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Significance: In order to elucidate therapeutic treatment to accelerate wound healing, it is crucial to understand the process underlying skin wound healing, especially re-epithelialization. Epidermis and scab detection is of importance in the wound healing process as their thickness is a vital indicator to judge whether the re-epithelialization process is normal or not. Since optical coherence tomography (OCT) is a real-time and non-invasive imaging technique that can perform a cross-sectional evaluation of tissue microstructure, it is an ideal imaging modality to monitor the thickness change of epidermal and scab tissues during wound healing processes in micron-level resolution. Traditional segmentation on epidermal and scab regions was performed manually, which is time-consuming and impractical in real time. Aim: We aim to develop a deep-learning-based skin layer segmentation method for automated quantitative assessment of the thickness of in vivo epidermis and scab tissues during a time course of healing within a rodent model. Approach: Five convolution neural networks were trained using manually labeled epidermis and scab regions segmentation from 1000 OCT B-scan images (assisted by its corresponding angiographic information). The segmentation performance of five segmentation architectures was compared qualitatively and quantitatively for validation set. Results: Our results show higher accuracy and higher speed of the calculated thickness compared with human experts. The U-Net architecture represents a better performance than other deep neural network architectures with 0.894 at F1-score, 0.875 at mean intersection over union, 0.933 at Dice similarity coefficient, and 18.28 μm at an average symmetric surface distance. Furthermore, our algorithm is able to provide abundant quantitative parameters of the wound based on its corresponding thickness maps in different healing phases. Among them, normalized epidermal thickness is recommended as an essential hallmark to describe the re-epithelialization process of the rodent model. Conclusions: The automatic segmentation and thickness measurements within different phases of wound healing data demonstrates that our pipeline provides a robust, quantitative, and accurate method for serving as a standard model for further research into effect of external pharmacological and physical factors.

The piezoelectricity of collagen is purported to be linked to many biological processes including bone formation and wound healing. Although the piezoelectricity of tissue-derived collagen has been documented across the length scales, little work has been undertaken to characterise the local electromechanical properties of processed collagen, which is used as a base for tissue-engineering implants. In this work, three chemically distinct treatments used to form structurally and mechanically stable scaffolds— EDC-NHS, genipin and tissue transglutaminase—are investigated for their effect on collagen piezolectricity. Crosslinking with EDC-NHS is noted to produce a distinct self-assembly of the fibres into bundles roughly 300 nm in width regardless of the collagen origin. These fibre bundles also show a localised piezoelectric response, with enhanced vertical piezoelectricity of collagen. Such topographical features are not observed with the other two chemical treatments, although the shear piezoelectric response is significantly enhanced upon crosslinking. These observations are reconciled by a proposed effect of the crosslinking mechanisms on the molecular and nanostructure of collagen. These results highlight the ability to modify the electromechanical properties of collagen using chemical crosslinking methods.

OBJECTIVES/HYPOTHESIS The aim of the study was to investigate the healing rates, the restoration of hearing, and the time for complete healing of paper patching versus watchful waiting for traumatic tympanic membrane perforations (TTMPs). STUDY DESIGN Systematic review with meta analysis. METHODS Publications were selected by a search on "PubMed," "Embase," and "Web of Science." A meta-analysis of risk ratios for paper patching (intervention arm) and watchful waiting (control arm) was performed. RESULTS Five studies describing 393 TTMPs were included in the quantitative meta-analysis. TTMP healing rates ranged between 84.2% and 95.2% in the intervention arm and between 76.7% and 84.8% in the control arm. The pooled risk ratio of healed TTMPs was significantly higher in the intervention arm than in the control arm (risk ratio: 1.12, 95% confidence interval: 1.04-1.21). CONCLUSIONS TTMPs have high healing potential with and without intervention. The healing rate of paper patching was superior to that of watchful waiting alone. LEVEL OF EVIDENCE NA Laryngoscope, 131:2091-2097, 2021.

Significance: Spatial frequency domain imaging (SFDI), a noncontact wide-field imaging technique using patterned illumination with multiple wavelengths, has been used to quantitatively measure structural and functional parameters of in vivo tissue. Using SFDI in a porcine model, we previously found that scattering changes in skin could potentially be used to noninvasively assess burn severity and monitor wound healing. Translating these findings to human subjects necessitates a better understanding of the variation in “baseline” human skin scattering properties across skin types and anatomical locations. Aim: Using SFDI, we aim to characterize the variation in the reduced scattering coefficient (μs′) for skin across a range of pigmentation and anatomic sites (including common burn locations) for normal human subjects. These measurements are expected to characterize baseline human skin properties to inform our use of SFDI for clinical burn severity and wound healing assessments. Approach: SFDI was used to measure μs′ in the visible- and near-infrared regime (471 to 851 nm) in 15 subjects at 10 anatomical locations. Subjects varied in age, gender, and Fitzpatrick skin type. Results: For all anatomical locations, the coefficient of variation in measured μs′ decreased with increasing wavelength. High intersubject variation in μs′ at visible wavelengths coincided with large values of the melanin extinction coefficient at those wavelengths. At 851 nm, where intersubject variation in μs′ was smallest for all anatomical locations and absorption from melanin is minimal, significant intrasubject differences in μs′ were observed at the different anatomical locations. Conclusions: Our study is the first report of wide-field mapping of human skin scattering properties across multiple skin types and anatomical locations using SFDI. Measured μs′ values varied notably between skin types at wavelengths where absorption from melanin was prominent. Additionally, μs′ varied considerably across different anatomical locations at 851 nm, where the confounding effects from melanin absorption are minimized.

There is a need for noninvasive, quantitative methods to characterize wound healing in the context of longitudinal investigations related to regenerative medicine. Such tools have the potential to inform the assessment of wound status and healing progression and aid the development of new treatments. We employed spatial frequency domain imaging (SFDI) to characterize the changes in optical properties of tissue during wound healing progression in a porcine model of split-thickness skin grafts and also in a model of burn wound healing with no graft intervention. Changes in the reduced scattering coefficient measured using SFDI correlated with structural changes reported by histology of biopsies taken concurrently. SFDI was able to measure spatial inhomogeneity in the wounds and predicted heterogeneous healing. In addition, we were able to visualize differences in healing rate, depending on whether a wound was debrided and grafted, versus not debrided and left to heal without intervention apart from topical burn wound care. Changes in the concentration of oxy- and deoxyhemoglobin were also quantified, giving insight into hemodynamic changes during healing.

Accurate assessment of burn severity is critical for wound care and the course of treatment. Delays in classification translate to delays in burn management, increasing the risk of scarring and infection. To this end, numerous imaging techniques have been used to examine tissue properties to infer burn severity. Spatial frequency-domain imaging (SFDI) has also been used to characterize burns based on the relationships between histologic observations and changes in tissue properties. Recently, machine learning has been used to classify burns by combining optical features from multispectral or hyperspectral imaging. Rather than employ models of light propagation to deduce tissue optical properties, we investigated the feasibility of using SFDI reflectance data at multiple spatial frequencies, with a support vector machine (SVM) classifier, to predict severity in a porcine model of graded burns. Calibrated reflectance images were collected using SFDI at eight wavelengths (471 to 851 nm) and five spatial frequencies (0 to 0.2 mm−1). Three models were built from subsets of this initial dataset. The first subset included data taken at all wavelengths with the planar (0 mm−1) spatial frequency, the second comprised data at all wavelengths and spatial frequencies, and the third used all collected data at values relative to unburned tissue. These data subsets were used to train and test cubic SVM models, and compared against burn status 28 days after injury. Model accuracy was established through leave-one-out cross-validation testing. The model based on images obtained at all wavelengths and spatial frequencies predicted burn severity at 24 h with 92.5% accuracy. The model composed of all values relative to unburned skin was 94.4% accurate. By comparison, the model that employed only planar illumination was 88.8% accurate. This investigation suggests that the combination of SFDI with machine learning has potential for accurately predicting burn severity.

Journal of biomedical optics 24(7), 070601 (2019). doi:10.1117/1.JBO.24.7.070601, Published by SPIE, Bellingham, Wash.

Objective:To study the clinical effect of lens cleaning paper patching on traumatic eardrum perforations.Methods:A total of 122 patients were divided into 2 groups, of which 56 patients were treated with lens cleaning paper patching and 66 acted as controls. The closure rate and healing time were compared between the two groups.Results:The healing rate of small perforations was 96.4 per cent (27 out of 28) in the patching group and 90 per cent (27 out of 30) in the control group. The difference was not statistically significant (p > 0.05). The healing rate of large perforations was 89.3 per cent (25 out of 28) and 80.6 per cent (29 out of 36) in the two groups, respectively. The difference was statistically significant (p < 0.05). The healing time of large perforations was shorter in the patching group than in the control group (p < 0.01).Conclusion:Patching with lens cleaning paper under an endoscope can accelerate the closure of large traumatic eardrum perforations.

Suturing of corneal incisions requires significant skill. We demonstrate a noncontact method that will simplify the bonding process. 5-mm-long penetrating vertical and slanted incisions were made in corneas of eyes, extracted from dead piglets. A fiber-optic laser system was used for laser soldering of the incisions, under close temperature control, using albumin solder. The burst-pressure PB immediately after the soldering was found to be PB ≈92 and 875 mmHg, for vertical and slanted incisions, respectively. PB=875 mmHg is an exceptionally high figure, ≈10 times the clinically acceptable value for sutured incisions. Laser soldering was then performed on penetrating incisions made in the corneas of live healthy piglets, of weight ≈10 Kg. After a healing period,the eyes were extracted,and the corneas were examined by histopathology and by optical coherence tomography. Our method immediately generated watertight and strong bonding without noticeable corneal shape distortion. These results would be beneficial for cataract surgery and for corneal transplantations. The fiber-optic system makes it much easier to bond corneal incisions. In the future, laser soldering could be automated and efficiently used by less experienced surgeons, thereby reducing the workload on the experienced ones.

Our work details the development and characterization of a portable luminescence imaging device for detecting inflammatory responses and infection in skin wounds. The device includes a CCD camera and close-up lens integrated into a customizable 3D printed imaging chamber to create a portable light-tight imager for luminescence imaging. The chamber has an adjustable light portal that permits ample ambient light for white light imaging. This imager was used to quantify in real time the extent of two-dimensional reactive oxygen species (ROS) activity distribution using a porcine wound infection model. The imager was used to successfully visualize ROS-associated luminescent activities in vitro and in vivo. Using a pig full-thickness cutaneous wound model, we further demonstrate that this portable imager can detect the change of ROS activities and their relationship with vasculature in the wound environment. Finally, by analyzing ROS intensity and distribution, an imaging method was developed to distinguish infected from uninfected wounds. We discovered a distinct ROS pattern between bacteria-infected and control wounds corresponding to the microvasculature. The results presented demonstrate that this portable luminescence imager is capable of imaging ROS activities in cutaneous wounds in a large animal model, indicating suitability for future clinical applications.

We investigated the effects of repairing large tympanic membrane (TM) perforations in rats with a thin silk patch compared with the commonly used paper patch. We performed bilateral myringotomies of 1.8 mm in diameter on 50 adult Sprague-Dawley rats with intact TMs. The perforations in the right ears of 40 rats were treated with a silk patch, and the perforations in the left ears of the same rats were treated with a paper patch. Ten rats acted as controls. The mean healing times of the TM perforations on the silk-patch-treated ears and the paper-patch-treated ears were 7.2+/-1.48 and 9.1+/-1.11 days, respectively (control 10.38+/-1.70 days). The difference between silk-patch- and paper-patch-treated ears was statistically significant, with a mean difference of 1.9 days (0.6-4.5 days). The mean perforation closure times were significantly shorter in silk-patch- and paper-patch-treated ears than in the control animals. The endoscopic and histological findings of this study provide evidence that silk-patch treatment accelerates wound healing and shortens TM perforation closure time. We suggest that the silk patch may prove to be an effective material for repairing TM perforations in human patients in an outpatient clinical setting.

Objectives Surgical intervention such as myringoplasty or tympanoplasty is an option in the current clinical management of chronic tympanic membrane perforation (TMP). Animal models of chronic TMP are needed for pre-clinical testing of new materials and to improve existing techniques. We evaluated several reported animal model techniques from the literature for the creation of chronic TMPs. The aim of this study was to evaluate production of chronic TMPs in a rat model using topical mitomycin C/dexamethasone, paper insertion into middle ear cavity (MEC) or re-myringotomy. Methods Forty male Sprague–Dawley rats underwent myringotomy of the right tympanic membrane (TM) and were randomly divided into 3 experimental groups: application of topical mitomycin C/dexamethasone, paper insertion into middle ear cavity, or re-myringotomy. Control perforations were allowed to close spontaneously. TMs were assessed regularly with otoscopy for 8 weeks. At the end of 8 weeks, animals were sacrificed for histology. Results The closure of TMPs was significantly delayed by mitomycin C/dexamethasone (mean patency, 18.9 days; P ≤ 0.01) compared with the control (mean patency, 7 days), but was not significantly delayed in the paper insertion group (mean patency, 9.4 days; P = 0.74). Repeated myringotomy of closed perforations (mean number of myringotomies, 8.9 per ear) stimulated acceleration of closure rather than delay. Histologically, the mitomycin C/dexamethasone group had almost normal TM morphology, while the paper insertion group revealed inflammatory and granulomatous responses. The re-myringotomy group had a thickened TM fibrous layer with collagen deposition. Conclusions Mitomycin C/dexamethasone delayed TMP closure in rats but the effect was not sufficiently long-lasting to be defined as a chronic TMP. Neither paper insertion into middle ear cavity nor re-myringotomy created chronic TMP in rats.

To date, heat conduction from heat sources to tissue has been estimated by complex mathematical modeling. In the present study, we developed an intuitive in vitro skin burn model that illustrates heat conduction patterns inside the skin. This was composed of tightly compressed thermal papers with compression frames. Heat flow through the model left a trace by changing the color of thermal papers. These were digitized and three-dimensionally reconstituted to reproduce the heat conduction patterns in the skin. For standardization, we validated K91HG-CE thermal paper using a printout test and bivariate correlation analysis. We measured the papers' physical properties and calculated the estimated depth of heat conduction using Fourier's equation. Through contact burns of 5, 10, 15, 20, and 30 seconds on porcine skin and our burn model using a heated brass comb, and comparing the burn wound and heat conduction trace, we validated our model. The heat conduction pattern correlation analysis (intraclass correlation coefficient: 0.846, p 0.001) and the heat conduction depth correlation analysis (intraclass correlation coefficient: 0.93, p 0.001) showed statistically significant high correlations between the porcine burn wound and our model. Our model showed good correlation with porcine skin burn injury and replicated its heat conduction patterns.

SIMSEK, GOKCE/0000-0001-5281-0986 WOS: 000345012000052 PubMed: 25377961 The purpose of this study was to compare the outcomes of patients with acute tympanic membrane perforation after spontaneous healing and paper-patching procedure. Methods: Design, Setting, and Participants: In this study, we performed a retrospective chart review with a prospective follow-up in 63 patients with tympanic membrane perforations. The patients undergoing a paper-patching procedure were assigned to group 1 (n = 33), whereas the patients that healed spontaneously were included in group 2 (n = 30). Retrospective analyses of the otoscopic examination findings and audiometric test results of the groups at the sixth-week follow-up were compared. Results: Eardrum healing was achieved in 90.9% of the patients in group 1 and 76.7% of the patients in group 2 at the sixth week (P > 0.05). The mean values of air conduction were significantly improved, and the air-bone gap was markedly decreased in the patients treated with paper patching, when compared with the patients in group 2 (P < 0.001). The area of perforation was found to be inversely related to the healing success. Conclusions: Early intervention by paper patching, which is a readily applicable procedure, may be offered to the patients with acute perforation of the tympanic membrane, because of the slightly better closure rates and significantly higher hearing functions when compared with simple observation.

Background/Aims—Calprotectin, a 36 kDa protein present in neutrophil cytoplasm, has antimicrobial and apoptosis inducing activities, which are reversed by the addition of zinc. Matrix metalloproteinases (MMPs), a family of zinc dependent enzymes, are important in many normal biological processes including embryonic development, angiogenesis, and wound healing, but also pathological processes such as inflammation, cancer, and tissue destruction. The aim of this study was to investigate whether calprotectin can inhibit MMP activity, and whether such inhibition could be overcome by the addition of zinc. Methods—MMP activity was measured by the degradation of substrates precoated on to microwells, and visualised by Coomassie blue staining of residual substrate. Seven metalloproteinases (MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, and MMP-13) were tested against two substrates: gelatin and α-casein. Results—All MMPs except MMP-1 were active against gelatin, whereas MMP-7 was the only enzyme active against α-casein. The addition of calprotectin inhibited the activity of all the MMPs, but different concentrations of the protein, from 0.3μM to > 11μM, were necessary to produce a 50% inhibition of the MMPs. Inhibition by calprotectin was largely overcome by the addition of zinc. Conclusions—The findings suggest that calprotectin inhibits MMPs by sequestration of zinc. The data also suggest that MMPs have different affinities for zinc and that calprotectin has a lower zinc affinity than the MMPs.

Thirty consecutive patients with permanent perforations of their tympanic membranes (TM) present from 2.5 to 50 years (mean 18.7 years) were admitted to a prospective study using two alternative methods of dressings for closure of the perforations. An adhesive-coated hydrocolloid material was compared with a conventional dressing of vaseline impregnated rice paper patch after de-epithelialization of the perforation border. Nine of the permanent TM perforations (30 per cent), five with the hydrocolloidal dressing and four with the rice paper patch had healed when followed-up after one year. The size of eight of the central perforations that had healed was equal to or less than 25 per cent of the TM. Also one perforation with a size of 65 per cent had healed. Seven perforations were located in the posterior part of the TM:Jour in the posterior-superior quadrant, one in the inferior quadrant, one had engulfed the posterior half of the TM and one included the anterior-inferior quadrant. Only two perforations out of 14, with a size of 25 per cent or less, located in the anterior-inferior quadrant, healed. No significant difference was demonstrated between the two types of dressings. Both groups noted an immediate improvement in hearing of 10.8 and 9.3 dB, respectively, after application of the dressing.The study demonstrates that application of an occlusive dressing or paper patch in 30 per cent of patients can promote the healing of long-standing perforations. The chances for healing are better if the perforation is located in the posterior part of the TM. This simple technique immediately improved hearing and should be tried before a patient is referred for myringoplasty surgery.

Video assisted thoracoscopic surgery (VATS) is used in lung surgery for diagnostic, staging, curative and palliative purposes. The port-sites are usually sutured with dissolvable sutures. The use of adhesive paper-tape for port-site closure was assessed by a prospective randomised doubleblind control trial comparing sutured to adhesive paper-tape closure. The following outcomes were assessed: incidence of clinically significant pneumothorax, wound healing using the ASEPSIS score, patient’s comfort (pain score using a visual analog score), the time difference between the two techniques of wound closure and cost savings. Thirty patients were recruited in each group. No clinically significant pneumothoraces occurred in either group.There were no significant differences between the two groups in terms of immediate post-operative pain scores, wound cosmesis and wound complications. It was quicker to close the wound with adhesive paper-tape with a mean time of closure per unit length of wound of 9.3 and 2.2 s/mm for the groups, respectively. The cost for wound closure (per patient) was $0.8 for the adhesive paper-tape group and $4.00 for the sutures. # 2007 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

The purpose of this study is to investigate the recovery rate in paper-patch and fat-plug myringoplasty in rats.Small and large perforations were inflicted on the tympanic membranes of 60 rats. Fat-plug and paper-patch myringoplasties were performed to different groups and another group was left for spontaneous healing.We found that for small perforations, the recovery rate was 94.7% in fat-plug myringoplasty, 94.4% in paper-patch myringoplasty, and 66.6% in control group. The recovery rates in large perforations were 52.9%, 56.2%, and 26.6%, respectively. On the other hand, in larger perforations, paper-patch or fat-plug myringoplasty have not been found effective.We believe that due to significant operational advantages, fat-plug or paper-patch myringoplasty can be suggested for the reconstruction of small and dry perforations of the tympanic membrane.

A new, simple method of producing optimal cuffs using thin paper and then setting it in resin for vascular reconstruction in canine liver transplantation is herein described. Thin Paper was cut into a paper tape strip. By fixing both ends of this paper tape, a cylinder paper core of any desired size could thus be obtained. The paper core was immersed into a two-liquid mixture-type resin, removed, and left to harden. The paper cuffs (0.2 mm or less in thickness) were then used for anastomoses of the portal vein and the infrahepatic inferior vena cava in a series of 10 consecutive canine liver transplantations. Out of 10 animals, 8 survived for more than 5 days. The vascular patency in these 8 animals at the cuff anastomotic sites was 100% at postmortem. We therefore conclude that this paper cuff appears to be useful for various types of experimental liver transplantations in large animals.

In a rat study, an occlusive double-layer transparent hydrocolloid dressing, Duo-DERM, was compared with a rice paper dressing in the treatment of tympanic membrane perforation. The Duo-DERM dressing manifested better healing properties, and the healed membrane was histologically similar to spontaneously healed membrane, being generally thin with moderate connective tissue thickening. If this dressing is found to have good healing properties in clinical trials, it would mean a great saving in health care resources. The method is simple, inexpensive, and gives immediate improvement in hearing.

A controlled randomized study was performed in 60 patients with 64 chronic, dry tympanic membrane (TM) perforations. The perforations were randomly allocated to either resection of the perforation rim and instillation of 1% hyaluronan (Healon; HYA) in the perforation gap once daily for 7 days (33 ears) or resection of the perforation margin and application of a sterile rice paper prosthesis (31 ears). The treatment effect was documented by TM photography and morphometric measurements of the perforation area. The hearing was assessed with puretone and high-frequency audiometry. After 2 months, 5 of the HYA-treated perforations (15%) and 4 of the rice-paper-treated TMs (13%) were healed. After 1 year, 18 perforations (9 in each treatment group) were healed. In neither group were there any persistent adverse effects on hearing. It is noteworthy that 28% (18/64) of the chronic, long-standing TM perforations could be repaired by these technically simple and time-saving methods. Both procedures should be considered as easy first-choice alternatives to myringoplasty in selected cases.

Wounds closed by adhesive tapes have less inflammatory reaction, a lower rate of wound infection, greater tensile strength and better cosmetic results than sutured or stapled wounds. Special backing tapes, such as Steri-Strip, have been reported to have satisfactory results in closing laparotomy wounds. However, they are more expensive than paper tape. Sterile paper tape had adequate adhesive and supporting strength in the closure of abdominal wounds. The wounds closed with paper tape healed well and had satisfactory cosmetic results. Paper tape is a nonexpensive and convenient alternative to close abdominal wounds.

Fat myringoplasty is a simple office technique for repairing tympanic membrane perforations. It involves wedging a piece of fat from the ear lobule into the perforation. A search of the literature failed to reveal any controlled studies on the efficacy of this method, which may allow patients to avoid more invasive procedures. Controlled perforations in guinea pig tympanic membranes were treated with fat myringoplasties, paper patches, or no intervention. Four weeks following the procedures, ears were examined and photographed under the microscope and studied histologically. The fat myringoplasty healing rate exceeded the rates of both the control and paper-patch groups. Results were stratified with respect to location and size of perforations. The results and histological studies suggest that controlled studies in humans are warranted.