Cutaneous damage mechanisms related to dynamic fragment impacts are dependent on the impact angle, impact energy, and fragment characteristics including shape, volume, contact friction, and ...orientation. Understanding the cutaneous injury mechanism and its relationship to the fragment parameters is lacking compromising damage classification, treatment, and protection. Here we develop a high-fidelity dynamic mechanics-driven model for partial-thickness skin injuries and demonstrate the influence of fragment parameters on the injury mechanism and damage sequence. The model quantitatively predicts the wound shape, area, and depth into the skin layers for selected impact angles, kinetic energy density, and the fragment projectile type including shape and material. The detailed sequence of impact damage including epidermal tearing that occurs ahead of the fragments initial contact location, subsequent stripping of the epidermal/dermal junction, and crushing of the underlying dermis are revealed. We demonstrate that the fragment contact friction with skin plays a key role in redistributing impact energy affecting the extent of epidermal tearing and dermal crushing. Furthermore, projectile edges markedly affect injury severity dependent on the orientation of the edge during initial impact. The model provides a quantitative framework for understanding the detailed mechanisms of cutaneous damage and a basis for the design of protective equipment.
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Topical skin formulations often include penetration enhancers that interact with the outer stratum corneum (SC) layer to chemically enhance diffusion. Alternatively, penetration can be mechanically ...enhanced with simple rubbing in the presence of solid particles sometimes included to exfoliate the top layers of the SC. Our goal was to evaluate micron-sized carbon dioxide bubbles included in a foamed moisturizing formulation as a mechanical penetration enhancement strategy. We show that moisturizing foam bubbles cause an increase in SC formulation penetration using both mechanical and spectroscopic characterization. Our results suggest viscous liquid film drainage between coalescing gaseous bubbles creates local regions of increased hydrodynamic pressure in the foam liquid layer adjacent to the SC surface that enhances treatment penetration. An SC molecular diffusion model is used to rationalize the observed behavior. The findings indicate marked increased levels of treatment concentration in the SC at 2 h and that persists to 18 h after exposure, far exceeding non-foamed treatments. The study suggests an alternate strategy for increasing formulation penetration with a non-chemical mechanism.
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•Carbonation enhances skin-care formulation penetration into stratum corneum.•Hydrodynamic pressure in the foam liquid layer likely increases skin penetration.•Mechanical and spectroscopic techniques capture 2 h and 18 h effects of carbonation.•Diffusion modeling supports a hydrodynamic pressure mechanism for penetration.
Abstract
Partial-thickness cutaneous injuries distributed over exposed body locations, such as the face and extremities, pose a significant risk of infection, function loss, and extensive scarring. ...These injuries commonly result from impact of kinetic debris from industrial accidents or blast weaponry such as improvised explosive devices. However, the quantitative connections between partial-thickness injuries and debris attributes (kinetic energy, shape, orientation, etc.) remain unknown, with little means to predict damage processes or design protection. Here we quantitatively characterize damage in near-live human skin after impact by debris-simulating kinetic projectiles at differing impact angles and energies. Impact events are monitored using high-speed and quantitative imaging to visualize skin injuries. These findings are utilized to develop a highly predictive, dynamic computational skin-injury model. Results provide quantitative insights revealing how the dermal-epidermal junction controls more severe wound processes. Findings can illuminate expected wound severity and morbidity risks to inform clinical treatment, and assess effectiveness of emerging personal protective equipment.
Humans rely increasingly on sensors to address grand challenges and to improve quality of life in the era of digitalization and big data. For ubiquitous sensing, flexible sensors are developed to ...overcome the limitations of conventional rigid counterparts. Despite rapid advancement in bench-side research over the last decade, the market adoption of flexible sensors remains limited. To ease and to expedite their deployment, here, we identify bottlenecks hindering the maturation of flexible sensors and propose promising solutions. We first analyze challenges in achieving satisfactory sensing performance for real-world applications and then summarize issues in compatible sensor-biology interfaces, followed by brief discussions on powering and connecting sensor networks. Issues en route to commercialization and for sustainable growth of the sector are also analyzed, highlighting environmental concerns and emphasizing nontechnical issues such as business, regulatory, and ethical considerations. Additionally, we look at future intelligent flexible sensors. In proposing a comprehensive roadmap, we hope to steer research efforts towards common goals and to guide coordinated development strategies from disparate communities. Through such collaborative efforts, scientific breakthroughs can be made sooner and capitalized for the betterment of humanity.
The biomechanical behavior of human stratum corneum (SC), the outermost layer of skin, is critical for its large role in providing the barrier function of human skin. The degradation of the SC's ...natural biomechanical function can thus lead to painful skin conditions such as atopic dermatitis, exacerbated wounds and scarring, and reduced compatibility of wearable electronic devices. However, the effects of synergistic environmental exposures and most topical cosmetic treatments on key mechanical properties such as stress and intercellular cohesion in the SC have not been previously quantified and their mechanisms of action remain poorly understood.Consequently, the first step necessary to make informed designs of protective or stress mitigating treatments is to elucidate the underlying mechanism in the SC of mechanical stress, the driving force for damage to the skin barrier function. As a result, the critical connection between water volume loss during drying and stress development is introduced. The effect of treatment molecules, such as emollients and moisturizers, on macroscopic stress and cohesion is then analyzed through the presented framework, thus significantly clarifying the treatment characteristics necessary to mitigate SC damage.After establishing the role of treatments to protect the skin, the impact of simultaneous ultraviolet (UV) light and heat exposure (to approximate infrared radiation) is quantified to demonstrate the ability of synergistic solar damage processes in the SC to enhance stress and reduce intercellular cohesion, thus increasing the risk of barrier function degradation. In this context, the efficacies of UVB absorbing molecules (and their carrier vehicle) to protect the SC biomechanical properties from UV damage is investigated. This results in a new understanding of multiple mechanisms (i.e. water loss, treatment molecule diffusion, environmental damage, photoabsorber protection) that may simultaneously affect SC biomechanics, a vital step towards the successful protection and maintenance of a healthy skin barrier function.
A Zr-catalyzed synthesis of tetrasubstituted 1,3-diacylpyrroles is reported that employs the direct use of N-acyl α-aminoaldehydes with 1,3-dicarbonyl compounds. The products were formed in up to 88% ...yield and shown to be hydrolytically and configurationally stable under the reaction conditions (THF/1,4-dioxane and H2O). The N-acyl α-aminoaldehydes were readily prepared from the corresponding α-amino acids. The reaction tolerates a wide array of substrate types including alkyl-, aryl-, heteroaryl-, and heteroatom-containing groups on the aminoaldehyde side chain. A variety of 1,3-dicarbonyls proved amenable to the reaction along with an aldehyde derived from a l,l-dipeptide, an aldehyde generated in situ, and an N-acylated glucosamine.
The purpose of this study was to analyze prognostic factors for patients with newly diagnosed primary CNS lymphoma (PCNSL) in order to establish a predictive model that could be applied to the care ...of patients and the design of prospective clinical trials.
Three hundred thirty-eight consecutive patients with newly diagnosed PCNSL seen at Memorial Sloan-Kettering Cancer Center (MSKCC; New York, NY) between 1983 and 2003 were analyzed. Standard univariate and multivariate analyses were performed. In addition, a formal cut point analysis was used to determine the most statistically significant cut point for age. Recursive partitioning analysis (RPA) was used to create independent prognostic classes. An external validation set obtained from three prospective Radiation Therapy Oncology Group (RTOG) PCNSL clinical trials was used to test the RPA classification.
Age and performance status were the only variables identified on standard multivariate analysis. Cut point analysis of age determined that patients age < or = 50 years had significantly improved outcome compared with older patients. RPA of 282 patients identified three distinct prognostic classes: class 1 (patients < 50 years), class 2 (patients > or =50; Karnofsky performance score KPS > or = 70) and class 3 (patients > or = 50; KPS < 70). These three classes significantly distinguished outcome with regard to both overall and failure-free survival. Analysis of the RTOG data set confirmed the validity of this classification. CONCLUSION The MSKCC prognostic score is a simple, statistically powerful model with universal applicability to patients with newly diagnosed PCNSL. We recommend that it be adopted for the management of newly diagnosed patients and incorporated into the design of prospective clinical trials.
Hydration of the outermost layer of human skin, the stratum corneum (SC), affects barrier function, physical appearance, and sensory perception of skin. Water loss, ubiquitously associated with dry ...skin conditions, results in the development of mechanical tensile stresses that lead to the perception of skin tightness and provide a driving force for damage in the form of chapping or cracking. Restorative moisturizing formulations contain molecular components that counteract the effects of water loss. However, the quantitative connection between water loss and SC mechanical behavior together with a predictive model has remained elusive. We develop a diffusional-based mechanics model that accurately predicts the SC mechanical behavior during hydration or dehydration over a wide range of ambient humidity conditions and presence of moisturizing ingredients. The model was validated with published studies including SC water diffusion, quantitative Raman spectroscopy, and mechanical property and stress characterization. The roles of mobile and partially bound water states are included together with one humectant and three cosmetic emollient molecules commonly used in moisturizing formulations. The model accurately predicts the effects of moisture content and moisturizer ingredients on SC mechanical behavior and provides a quantitative predictive capability that can be employed in the design of efficacious treatments.
The impact of sunscreen formulations on the barrier properties of human skin are often overlooked leading to formulations with components whose effects on barrier mechanical integrity are poorly ...understood. The aim of this study is to demonstrate the relevance of carrier selection and sunscreen photostability when designing sunscreen formulations to protect the biomechanical barrier properties of human stratum corneum (SC) from solar ultraviolet (UV) damage. Biomechanical properties of SC samples were assayed after accelerated UVB damage through measurements of the SC's mechanical stress profile and corneocyte cohesion. A narrowband UVB (305-315 nm) lamp was used to expose SC samples to 5, 30, 125, and 265 J cm
in order to magnify damage to the mechanical properties of the tissue and characterize the UV degradation dose response such that effects from smaller UV dosages can be extrapolated. Stresses in the SC decreased when treated with sunscreen components, highlighting their effect on the skin prior to UV exposure. Stresses increased with UVB exposure and in specimens treated with different sunscreens stresses varied dramatically at high UVB dosages. Specimens treated with sunscreen components without UVB exposure exhibited altered corneocyte cohesion. Both sunscreens studied prevented alteration of corneocyte cohesion by low UVB dosages, but differences in protection were observed at higher UVB dosages indicating UV degradation of one sunscreen. These results indicate the protection of individual sunscreen components vary over a range of UVB dosages, and components can even cause alteration of the biomechanical barrier properties of human SC before UV exposure. Therefore, detailed characterization of sunscreen formulation components is required to design robust protection from UV damage.
Bacterial infections remain a leading threat to global health because of the misuse of antibiotics and the rise in drug‐resistant pathogens. Although several strategies such as photothermal therapy ...and magneto‐thermal therapy can suppress bacterial infections, excessive heat often damages host cells and lengthens the healing time. Here, a localized thermal managing strategy, thermal‐disrupting interface induced mitigation (TRIM), is reported, to minimize intercellular cohesion loss for accurate antibacterial therapy. The TRIM dressing film is composed of alternative microscale arrangement of heat‐responsive hydrogel regions and mechanical support regions, which enables the surface microtopography to have a significant effect on disrupting bacterial colonization upon infrared irradiation. The regulation of the interfacial contact to the attached skin confines the produced heat and minimizes the risk of skin damage during thermoablation. Quantitative mechanobiology studies demonstrate the TRIM dressing film with a critical dimension for surface features plays a critical role in maintaining intercellular cohesion of the epidermis during photothermal therapy. Finally, endowing wound dressing with the TRIM effect via in vivo studies in S. aureus infected mice demonstrates a promising strategy for mitigating the side effects of photothermal therapy against a wide spectrum of bacterial infections, promoting future biointerface design for antibacterial therapy.
A localized thermal‐management strategy from thermal‐disrupting interface induced mitigation (TRIM) is developed to maintain intercellular cohesion and reduce function loss of epidermis tissue for topical antibacterial therapy. A dressing film with the TRIM effect inhibits aggregation of bacteria, promotes selective elimination of pathogens, and shortens the healing process.
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