rate.

Porcupine-inspired microneedles coupled with an adhesive back patching as dressing for accelerating diabetic wound healing.

Diabetes chronic wound is a severe and frequently occurring medical issue in patients with diabetes that often leads to more serious complications. Microneedles (MNs) can be used for wound healing as they can effectively pierce the epidermis and inject drugs into the wound tissue. However, common MN patches cannot provide sufficient skin adhesion to prevent detachment from the wound area. Inspired by the barb hangnail microstructure of porcupine quills, a porcupine quill-like multilayer MN patch with an adhesive back patching for tissue adhesion and diabetic wound healing was designed. Sodium hyaluronate-modified CaO2 nanoparticles and metformin (hypoglycemic agent) were loaded into the polycaprolactone tips of MNs, endowing them with exceptional antibacterial ability and hypoglycemic effect. A flexible and adhesive back patching was formed by polyacrylamide-polydopamine/Cu2+ composite hydrogel, which ensures that the MN patches do not peel off from the application sites and reduce bacterial infection. The bioinspired multilayer structure of MN patches exhibits satisfactory mechanical and antibacterial properties, which is a potential multifunctional dressing platform for promoting wound healing. STATEMENT OF SIGNIFICANCE: The porcupine quill-like microneedles (MNs) with PAM-PDA/Cu2+ (PPC) composite hydrogel back patching have been fabricated, which can enhance the adhesion property of MNs to the skin through a physical interlock of multilayer MNs and chemical bonding of hydrogel patching. CaO2-HA NPs and metformin were loaded into the polycaprolactone tips of MNs, endowing them with the exceptional antibacterial ability and hypoglycemic effect, which could accelerate diabetic wound healing. As a safe and effective strategy in transdermal delivery of drugs, the as-fabricated flexible multilayer MN patch with good antibacterial, hypoglycemic, and biocompatibility has been used to promote the healing of diabetic wound by releasing oxygen and inhibiting inflammation at the wound site.

Fe(III)-coordinated N-[tris(hydroxymethyl)methyl]acrylamide-modified acrylic pressure-sensitive adhesives with enhanced adhesion and cohesion for efficient transdermal application.

Pressure-sensitive adhesives are critical to the product's safety, efficacy, and quality in transdermal drug delivery systems. However, many defects of transdermal patches (e.g., insufficient adhesion, patch displacement, and "dark ring" phenomenon) remain. Herein, the N-[tris(hydroxymethyl)methyl]acrylamide (NAT)-modified acrylic pressure-sensitive adhesive coordinated with Fe(III) (AA-NAT/Fe3+) was creatively proposed. Results demonstrated that the adhesiveness and cohesiveness of the optimized AA-NAT/Fe3+ were higher by 1.8- and 9.7-fold, respectively, than those of commercially available DURO-TAK® 87-4098 due to the hydrogen bonding interaction of NAT-skin interface and coordination of NAT-Fe3+. Moreover, compared with that of DURO-TAK® 87-4098, the adhesion time of AA-NAT/Fe3+ on the human forearm was remarkably prolonged, and no "dark ring" phenomenon was observed for AA-NAT/Fe3+ after removal. After clonidine (CLO) was loaded into AA-NAT/Fe3+, controlled drug release and a drug transdermal behavior were endowed for CLO@AA-NAT/Fe3+in vitro and in vivo. AA-NAT/Fe3+ still maintained superiority in adhesion and cohesion properties after CLO loading. These observations would contribute to the development of pressure-sensitive adhesives with outstanding adhesion and cohesion for transdermal patches. STATEMENT OF SIGNIFICANCE: This N-[tris(hydroxymethyl)methyl]acrylamide-modified acrylic pressure-sensitive adhesive coordinated with Fe(III) has enhanced adhesion and cohesion properties, which provide a simple but effective strategy to solve the problems (e.g., insufficient adhesion, patch displacement, and "dark ring" phenomenon) in existing transdermal patches.

Evaluation of an Efficient and Skin-Adherent Semisolid Sunscreen Nanoformulation.

INTRODUCTION: Sunscreens are substances applied on the skin surface to protect the skin from the harmful effects of UV light. Nanoparticles can increase the retention time of the sunscreen on the skin surface and its efficacy, by acting as physical barriers. The present investigation aimed to evaluate the influence of the chitosan coating of benzophenone-3-loaded lipid-core nanocapsules (CH-LCN) on the skin adhesion and photoprotective effect of the sunscreen. METHODS: CH-LNC were obtained by the interfacial deposition of preformed polymer. A suitable semisolid formulation was obtained by using hydroxyethyl cellulose as the gel-forming polymer. Skin adhesion experiments were performed in vitro by applying the formulation on porcine skin and keeping it under water at 32 °C for up to 60 min. Photoprotective effect was analyzed in vitro by the capacity of the formulations to protect a photo unstable substance (resveratrol) from degradation under UV light. RESULTS: CH-LNC presented size of around 150 nm, with low polydispersity, positive zeta potential, due to chitosan, and benzophenone-3 encapsulation efficiency of close to 100% (3 mg/mL). The proposed gel presented suitable consistence and pH for skin application and benzophenone-3 concentration of around 3 mg/g. Although coated and uncoated lipid-core nanocapsules increased benzophenone-3 skin adhesion after 10 min of water immersion, only the nanoparticles coated with chitosan were able to do so after 60 min. The chitosan coating of the nanocapsules increased the photoprotection of the sunscreen under UVA and UVB light after 60 min of exposure, probably due to the film-forming properties of chitosan. CONCLUSION: The chitosan coating of CH-LCN increased the skin adhesion and the photoprotective effect of the sunscreen.

Development of a Tough, Self-Healing Polyampholyte Terpolymer Hydrogel Patch with Enhanced Skin Adhesion via Tuning the Density and Strength of Ion-Pair Associations.

Polyampholyte (PA) hydrogels have great potential for biomedical applications, owing to their high toughness and good self-recovery and self-healing (SELF) behavior in addition to their physical properties similar to human tissue. However, their implementation as practical biomedical skin patches or wearable devices has so far been limited by their insufficient transdermal adhesion strength. In this work, a new polyampholytic terpolymer (PAT) hydrogel with enhanced skin adhesion was developed using a novel and simple strategy that tunes the structure of ion-pair associations (IPAs), acting as cross-links, in the hydrogel via adding an extra neutral monomer component into the network without changing the total charge balance. The PAT hydrogels were synthesized by the terpolymerization of the neutral monomer N,N-dimethylacrylamide (DMAAm) (or 2-hydroxyethyl methacrylate (HEMA)) as well as the cationic monomer 3-(methacryloylamino) propyl-trimethylammonium chloride (MPTC) and the anionic monomer sodium p-styrenesulfonate (NaSS). Their IPA, which determines their network structure, was modulated by varying the feed concentration of the neutral monomer, Cnm. An increase of Cnm within an optimized Cnm window (0.3-0.4 M) decreased the cross-linking density (strength and density of the IPAs) of the PAT hydrogels, reducing the softening temperature and Young's modulus, which increased compliance but maintained sufficient mechanical strength and thereby maximized the contact surface and enhanced skin adhesion. The DMAAm monomers, compared to the HEMA monomers, produced the higher skin adhesion of the PAT hydrogel, which was explained by the difference in their reactivity to the MPTC and NaSS. This study demonstrated this new method to develop the PAT hydrogels with excellent skin adhesion and biocompatibility while maintaining good toughness, compliance, and SELF behavior and the potential of the PAT hydrogels for biomedical skin patches and wearable devices.