Use of acellular matrices as scaffolds in cartilage regeneration - a systematic review.

SIGNIFICANCE: Cartilage regeneration remains a significant challenge in the field of regenerative medicine. Acellular matrix-based cartilage tissue regeneration offers an innovative approach to repairing cartilage defects by providing a scaffold for new tissue growth. Its significance lies in its potential to restore joint function, mitigate pain, and improve the quality of life for patients suffering from cartilage-related injuries and conditions. RECENT ADVANCES: Recent advances in acellular matrix-based cartilage regeneration have focused on enhancing scaffold properties for improved cell adhesion, proliferation, and differentiation. Moreover, several scaffold techniques such as combining ADM and ACM with cartilage tissue, as well as biphasic scaffolding enjoy rising research activity. Incorporating bioactive factors and advanced manufacturing techniques holds promise for producing more biomimetic scaffolds, advancing efficient cartilage repair and regeneration. CRITICAL ISSUES: Obstacles in acellular matrix-based cartilage regeneration include achieving proper integration with surrounding tissue and ensuring long-term durability of the regenerated cartilage. Further, issues such as high costs and limited availability of suitable cells for scaffold seeding must be considered. The heterogeneity and limited regenerative capabilities of cartilage need to be addressed for successful clinical translation. FUTURE DIRECTIONS: Research should focus on exploring advanced biomaterials and developing new techniques, regarding easily reproductible scaffolds, ideally constructed from clinically validated and readily available commercial products. Findings underline the potential of AM-based approaches, especially rising exploration of tissue-derived ADM and ACM. In future, the primary objective should not only be the regeneration of small cartilage defects, but rather focus on fully regenerating a joint or larger cartilage defect.

Biocompatibility of Synechococcus sp. PCC 7002 with Human Dermal Cells In Vitro.

Being the green gold of the future, cyanobacteria have recently attracted considerable interest worldwide. This study investigates the adaptability and biocompatibility of the cyanobacterial strain Synechococcus sp. PCC 7002 with human dermal cells, focusing on its potential application in biomedical contexts. First, we investigated the adaptability of Synechococcus PCC 7002 bacteria to human cell culture conditions. Next, we evaluated the biocompatibility of cyanobacteria with common dermal cells, like 3T3 fibroblasts and HaCaT keratinocytes. Therefore, cells were directly and indirectly cocultured with the corresponding cells, and we measured metabolic activity (AlamarBlue assay) and proliferation (cell count and PicoGreen assay). The lactate dehydrogenase (LDH) assay was performed to determine the cytotoxic effect of cyanobacteria and their nutrition medium on human dermal cells. The cyanobacteria exhibited exponential growth under conventional human cell culture conditions, with the temperature and medium composition not affecting their viability. In addition, the effect of illumination on the proliferation capacity was investigated, showing a significant impact of light exposure on bacterial growth. The measured oxygen production under hypoxic conditions demonstrated a sufficient oxygen supply for further tissue engineering approaches depending on the number of bacteria. There were no significant adverse effects on human cell viability and growth under coculture conditions, whereas the LDH assay assessed signs of cytotoxicity regarding 3T3 fibroblasts after 2 days of coculturing. These negative effects were dismissed after 4 days. The findings highlight the potential of Synechococcus sp. PCC 7002 for integration into biomedical approaches. We found no cytotoxicity of cyanobacteria on 3T3 fibroblasts and HaCaT keratinocytes, thus paving the way for further in vivo studies to assess long-term effects and systemic reactions.

Subjective Discomfort during Botulinumtoxin Injections Dependent on Injection Site and Needle Size: A Comparison Between 30G, 33G and 34G Needles.

BACKGROUND: Botulinumtoxin application in the face is amongst the most common aesthetic procedures in the head and neck region. It also has numerous medical uses. One of the main reasons for patients to refrain from it is the subjective discomfort that is experienced during injections. OBJECTIVES: The study at hand aimed to determine whether needles with 33G and 34G offer an advantage in terms of individual pain perception during botulinumtoxin injections. METHODS: We conducted a prospective study where patients were asked to grade subjective discomfort on a visual analogue scale for each region (forehead, glabella, temple) that was treated directly after treatment and 15 minutes after. Patients were treated with 30G, 33G or 34G needles, respectively. RESULTS: Ninety-nine patients that underwent treatment of 189 regions were included in the study. Patients were evenly distributed amongst the different needle sizes and regions. Subjective discomfort was greatest in all regions for 30G needles (3.9 ± 1.6 forehead, 4.3 ± 1.7 glabella and 4.0 ± 1.6 temple) followed by 33G (2.7 ± 1.5 forehead, 2.7 ± 1.9 glabella and 2.2 ± 1.2 temple) and 34G (1.7 ± 1.2 forehead, 1.6 ± 1.4 glabella and 1.6 ± 1.4 temple). All differences between needle size were statistically significant (p < 0.05) CONCLUSION: 33G and 34G needles seem to offer smaller discomfort during BTX treatments of the head and neck, with 34G being superior to 33G. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

[Searching for Evidence: A Systematic Review of the Pathology of Lipoedema]. / Auf der Suche nach der Evidenz: Eine systematische Übersichtsarbeit zur Pathologie des Lipödems.

BACKGROUND: Lipoedema is a symmetrically localised, painful hypertrophy of subcutaneous adipose tissue in the extremities with marked disproportion to the trunk, and almost exclusively affects females. Despite being first described over 80 years ago, the aetiology and pathogenesis of the disease are largely unknown and are currently the subject of intensive research efforts. METHODS: To summarise the current evidence-based literature on the cellular pathologies and aetiology of lipoedema, a PRISMA-based systematic review was conducted within the National Library of Medicine and Cochrane databases. RESULTS: A total of 53 studies were identified and included in this review. The results were classified and summarised into categories. CONCLUSION: Although there has been a significant increase in research activity and recent publication of extensive studies with a histological and molecular genetic focus, the fundamental aetiology and pathology of lipoedema remains largely unclear. The current data shows discrepancies across studies, particularly with regard to the "oedematous" component of lipoedema. The frequently present comorbidities "lymphoedema" and "obesity", primarily in advanced stages of lipoedema, complicate the diagnostic differentiation and clear definition of study cohorts in scientific research.

[Multidrug-resistant bacterial colonisation in Ukrainian war injuries: a need for multimodal therapy]. / Multiresistente Keimbesiedelung bei ukrainischen Kriegsverletzten: Notwendigkeit zur multimodalen Therapie.

This case report describes the interdisciplinary treatment of a complex shrapnel injury to the right femur of an 18-year-old Ukrainian soldier. This open multifragmentary fractur of the femur with a large bone defect, soft tissue damage and osteomyelitis was complicated by several multidrug-resistant bacteria, including Acinetobacter baumanii, which could not be eradicated by antibiotic treatment. Sterility was only achieved by multiple radical debridement and by negative pressure wound therapy with instillation (NPWTi) using hypochlorous acid. The femur was then reconstructed with a chimeric double-barrel fibula free flap. This report highlights the importance of multimodal antimicrobial wound treatments in an era of increasing antibiotic resistance to enable a successful und functional reconstruction of complex and infected fractures.

The use of commercial fibrin glue in dermal replacement material reduces angiogenic and lymphangiogenic gene and protein expression in vitro.

BACKGROUND: Commercial fibrin glue is increasingly finding its way into clinical practice in surgeries to seal anastomosis, and initiate hemostasis or tissue repair. Human biological glue is also being discussed as a possible cell carrier. To date, there are only a few studies addressing the effects of fibrin glue on the cell-molecular level. This study examines the effects of fibrin glue on angiogenesis and lymphangiogenesis, as well as adipose-derived stem cells (ASCs) with a focus on gene and protein expression in scaffolds regularly used for tissue engineering approaches. METHODS: Collagen-based dermal regeneration matrices (DRM) were seeded with human umbilical vein endothelial cells (HUVEC), human dermal lymphatic endothelial cells (LECs), or adipose-derived stem cells (ASC) and fixed with or without fibrin glue according to the experimental group. Cultures were maintained for 1 and 7 days. Finally, angiogenic and lymphangiogenic gene and protein expression were measured with special regard to subtypes of vascular endothelial growth factor (VEGF) and corresponding receptors using Multiplex-qPCR and ELISA assays. In addition, the hypoxia-induced factor 1-alpha (HIF1a) mediated intracellular signaling pathways were included in assessments to analyze a hypoxic encapsulating effect of fibrin polymers. RESULTS: All cell types reacted to fibrin glue application with an alteration of gene and protein expression. In particular, vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor B (VEGFB), vascular endothelial growth factor C (VEGFC), vascular endothelial growth receptor 1 (VEGFR1/FLT1), vascular endothelial growth receptor 2 (VEGFR2/KDR), vascular endothelial growth receptor 3 (VEGFR3/FLT4) and Prospero Homeobox 1 (PROX1) were depressed significantly depending on fibrin glue. Especially short-term fibrin effect led to a continuous downregulation of respective gene and protein expression in HUVECs, LECs, and ASCs. CONCLUSION: Our findings demonstrate the impact of fibrin glue application in dermal regeneration with special regard to angiogenesis and lymphangiogenesis. In particular, a short fibrin treatment of 24 hours led to a decrease in gene and protein levels of LECS, HUVECs, and ASCs. In contrast, the long-term application showed less effect on gene and protein expressions. Therefore, this work demonstrated the negative effects of fibrin-treated cells in tissue engineering approaches and could affect wound healing during dermal regeneration.

Adipose-Derived Stem Cells Improve Angiogenesis and Lymphangiogenesis in a Hypoxic Dermal Regeneration Model In Vitro.

Background and Objectives: Impaired wound healing represents an unsolved medical issue with a high impact on patients' quality of life and global health care. Even though hypoxia is a significant limiting factor for wound healing, it reveals stimulating effects in gene and protein expression at cellular levels. In particular, hypoxically treated human adipose tissue-derived stem cells (ASCs) have previously been used to stimulate tissue regeneration. Therefore, we hypothesized that they could promote lymphangiogenesis or angiogenesis. Materials and Methods: Dermal regeneration matrices were seeded with human umbilical vein endothelial cells (HUVECs) or human dermal lymphatic endothelial cells (LECs) that were merged with ASCs. Cultures were maintained for 24 h and 7 days under normoxic or hypoxic conditions. Finally, gene and protein expression were measured regarding subtypes of VEGF, corresponding receptors, and intracellular signaling pathways, especially hypoxia-inducible factor-mediated pathways using multiplex-RT-qPCR and ELISA assays. Results: All cell types reacted to hypoxia with an alteration of gene expression. In particular, vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor B (VEGFB), vascular endothelial growth factor C (VEGFC), vascular endothelial growth factor receptor 1 (VEGFR1/FLT1), vascular endothelial growth factor receptor 2 (VEGFR2/KDR), vascular endothelial growth factor receptor 3 (VEGFR3/FLT4), and prospero homeobox 1 (PROX1) were overexpressed significantly depending on upregulation of hypoxia-inducible factor 1 alpha (HIF-1a). Moreover, co-cultures with ASCs showed a more intense change in gene and protein expression profiles and gained enhanced angiogenic and lymphangiogenic potential. In particular, long-term hypoxia led to continuous stimulation of HUVECs by ASCs. Conclusions: Our findings demonstrated the benefit of hypoxic conditioned ASCs in dermal regeneration concerning angiogenesis and lymphangiogenesis. Even a short hypoxic treatment of 24 h led to the stimulation of LECs and HUVECs in an ASC-co-culture. Long-term hypoxia showed a continuous influence on gene expressions. Therefore, this work emphasizes the supporting effects of hypoxia-conditioned-ASC-loaded collagen scaffolds on wound healing in dermal regeneration.

Evaluation of the Usability of a Low-Cost 3D Printer in a Tissue Engineering Approach for External Ear Reconstruction.

The use of alloplastic materials instead of autologous cartilage grafts offers a new perspective in craniofacial reconstructive surgery. Particularly for regenerative approaches, customized implants enable the surgeon to restore the cartilaginous framework of the ear without donor site morbidity. However, high development and production costs of commercially available implants impede clinical translation. For this reason, the usability of a low-cost 3D printer (Ultimaker 2+) as an inhouse-production tool for cheap surgical implants was investigated. The open software architecture of the 3D printer was modified in order to enable printing of biocompatible and biologically degradable polycaprolactone (PCL). Firstly, the printing accuracy and limitations of a PCL implant were compared to reference materials acrylonitrile butadiene styrene (ABS) and polylactic acid (PLA). Then the self-made PCL-scaffold was seeded with adipose-tissue derived stem cells (ASCs), and biocompatibility was compared to a commercially available PCL-scaffold using a cell viability staining (FDA/PI) and a dsDNA quantification assay (PicoGreen). Secondly, porous and solid patient-customized ear constructs were manufactured from mirrored CT-imagining data using a computer-assisted design (CAD) and computer-assisted manufacturing (CAM) approach to evaluate printing accuracy and reproducibility. The results show that printing of a porous PCL scaffolds was possible, with an accuracy equivalent to the reference materials at an edge length of 10 mm and a pore size of 0.67 mm. Cell viability, adhesion, and proliferation of the ASCs were equivalent on self-made and the commercially available PCL-scaffolds. Patient-customized ear constructs could be produced well in solid form and with limited accuracy in porous form from all three thermoplastic materials. Printing dimensions and quality of the modified low-cost 3D printer are sufficient for selected tissue engineering applications, and the manufacturing of personalized ear models for surgical simulation at manufacturing costs of EUR 0.04 per cell culture scaffold and EUR 0.90 (0.56) per solid (porous) ear construct made from PCL. Therefore, in-house production of PCL-based tissue engineering scaffolds and surgical implants should be further investigated to facilitate the use of new materials and 3D printing in daily clinical routine.

Zone-Dependent Architecture and Biochemical Composition of Decellularized Porcine Nasal Cartilage Modulate the Activity of Adipose Tissue-Derived Stem Cells in Cartilage Regeneration.

Previous anatomical studies have shown different functional zones in human nasal septal cartilage (NC). These zones differ in respect to histological architecture and biochemical composition. The aim of this study was to investigate the influence of these zones on the fate of stem cells from a regenerative perspective. Therefore, decellularized porcine septal cartilage was prepared and subjected to histological assessment to demonstrate its equivalence to human cartilage. Decellularized porcine NC (DPNC) exposed distinct surfaces depending on two different histological zones: the outer surface (OS), which is equivalent to the superficial zone, and the inner surface (IS), which is equivalent to the central zone. Human adipose tissue-derived stem cells (ASCs) were isolated from the abdominal fat tissue of five female patients and were seeded on the IS and OS of DPNC, respectively. Cell seeding efficiency (CSE), vitality, proliferation, migration, the production of sulfated glycosaminoglycans (sGAG) and chondrogenic differentiation capacity were evaluated by histological staining (DAPI, Phalloidin, Live-Dead), biochemical assays (alamarBlue®, PicoGreen®, DMMB) and the quantification of gene expression (qPCR). Results show that cell vitality and CSE were not influenced by DPNC zones. ASCs, however, showed a significantly higher proliferation and elevated expression of early chondrogenic differentiation, as well as fibrocartilage markers, on the OS. On the contrary, there was a significantly higher upregulation of hypertrophy marker MMP13 (p < 0.0001) and GAG production (p = 0.0105) on the IS, whereas cell invasion into the three-dimensional DPNC was higher in comparison to the OS. We conclude that the zonal-dependent distinct architecture and composition of NC modulates activities of ASCs seeded on DPNC. These findings might be used for engineering of cartilage substitutes needed in facial reconstructive surgery that yield an equivalent histological and functional structure, such as native NC.

[The frequency of performing vascular anastomoses determines the learning curve in a retrospective analysis of 212 participants of the Munich course of microsurgery]. / Die Häufigkeit der Durchführung einer Gefäßanastomose ist der entscheidende Faktor auf den Lernerfolg in einer retrospektiven Analyse von 212 Teilnehmern des Münchner Mikrochirurgiekurses.

OBJECTIVE: Microsurgical courses are a widely accepted and common method of acquiring microsurgical skills outside of the operation theatre. In-vivo models are often used to prepare surgeons for vascular microsurgery in patients. Although microsurgical courses are commonly offered and attended, the learning curve acquired in such courses remains elusive. MATERIAL AND METHODS: The patency of end-to-end anastomoses performed by a total of 212 participants with different education levels and from different specialist fields were assessed in models of living rats. Participants attended the annually held microsurgical course at the Department for Hand, Plastic and Aesthetic Surgery, Ludwig Maximilian University of Munich, between 2013 and 2018. RESULTS: A highly significant correlation (rp = 0,658; p < 0,001) between number of trials and patent anastomoses was observed. There was no significant correlation between years of surgical experience and age and total number of patent anastomoses achieved during the course. No statistically significant difference of total number of patent anastomoses between residents and board-certified surgeons was detected. CONCLUSION: Looking at the steep learning curves of our participants and the high rate of patent anastomoses, we recommend the setting of microsurgical courses using in-vivo models to overcome potential failures in the beginning of vascular microsurgery careers.

Experimental approach to nasal septal cartilage regeneration with adipose tissue-derived stem cells and decellularized porcine septal cartilage.

BACKGROUND: Cartilage shortage is a major problem in facial reconstructive surgery. Prior studies have shown that decellularized porcine nasal septal cartilage (DPNC) seeded with primary human nasal chondrocytes enabled cartilage regeneration and showed potential as a replacement material for nasal cartilage. Since adipose tissue-derived stem cells (ASCs) are easily accessible and almost abundantly available, they appear to be a promising alternative to limited chondrocytes making the combination of DPNC and ASCs a feasible approach towards clinical translation. Thus, this study was intended to investigate the interactions between ASCs and DPNC in an in vitro model. METHODS: DPNCs were seeded and 3D-cultured with primary human ASCs that were priorly characterized with trilineage differentiation and flow cytometry. Cell vitality and proliferation were evaluated by Live-Dead, alamarBlue, and PicoGreen assays. Chondrogenic differentiation was examined by DMMB assay and cryosectioning-based histology. Cell invasion within DPNC was visualized and quantified by fluorescent histology (DAPI, Phalloidin). RESULTS: ASCs showed good adherence to DPNC and Live-Dead assay proved their viability over 2 weeks. AlamarBlueassay showed an increase in metabolic activity compared to 2D cultures, and PicoGreen assay demonstrated an increase of cell number within DPNC over time. Biochemical assays and histology added evidence of chondrogenic differentiation of 3D-cultured ASCs under the influence of chondrogenic induction medium. Fluorescent image analysis showed a significant increase of cell-occupied areas of scaffolds over time (P < .05). CONCLUSIONS: DPNC scaffolds provided a suitable environment for ASCs that allowed good cell vitality, high proliferation, and chondrogenic differentiation. Thus, the use of ASCs and DPNC yields a promising alternative to the use of primary human chondrocytes. For facial cartilage tissue engineering, we regard ASCs as an attractive alternative to human nasal chondrocytes due to their better accessibility and availability. Further research will be necessary to determine long-term effects and in vivo outcomes of ASCs and DPNC in cartilage regeneration of the face.

[Current review of factors in the stem cell donor that influence the regenerative potential of adipose tissue-derived stem cells]. / Eine aktuelle Übersicht über die Einflussfaktoren der Stammzellspender auf das regenerative Potential von Fettgewebsstammzellen.

BACKGROUND: Regenerative therapies like cell-assisted lipotransfer or preclinical experimental studies use adipose tissue-derived stem cells (ASCs) as the main therapeutic agent. But there are also factors depending on the clinical donor that influence the cell yield and regenerative potential of human ASCs and stromal vascular fraction (SVF). Therefore, the aim of this review was to identify and evaluate these factors according to current literature. METHODS: For this purpose, a systematic literature review was performed with focus on factors affecting the regenerative potential of ASCs and SVF using the National Library of Medicine. RESULTS: Currently, there is an abundance of studies regarding clinical donor factors influencing ASCs properties. But there is some contradiction and need for further investigation. Nevertheless, we identified several recurrent factors: age, sex, weight, diabetes, lipoedema, use of antidepressants, anti-hormonal therapy and chemotherapy. CONCLUSION: We recommend characterisation of the ASC donor cohort in all publications, regardless of whether they are experimental studies or clinical trials. By these means, donor factors that influence experimental or clinical findings can be made transparent and results are more comparable. Moreover, this knowledge can be used for study design to form a homogenous donor cohort by precise clinical history and physical examination.

[The COVID-19 Pandemia and its consequences for plastic surgery and hand surgery]. / Die COVID-19 Pandemie und ihre Folgen für die Plastische Chirurgie und Handchirurgie.

The first case of a SARS-Cov-2 virus infection was confirmed on January 27th in Munich. For both, plastic and hand surgeons it is crucial to act responsible, minimize the transmission of the virus and aid in reasonable and adequate allocation of resources for the treatment of affected patients during this pandemia. This article aims to provide an overview over the latest developments and insights that affect plastic and hand surgeons. At the same time plastic and hand surgeons are required to participate actively in the discussion of new regulatory measures that on one hand aim to ensure a proper medical care of COVID-19 patients and on the other hand need to guarantee coverage of all other patients. Furthermore exit - strategies after the pandemia need to be discussed by our societies. Naturally, this manuscript provides insight into the current situation, which might undergo changes due to the swift progression of the pandemia.

Differences between human septal and alar cartilage with respect to biomechanical features and biochemical composition.

Cartilage grafts have become popular in facial plastic surgery to reconstruct defects or to improve aesthetic outcomes in various applications. But there is a considerable rate of graft failure like resorption or deformation. To improve graft survival and function, accurate understanding of the properties of the recipient site is indispensable. Therefore 10 noses of human cadavers were meticulously dissected and specimens of alar and septal cartilage subjected to confined compression and tensile tests. Furthermore, cell number, glycosaminoglycan and hydroxyproline content were measured. RESULTS: showed a significant difference (p < 0.05) of alar and septal cartilage regarding Equilibrium Modulus, cell number and glycosaminoglycan but not hydroxyproline content. Tensile tests showed a significant difference (p < 0.001) between alar and septal cartilage (vertical vector of force) for E-modulus, maximal force and maximal strain but not for horizontal vector of force. There was a significant difference (p < 0.05) within septal cartilage samples depending on vector of force (vertical vs. horizontal). Finally multifactorial linear regression allowed an estimation of Equilibrium Modulus depending on compression, glycosaminoglycan content and cell number with statistical significance (p < 0.05). In conclusion, nasal cartilage differs in function and composition depending on anatomical location and the prevalent forces. Therefore further research will be necessary to evaluate if graft failure depends on a mismatch of functional properties and if grafts can be adapted to the recipient site.

Novel Pulmonary Function Parameter Shifts in High-Grade Upper Airway Stenoses.

Upper airway stenosis (UAS) is a common problem for anesthesiologists in laryngology as well as head and neck surgery, but it may lead to life-threatening situations if it is undetected. This retrospective case series was performed on patients who had UAS and presented with severe dyspnea or encountered difficulties in airway management. To assess the severity of UAS, the degree of stenosis was calculated using computed tomography scans and direct endoscopy. Lung function test was collected, and measured values were extracted as percentage of predicted reference values. Lower and higher grade stenoses were defined by Cotton-Myer classification and median degree of stenosis. Median of detected stenoses was 73% (64%-85%), with 7 of 10 patients classified as Cotton-Myer grade 3. Lung function tests showed typical parameter shifts as known from obstructive pulmonary diseases (OPDs). Furthermore, statistical analyses showed a significant higher value of residual volume (RV)/total lung capacity (TLC) in patients with higher grade stenosis (P < .05), whereas forced expiratory volume in 1 second /vital capacity (FEV1/VC) did not show a significant difference in same subgroups. In conclusion, the elevation of RV/TLC with concomitant normal FEV1/VC in symptomatic patients could be used to demarcate rare UAS from common OPD. Moreover, RV-TLC ratio might be used to distinguish between low- and high-grade UAS. But further epidemiological studies will be necessary to validate these findings. Level of evidence: 4.

The distribution patterns of COMP and matrilin-3 in septal, alar and triangular cartilages of the human nose.

The biomechanical characteristics of septal cartilage depend strongly on the distinct extracellular matrix of cartilage tissue; therefore, it is essential that the components of this matrix are identified and understood. Cartilage oligomeric matrix protein (COMP) and matrilin-3 are localised in articular cartilage. This study was the first to examine all subtypes of mature human nasal cartilages (alar, triangular and septal) with specific attention to the distribution of COMP and matrilin-3. Three whole fresh-frozen noses from human donors were dissected, and exemplary biopsies were examined using histochemical staining (haematoxylin and eosin and Alcian blue) and immunohistochemistry (collagen II, COMP and matrilin-3). The following three zones within the nasal cartilage were identified: superficial, intermediate and central. COMP was detected as highest in the intermediate zones in all three subtypes of nasal cartilage, whereas matrilin-3 was detected with pericellular deposition mainly within septal cartilage predominantly in the superficial zones. The distinct staining patterns of COMP and matrilin-3 underscore the different functional roles of both proteins in nasal cartilage. According to the literature, COMP might be involved with collagen II in the formation of networks, whereas matrilin-3 is reported to prevent ossification or regulate mechanosensitivity. The predominant staining observed in septal cartilage suggests matrilin-3's modulatory role because of its presence in the osteochondral junctional zone and given that the biomechanical load in septal cartilage is different from that in alar or triangular cartilage. In conclusion, COMP and matrilin-3 were detected in mature human nasal cartilage but displayed different staining patterns that might be explained by the functional roles of the respective matrix protein; however, further research is necessary to identify and define the functional aspects of this morphological difference.

[Application of vacuum wound therapy with split thickness skin grafts in the head and neck area]. / Anwendung von Vakuum-Wundtherapie bei Spalthaut-Transplantaten im Kopf-Hals-Bereich.

OBJECTIVE: In vacuum wound therapy (VAC) a negative pressure can continuously clean effusions and enhance the formation of granulation tissue significantly. In visceral, trauma and burns surgery this technique is used frequently in critical wounds. In the head and neck area there is limited experience and publications. Especially in the combined use of split-thickness-skin grafts (STSG) and VAC there is no published evidence. MATERIAL AND METHODS: A retrospective database analysis was done and resulted in 36 single VAC therapies in 13 patients. They were treated between 2012 and 2017 in the Department of Otorhinolaryngology of the University Medical Center Ulm, Germany. A data analysis was performed relating to indications, diagnoses, comorbidities as well as the clinical course and outcome with special focus on STSG. RESULTS: Besides classical indications as pharyngo-cutaneous fistulas and troublesome would healing after flap surgery, 7 cases of VAC use with split-thickness skin grafts were identified. The median treatment duration was 11 days, the VAC dressing was changed twice in average, the median negative pressure was 70 mmHg. Wound closure was successful in 13/13 cases, in 7/13 cases wound closure was achieved by split-thickness skin graft with synchronous VAC therapy, 4/13 cases showed healing by secondary intention, in 2/13 cases a local or distant flap was used. CONCLUSIONS: We first describe the successful use of VAC therapy in combination with STSG in the head and neck area. This was effective in radiated patients and in critically ill patients with sepsis and necrotizing fasciitis.

Cartilage engineering in reconstructive surgery: auricular, nasal and tracheal engineering from a surgical perspective.

This review provides an update on cartilage tissue engineering with particular focus on the head and neck. It is aimed at scientists and clinicians who are interested in tissue engineering and its clinical applicability. Principal tissue engineering strategies are summarized in the first part of this review. In the second part, current clinical approaches to auricular, nasal and tracheal reconstruction are discussed from a surgical perspective. By this approach, the requirements for clinical applicability are outlined and new insight into relevant aims of research is given to accelerate the transfer from bench to bedside.