Ex Vivo Infection of Human Skin Models with Herpes Simplex Virus 1: Accessibility of the Receptor Nectin-1 during Formation or Impairment of Epidermal Barriers Is Restricted by Tight Junctions.

Herpes simplex virus 1 (HSV-1) must overcome epidermal barriers to reach its receptors on keratinocytes and initiate infection in human skin. The cell-adhesion molecule nectin-1, which is expressed in human epidermis, acts as an efficient receptor for HSV-1 but is not within reach of the virus upon exposure of human skin under nonpathological conditions. Atopic dermatitis skin, however, can provide an entry portal for HSV-1 emphasizing the role of impaired barrier functions. Here, we explored how epidermal barriers impact HSV-1 invasion in human epidermis and influence the accessibility of nectin-1 for the virus. Using human epidermal equivalents, we observed a correlation of the number of infected cells with tight-junction formation, suggesting that mature tight junctions prior to formation of the stratum corneum prevent viral access to nectin-1. Consequently, impaired epidermal barriers driven by Th2-inflammatory cytokines interleukin 4 (IL-4) and IL-13 as well as the genetic predisposition of nonlesional atopic dermatitis keratinocytes correlated with enhanced infection supporting the impact of functional tight junctions for preventing infection in human epidermis. Comparable to E-cadherin, nectin-1 was distributed throughout the epidermal layers and localized just underneath the tight-junctions. While nectin-1 was evenly distributed on primary human keratinocytes in culture, the receptor was enriched at lateral surfaces of basal and suprabasal cells during differentiation. Nectin-1 showed no major redistribution in the thickened atopic dermatitis and IL-4/IL-13-treated human epidermis in which HSV-1 can invade. However, nectin-1 localization toward tight junction components changed, suggesting that defective tight-junction barriers make nectin-1 accessible for HSV-1 which enables facilitated viral penetration. IMPORTANCE Herpes simplex virus 1 (HSV-1) is a widely distributed human pathogen which productively infects epithelia. The open question is which barriers of the highly protected epithelia must the virus overcome to reach its receptor nectin-1. Here, we used human epidermal equivalents to understand how physical barrier formation and nectin-1 distribution contribute to successful viral invasion. Inflammation-induced barrier defects led to facilitated viral penetration strengthening the role of functional tight-junctions in hindering viral access to nectin-1 that is localized just underneath tight junctions and distributed throughout all layers. We also found nectin-1 ubiquitously localized in the epidermis of atopic dermatitis and IL-4/IL-13-treated human skin implying that impaired tight-junctions in combination with a defective cornified layer allow the accessibility of nectin-1 to HSV-1. Our results support that successful invasion of HSV-1 in human skin relies on defective epidermal barriers, which not only include a dysfunctional cornified layer but also depend on impaired tight junctions.

Herpes Simplex Virus 1 Can Bypass Impaired Epidermal Barriers upon Ex Vivo Infection of Skin from Atopic Dermatitis Patients.

To infect its human host, herpes simplex virus 1 (HSV-1) must overcome the protective barriers of skin and mucosa. Here, we addressed whether pathological skin conditions can facilitate viral entry via the skin surface and used ex vivo infection studies to explore viral invasion in atopic dermatitis (AD) skin characterized by disturbed barrier functions. Our focus was on the visualization of the onset of infection in single cells to determine the primary entry portals in the epidermis. After ex vivo infection of lesional AD skin, we observed infected cells in suprabasal layers indicating successful invasion in the epidermis via the skin surface which was never detected in control skin where only sample edges allowed viral access. The redistribution of filaggrin, loricrin, and tight-junction components in the lesional skin samples suggested multiple defective mechanical barriers. To dissect the parameters that contribute to HSV-1 invasion, we induced an AD-like phenotype by adding the Th2 cytokines interleukin 4 (IL-4) and IL-13 to healthy human skin samples. Strikingly, we detected infected cells in the epidermis, implying that the IL-4/IL-13-driven inflammation is sufficient to induce modifications allowing HSV-1 to penetrate the skin surface. In summary, not only did lesional AD skin facilitate HSV-1 penetration but IL-4/IL-13 responses alone allowed virus invasion. Our results suggest that the defective epidermal barriers of AD skin and the inflammation-induced altered barriers in healthy skin can make receptors accessible for HSV-1. IMPORTANCE Herpes simplex virus 1 (HSV-1) can target skin to establish primary infection in the epithelium. While the human skin provides effective barriers against viral invasion under healthy conditions, a prominent example of successful invasion is the disseminated HSV-1 infection in the skin of atopic dermatitis (AD) patients. AD is characterized by impaired epidermal barrier functions, chronic inflammation, and dysbiosis of skin microbiota. We addressed the initial invasion process of HSV-1 in atopic dermatitis skin to understand whether the physical barrier functions are sufficiently disturbed to allow the virus to invade skin and reach its receptors on skin cells. Our results demonstrate that HSV-1 can indeed penetrate and initiate infection in atopic dermatitis skin. Since treatment of skin with IL-4 and IL-13 already resulted in successful invasion, we assume that inflammation-induced barrier defects play an important role for the facilitated access of HSV-1 to its target cells.

Sublesional fat grafting leads to a temporary improvement of wound healing in chronic leg ulcers: A prospective, randomised clinical trial.

Chronic wounds remain a therapeutic and financial challenge for physicians and the health care systems. Innovative, inexpensive and effective treatment methods would be of immense value. The sublesional fat grafting could be such treatment, although effectiveness and safety have only been assessed in a few randomised clinical trials. The fat graft was obtained by liposuction, washed with the Coleman method and then injected sublesional and into the wound margins after surgical debridement. For the control group, saline solution was used instead of fat. The primary endpoint was to determine the wound size reduction in both groups. The wounds were measured preoperatively, intraoperatively and 3, 7, 21 and 60 days after the intervention. A p-value of <0.05 was considered significant. Furthermore, histology and microbiology of the wounds and pain were assessed. A temporary effect of the treatment was observed after 14 and 21 days. The wound size reduction was significantly larger in the intervention group, whereas after 60 days, no significant difference was detected between both groups. No adverse events could be reported and the pain level was almost equal in the control and intervention group. Sublesional fat grafting temporarily enhanced healing of chronic wounds. The procedure was safe and the pain level was low. Repeated interventions could lead to complete wound closure, which should be determined in future studies.

Osteosynthesis-associated infection in maxillofacial surgery by bacterial biofilms: a retrospective cohort study of 11 years.

OBJECTIVES: The aim of this retrospective cohort study was to determine risk factors for osteosynthesis-associated infections (OAI) with subsequent necessity of implant removal in oral and maxillofacial surgery. MATERIALS AND METHODS: A total of 3937 records of patients who received either orthognathic, trauma, or reconstructive jaw surgery from 2009 to 2021 were screened for osteosynthetic material removal due to infection. Treatment-intervals, volume of applied osteosynthetic material, and respective surgical procedures were also assessed. Moreover, intraoperatively harvested microbial flora was cultured and subsequently identified by MALDI TOF. Bacteria were then screened for antibiotic resistance via VITEK system or, if necessary, via agar diffusion or epsilometer test. Data was analyzed utilizing SPSS statistical software. For statistical analysis of categorical variables, chi-square tests or Fisher exact tests were used. Continuous variables were compared via non-parametric tests. The level of significance for p-values was set at < 0.05. Descriptive analysis was also performed. RESULTS: The lower jaw was more prone to OAI than the mid face region. Larger volumes of osteosynthetic material led to significantly more OAI, resulting in reconstruction plates bearing the highest risk for OAI especially when compared to small-volume mini-plates frequently applied in trauma surgery. Among OAI associated with implant volumes smaller than 1500 mm3, the detection of Streptococcus spp., Prevotella spp., Staphylococcus spp., and Veillonella spp. was significantly elevated, whereas implant volumes larger than 1500 mm3 showed a significant increase of Enterococcus faecalis, Proteus mirabilis and Pseudomonas aeruginosa. High susceptibility rates (87.7-95.7%) were documented for 2nd- and 3rd-generation cephalosporines and piperacillin/tazobactam. CONCLUSION: High material load and lower jaw reconstruction bear the greatest risks for OAI. When working with large volume osteosynthetic implants, gram-negative pathogens must be considered when choosing an appropriate antibiotic regime. Suitable antibiotics include, e.g., piperacillin/tazobactam and 3rd-generation cephalosporines. CLINICAL RELEVANCE: Osteosynthetic material utilized in reconstructive procedures of the lower jaw may be colonized with drug-resistant biofilms.

Ex Vivo Infection of Human Skin with Herpes Simplex Virus 1 Reveals Mechanical Wounds as Insufficient Entry Portals via the Skin Surface.

Herpes simplex virus 1 (HSV-1) enters its human host via the skin and mucosa. The open question is how the virus invades this highly protective tissue in vivo to approach its receptors in the epidermis and initiate infection. Here, we performed ex vivo infection studies in human skin to investigate how susceptible the epidermis and dermis are to HSV-1 and whether wounding facilitates viral invasion. Upon ex vivo infection of complete skin, only sample edges with integrity loss demonstrated infected cells. After removal of the dermis, HSV-1 efficiently invaded the basal layer of the epidermis and, from there, gained access to suprabasal layers. This finding supports a high susceptibility of all epidermal layers which correlated with the surface expression of the receptors nectin-1 and herpesvirus entry mediator (HVEM). In contrast, only single infected cells were detected in the separated dermis, where minor expression of the receptors was found. Interestingly, after wounding, nearly no infection of the epidermis was observed via the skin surface. However, if the wounding of the skin samples led to breaks through the dermis, HSV-1 infected mainly keratinocytes via the damaged dermal layer. The application of latex beads revealed only occasional entry via the wounded dermis; however, it facilitated penetration via the wounded skin surface. Thus, we suggest that although the wounded human skin surface allows particle penetration, the skin still provides barriers that prevent HSV-1 from reaching its receptors. IMPORTANCE The human pathogen herpes simplex virus 1 (HSV-1) invades its host via the skin and mucosa, which leads to primary infection of the epithelium. As the various epithelial barriers effectively protect the tissue against viral invasion, successful infection most likely depends on tissue damage. We addressed the initial invasion process in human skin by ex vivo infection to understand how HSV-1 overcomes physical skin barriers and reaches its receptors to enter skin cells. Our results demonstrate that intact skin samples allow viral access only from the edges, while the epidermis is highly susceptible once the basal epidermal layer serves as an initial entry portal. Surprisingly, mechanical wounding did not facilitate HSV-1 entry via the skin surface, although latex beads still penetrated via the lesions. Our results imply that successful invasion of HSV-1 depends on how well the virus can reach its receptors, which was not accomplished by skin lesions under ex vivo conditions.

Correlation analysis of resected breast tissue and implant volume after mastectomy and its association with breast density.

BACKGROUND: The current methods for calculating the ideal implant volume for breast reconstruction are based on pre- or intraoperative volume measurements of the existing breast volume and do not take into account the individual breast density of the woman. This study aims is to identify objective parameters that can help to improve the optimal implant selection. MATERIALS AND METHODS: This retrospective analysis includes 198 breast cancer patients who underwent mastectomy. Breast densities (ACR) measured in mammography and MRI were compared with the removed breast tissue weight and volume of the implants used. In addition, the resected weight was compared directly with the implant volume to calculate a mathematical function. RESULTS: There was no significant correlation between the ACR values and the resected weights [correlation coefficient: mammography:- 0.117 (p = 0.176), MRI - 0.033 (p = 0.756)]. A negative correlation between the implant volumes and both imaging methods could be demonstrated [correlation coefficient: mammography - 0.268; p = 0.002; MRI was - 0.200 (p = 0.055)]. A highly significant correlation between the resected weights and the implant volumes (correlation coefficient 0.744; p < 0.001) was observed. This correlation corresponds to a power function (y = 34.71 x0.39), in which any resected weight can be used for the variable x to calculate the implant volume. CONCLUSION: We were able to show that there is a significant correlation between the resected breast tissue and the implant volume. With our novel potency function, the appropriate implant volume can be calculated for any resected weight making it easier for the surgeon to choose a fitting implant in a simple and more objective manner.

Platelet-rich plasma (PRP) in oncological patients: long-term oncological outcome analysis of the treatment of subcutaneous venous access device scars in 89 breast cancer patients.

PURPOSE: Platelet-rich plasma (PRP) is widely used product, and meta-analyses showed this product to be beneficial when applied to a wound area. This study group has already demonstrated increased patient satisfaction and lower complication rates in breast cancer patients who received PRP after removal of their subcutaneous venous access device. This work is a follow-up analysis focusing on oncologic safety. Currently, there is no long-term data on the use of PRP products in cancer patients available yet. METHODS: Between the years 2012-2016, venous access device removal was supported with the application of Arthrex ACP® (Autologous Conditioned Plasma)-a PRP product to improve the wound-healing process. All surgeries were performed in the breast cancer center of the municipal hospital of Cologne, Holweide, Germany. 35 patients received an application of Arthrex ACP® after port removal compared to the control group of 54 patients. Endpoints were local recurrence-free, distant recurrence-free as well as overall survival. RESULTS: Median follow-up was 45 months. No (0) adverse events were shown for cancer recurrence within the subcutaneous venous access device scar area. Thus, there seems to be no local oncogenic potential of the PRP product. All other endpoints as well as any-cause death numerically favor PRP use. CONCLUSION: PRP products such as Arthrex ACP® seem to be oncological inert when applied after removal of subcutaneous access devices. This is the first study providing long-term data about overall survival, distant recurrence-free and local recurrence-free survival after applying PRP in high-risk cancer patients.

#facialtraumasurgery: Educational Content of Instagram as a Social Media Source for Facial Trauma Surgery.

ABSTRACT: With an uprising influence of social media platforms like Instagram during the last decade, medical and healthcare related posts have accumulated majorly. In particular the head and face characterizes and signifies each individual's human character, which may be the reason why numerous posts are shared on social media platforms. The purpose of this investigation was to assess the content associated with facial trauma surgery and evaluate its educational quality.The authors performed a retrospective investigation on 550 Instagram posts by #facialtraumasurgery due to number of "likes," comments, type of post, language, its purpose, and source. Furthermore, posts were evaluated due to their educational quality by 3 examiners of different educational levels.The majority of posts showed 0 to 50 "likes" and 0 to 5 comments in English language. The major post type were single photographs (289; 52.5%), multiple photographs (188; 34.2%), videos (73; 13.3%) and predominantly case reports (233; 42.4%). The source was 322 (58.5%) posts by surgeons, followed by 185 (33.6%) clinic posts. Only 10% to 18% of the posts were rated "excellent." Interrater reliability between all 3 examiners presented a high concordance with 89% (P = 0.000).Our study presents an analysis of quantity and quality of social media content according to facial trauma surgery. It supports the deduction that most of the content on Instagram is shared by patients and unclear sources and thus is limited informative. Nevertheless, influence of social media on medical information is increasing and practitioners have to face its effect on their patients.

Oral recipient site infections in reconstructive surgery - impact of the graft itself and the perioperative antibiosis.

OBJECTIVES: This study was designed to assess the influence of peri/post-operative antibiotic prophylaxis (POABP) and the reconstructive graft itself on recipient sites infections in head and neck surgery. MATERIALS AND METHODS: In this retrospective cohort study, 322 consecutive patients with reconstructive surgery were investigated. The primary objective was to analyze the differences of commonly applied reconstructive grafts on the occurrence of oral recipient site infections. Moreover, differences of POABP regimes (namely: ampicillin/sulbactam, 2nd generation cephalosporins, clindamycin) and antibiotic alternatives were investigated. In addition, patients' length of in-hospital stay was analyzed in regard to reconstructive graft and POABP regime. RESULTS: The free radial forearm flap and split-thickness skin graft presented significantly less recipient site infections and shorter length of in-hospital stays (LOS) in comparison to further six reconstructive technique with pedicled tissue transfer or bone transfers. LOS was significantly shorter for patients with ampicillin/sulbactam than with 2nd generation cephalosporins as POABP. 91% of the harvested pathogens (n=193) were susceptible to the combination of 2nd and 3rd generation cephalosporins. Secondly, 92 out 113 (81%) harvested pathogens presented susceptibility to moxifloxacin. CONCLUSION: Smaller tissue transfers are less prone to infections of the recipient site and present low LOS. For an POABP regime, the combination of 2nd and 3rd generation cephalosporins presents substantial results in recipient site infections. In cases of allergy, potential pathogens show adequate susceptibility to moxifloxacin. CLINICAL RELEVANCE: A combination of 2nd and 3rd generation cephalosporins may be used to prevent recipient sites in head and neck surgery.

Influence of the Casting Concentration on the Mechanical and Optical Properties of FA/CaCl2-Derived Silk Fibroin Membranes.

In this study, we describe the manufacturing and characterization of silk fibroin membranes derived from the silkworm Bombyx mori. To date, the dissolution process used in this study has only been researched to a limited extent, although it entails various potential advantages, such as reduced expenses and the absence of toxic chemicals in comparison to other conventional techniques. Therefore, the aim of this study was to determine the influence of different fibroin concentrations on the process output and resulting membrane properties. Casted membranes were thus characterized with regard to their mechanical, structural and optical assets via tensile testing, SEM, light microscopy and spectrophotometry. Cytotoxicity was evaluated using BrdU, XTT, and LDH assays, followed by live-dead staining. The formic acid (FA) dissolution method was proven to be suitable for the manufacturing of transparent and mechanically stable membranes. The fibroin concentration affects both thickness and transparency of the membranes. The membranes did not exhibit any signs of cytotoxicity. When compared to other current scientific and technical benchmarks, the manufactured membranes displayed promising potential for various biomedical applications. Further research is nevertheless necessary to improve reproducible manufacturing, including a more uniform thickness, less impurity and physiological pH within the membranes.

Microbial diversity in infections of patients with medication-related osteonecrosis of the jaw.

OBJECTIVES: A central role of infections in the treatment of MRONJ patients is widely accepted. An investigation of the MRONJ lesions' biofilms as potential pathogens seems logical. MATERIALS AND METHODS: We investigated the clinical data of our MRONJ patients who received surgery in advanced stage of the disease. Special attention was granted to the local colonizers harvested from osseous MRONJ specimens and submucosal putrid infections. RESULTS: Eleven out of 71 patients presented a spontaneous onset of the disease and for 60 out of 71 patients a trigger was detected. Breast cancer (29.6%) and prostate cancer (22.5%) were the most frequent underlying disease for prescription of an antiresorptive therapy, mostly zoledronate. Submucosal soft tissue biofilms significantly differed from biofilms harvested from the MRONJ lesions bottom, yet the most frequent bacteria were equally present in both groups: Streptococcus species (spp.), Prevotella spp., Actinomyces spp., Veillonella spp., and Parvimonas micra. The cephalosporins, cefuroxime and cefotaxime, and ß-lactam antibiotics with ß-lactamase inhibitor revealed the greatest susceptibility for the detected bacteria. CONCLUSION: The bacteria from the submucosal areas and the bottom of the infected bone presented comparable susceptibility to the common antibiotics regimes. Streptococcus spp., Prevotella spp., and Veillonella spp. present a high abundance in MRONJ lesions beside Actinomyces spp. The MRONJ lesions bottom is in many cases not infected by Actinomyces spp. CLINICAL RELEVANCE: The removal of the necrotic bone reduces the variety of bacteria found in MRONJ lesions, in particular at the bottom of the lesion.

The Importance of Serological Procalcitonin Levels After Autologous Microsurgical Transplantation.

INTRODUCTION: Published data on procalcitonin (PCT) levels after microsurgical interventions are very scarce, although infection within these patients is not only associated with severe morbidity but also significantly higher mortality rates. MATERIAL AND METHODS: Retrospective study on 20 patients, who were operated on by a single experienced plastic and reconstructive surgeon within one year (June 2017-June 2018). The authors included all patients, who received microvascular transplants for reconstruction of soft tissue defects. Furthermore, age above 18 years and appropriate documentation allowing sufficient data collection were defined as inclusion criteria. The authors excluded all patients with perioperative systemic inflammation and transplant loss, as our aim was to solely determine and evaluate potential alterations of serological PCT levels after microsurgical interventions. RESULTS: The PCT cutoff level to differentiate physiological and pathological levels was defined as 0.1 µg/L. There was no detectable increase in procalcitonin in all of our 20 patients, for whom the authors performed microvascular transplantation to reconstruct soft tissue defects. CONCLUSION: Serological PCT levels remain stable after the considered surgical interventions and therefore PCT levels might be utilized to identify systemic inflammation, thus helping to reduce severe complications by early individualized antiinfective treatment strategies.

Incidental findings on craniomaxillofacial cone beam computed tomography in orthodontic patients.

PURPOSE: Cone beam computed tomography (CBCT) in orthodontics is increasingly used for detecting impacted or ectopic teeth or for orthognathic and cleft lip and palate treatment. Incidental findings (IFs) are frequently encountered and often relevant. The aim of this study was to detect the prevalence of relevant pathologies on CBCT scans of orthodontic patients. METHODS: Over a 6-year period, incidental imaging findings were analyzed in 345 CBCT scans (181 men; 164 women; age 16.3 ± 8.4 years), and subdivided into dental (Group 1), skeletal (Group 2), sinunasal (Group 3), and infrequent other pathologies (Group 4). RESULTS: A total of 502 IFs were detected in 345 patients (1.4 IFs per patient, on average). Most IFs were found in Group 1 (358 IFs; 71.3%), followed by Group 2 (129 IFs; 25.7%), Group 3 (14 IFs; 2.8%), and Group 4 (1 IF; 0.2%). There were 119 (34.5%) patients with a missing wisdom tooth, 94 (27.3%) with dental aplasia, 71 (20.6%) with dislocations, 33 (9.6%) with partial opacifications, and 27 (7.8%) with signs of sinusitis. CONCLUSIONS: This study found that IFs in orthodontic CBCT scans are frequently encountered, even in younger orthodontic patients. When interpreting CBCT scans, orthodontists should be aware of potential relevant IFs that may require further investigation, change patients' treatment or affect their quality of life.

Computer-Designed Splints for Surgical Transfer of 3D Orthognathic Planning.

Advances in computers and imaging have permitted the adoption of three-dimensional (3D) planning protocols in orthognathic surgery, which may allow a paradigm shift when the computer-assisted planning can be transferred properly. The purpose of this investigation was to introduce an innovative clinical protocol using computer-aided designed and computer-aided manufactured (CAD/CAM) surgical splints for surgical transfer of 3D orthognathic planning compared with the classic technique using arbitrary occlusal splints. The clinical protocols consisted of computed tomography (CT) or cone-beam CT (CBCT) maxillofacial imaging, bone segmentation, 3D diagnosis, computer-assisted surgical treatment planning, and CAD/CAM surgical splints (group A) and manufacture of arbitrary occlusal splints (group B) for intraoperative surgical planning transfer. The observed patients underwent bimaxillary osteotomies and, if necessary, an additional genioplasty. Both techniques were evaluated by applying 13 hard tissue parameters to compare the 3D orthognathic planning (T0) with the postoperative result (T1) using 3D cephalometry. The CAD/CAM splints showed significant better precision for the maxilla (ΔT < 0.23 mm) and mandible (ΔT < 0.33 mm) compared with a maxillary deviation of 1.3 mm and a mandibular deviation of 1.8 mm when using the arbitrary splints. Computer-assisted diagnosis and preoperative surgical planning provide clinicians with valuable tools and allow 3D imagination. CAD/CAM splints provide a reliable, innovative, and precise approach for the transfer of 3D orthognathic planning, which is more precise compared with the conventional arbitrary occlusal splints.

Adipose-derived stem cells and keratinocytes in a chronic wound cell culture model: the role of hydroxyectoine.

Chronic wounds represent a major socio-economic problem in developed countries today. Wound healing is a complex biological process. It requires a well-orchestrated interaction of mediators, resident cells and infiltrating cells. In this context, mesenchymal stem cells and keratinocytes play a crucial role in tissue regeneration. In chronic wounds these processes are disturbed and cell viability is reduced. Hydroxyectoine (HyEc) is a membrane protecting osmolyte with protein and macromolecule stabilising properties. Adipose-derived stem cells (ASC) and keratinocytes were cultured with chronic wound fluid (CWF) and treated with HyEc. Proliferation was investigated using MTT test and migration was examined with transwell-migration assay and scratch assay. Gene expression changes of basic fibroblast growth factor (b-FGF), vascular endothelial growth factor (VEGF), matrix metalloproteinases-2 (MMP-2) and MMP-9 were analysed by quantitative real-time polymerase chain reaction (qRT-PCR). CWF significantly inhibited proliferation and migration of keratinocytes. Addition of HyEc did not affect these results. Proliferation capacity of ASC was not influenced by CWF whereas migration was significantly enhanced. HyEc significantly reduced ASC migration. Expression of b-FGF, VEGF, MMP-2 and MMP-9 in ASC, and b-FGF, VEGF and MMP-9 in keratinocytes was strongly induced by chronic wound fluid. HyEc enhanced CWF induced gene expression of VEGF in ASC and MMP-9 in keratinocytes. CWF negatively impaired keratinocyte function, which was not influenced by HyEc. ASC migration was stimulated by CWF, whereas HyEc significantly inhibited migration of ASC. CWF induced gene expression of VEGF in ASC and MMP-9 in keratinocytes was enhanced by HyEc, which might partly be explained by an RNA stabilising effect of HyEc.

A paradigm shift in orthognathic surgery? A comparison of navigation, computer-aided designed/computer-aided manufactured splints, and "classic" intermaxillary splints to surgical transfer of virtual orthognathic planning.

PURPOSE: Advances in computers and imaging have permitted the adoption of 3-dimensional (3D) virtual planning protocols in orthognathic surgery, which may allow a paradigm shift when the virtual planning can be transferred properly. The purpose of this investigation was to compare the versatility and precision of innovative computer-aided designed and computer-aided manufactured (CAD/CAM) surgical splints, intraoperative navigation, and "classic" intermaxillary occlusal splints for surgical transfer of virtual orthognathic planning. MATERIAL AND METHODS: The protocols consisted of maxillofacial imaging, diagnosis, virtual orthognathic planning, and surgical planning transfer using newly designed CAD/CAM splints (approach A), navigation (approach B), and intermaxillary occlusal splints (approach C). In this prospective observational study, all patients underwent bimaxillary osteotomy. Eight patients were treated using approach A, 10 using approach B, and 12 using approach C. These techniques were evaluated by applying 13 hard and 7 soft tissue parameters to compare the virtual orthognathic planning (T0) with the postoperative result (T1) using 3D cephalometry and image fusion (ΔT1 vs T0). RESULTS: The highest precision (ΔT1 vs T0) for the maxillary planning transfer was observed with CAD/CAM splints (<0.23 mm; P > .05) followed by surgical "waferless" navigation (<0.61 mm, P < .05) and classic intermaxillary occlusal splints (<1.1 mm; P < .05). Only the innovative CAD/CAM splints kept the condyles in their central position in the temporomandibular joint. However, no technique enables a precise prediction of the mandible and soft tissue. CONCLUSIONS: CAD/CAM splints and surgical navigation provide a reliable, innovative, and precise approach for the transfer of virtual orthognathic planning. These computer-assisted techniques may offer an alternate approach to the use of classic intermaxillary occlusal splints.

An Overview of Scaffolds and Biomaterials for Skin Expansion and Soft Tissue Regeneration: Insights on Zinc and Magnesium as New Potential Key Elements.

The utilization of materials in medical implants, serving as substitutes for non-functional biological structures, supporting damaged tissues, or reinforcing active organs, holds significant importance in modern healthcare, positively impacting the quality of life for millions of individuals worldwide. However, certain implants may only be required temporarily to aid in the healing process of diseased or injured tissues and tissue expansion. Biodegradable metals, including zinc (Zn), magnesium (Mg), iron, and others, present a new paradigm in the realm of implant materials. Ongoing research focuses on developing optimized materials that meet medical standards, encompassing controllable corrosion rates, sustained mechanical stability, and favorable biocompatibility. Achieving these objectives involves refining alloy compositions and tailoring processing techniques to carefully control microstructures and mechanical properties. Among the materials under investigation, Mg- and Zn-based biodegradable materials and their alloys demonstrate the ability to provide necessary support during tissue regeneration while gradually degrading over time. Furthermore, as essential elements in the human body, Mg and Zn offer additional benefits, including promoting wound healing, facilitating cell growth, and participating in gene generation while interacting with various vital biological functions. This review provides an overview of the physiological function and significance for human health of Mg and Zn and their usage as implants in tissue regeneration using tissue scaffolds. The scaffold qualities, such as biodegradation, mechanical characteristics, and biocompatibility, are also discussed.

CBCT device dependency on the transfer accuracy from computer-aided implantology procedures.

OBJECTIVES: To evaluate the potential influence of different cone-beam computed tomography (CBCT) devices on the transfer accuracy of an open-source system for computer-aided implantology (CAI). MATERIAL AND METHODS: A total of 108 implants in 18 partially edentulous patient-equivalent models were planned and fully guided implants were inserted using an open-source CAI system with three different CBCT devices. After follow-up CBCT and fiducial marker-matching procedure, linear horizontal, vertical, and maximal three-dimensional deviations, as well as angle deviations between the virtual planning data and the surgical results were calculated. Variance analysis was carried out to prove whether or not the observed differences between the CBCT devices were statistically significant. RESULTS: The observed mean three-dimensional deviation rates between virtually planned and achieved implant positions varied by around 400 µm (45%) at the implant's base and around 540 µm (50%) at the implant's tip in dependence to the applied CBCT device. Mean vertical deviations varied around 370 µm (76%) at the implant's base and 350 µm (69%) at the implant's tip, whereas axes deviations varied around 0.81° (40%) between the three investigated CBCT devices. Except for the axes deviations and the horizontal linear deviations at the implants base, observed differences reached significance level between the CBCT devices. CONCLUSIONS: Until now, the potential influence from different CBCT devices on the transfer accuracy of CAI systems has not yet been investigated. Data from the present study confirm for the first time the in vitro CBCT device dependency on the transfer accuracy of CAI systems reaching up to axes deviations of 0.6 angle degree and linear deviations around half a millimeter.

Surgical side infections of the tracheostomy - A retrospective cohort study of patients with head and neck cancer in intensive care.

This study was conducted to reveal the relevant risk factors for surgical site infections (SSI) of the tracheostomy in ICU tracheostomy patients with oncologic history. Retrospectively, medical and ICU records of patients who received open tracheostomy in a uniform manner were investigated. Of 187 consecutive patients in total, patients with a peri/post-operative antibiotic prophylaxis (POABP) experienced significantly more Organ-Space SSI, whereas patients with a POABP developed less Superficial Incisional SSI and Deep Incisional SSI. Neck Dissection (p = 0.025), especially the more levels are included, and POABP (p = 0.005) have a significant impact on the occurrence of an SSI of the tracheostomy. Deep incisional SSI significantly prolonged a patient's dependency on a ventilator (p = 0.045, M = 3.92, SD = 4.718). The difference between Superficial Incisional, Deep Incisional and Organ-Space SSI should be taken in consideration regarding risk evaluation and treatment. Furthermore, a gram-negative facultative anaerobic biofilm should be taken into consideration in treatment options and thus an escalation regarding antibiotic treatment as a POABP. For fulminant SSI of the tracheostomy the use of piperacillin/tazobactam or 3rd generation cephalosporines or carbapenems is recommendable.

Development and validation of a parametric human mandible model to determine internal stresses for the future design optimization of maxillofacial implants.

Large segmental mandible bone defects still represent a challenge for endogenous regeneration. Despite the bone's capacity to heal in many clinical situations, bone defects over a critical size do not heal spontaneously. An emerging treatment of critically sized mandibular defects is the implantation of individually manufactured scaffolds consisting of biodegradable magnesium alloys. Biomedical engineers faced the challenge of developing a scaffold structure that not only provides sufficient stability, but also stimulates and promotes bone growth while considering the degradation of the magnesium alloy. The porosity of the scaffold must also support bone ingrowth and neovascularization. For an optimal design and subsequent structural optimization knowledge of external load cases is essential. However, currently the muscle and joint forces of the mandible cannot be measured directly. The aim of our study was therefore the development of a parametric human mandible model to determine the relevant boundary conditions for the subsequent structural optimization of individual jawbone implants. Using a model-based approach, determining the essential external load of the mandible as a function of the age and sex of a patient individually and the realistic simulation of the mechanical stress for patient-specific loads and anatomies has been realized. The developed model is successfully validated by evaluating the deformations and stresses of the lower jaw of a possible patient and comparing them with the results of dental research. Based on the results of the modelling, in a subsequent optimization process section forces at the interface between the bone tissue and jawbone implant can be determined and used to optimize the design of the jawbone implant.