Effect of Localized Mechanical Indentation on Skin Water Content Evaluated Using OCT

The highly disordered refractive index distribution in skin causes multiple scattering of incident light and limits optical imaging and therapeutic depth. We hypothesize that localized mechanical compression reduces scattering by expulsing unbound water from the dermal collagen matrix, increasing protein concentration and decreasing the number of index mismatch interfaces between tissue constituents. A swept-source optical coherence tomography (OCT) system was used to assess changes in thickness and group refractive index in ex vivo porcine skin, as well as changes in signal intensity profile when imaging in vivo human skin. Compression of ex vivo porcine skin resulted in an effective strain of −58.5%, an increase in refractive index from 1.39 to 1.50, and a decrease in water volume fraction from 0.66 to 0.20. In vivo OCT signal intensity increased by 1.5 dB at a depth of 1 mm, possibly due to transport of water away from the compressed regions. These finding suggest that local compression could be used to enhance light-based diagnostic and therapeutic techniques

Characterization of in vivo human skin in response to mechanical indentation using optical coherence tomography

The biomechanical response of skin can reflect not only health or localized pathology, but also systemic disease or an abnormal physiological condition of an individual. Both the intrinsic stiffness of the solid constituents and the time-evolved redistribution of fluid within skin tissue can influence the biomechanical response to external forces. Therefore, it is important not only to evaluate the responding skin dynamics upon mechanical perturbation, but also to understand the intrinsic viscoelastic properties and fluid dynamics in the skin. While the clinical diagnosis of skin pathologies relies mostly on visual inspection and manual palpation, a more quantitative tissue characterization is highly desirable. Optical coherence tomography (OCT) is an interferometry-based imaging modality that offers an imaging resolution (cellular level) that surpasses those of most standard clinical imaging tools and has shown to be able suitable for in vivo skin imaging. Therefore, this thesis investigates OCT-guided characterization of the biomechanical response of skin, as well as the viscoelastic properties and the characteristics of local fluid transport. Quantitative analysis metrics were developed and demonstrated on in vivo human subjects, and a significant difference between the mechanically-perturbed and non-perturbed skins is revealed. Additionally, the quantitative results exhibit differences in the post-indentation scenarios between the young skin and the aged skin. Functional OCT techniques, such as optical coherence elastography (OCE) and Doppler OCT, are demonstrated to assess the stiffness and fluid dynamics of in vivo human tissue as well. The OCE results successfully reveal the stiffness at different anatomical sites, and the Doppler OCT shows the existence of the micro-vessels. This thesis research demonstrates the feasibility of quantitative skin characterization, the assessment of skin elasticity, and the revelation of fluid flows. With these information combined, a more objective and potentially more accurate diagnosis tool for skin pathologies may be possible in the future

A dose-ranging, parallel group, split-face, single-blind phase II study of light emitting diode-red light (LED-RL) for skin scarring prevention: study protocol for a randomized controlled trial.

BackgroundSkin fibrosis is a significant global health problem that affects over 100 million people annually and has a profoundly negative impact on quality of life. Characterized by excessive fibroblast proliferation and collagen deposition, skin fibrosis underlies a wide spectrum of dermatologic conditions ranging from pathologic scars secondary to injury (e.g., burns, surgery, trauma) to immune-mediated diseases. Effective anti-scarring therapeutics remain an unmet need, underscoring the importance of developing novel approaches to treat and prevent skin fibrosis. Our in vitro data show that light emitting diode-red light (LED-RL) can modulate key cellular and molecular processes involved in skin fibrosis. In two phase I clinical trials (STARS 1 and STARS 2), we demonstrated the safety and tolerability of LED-RL at fluences of 160 J/cm2 up to 480 J/cm2 on normal human skin.Methods/designCURES (Cutaneous Understanding of Red-light Efficacy on Scarring) is a dose-ranging, randomized, parallel group, split-face, single-blind, mock-controlled phase II study to evaluate the efficacy of LED-RL to limit post-surgical skin fibrosis in subjects undergoing elective mini-facelift surgery. Thirty subjects will be randomly allocated to three treatment groups to receive LED-RL phototherapy or temperature-matched mock irradiation (control) to either periauricular incision site at fluences of 160 J/cm2, 320 J/cm2, or 480 J/cm2. Starting one week post-surgery (postoperative days 4-8), treatments will be administered three times weekly for three consecutive weeks, followed by efficacy assessments at 30 days, 3 months, and 6 months. The primary endpoint is the difference in scar pliability between LED-RL-treated and control sites as determined by skin elasticity and induration measurements. Secondary outcomes include clinical and photographic evaluations of scars, 3D skin imaging analysis, histological and molecular analyses, and adverse events.DiscussionLED-RL is a therapeutic modality of increasing importance in dermatology, and has the potential to limit skin fibrosis clinically by decreasing dermal fibroblast activity and collagen production. The administration of LED-RL phototherapy in the early postoperative period may optimize wound healing and prevent excessive scarring. The results from this study may change the current treatment paradigm for fibrotic skin diseases and help to pioneer LED-RL as a safe, non-invasive, cost-effective, portable, at-home therapy for scars.Trial registrationClinicalTrials.gov, NCT03795116 . Registered on 20 December 2018

Understanding the effect of skin mechanical properties on the friction of human finger-pads

The aim of this work is to achieve an understanding of the effect of skin mechanical properties on the friction of human finger-pads. This project primarily concentrates on gaining a more fundamental understanding of the frictional properties of skin. To achieve this, various parameters (epidermis thickness, sweat-gland counts, etc.) affecting skin friction were evaluated using an in-vivo technique, Optical Coherence Tomography (OCT) and a friction testing device. This project is also interested in investigating how those parameters alter the friction for different ages, genders, ethnicities and different contact conditions, such as moisture, temperature, loads, etc. Experimental studies were conducted to investigate the skin frictional behaviour. The findings showed that the skin friction obeys a two-term relationship. The skin friction was found to be strongly associated with its Young’s modulus. Tests on the skin structural properties showed the moisture level of the skin, skin thickness and skin morphological properties play important roles in determining the skin friction. The findings gained can be applied to explain how the skin friction varies among different participants. Further tests showed that physico-chemical properties of the skin can have a significant effect on the skin friction. The OCT system was combined with a multi-axis force plate to measure the contact area between fingers and smooth surfaces. Static measurement showed both apparent and real contact area increase with normal load following a power-law relationship. This is associated with the skin mechanical properties. The dynamic contact area was investigated using a Digital Image Correlation (DIC) method. As a finger was sliding along a flat surface, the dynamic apparent contact area was found to decrease with time

Features of the dynamics of the optical and physiological properties of muscle tissue in vitro during its compression

Background and Objectives: The compression of human skin is one of the mechanisms of mechanical biotissue optical clearing. In this study we investigated the effects of compression of in vitro cow muscle tissue samples on diffuse reflectance spectra of tissue and changes of its physiological properties. The purpose of research was to identify the correlation between diffuse reflectance of muscle tissue and its compression. Material and Methods: Samples of muscle tissue used in the experiments with a size of 70–50 mm and a thickness of 25 mm were cut from one volume of the loin hart of a cow. After applying pressure to the sample for a time of about 20 minutes, reflectance spectra of the samples were recorded with a time step of 5 seconds. In the experiments, sensors of different sizes were varied with different values of the applied external compression. Results: The dynamics of myoglobin and hemoglobin content in muscle tissue ex vivo in the compression process was determined. In the case of muscle tissue ex vivo, the blood content in it decreases when compression is applied. A similar effect was observed for skin tissue in vivo, but there are also significant differences: if for skin tissue capillary blood, and hemoglobin, when a pressure of about 105 Pa is applied, is completely removed from biological tissue, then myoglobin from muscle tissue samples is not completely removed, the oxygenated form of myoglobin turns into deoxygenated and deoxygenation of myoglobin occurs within a few minutes after the application of compression. Conclusion: In perspective compression of muscle tissue ex vivo can become the basis for a method for controlling the content of hemoglobin and myoglobin derivatives and, as a result, for controlling the color of biological tissue

Topical capsaicin in PLGA NPs decreases acute itch and heat pain

Background: Capsaicin, the hot pepper agent, produces burning followed by desensitization. To treat localized itch or pain with minimal burning, low capsaicin concentrations can be repeatedly applied. We hypothesized that alternatively controlled release of capsaicin from poly(lactic-co-glycolic acid) (PLGA) nanoparticles desensitizes superficially terminating nociceptors, reducing burning. Methods: Capsaicin-loaded PLGA nanoparticles were prepared (single-emulsion solvent evaporation) and characterized (size, morphology, capsaicin loading, encapsulation efficiency, in vitro release profile). Capsaicin-PLGA nanoparticles were applied to murine skin and evaluated in healthy human participants (n = 21) for 4 days under blinded conditions, and itch and nociceptive sensations evoked by mechanical, heat stimuli and pruritogens cowhage, β-alanine, BAM8-22 and histamine were evaluated. Results: Nanoparticles (loading: 58 µg capsaicin/mg) released in vitro 23% capsaicin within the first hour and had complete release at 72 h. In mice, 24 h post-application Capsaicin-PLGA nanoparticles penetrated the dermis and led to decreased nociceptive behavioral responses to heat and mechanical stimulation (desensitization). Application in humans produced a weak to moderate burning, dissipating after 3 h. A loss of heat pain up to 2 weeks was observed. After capsaicin nanoparticles, itch and nociceptive sensations were reduced in response to pruritogens cowhage, β-alanine or BAM8-22, but were normal to histamine. Conclusions: Capsaicin nanoparticles could be useful in reducing pain and itch associated with pruritic diseases that are histamine-independent