Diagnostics of skin features through 3D skin mapping based on electro-controlled deposition of conducting polymers onto metal-sebum modified surfaces and their possible applications in skin treatment
Graphical abstract
Introduction
Skin is the largest organ of human body, which in turn is nearly entirely exposed to the external environment [1]. As a natural barrier for the inner organs, skin often suffers from mechanical damages, skin diseases, bacterial, fungal and viral infections and develops pathological growth [2]. Thus, appropriate and precise dermatologic analytical diagnosis is highly needed to recognize and evaluate those abnormal skin conditions for an adequate treatment. Current practice of dermatologic diagnosis in epidermis is based on visual inspection and assistance of optical imaging devices. Various high-resolution digital cameras are currently used to obtain 2D images of patient’s skin. Besides, optical coherence tomography (OCT) is used to provide 3D images of skin tissues [3], technique which is most widely used in ophthalmology. The OCT is used in analytical diagnosis of multiple skin conditions and skin related processes, such as psoriasis vulgaris [4], differentiating blisters [5], actinic keratoses [6] and wound healing [7]. Furthermore, a Laser Doppler Imaging (LDI) can capture moving objects [8,9]. It is used to assess vascular lesions and provide skin related information via targeting the flow of red blood cells. In clinical treatments, the LDI is used to monitor Kaposi sarcoma [8] and evaluate skin blood perfusion after cold stimulation in patients with systemic scleroderma [10]. A Diffuse multispectral imaging (DMI) is another optical method used in skin diagnosis. The DMI uses light sources of multiple wavelength to provide 2D images of skin, e.g. evaluate treatment response of Kaposi sarcoma patients [11] and differentiate malignant from benign lesions [12]. Other common optical techniques for analytical skin condition diagnosis include confocal microscopy, Raman spectroscopy and dermoscopy [[13], [14], [15]]. Besides the optical methods, other techniques such as ultrasound imaging provide 3D images, but it is more popular for its B-mode that provide 2D images of organs. In fact, it has the ability to generate images with resolution of 200–300 μm [16,17]. It is also used to characterize skin lesions [18] and evaluate their response to treatment [19]. In addition, magnetic resonance imaging (MRI) is also used in analytical skin diagnosis [20]. Despite many advanced analytical techniques and devices, none of them can be carried by dermatologists on a daily basis. Moreover, the resolution of most techniques is still limited. While the OCT and the ultrasound imaging can provide 3D images of internal tissues, none of them can provide clear 3D images of skin surface. Furthermore, all of those are restricted to the diagnosis stage only while for skin treatments such as drug release and wound healing through electrostimulation are not possible. For that purpose, a 3D and conducting skin mapping technique was proposed previously [21]. The 3D structure of skin pattern was achieved through selective growth of the conducting polymers onto the conducting surface modified with the insulating stamp correlating to the skin surface topography.
Conducting polymers have been widely investigated in many fields, e.g. electronics [[22], [23], [24]] and sensors [[25], [26], [27]]. Due to the fact that organic monomers usually have certain degree of toxicity, conducting polymers’ application in biomedical field, included bio imaging, has been limited [28]. However, an increasing number of studies have been conducted over the past decades using conducting polymer for healthcare applications [21,[29], [30], [31]] because contrary to the monomers, the polymeric forms of conducting polymers have adequate biocompatibility [21,[30], [31], [32]]. Among different types of conducting polymers, poly (3,4-ethylenedioxythiophene) (PEDOT), polypyrrole (PPy) and polyaniline (PANI) are the most investigated and proved suitable for biomedical applications [31]. In 2015, the use of conducting polymers for skin features enhancement was investigated by Hillman et al. [33] in the use of PPy and PEDOT co-polymers films to increase visibility, thus allow identification of latent fingerprints on stainless steel for forensic detection [33]. The fingerprint enhancement was based on the fact that skin leaves an insulating mark/stamp on any surface that it is in contact with and if that surface/substrate is electrically conducting, the localized electropolymerization of the co-polymer in the presence of the fingerprint results in the clear visualization of the fingerprint through increasing contrast between dark conducting co-polymer and deposited sebum [33]. Besides surface enhancement, conducting polymers and their composites were also investigated in treatment of pathological skin conditions owning to their physio-chemical properties, such as possibility to conduct controlled therapeutic agents delivery to the wound, e.g. ions and drugs [[34], [35], [36]], electro-stimulation [[37], [38], [39]], and antimicrobial properties [[40], [41], [42]].
In this work, a portable and fast analytical technique to map various skin features was carefully optimized in the context of advancement of dermatological diagnosis (producing 3D models of skin topography) and subsequent skin treatment (investigating suitability of the developed 3D skin patterns for selective skin treatment, such as wound healing). In specific, we report the full study of the 3D skin mapping technique, aimed to: (i) thoroughly optimize the technique in terms of electrosynthesis specifications and insulating reagent (IR) deposition control; (ii) broaden the applicable range via exploring substrate choices with different flexibility and metal coverage; (iii) explore the promising potential of developed skin maps as scaffolds for possible pathological skin treatment through controlled release of therapeutic ions and (iv) design and application of the portable analytical diagnostic device based on the well-optimized technique.
Section snippets
Reagents and materials
Polystyrene sulfonate (PSS), 3,4-ethylenedioxythiophene (EDOT), ethanol (98%), Pyrrole (Py; 98%), potassium chloride (KCl), copper chloride dihydrate (CuCl2·2H2O), zinc chloride (ZnCl2), glycerol trioleate and silicone oil were obtained from Sigma-Aldrich (Merck KGaA, USA) and directly used as obtained without any further purification. Sputter coater targets of gold (99.999%) and platinum (99.95%) were purchased from Ted Pella, Singapore. Polyethylene terephthalate (PET) (0.26 mm thick) were
Fabrication procedure, basic mechanism and realization of portable analytical diagnostic device
Despite the details provided in the experimental section, for a better understanding of a general procedure for the analytical diagnostics of the skin features via skin mapping, a depiction of the proposed skin mapping technique is illustrated in Fig. 1. The fabrication protocol of 3D skin patterns consists of two steps, namely skin stamp sampling and 3D skin patterning. The skin stamp sampling (Fig. 1 a) is realized as the skin leaves a mark in the shape of its pattern after the contact with
Conclusions
The developed skin patterning technique demonstrated adequate capability for recognition and reproduction of various skin features. It supported a resolution of up to μm-level, which encompass most circumstances in dermatological analytical diagnostics. Besides, this technique showed broad tolerance to most of the practical parameters including polymerization durations, monomer choices, depositing IRs, depositing pressure, and supporting substrates. The technique indicates potential to serve in
Author contributions
The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript.
CRediT authorship contribution statement
Xiaoxu Fu: Methodology, Validation, Investigation, Writing - original draft. Yi-Heng Cheong: Investigation, Methodology. Ashiq Ahamed: Conceptualization, Methodology. Chao Zhou: Methodology, Validation. Chima Robert: Methodology, Validation. Vida Krikstolaityte: Validation. Keith C. Gordon: Conceptualization, Methodology. Grzegorz Lisak: Conceptualization, Methodology, Validation, Supervision.
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgment
The authors also acknowledge the management of Nanyang Environment and Water Research Institute and Economic Development Board, Singapore for the support.
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