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Abstract Background Carbapenem-resistant Acinetobacter baumannii (CRAB) frequently causes both healthcare-associated infections and nosocomial outbreaks in burn medicine/plastic surgery and beyond. Owing to the high antibiotic resistance, infections are difficult to treat, and patient outcomes are often compromised. The environmental persistence capability of CRAB favors its transmission in hospitals. A comprehensive analysis and understanding of CRAB epidemiology and microbiology are essential for guiding management. Methods A three-year retrospective cohort study (2020–2022) was conducted in a German tertiary burn and plastic surgery center. In addition to epidemiological analyses, microbiological and molecular techniques, including whole-genome sequencing, were applied for the comprehensive examination of isolates from CRAB-positive patients. Results During the study period, eight CRAB cases were found, corresponding to an overall incidence of 0.2 CRAB cases per 100 cases and an incidence density of 0.35 CRAB cases per 1000 patient-days. Six cases (75%) were treated in the burn intensive care unit, and four cases (50%) acquired CRAB in the hospital. Molecular analyses comprising 74 isolates supported the epidemiologic assumption that hospital acquisitions occurred within two separate clusters. In one of these clusters, environmental CRAB contamination of anesthesia equipment may have enabled transmission. Furthermore, molecular diversity of CRAB isolates within patients was observed. Conclusions CRAB can pose a challenge in terms of infection prevention and control, especially if cases are clustered in time and space on a ward. Our study demonstrates that high-resolution phylogenetic analysis of several bacterial isolates from single patients can greatly aid in understanding transmission chains and helps to take precision control measures.

Intraoperative use of vasopressors in free flap surgeries is controversially debated. The predominant concern is that pedicle blood supply will decrease leading to post-operative complications. This study examined the role of intraoperative vasopressors, specifically norepinephrine, in free flap partial necrosis based on the patients’ comorbidities. We retrospectively analyzed 192 patients who received free flap treatment between 2006 and 2021 and were stratified based on vascular comorbidities. We assessed the role of intraoperative vasopressors using multivariate analysis. Patients who were administered vasopressors did not have a significantly higher risk of partial flap necrosis compared to patients who were not administered vasopressors (OR: 1.439, 95% CI: 0.618-3.348, p=0.399). Upon stratifying by vascular comorbidities, we found that patients with two or more vascular comorbidities who were administered vasopressors had a significantly higher risk of developing flap necrosis (OR: 3.882, 95% CI: 1.266-14.752, p=0.046), indicating that vasopressor use in patients with multiple vascular comorbidities is a risk factor for partial flap necrosis. To minimize the risk of flap marginal necrosis in patients with vascular comorbidities, we recommend limited use of vasopressors or minimizing the flap area to preserve vascularization.

The treatment of severe burn injuries, which occur particularly in the context of armed conflicts, is based on a multimodal treatment concept. In addition to complex intensive care therapy, the surgical reconstruction options of plastic surgery and typical antiseptic wound treatment are the main focuses. In recent years, atmospheric cold plasma therapy (ACPT) has also become established for topical, antiseptic wound treatment and for the optimization of re-epithelialization. This case report shows a successful treatment of extensive burn injuries using dermal skin substitute matrix and topical treatment with a large-area cold plasma device to control multi-resistant pathogen colonization. This case report illustrates the importance of ACPT in burn surgery. However, larger case series and randomized controlled trials in specialized centers are needed to assess its place in future clinical practice.

Abstract Introduction Hand injuries constitute up to 30% of the total cases treated in emergency departments. Over time, demographic changes, especially an aging population, and shifts in workplace safety regulations and healthcare policies have significantly impacted the landscape of hand trauma. This study aims to identify and analyze these evolving trends over nearly two decades. Methods In this retrospective, cross-sectional study, we investigated patients who were admitted to the high-volume regional hand trauma center of a university hospital between January 2007 and December 2022. We analyzed trends in patients’ demographics and annual alterations of injuries. For the comparative analysis, patients were divided into two groups based on the time of presentation: the early cohort (2007–2014) and the current cohort (2015–2022). Results A total of 14,414 patients were admitted to our emergency department within the study period. A significant annual increase in patient age was identified (R2 = 0.254, p = 0.047). The number of presentations increased annually by an average of 2% (p

SUMMARY: Introduction: Chest contouring or subcutaneous mastectomy (SCM) in female-to-male (FtM) transgender individuals is the primary surgery in the gender reassignment process. Many authors report high rates of postoperative bleeding in these patients and discuss a possible influence of preoperative hormone therapy. However, there is a lack of data on the analysis between different surgical techniques and postoperative bleeding risk. Materials and Methods: In this retrospective study, we included 22 FtM transgender individuals who underwent bilateral SCM using 4 different techniques (44 breasts) between June 2014 and September 2023. Postoperative complications regarding surgical techniques and patient demographics were collected and analyzed. Results: SCM with free nipple grafting was the most commonly used technique (n = 12, 54.5%). The mean operative time was 163.4 ± 49.2 minutes. There were no significant differences in operative time between the surgical techniques (p ≥ 0.20 in all cases). The rate of acute postoperative bleeding was 20.5% (n = 9). Acute postoperative bleeding occurred most frequently in patients who received a semi-circular incision for SCM. There was no significant difference in the rate of acute postoperative bleeding between the different surgical techniques. BMI, breast weight, and duration of surgery were not associated with the rate of acute complications (p > 0.17 in all cases). Conclusions: Less invasive SCM techniques in FtM transgender individuals are associated with higher postoperative bleeding risk.

Lymphocele formation is a rare complication after surgical procedures involving the mediastinum. While uncomplicated lymphoceles show high rates of spontaneous closure and are usually treated conservatively, surgical treatment might be required in cases with persistent or recurrent lymphoceles. We present the case of a 53-year-old male with reoccurring cervical swelling after two surgeries of the thoracic aorta. After 1.5 years, the swelling occurred for the first time and appeared for the next 2 years repeatedly without clinical or laboratory signs of infection. A cervical lymphocele was suspected, and the decision for surgical revision was made. Fibrin glue was applied to the potential leakage of the thoracic duct, and the cavity was filled with a free omental flap. This resulted in a complete regression of the swelling.

Background: E-cigarette abuse, also known as vaping, is a widespread habit. Recently, there have been increasing reports of explosions of these devices resulting in serious burn injuries, especially to the groin, hand, and face. Overheating rechargeable lithium-ion batteries are supposed to be the responsible mechanism, especially in low quality fabrications. Methods: In this single-center retrospective study, data of 46 patients are presented and analyzed. In addition to information on demographics, injury patterns, and treatment options, this is the first study investigating outcome after an average of 13 months via a standardized telephone interview of 31 patients (67%). Patients were specifically asked regarding their outcome, vaping habits, technical modifications to their devices and supply source. Results: Patients were mainly male (98.2%) with a median age of 36 years. Typical injury patterns included the groin region (n = 32; 69%), hands (n = 12; 25%) and face (n = 3; 7%). All patients underwent debridement, in nine cases hydrotherapeutically. 61% (n = 28) underwent consecutive tangential necrectomy and subsequent split thickness skin graft transplantation. Wound infection was observed in 18 patients (39%), with burn depth as a significant risk factor (p < 0.001). 91% of the followed-up patients were satisfied. Surprisingly, 38% were still using e-cigarettes. 42% (n = 13) reported manual modifications of their devices to prolong battery life or increasing smoke production. Conclusions: Injuries from exploding e-cigarettes can be serious and should be treated in a specialized burn center. E-cigarette explosions lead to characteristic injury patterns and often need surgical treatment. This should be made more public to reduce their use and keep people from modifying the devices. The counterintuitive and irrational observation of a high rate of abuse even after the injury underlines their addiction potential.

Background: Acquired factor XIII deficiency is an underestimated risk in patients with large surface burns, which potentially exposes these patients to prolonged bleeding and delayed wound healing if undetected. Methods: A retrospective matched-pair analysis of the burn registry of the Department of Plastic, Aesthetic, Hand, and Reconstructive Surgery of Hannover Medical School was performed from 2018 to 2023. Results: A total of 18 patients were included. Acquired factor XIII deficiency was not statistically significant correlated with age, sex, or body mass index. Patients who developed acquired factor XIII deficiency had a significantly longer hospital stay (72.8 days) compared with those in the matched group (46.4 days), although burn depths, total body surface area, and Abbreviated Burn Severity Index were not statistically correlated with factor XIII deficiency. Conclusions: Little is known about acquired factor XIII deficiency in patients with burns. Factor XIII supplementation may improve hemostasis, wound healing, and general outcome while reducing the patient's exposure to blood products.

Abstract Flap surgery is a common treatment for severe wounds and a major determinant of surgical outcome. Flap survival and healing depends on adaptation of the local flap vasculature. Using a novel and defined model of fasciocutaneous flap surgery, we demonstrate that the Notch ligand Delta-like 1 (Dll1), expressed in vascular endothelial cells, regulates flap arteriogenesis, inflammation and flap survival. Utilizing the stereotyped anatomy of dorsal skin arteries, ligation of the major vascular pedicle induced strong collateral vessel development by end-to-end anastomosis in wildtype mice, which supported flap perfusion recovery over time. In mice with heterozygous deletion of Dll1, collateral vessel formation was strongly impaired, resulting in aberrant vascularization and subsequent necrosis of the tissue. Furthermore, Dll1 deficient mice showed severe inflammation in the flap dominated by monocytes and macrophages. This process is controlled by endothelial Dll1 in vivo, since the results were recapitulated in mice with endothelial-specific deletion of Dll1. Thus, our model provides a platform to study vascular adaptation to flap surgery and molecular and cellular regulators influencing flap healing and survival.

Summary: The modified 5-item frailty index (mFI-5), as a measure of frailty and biological age, has been shown to be a reliable predictor of complications and mortality in a variety of surgical specialties. However, its role in burn care remains to be fully elucidated. We, therefore, correlated frailty with in-hospital mortality and complications after burn injury. The medical charts of all burn patients admitted between 2007 and 2020 who had ≥ 10 % of their total body surface area affected were retrospectively reviewed. Data on clinical, demographic, and outcome parameters were collected and evaluated, and mFI-5 was calculated on the basis of the data obtained. Univariate and multivariate regression analyses were used to investigate the association between mFI-5 and medical complications and in-hospital mortality. A total of 617 burn patients were included in this study. Increasing mFI-5 scores were significantly associated with increased in-hospital mortality (p < 0.0001), myocardial infarction (p = 0.03), sepsis (p = 0.005), urinary tract infections (p = 0.006), and perioperative blood transfusions (p = 0.0004). They were also associated with an increase in the length of hospital stay and the number of surgical procedures, albeit without statistical significance. An mFI-5 score of ≥ 2 was a significant predictor of sepsis (odds ratio [OR] = 2.08; 95% confidence interval [CI]: 1.03 to 3.95; p = 0.04), urinary tract infection (OR = 2.82; 95% CI: 1.47 to 5.19; p = 0.002), and perioperative blood transfusions (OR = 2.61; 95% CI: 1.61 to 4.25; p = 0.0001). Multivariate logistic regression analysis revealed that an mFI-5 score of ≥ 2 was not an independent risk factor for in-hospital mortality (OR = 1.44; 95% CI: 0.61 to 3.37; p = 0.40). mFI-5 is a significant risk factor for only a few select complications in the burn population. It is not a reliable predictor of in-hospital mortality. Therefore, its utility as a risk stratification tool in the burn unit may be limited.

Abstract Background Free flap design must fulfill different criteria to ensure functional and aesthetic reconstruction of different types of defects in different body areas. A four-dimensional planning concept was used including flap length, width, thickness and tissue composition. This study evaluates if body-mass-index (BMI) has a predictive value for flap design. Methods A prospective study including hospitalized patients in the Department of Plastic, Aesthetic, Hand and Reconstructive Surgery was conducted. Not taking into account the reason for admission, the patients were examined based on age, weight, height, BMI and sex. The areas of a potential harvest of free fasciocutaneous and perforator flaps were measured using ultrasound examination to determine the thickness of the subcutaneous layers and prove blood perfusion. Results Over the period of four months, a total of 101 patients (36 females and 65 males) were included in this study and gave written consent. No statistical significance regarding the demographic data such as age, sex and BMI could be identified. An average to high correlation between free flap thickness and BMI was shown for the thoracodorsal artery perforator (TDAP), anterior lateral thigh (ALT) and deep inferior epigastric perforator (DIEP) flap in both, male and female patients. Free flaps of distal body parts such as the interosseous posterior flap, showed a lower correlation. No correlation using the Pearson coefficient could be found for age and volume. Conclusion Our study demonstrated that the BMI is a predictive indicator that can be used in the preoperative planning of reconstructions using free flaps. Depending on the defect location, the BMI can be considered to predict the thickness of the free flap and may influence the surgeon’s choice. On the other hand, a lower correlation between BMI and flap thickness encourages the use of standard flaps if more volume is desired, as the DIEP flap might be sufficient even in normal-weight women. Flaps of distal body parts, such as the forearm or lower leg, are not prone to such predictions and require other selection criteria.

Abstract Aims Dupuytren’s contracture (DC) is a chronic debilitating fibroproliferative disorder. Common treatment options include collagenase clostridium histolyticum injections (CI), percutaneous needle fasciotomy (NF) and limited fasciectomy (LF). Superiority of one specific treatment remains controversial. This study aims to assess the short-term efficacy and safety of CI, NF, and LF for the treatment of DC. Methods We included randomized controlled trials of CI compared with placebo, NF and LF for patients with DC. PubMed, Embase and the Cochrane Library were searched from inception to August 2021. Contracture reduction rates in treated joints (within 0–5° of full extension within 30 days), relative reduction in total passive extension deficit (TPED), occurrence of one or more adverse events and number of treatment-related adverse events per patient were the outcomes of interest. The Cochrane risk-of-bias tool was employed for quality assessment of the studies. A network meta-analysis was performed using MetaXL. Results Nine studies met our inclusion criteria (n = 903). Overall, risk bias was mixed and mostly low. Short term TPED reduction achieved with LF was superior compared to CI and NF. Although CI achieved greater TPED reduction compared to NF, it was associated with the highest risk of overall adverse effects. The analyzed data was limited to a maximum three-year follow-up period and therefore insufficient for long-term outcome evaluation. Conclusions In DC, LF may be able to provide patients with severe disease, superior flexion contracture release postoperatively. CI is a valid treatment alternative to NF, however the higher risk of overall adverse effects must be considered. The quality-of-evidence is limited due to short-term follow-up periods and a lack of standardized definitions of complications and adverse events.

Traumatic finger injuries are very common in emergency medicine. When patients present with finger injuries, there is often damage to the vascular nerve bundles, which requires subsequent reconstruction. It is unknown if repairing a unilaterally injured artery affects patients’ recovery in a well-perfused finger. This retrospective cohort study compares the clinical outcomes of 11 patients with one-vessel supply (mean age 48.3 years; 7 males, 4 females) to 14 patients with two-vessel supply (mean age 44.5 years; 8 males, 6 females). The patient outcomes were assessed using patient questionnaires (Disabilities of Arm, Shoulder, and Hand (DASH), European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L), and EuroQol visual analog scale (EQ-VAS)) and a clinical examination of hand function and imaging of circulatory efficiency. No significant changes were observed in the DASH, EQ-5D-5L, and EQ-VAS questionnaires. Clinical evaluation of hand function, measured by cold sensitivity, two-point discrimination, pain numerical analog scale, and grip strength also revealed no significant differences between cohorts. Blood flow measurements using thermal imaging revealed no effects on circulation in the affected digit. Collectively, the study finds reconstruction is not absolutely necessary when there is one intact digital artery as it is sufficient for healing and functional outcomes. We recommend finger artery reconstruction when both digital arteries are injured or if an immediate tension-free suture is possible.

Abstract Background Hand injuries are common in sports and associated with high dropout rates and costs. Hence, efforts should strive for further risk prevention measures in order to increase safety in sports. This implies knowledge of sports injury risk profiles. So far, major surveillance programs exist mainly in Anglo-American countries, reflecting the specific concerns of sports in this part of the world. Data on sports injuries within Europe are scarce. As sports behaviour appears to vary demographically, we hypothesised that risk injury profiles differ as well. Methods To assess whether the described sports injuries of the hand are applicable to the German population, we performed a five-year retrospective, single-centre analysis of sports-related hand injuries, using data from the Enterprise Clinical Research Data Warehouse of the Hannover Medical School. Results Notable differences in comparison to other data were observed. Ball sports, cycling and equestrian sports caused most of the recorded hand injuries, which were predominantly fractures of the wrist and hand. Hand injuries in equestrian sports were associated with significantly higher operation and hospitalisation rates as well as a significantly longer inpatient treatment. Conclusion Risk profiles for sports-related hand injuries appear to differ not only in terms of age- and sex, but also geographically. Nation- and Europe-wide hand trauma registries as well as a broad registry participation are necessary in order to accurately assess the risk patterns in Europe; henceforth reducing hand injuries and their sequelae.

Abstract Background Limb loss has a drastic impact on a patient’s life. Severe trauma to the extremities is common in current military conflicts. Among other aspects, “life before limb” damage control surgery hinders immediate replantation within the short post-traumatic timeframe, which is limited in part by the ischemic time for successful replantation. Ex vivo limb perfusion is currently being researched in animal models and shows promising results for its application in human limb replantation and allotransplantation. Presentation of the hypothesis The current lack of replantation possibilities in military operations with high rates of amputation can be addressed with the development of a portable ex vivo limb perfusion device, as there are several opportunities present with the introduction of this technique on the horizon. We hypothesize that ex vivo limb perfusion will enable overcoming the critical ischemic time, provide surgical opportunities such as preparation of the stump and limb, allow for spare-part surgery, enable rigorous antibiotic treatment of the limb, reduce ischemia-reperfusion injuries, enable a tissue function assessment before replantation, and enable the development of large limb transplant programs. Testing the hypothesis Data from in vivo studies in porcine models are limited by the relatively short perfusion time of 24 h. In the military setting, notably longer perfusion times need to be realized. Therefore, future animal studies must focus especially on long-term perfusion, since this represents the military setting, considering the time for stabilization of the patient until evacuation to a tertiary treatment center. Implications of the hypothesis The development and clinical introduction of ex vivo limb perfusion in the military setting could lead to a drastic reduction in the number of limb amputations among service members. Ex vivo limb perfusion enables replantation surgery in Role 4 facilities and changes the clinical setting from a highly urgent, life-threatening situation to a highly methodical, well-prepared starting point for optimal treatment of the wounded service member. With its introduction, the principle of “life before limb” will change to “life before limb before elective replantation/allotransplantation after ex vivo limb perfusion”.

Intraneural ganglia are benign mucinous cysts located within the epineurium of a peripheral nerve. The pathogenesis and formation of intraneural ganglia are controversial. The main theories described in the literature are of degenerative, synovial or de novo occurrence. We present the case of a 14-year-old boy who presented in our outpatient clinic with a complaint of interdigital neuralgia between hallux and second toe, as well as left foot drop. MRI examination showed a hyperintense cystic distension of the common peroneal nerve measuring 130 mm × 5 mm extending from the poplitea to the anterior compartment of the leg. We performed microscopic decompression and neurolysis surgery. The cyst showed a sac-like distension at its distal end with connection to the tibiofibular joint and was resected. After 8 weeks, postoperatively, the boy claimed to be pain-free and slight recovery of the superficial peroneal nerve was noticed. At 6 months postoperative, the patient showed a continuous improvement of motor function, demonstrating foot eversion with 3/5 muscle strength and foot extension with 2/5 muscle strength. Intraneural ganglia reported for pediatric patients represent a very rare entity. To the best of our knowledge, less than 15 cases have been described within the English-speaking literature.

After spinal cord injury, gliomesenchymal scaring inhibits axonal regeneration as a physical barrier. In peripheral nerve injuries, native spider silk was shown to be an effective scaffold to facilitate axonal re-growth and nerve regeneration. This study tested a two-composite scaffold made of longitudinally oriented native spider silk containing a Haemocomplettan fibrin sheath to bridge lesions in the spinal cord and enhance axonal sprouting. In vitro cultivation of neuronal cells on spider silk and fibrin revealed no cytotoxicity of the scaffold components. When spinal cord tissue was cultured on spider silk that was reeled around a metal frame, migration of different cell types, including neurons and neural stem cells, was observed. The scaffold was implanted into spinal cord lesions of four Wistar rats to evaluate the physical stress caused on the animals and examine the bridging potential for axonal sprouting and spinal cord regeneration. However, the implantation in-vivo resulted in a granulomatous foreign body reaction. Spider silk might be responsible for the strong immune response. Thus, the immune response to native spider silk seems to be stronger in the central nervous system than it is known to be in the peripheral body complicating the application of native spider silk in spinal cord injury treatment.

Ray and proximal phalanx amputations present valid surgical options for the management of severe traumatic finger injuries. However, among these procedures, the superior one for optimal functionality and quality of life for patients still remains unknown. This retrospective cohort study compares the postoperative effects of each amputation type to provide objective evidence and to create a paradigm for clinical decision-making. A total of forty patients who had received either ray or proximal phalanx-level amputations reported on their functional outcomes using a combination of questionnaires and clinical testing. We found a decreased overall DASH score following ray amputation. Particularly, Part A and Part C of the DASH questionnaire were consistently lower compared with amputation at the proximal phalanx. Pain measurements in the affected hand were also significantly decreased during work and at rest in ray amputation patients, and they reported decreased cold sensitivity. Range of motion and grip strength were lower in ray amputations, which is an important preoperative consideration. We found no significant differences in reported health condition, evaluated according to the EQ-5D-5L, and blood circulation in the affected hand. We present an algorithm for clinical decision-making based on patients’ preferences to personalize treatment.

Functional construction of tissue-engineered vessels as an alternative to autologous vascular grafts has been shown to be feasible, however the proliferation of seeded smooth-muscle cells remains a limiting factor. We employed a rotating bioreactor system to improve myoblast cell differentiation on a spider silk scaffold for tissue-engineered vessel construction. C2C12 myofibroblast cells were seeded on the surface of spider silk scaffold constructs and cultivated in a rotating bioreactor system with a continuous rotation speed (1 rpm). Cell function, cell growth and morphological structure and expression of biomarkers were analyzed using scanning electron microscopy, the LIVE/DEAD® assay, Western blot and quantitative real-time PCR analyses. A dense myofibroblast cell sheet could be developed which resembled native blood vessel muscular tissue in morphological structure and in function. Bioreactor perfusion positively affected cell morphology, and increased cell viability and cell differentiation. The expression of desmin, MYF5 and MEF2D surged as an indication of myoblast differentiation. Cell-seeded scaffolds showed a tear-down at 18 N when strained at a set speed (20 mm min−1). Spider silk scaffolds appear to offer a reliable basis for engineered vascular constructs and rotating bioreactor cultivation may be considered an effective alternative to complex bioreactor setups to improve cell viability and biology.

Complex and chronic wounds represent a highly prevalent condition worldwide that requires a multimodal and interdisciplinary treatment approach to achieve good functional and aesthetic outcomes. Due to increasing costs of health care, an aging population and an increase in difficult-to-treat microbial colonization of wounds, complex wounds will become a substantial clinical, social and economic challenge in the upcoming years. In plastic reconstructive surgery, a variety of dermal skin substitutes have been established for clinical use. Since its approval as a dermal skin substitute in Germany, NovoSorb® Biodegradable Temporising Matrix (BTM) has become a valuable therapeutic option for the treatment of full-thickness wound defects. The clinical data published to date are limited to case reports and small-scale case series with the main focus on single wounds. The aim of this single-center study was a retrospective analysis of our own patient collective that has received treatment with BTM for complex wounds. Overall, BTM showed to be a reliable and versatile reconstructive option, especially for patients with multiple co-morbidities and microbiologically colonized wounds. Although the preliminary findings have produced promising results, further investigation and research are warranted regarding long-term outcomes and additional clinical applications.

Breast carcinoma is one of the most common malignant tumors in women. In cases of hormone-sensitive cells, tamoxifen as an anti-estrogenic substance is a first line medication in the adjuvant setting. The spectrum of autologous breast reconstructions ranges from fat infiltrations to complex microsurgical procedures. The influence of adipose-derived stem cells (ASC) on the tumor bed and a possibly increased recurrence rate as a result are critically discussed. In addition, there is currently no conclusive recommendation regarding tamoxifen-treated patients and autologous fat infiltrations. The aim of the present study was to investigate the effect of tamoxifen on the gene expression of a variety of genes involved in tumorigenesis, cell growth and transformation. Mammary epithelial cell line and mammary carcinoma cell lines were treated with tamoxifen in vitro as well as co-cultured with ASC. Gene expression was quantified by PCR arrays and showed increased expression in the mammary carcinoma cell lines with increasing time of treatment and concentration of tamoxifen. The data presented can be considered as an addition to the controversial discussion on the relationship between ASC and breast carcinoma cells. Further studies are needed to quantify the in vivo interaction of ASC and mammary carcinoma cells and to conclusively assess the impact of tamoxifen in reconstructive cases with fat grafting.

Abstract Background Scaphoid fractures are the most common carpal fractures. They often need to be treated by surgery, where the use of a compression screw is the globally accepted gold standard. Surgeons may choose between different implant materials including titanium alloys, which remain in the body or are removed after healing. An alternative are biodegradable magnesium-based implants. Properties of magnesium alloys include high stability, osteoconductivity, potential reduction of infections and few artifacts in magnetic resonance imaging (MRI). The aim of this trial is to demonstrate non-inferiority of magnesium-based compression screws compared with titanium Herbert screws for scaphoid fractures. Methods The trial is designed as a multicenter, blinded observer, randomized controlled parallel two-group post market trial. Approximately 190 patients will be randomized (1:1) with stratification by center either to titanium or magnesium-based compression screws. Follow-up is 1 year per patient. Surgical procedures and aftercare will be performed according to the German treatment guideline for scaphoid fractures. The first primary endpoint is the patient-rated wrist evaluation (PRWE) score after 6 months. The second primary endpoint is a composite safety endpoint including bone union until 6 months, no adverse device effect (ADE) during surgery or wound healing and no serious ADE or reoperation within 1 year. The third primary endpoint is the difference in change MRI artifacts over time. Non-inferiority will be investigated for primary endpoints 1 (t-test confidence interval) and 2 (Wilson’s score interval) using both the full analysis set (FAS) and the per protocol population at the one-sided 2.5% test-level. Superiority of magnesium over titanium screws will be established using the FAS at the two-sided 5% test-level (Welch test) only if non-inferiority has been established for both primary endpoints. Secondary endpoints include quality of life. Discussion This study will inform care providers whether biodegradable magnesium-based implants are non-inferior to standard titanium Herbert screws for the treatment of scaphoid fractures in terms of wrist function and safety. Furthermore, superiority of magnesium-based implants may be demonstrated using MRI, which is used as surrogate endpoint for screw degradation. Trial registration DRKS, DRKS00013368. Registered Dec 04, 2017.

Summary: Background: Despite the obvious advantages, face transplantation requires strict patient selection to guarantee optimal outcomes. Therefore, it is not suitable for all patients with severe facial disfigurements. Simultaneously, conventional plastic and reconstructive surgery techniques, as well as medical spa techniques, have evolved, offering minimally invasive treatment of complex deformities. Methods: The entire face of a young woman was severely disfigured because of a mistreated juvenile acne, with severe ectropions, oral incompetence and substantial midfacial tissue defect. We are describing the reconstruction with a combination of conventional reconstructive methods, such as scar release, skin transplantation, local flaps, medical needling and lipofilling. Results: Oral competence, unhindered breathing and adequate lid closure was achieved. Previously unable to participate in social life in any meaningful way, our patient was able to reintegrate fully and take a job. Conclusion: For selected patients, combined, invasive and non-invasive conventional techniques can provide satisfying outcomes in complex facial reconstruction. Modern regenerative approaches such as lipofilling and medical needling should be considered as integral parts of treatment strategies. Keywords: Face transplantation, Facial disfigurement, Vascularized composite allotransplantation

Autologous fat grafting represents an attractive source for tissue engineering applications in the field of reconstructive medicine. However, in adipogenic differentiation protocols for human adipose-derived stem cells, the concentration of glucose and insulin varies considerably. With the intent to gain maximum tissue augmentation, we focused on the late phase of adipogenesis. In this study, we modified the differentiation protocol for adipose-derived stem cells by prolongation of the induction period and the application highly concentrated glucose and insulin. Human adipose-derived stem cells were isolated from subcutaneous depots and differentiated in a standard induction medium for the first two weeks, followed by two weeks with varying glucose and insulin concentrations. Morphological changes assessed using Oil-Red-O staining were examined for corresponding alterations in the expression of the adipogenic markers peroxisome proliferator-activated receptor gamma (PPARγ) and lipoprotein lipase (LPL). Furthermore, glucose and lactate levels in conditioned media were monitored over the period of differentiation. We found high-glucose media increasing the level of lipid accumulation and the size of single droplets whereas insulin significantly showed a dose-dependent negative effect on fat storage. However, whereas high glucose stimulated PPARγ transcription, expression levels in insulin-treated cells remained constant. Results permit assumptions that a high-glucose medium intensifies the degree of differentiation in mature adipocytes providing conditions to promote graft volume while we have identified highly concentrated insulin treatment as an inhibitor of lipid storage in the late adipogenic differentiation.

Scars can lead to aesthetic and functional impairments. The treatment of scars requires meticulous planning and an individually adapted therapeutic strategy. A conceptual algorithm for scar treatment makes everyday clinical work easier for the practitioner and offers more safety for the patient. Based on a retrospective analysis of 1427 patients who presented for treatment of a variety of scars, we developed an algorithm for scar management and treatment. The treatments are presented using case descriptions. Additionally, an electronic search of MEDLINE, EMBASE, and ClinicalTrials.gov databases was performed utilizing combinations of relevant medical subject headings for “scar treatment”, “hypertrophic scar treatment” and “keloid treatment”. Reference lists of relevant articles and reviews were hand-searched for additional reports. Observed outcomes included: conservative scar therapy, minimally invasive scar therapy, and surgical scar therapy using local, regional and free flaps. With this work, we provide an algorithm for safe scar treatment. For better understanding, we have described a clinical case for each algorithm modality.

Objectives: In addition to its use as a volume filler, fat grafting may have a potential role in wound healing based on the concentration of growth factors in the lipoaspirate. In this study, we compare the quantitative and qualitative concentration of the various growth factors and adipokines using the Shippert or the Coleman techniques to prepare the lipoaspirate. Methods: We measured leptin, adiponectin and the growth factors, i.e., acidic fibroblast growth factor (aFGF), basic FGF (bFGF), keratinocyte growth factor (KGF), bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) by ELISA in solid and liquid fractions obtained with both techniques in human fat obtained with Coleman technique and Shippert technique. Results: All of these peptides, except BMP-2, were detected in relevant quantities in the solid fraction. The Coleman but not the Shippert technique resulted in statistically higher adiponectin concentrations in the solid tissue fraction. The other four growth factors occurred in significantly higher concentrations in the solid fractions compared to the liquid fractions, independent of the processing technique. Conclusion: In summary, we demonstrated that KGF, aFGF, bFGF and VEGF, as well as leptin and adiponectin, are contained in fat suspensions obtained by liposuction and in the supernatant. Only the concentration of adiponectin was in the range reported to contribute to wound healing.

Background:. Following liposuction, abdominoplasty is the most frequent body-contouring intervention in the world. The transection of small blood vessels in large areas and subsequent bleeding is a viable risk during this procedure. The resulting microvascular bleedings should be stopped thoroughly to reduce the probability of related complications. In this prospective, monocentric, randomized study, the efficacy of the polysaccharide-based hemostat 4DryField PH (4DF) (PlanTec Medical, Lueneburg, Germany) is examined in classic abdominoplasty and lower body lift after Lockwood. Methods:. For this prospective, monocentric, randomized study, 40 patients underwent surgery for both interventions. Twenty patients received an abdominoplasty, and 20 patients underwent a body lift. In each group, 10 patients have been treated with 4DF, whereas 10 have been served as the untreated control group. Results:. 4DF had neither a beneficial nor a negative effect on necessity of drainages, drainage volume and duration, length of hospital stay or frequency of postoperative seromas, wound healing disturbances, and infections, independent of surgical intervention. Patients in the 4DF group, however, had more individual risk factors, and required extended surgical interventions that might mask primary outcome results. Conclusions:. This is the first prospective, monocentric, randomized study on 4DF in body-contouring surgery. The use of 4DF did not lead to a better postoperative outcome regarding hemostasis and lymphostasis. Potential benefits need further evaluation in high-volume studies.

Due to groundbreaking and pioneering developments in the last century, significant improvements in the care of burn patients have been achieved. In addition to the still valid therapeutic standard of autologous split-thickness skin grafting, various commercially available skin substitutes are currently available. Significant progress in the field of tissue engineering has led to the development of promising therapeutic approaches. However, scientific advances in the field of allografting and transplant immunology are of great importance. The achievement of various milestones over the past decades has provided thought-provoking impulses in the field of skin allotransplantation. Thus, biologically viable skin allotransplantation is still not a part of the clinical routine. The purpose of this article is to review the achievements in burn surgery with regards to skin allotransplantation in recent years.

Even though the administration of chemotherapeutic agents such as erlotinib is clinically established for the treatment of breast cancer, its efficiency and the therapy outcome can be greatly improved using RNA interference (RNAi) mechanisms for a combinational therapy. However, the cellular uptake of bare small interfering RNA (siRNA) is insufficient and its fast degradation in the bloodstream leads to a lacking delivery and no suitable accumulation of siRNA inside the target tissues. To address these problems, non-ionic surfactant vesicles (niosomes) were used as a nanocarrier platform to encapsulate Lifeguard (LFG)-specific siRNA inside the hydrophilic core. A preceding entrapment of superparamagnetic iron-oxide nanoparticles (FexOy-NPs) inside the niosomal bilayer structure was achieved in order to enhance the cellular uptake via an external magnetic manipulation. After verifying a highly effective entrapment of the siRNA, the resulting hybrid niosomes were administered to BT-474 cells in a combinational therapy with either erlotinib or trastuzumab and monitored regarding the induced apoptosis. The obtained results demonstrated that the nanocarrier successfully caused a downregulation of the LFG gene in BT-474 cells, which led to an increased efficacy of the chemotherapeutics compared to plainly added siRNA. Especially the application of an external magnetic field enhanced the internalization of siRNA, therefore increasing the activation of apoptotic signaling pathways. Considering the improved therapy outcome as well as the high encapsulation efficiency, the formulated hybrid niosomes meet the requirements for a cost-effective commercialization and can be considered as a promising candidate for future siRNA delivery agents.

Tendon injuries still pose a challenge to reconstructive surgeons. Tendon tissue is a bradytrophic tissue and has a poor tendency to heal. Autologous tendon grafts are, therefore, still the gold standard in restorative operations but are associated with significant donor side morbidity. The experimental approach of the present study focused on the use of the biomaterial spider silk as a biocompatible and very stable carrier matrix in combination with a collagen type I hydrogel and adipose-derived stromal cells. The constructs were differentiated by axial strain to tendon-like tissue using a custom-made bioreactor. Macroscopically, tendon-like tissue could be detected which histologically showed high cell vitality even in long-term cultivation. In addition, cell morphology comparable to tenocytes could be detected in the bioreactor-stimulated tendon-like constructs compared to the controls. Immunohistochemically, tendon tissue-specific markers could be detected. Therefore, the developed tendon-like construct represents a promising approach towards patient specific tendon reconstruction, but further studies are needed.

Like other urodela amphibians, axolotls are able to regenerate lost appendages, even as adults, rendering them unique among higher vertebrates. In reaction to the severe trauma of a lost limb, apoptosis seems to be primarily implicated in the removal of injured cells and tissue homeostasis. Little, however, is known about apoptotic pathways and control mechanisms. Therefore, here we provide additional information regarding the mechanisms of tissue degradation. Expression patterns of Bcl-2 family members were analyzed using reverse transcriptase-PCR, western blotting and immunofluorescence. In our study, we identified ten putative axolotl orthologs of the Bcl-2 family. We demonstrated that BH3-only proteins are differentially expressed in some axolotl organs, while they are expressed broadly in tail composite tissue and limb regeneration blastema. The importance of Bcl-2 family members is also indicated by detecting the expression of proapoptotic protein Bak in spatial congruence to apoptosis in the early stages of limb regeneration, while Bcl-2 expression was slightly modified. In conclusion, we demonstrate that Bcl-2 family members are conserved in the axolotl and might be involved in the tissue degradation processes that occur during limb regeneration.

Skin transplantation, especially in burn patients, is still challenging because surgeons are faced with limited disposability of autologous donor side material. The in vitro culture of keratinocytes has become an important reconstructive option. However, only non-immunogenic allogenic keratinocytes offer the opportunity to develop a skin graft that can overcome rejection. The purpose of the study was to develop targeted gene modification of keratinocytes in order to reduce immunogenicity for the use as allogenic transplantable skin graft by decreasing the expression of MHC class I. To reduce MHC class I expression, viral vectors containing the US11 gene of human cytomegalovirus were generated and tested on their functionality using Western blotting, indirect immunofluorescence staining, and flow cytometry. Transfected keratinocytes were seeded on commercially available bovine collagen-elastin matrices and further cultured for histological and cell survival assays. Results showed transient down-regulation of MHC class I after 24 h post-transfection, with recovery of MHC class I expression after 48 h. Histological assessments showed long-term cell survival as well as histological patterns comparable to epidermal layers of healthy human skin. The data postulates the potential application of US11 transfected keratinocytes as an approach towards an immune-privileged skin substitute. Nevertheless, further studies and data are needed.

New skin substitutes for burn medicine or reconstructive surgery pose an important issue in plastic surgery. Matriderm® is a clinically approved three-dimensional bovine collagen-elastin matrix which is already used as a dermal substitute of full thickness burn wounds. The drawback of an avital matrix is the limited integration in full thickness skin defects, depending on the defect size. To further optimize this process, Matriderm® has also been studied as a matrix for tissue engineering of skin albeit long-term cultivation of the matrix with cells has been difficult. Cells have generally been seeded onto the matrix with high cell loss and minimal time-consuming migration. Here we developed a cell seeded skin equivalent after microtransfer of cells directly into the matrix. First, cells were cultured, and microinjected into Matriderm®. Then, cell viability in the matrix was determined by histology in vitro. As a next step, the skin substitute was applied in vivo into a full thickness rodent wound model. The wound coverage and healing was observed over a period of two weeks followed by histological examination assessing cell viability, proliferation and integration into the host. Viable and proliferating cells could be found throughout the entire matrix. The presented skin substitute resembles healthy skin in morphology and integrity. Based on this study, future investigations are planned to examine behaviour of epidermal stem cells injected into a collagen-elastin matrix under the aspects of establishment of stem cell niches and differentiation.

Nerve reconstruction of extended nerve defect injuries still remains challenging with respect to therapeutic options. The gold standard in nerve surgery is the autologous nerve graft. Due to the limitation of adequate donor nerves, surgical alternatives are needed. Nerve grafts made out of either natural or artificial materials represent this alternative. Several biomaterials are being explored and preclinical and clinical applications are ongoing. Unfortunately, nerve conduits with successful enhancement of axonal regeneration for nerve defects measuring over 4.0 cm are sparse and no conduits are available for nerve defects extending to 10.0 cm. In this study, spider silk nerve conduits seeded with Schwann cells were investigated for in vitro regeneration on defects measuring 4.0 cm, 10.0 cm and 15.0 cm in length. Schwann cells (SCs) were isolated, cultured and purified. Cell purity was determined by immunofluorescence. Nerve grafts were constructed out of spider silk from Nephila edulis and decellularized ovine vessels. Finally, spider silk implants were seeded with purified Schwann cells. Cell attachment was observed within the first hour. After 7 and 21 days of culture, immunofluorescence for viability and determination of Schwann cell proliferation and migration throughout the conduits was performed. Analyses revealed that SCs maintained viable (>95%) throughout the conduits independent of construct length. SC proliferation on the spider silk was determined from day 7 to day 21 with a proliferation index of 49.42% arithmetically averaged over all conduits. This indicates that spider silk nerve conduits represent a favorable environment for SC attachment, proliferation and distribution over a distance of least 15.0 cm in vitro. Thus spider silk nerve implants are a highly adequate biomaterial for nerve reconstruction.

Background: Plastic and reconstructive surgeons are commonly faced with chronic ulcerations and consecutive wound infections of the feet as complications in patients with diabetes and/or peripheral arterial occlusive disease (PAOD). Microcirculatory changes seem to play an important role. However, the evaluation of functional changes in the soft tissue microcirculation at the plantar foot using combined Laser-Doppler and Photospectrometry System has not yet been performed in patients with DM or PAOD. Methods: A prospective, controlled cohort study was designed consisting of a total of 107 subjects allocated to 1 of 3 groups—group A: healthy subjects (57% males, 63.3 y); group B: patients with diabetes mellitus (DM) (53% males, 59.4 y); and group C: patients with PAOD (81% males, 66.1 y). Microcirculatory data were assessed using a combined Laser-Doppler and Photospectrometry System. Results: Global cutaneous oxygen saturation microcirculation at the plantar foot of healthy individuals was 8.4% higher than in patients with DM and 8.1% higher than in patients with PAOD (both P = 0.033). Patients with diabetes did not show significant differences in global cutaneous blood flow when compared with either healthy subjects or patients suffering from PAOD. Conclusions: Functional microcirculation at the plantar foot differs between healthy subjects and patients suffering from diabetes or PAOD of the same age. Patients with either diabetes or PAOD demonstrate deteriorated cutaneous oxygen saturation with equivalent blood perfusion at the plantar foot. More clinical studies have to be conducted to evaluate therapeutical methods that might ameliorate cutaneous oxygen saturation within diabetic foot disease and PAOD.

Advanced strategies in reconstructive microsurgery and especially free tissue transfer with advanced microvascular techniques have been routinely applied and continously refined for more than three decades in day-to-day clinical work. Bearing in mind the success rates of more than 95%, the value of these techniques in patient care and comfort (one-step reconstruction of even the most complex tissue defects) cannot be underestimated. However, anticoagulative protocols and practices are far from general acceptance and – most importantly – lack the benchmark of evidence basis while the reconstructive and microsurgical methods are mostly standardized. Therefore, the aim of our work was to review the actual literature and synoptically lay out the mechanisms of action of the plethora of anticoagulative substances. The pharmacologic prevention and the surgical intervention of thrombembolic events represent an established and essential part of microsurgery. The high success rates of microvascular free tissue transfer as of today are due to treatment of patients in reconstructive centers where proper patient selection, excellent microsurgical technique, tissue transfer to adequate recipient vessels, and early anastomotic revision in case of thrombosis is provided. Whether the choice of antithrombotic agents is a factor of success remains still unclear. Undoubtedly however the lack of microsurgical experience and bad technique can never be compensated by any regimen of antithrombotic therapy. All the more, the development of consistent standards and algorithms in reconstructive microsurgery is absolutely essential to optimize clinical outcomes and increase multicentric and international comparability of postoperative results and complications.

Strategies for improvement of nerve regeneration and optimal conditions to prevent Schwann cell (SC) loss within a nerve transplant procedure are critical. The purpose of this study was to examine SC viability, which plays an important role in peripheral nerve regeneration, under various incubation conditions up to three hours. To address this issue, Schwann cell metabolic activity was determined using different independent test methods. The following experimental conditions were compared: SCs prepared from nerves were incubated in (1) isotonic saline solution (2) Dulbecco's modified Eagles medium as used for cell culturing, (3) Hannover bioreactor medium, and (4) Leibovitz's medium. SC metabolic activity of excised rat sciatic nerve was determined at 4°C, 18°C, and 37°C over 3 hrs. The results indicate that SC activity was optimized by the usage of Leibovitz's medium or HBRM at 37°C. Greater SC viability at the time of surgical nerve grafting could contribute to improved axonal regeneration and remyelination after nerve transplantation, and thus more successful functional recovery.

Traumatic events, such as work place trauma or motor vehicle accident violence, result in a significant number of severe peripheral nerve lesions, including nerve crush and nerve disruption defects. Transplantation of myelin-forming cells, such as Schwann cells (SCs) or olfactory ensheathing cells (OECs), may be beneficial to the regenerative process because the applied cells could mediate neurotrophic and neuroprotective effects by secretion of chemokines. Moreover, myelin-forming cells are capable of bridging the repair site by establishing an environment permissive to axonal regeneration. The cell types that are subject to intense investigation include SCs and OECs either derived from the olfactory bulb or the olfactory mucosa, stromal cells from bone marrow (mesenchymal stem cells, MSCs), and adipose tissue-derived cells. OECs reside in the peripheral and central nervous system and have been suggested to display unique regenerative properties. However, so far OECs were mainly used in experimental studies to foster central regeneration and it was not until recently that their regeneration-promoting activity for the peripheral nervous system was recognized. In the present review, we summarize recent experimental evidence regarding the regenerative effects of OECs applied to the peripheral nervous system that may be relevant to design novel autologous cell transplantation therapies.

The Fas ligand/Fas interaction plays an important role in the regulation of immune responses. Allografted cells undergo Fas-mediated apoptosis induced by CD8+ T cells. Our objective was to prevent human keratinocytes from immunologically induced apoptosis. We focused on three proteins with inhibitory function on Fas-mediated apoptosis. Human keratinocytes were transfected with either Flip, Faim, or Lifeguard (LFG). The treatment proved to be practicable and efficient. The recombinant keratinocytes with expression of our target proteins were cocultured with CD8+ T cells and the apoptotic activity was then evaluated. Activation of caspase-8 was detectable in control but not in the recombinant cells. Quantitative analysis revealed significant induction of T-cell-induced apoptosis in nontransfected keratinocytes (p = 0.04, n = 12) but not in Flip (p = 0.66), Faim (p = 0.42), or LFG (p = 0.44) expressing cells. Our results suggest that heterotopic expression of antiapoptotic proteins can induce the resistance of keratinocytes to a major mechanism of rejection.