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An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

With every hospital admission, a vast amount of data is collected from every patient. Big data can help in data mining and processing of this volume of data. The goal of this study is to investigate the potential of big data analyses by analyzing clinically relevant data from the immediate postoperative phase using big data mining techniques. A second aim is to understand the importance of different postoperative parameters. We analyzed all data generated during the admission of 739 women undergoing a free DIEAP flap breast reconstruction. The patients' complete midcare nursing report, laboratory data, operative reports and drug schedule were examined (7,405,359 data points). The duration of anesthesia does not predict the need for revision. Low Red Blood cell Counts (3.53 × 106/µL versus 3.79 × 106/µL, p < 0.001) and a low MAP (MAP = 73.37 versus 76.62; p < 0.001) postoperatively are correlated with significantly more revisions. Different drugs (asthma/COPD medication, Butyrophenones) can also play a significant role in the success of the free flap. In a world that is becoming more data driven, there is a clear need for electronic medical records which are easy to use for the practitioner, nursing staff, and the researcher. Very large datasets can be used, and big data analysis allows a relatively easy and fast interpretation all this information. [ABSTRACT FROM AUTHOR]

Non-invasive scar management typically involves pressure therapy, hydration with silicones or moisturizers, and UV protection. Moisture loss from scars can lead to hypertrophic scar formation. Pressure therapy reduces blood flow, fibroblast activity, and transforming growth factor beta 1 (TGF-β1) release. This study examined various moisturizers and liquid silicone gel's impact on microcirculation. 40 volunteers participated in a study where superficial abrasions were created to induce trans epidermal water loss (TEWL). Five moisturizers (TEDRA®, TEDRA® NT1, TEDRA® NT3, Alhydran®, Lipikar®) and BAP Scar Care® silicone gel were tested. TEWL, hydration, and blood flow were measured up to 4 h post-application. Results showed that silicone had the least impact on occlusion and hydration. Alhydran® reduced blood flow the most, while Lipikar® increased it the most. TEDRA® NT1 had reduced flow compared to TEDRA® and TEDRA® NT3. All TEDRA® products exhibited high hydration, and all but silicone showed good occlusion. Moisturizers influenced skin microcirculation, with some causing decrease, while others increased flow. However, the clinical impact on scarring remains unclear compared to the evident effects of hydration and occlusion. More research is necessary to study moisturizers alone and with pressure therapy on scars, along with potential adverse effects of increased microcirculation on scars. [ABSTRACT FROM AUTHOR]

Hypertrophic scarring is a deviate occurrence after wound closure and is a common burn sequela. The mainstay of scar treatment consists of a trifold approach: hydration, UV-protection and the use of pressure garments with or without extra paddings or inlays to provide additional pressure. Pressure therapy has been reported to induce a state of hypoxia and to reduce the expression pattern of transforming growth factor-β1 (TGF-β1), therefore limiting the activity of fibroblasts. However, pressure therapy is said to be largely based on empirical evidence and a lot of controversy concerning the effectiveness still prevails. Many variables influencing its effectivity, such as adherence to treatment, wear time, wash frequency, number of available pressure garment sets and amount of pressure remain only partially understood. This systematic review aims to give a complete and comprehensive overview of the currently available clinical evidence of pressure therapy. A systematic search for articles concerning the use of pressure therapy in the treatment and prevention of scars was performed in 3 different databases (Pubmed, Embase, and Cochrane library) according to the PRISMA statement. Only case series, case-control studies, cohort studies, and RCTs were included. The qualitative assessment was done by 2 separate reviewers with the appropriate quality assessment tools. The search yielded 1458 articles. After deduplication and removal of ineligible records, 1280 records were screened on title and abstract. Full text screening was done for 23 articles and ultimately 17 articles were included. Comparisons between pressure or no pressure, low vs high pressure, short vs long duration and early vs late start of treatment were investigated. There is sufficient evidence that indicates the value of prophylactic and curative use of pressure therapy for scar management. The evidence suggests that pressure therapy is capable of improving scar color, thickness, pain, and scar quality in general. Evidence also recommends commencing pressure therapy prior to 2 months after injury, and using a minimal pressure of 20–25 mmHg. To be effective, treatment duration should be at least 12 months and even preferably up to 18–24 months. These findings were in line with the best evidence statement by Sharp et al. (2016). • There is sufficient evidence to support the prophylactic and curative use of pressure therapy for scar management. • Pressure therapy is capable of improving scar color, thickness, pain and scar quality in general. • Pressure therapy should be commenced prior to 2 months post-injury and preferably as early as possible. • Pressure therapy should be done at least 12 months and last up to 18–24 months while using minimal pressures of 20-25 mmHg. • The findings of this study are in accordance with the best evidence statements. [ABSTRACT FROM AUTHOR]

The consensus in aging is that inflammation, cellular senescence, free radicals, and epigenetics are contributing factors. Skin glycation through advanced glycation end products (AGEs) has a crucial role in aging. Additionally, it has been suggested that their presence in scars leads to elasticity loss. This manuscript reports fructosamine-3-kinase (FN3K) and fructosyl-amino acid oxidase (FAOD) in counteracting skin glycation by AGEs. Skin specimens were obtained (n = 19) and incubated with glycolaldehyde (GA) for AGE induction. FN3K and FAOD were used as monotherapy or combination therapy. Negative and positive controls were treated with phosphate-buffered saline and aminoguanidine, respectively. Autofluorescence (AF) was used to measure deglycation. An excised hypertrophic scar tissue (HTS) (n = 1) was treated. Changes in chemical bonds and elasticity were evaluated using mid-infrared spectroscopy (MIR) and skin elongation, respectively. Specimens treated with FN3K and FAOD in monotherapy achieved an average decrease of 31% and 33% in AF values, respectively. When treatments were combined, a decrease of 43% was achieved. The positive control decreased by 28%, whilst the negative control showed no difference. Elongation testing of HTS showed a significant elasticity improvement after FN3K treatment. ATR-IR spectra demonstrated differences in chemical bounds pre- versus post-treatment. FN3K and FAOD can achieve deglycation and the effects are most optimal when combined in one treatment. [ABSTRACT FROM AUTHOR]

The mainstay of non-invasive scar management, consists of pressure therapy with customized pressure garments often combined with inlays, hydration by means of silicones and/or moisturizers as well as UV protection. It is generally accepted that scar dehydration resulting from impaired barrier function of the stratum corneum and expressed by raised trans epidermal water loss (TEWL) values, can lead to increased fibroblast activity and thereby hypertrophic scar formation. However, we have reached no consensus on exactly what optimal scar hydration is nor on barrier function repair: by means of silicone sheets, liquid silicone gels or moisturizers. Occlusive silicone sheets almost completely prevent TEWL and have been shown to be effective. Nevertheless, many important disadvantages due to excessive occlusion such as difficulties in applying the sheets exceeding 10–12 h, pruritus, irritation, and maceration of the skin are limiting factors for its use. To avoid these complications and to facilitate the application, liquid silicone gels were developed. Despite a reduced occlusion, various studies have shown that the effects are comparable to these of the silicone sheets. However, major limiting factors for general use are the long drying time, the shiny aspect after application, and the high cost especially when used for larger scars. Based on excellent clinical results after using three specific moisturizers for scar treatment in our patients, we wanted to investigate whether these moisturizers induce comparable occlusion and hydration compared to both each other and the widely recognized liquid silicone gels. We wanted to provide a more scientific basis for the kind of moisturizers that can be used as a full-fledged and cost-effective alternative to silicone gel. A total of 36 healthy volunteers participated in this study. Increased TEWL was created by inducing superficial abrasions by rigorous (20x) skin stripping with Corneofix® adhesive tape in squares of 4 cm². Three moisturizers and a fluid silicone gel were tested: DermaCress, Alhydran, Lipikar and BAP Scar Care silicone gel respectively. TEWL reducing capacities and both absolute (AAH) and cumulative (CAAH) absolute added hydration were assessed using a Tewameter® TM300 and a Corneometer® CM825 at different time points for up to 4 h after application. We found an immediate TEWL increase in all the zones that underwent superficial abrasions by stripping. Controls remained stable over time, relative to the ambient condition. The mean percentage reduction (MPR) in TEWL kept increasing over time with Alhydran and DermaCress, reaching a maximum effect 4 h after application. Silicone gel reached maximal MPR almost immediately after application and only declined thereafter. The silicone gel never reached the minimal MPR of Alhydran or DermaCress. Hydration capacity assessed through CAAH as measured by the Corneometer was significantly less with silicone gel compared to the moisturizers. Compared to silicone gel Lipikar provided similar occlusion and the improvement in hydration was highly significant 4 h after application. Based on the results of both our previous research and this study it is clearly demonstrated that the occlusive and hydrative effect of fluid silicone gel is inferior to the moisturizers used in our center. Lipikar hydrates well but is less suitable for scar treatment due to the lack of occlusion. A well-balanced occlusion and hydration, in this study only provided by Alhydran and DermaCress, suggests that moisturizers can be used as a scar hydration therapy that replaces silicone products, is more cost-effective and has a more patient-friendly application. • Unbalanced moisturizers provide hydration without adequate occlusion and can paradoxically lead to skin dehydration. • Well-balanced moisturizers provide strong occlusion and hydration of the stratum corneum with high longevity. • Well-balanced moisturizers are an alternative to silicone products in scar prevention and management. • DermaCress and Alhydran are examples of well-balanced moisturizers, making them ideal for scar hydration. • The occlusive properties of fluid silicone gels might be overrated and they do not provide true skin barrier restoration. [ABSTRACT FROM AUTHOR]

Advancements in resuscitative care and burn surgery have improved survival rates after extensive burn injuries, shifting focus to enhancing the quality of survival. Conventional treatment with split-thickness skin grafts (STSG) presents limitations such as donor-site morbidity, limited availability in extensive burn injuries, and hypertrophic scarring. Tissue engineering aims to address these drawbacks by developing optimal skin substitutes. This systematic review aims to provide an overview of the current applications of cultured cells in burn surgery, encompassing diverse approaches and addressing existing challenges to enhance burn wound management and improve patient outcomes. Following PRISMA guidelines, a comprehensive search was performed across three databases (PubMed, Embase, Cochrane Library) for articles on cultured cell use in burn treatment. Only clinical studies were included. Articles were screened by two independent reviewers. Quality assessment was performed. The search yielded 167 articles, of which 14 met the eligibility criteria. The selection included 8 randomized controlled trials, 5 prospective cohort trials, and 1 retrospective cohort study. Various tissue-engineered skin substitutes, from cultured epidermal autografts to dermal regeneration templates seeded with cultured cells, showed promising outcomes. Several substitutes exhibited take rates comparable to STSG with improved scar quality. Results are promising, though standardization of cultured skin substitutes and robust clinical trials with larger populations and appropriate comparators are still lacking. • Ideal skin substitutes comprise a stratifying epidermal layer and a dermal matrix. • Cultured Epidermal Autografts (CEA) show promise but are limited by graft fragility and suboptimal aesthetics. • Dermal Regeneration Templates (DRT) aim to restore dermis but face challenges in efficacy and cost-effectiveness. • Challenges of cultured cells are high costs, culture times and variable graft take. • Future directions include exploring the use of stem cells and 3D bioprinting. [ABSTRACT FROM AUTHOR]

The human face is crucial in social interaction and demonstrates cues of health, trustworthiness, emotions, and much more. A peripheral facial palsy (PFP) refers to a lower motor neuron lesion of the facial nerve and, due to its anatomy, could have many etiologies, such as traumatic, idiopathic, infectious, and oncological. Approximately 30% are left with long-term sequelae and 4% with severe dysfunction. For facial plastic surgeons, a PFP represents a great reconstructive challenge. It is a debilitating condition with functional (corneal exposure, epiphora, oral incompetence, and nasal obstruction, among others) and aesthetic sequelae that often result in physical, psychosocial, communicative, and quality-of-life losses. It remains the question how we measure the effects of the treatment of patients with a facial palsy, since there are many variety in cosmetic appreciation, surgical goals, patients' needs, and measuring tools. The aims of this narrative review are: 1) to give an overview of conservative measuring and classification tools, 2) clinician-graded instruments versus patient-graded instruments, and 3) which domains should be considered when assessing effects of our treatment. Level of evidence: Not gradable. [ABSTRACT FROM AUTHOR]

Background: Silicone products, either as a sheet or in fluid form, are universally considered as the first line therapy in the prevention and treatment of hypertrophic scars and keloids. However, the study results have been questioned by different authors and there has never been a large systematic synopsis published on the efficacy of fluid silicone gels. This systematic review aims to elucidate the available evidence of the results obtained by fluid silicone gels and present a complete and comprehensive overview of the available literature as well as a meta-analysis of the pooled data.Methods: A systematic search for articles concerning the use of silicone gel in the treatment and prevention of scars was performed on 3 different databases (Pubmed, Embase and Cochrane library) according to the PRISMA statement. Only RCT's were included. Qualitative assessment was done by 2 separate reviewers using the Cochrane risk of bias (RoB 2) assessment tool. Revman 5.4.1 software was used for meta-analysis.Results: The search yielded 507 articles. Two articles were identified through other sources. After deduplication and removal of ineligible records, 340 records were screened on title and abstract. Full text screening was done for 23 articles and ultimately 18 articles were included. A meta-analysis comparing fluid silicone gel to no treatment or placebo gels was conducted.Conclusion: Studies on the effects of liquid silicone gels on hypertrophic scars are numerous and this systematic review shows that the use of liquid silicone gels is associated with both a prophylactic and a curative effect on scars. However, a considerable amount of the available 'high evidence' trials are at a high risk for bias and it is uncertain whether or not the effects of silicone gels are comparable to silicone sheets and if the additional components present in many silicone gels are partially responsible for their scar improving capacity. [ABSTRACT FROM AUTHOR]

Current soft tissue repair techniques for women with breast cancer remain associated with several drawbacks including surgical complications and a high resorption rate for lipofilling techniques. Hence, the need to develop improved adipose tissue reconstruction strategies. Additive manufacturing can be a promising tool towards the development of patient-specific scaffolds which are able to support adipose tissue engineering. In the present work, scaffolds composed of both methacrylamide-modified gelatin (Gel-MA) and methacrylated κ-carrageenan (Car-MA), i.e. hydrogel blends, were developed using extrusion-based 3D printing in order to establish a close resemblance to the native extracellular matrix. The hydrogel blends were benchmarked to scaffolds constituting of only Gel-MA. Our results indicate that both types of scaffolds remain stable over time (21 days), are able to absorb large amounts of water and exhibit mechanical properties comparable to those of native breast tissue (2 kPa). Furthermore, a similar cell viability (> 90%) and proliferation rate after 14 days was obtained for adipose tissue-derived stem cells (ASCs) upon seeding onto both types of scaffolds. Additionally, the ASCs were able to differentiate into the adipogenic lineage on the hydrogel blend scaffolds, although their differentiation potential was lower compared to that of ASCs seeded onto the Gel-MA scaffolds. [ABSTRACT FROM AUTHOR]

Objective: To measure breast tissue and serum LNG concentrations in women using a LNG-IUS.Study Design: This pilot study was performed in 25 healthy women undergoing breast surgery at the Ghent University hospital. LNG concentrations were measured in serum and microdissected breast tissue samples using a validated ultra-performance liquid chromatography/tandem mass spectrometry assay.Result(s): The mean LNG concentration in the 18 LNG-IUS users was 0.18±0.16 ng/mL in serum and 0.26±0.28 ng/g in breast tissue. For four women without any form of hormonal contraceptive (the negative controls), the mean concentrations were below the limit of quantification, i.e., 0.15 ng/mL and 0.20 ng/g, for serum and breast tissue, respectively. For the three positive controls the concentrations in the serum (20.5 and 3.4 ng/ml) and the breast (3.74 and 1.24 ng/g) were respectively for the 20 μg EE/100 μg users and 315 pg/ml in the serum and 1.17 ng/g in the breast for the minipill user. The intracellular free fraction of LNG may be as low as 0.008 ng/g.Conclusion(s): The concentration of LNG in breast epithelium cells in women using the LNG-IUS is very low.Implications: The relationship between the serum and breast tissue levels of LNG was studied in women using a LNG-IUS or oral LNG-containing contraception. Compared to oral contraception, the tissue levels of LNG in LNG-IUS users are much lower in the breast. It is not known what level of LNG exposure in the breast would stimulate RANKL and WNT4 expression; such information is needed. [ABSTRACT FROM AUTHOR]

In this study, a new type of single quadrupole mass spectrometric detector was implemented in transdermal research. The local skin pharmacokinetic properties of the plant N -alkylamides (NAAs) pellitorine and anacycline, present in an Anacyclus pyrethrum extract, and spilanthol, present in a Spilanthes acmella extract were investigated. This single quad MS detection method showed great advantages compared to the traditional UV detector. The NAAs could be identified and quantified in the samples with an ultra performance liquid chromatography (UPLC)–single quad MS detection system, even if they were not separated, which is a requirement when using an UV–detector. Another advantage of the UPLC–MS system is that lower limit of detection values could be obtained allowing a more accurate and precise determination of the experimental lag time in the in vitro skin permeation experiments. To conclude, this single quad MS detector coupled to UPLC is a useful analytical tool with improved performance compared to high performance liquid chromatography (HPLC)–UV for biomedical-pharmaceutical purposes in transdermal research. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this study is to document the longitudinal progress of speech intelligibility, speech acceptability, voice, resonance, articulation and oromyofunctional behavior in a male facial transplant patient 8 days, 15 days, 5 months, 12 months and, finally, 21 months after surgery. Method Identical objective (Dysphonia Severity Index, nasometry, acoustic analysis) and subjective (consensus perceptual evaluation, Dutch speech intelligibility test; flexible videolaryngostroboscopy/naso-endoscopy) assessment techniques and questionnaires (speech and voice handicap index, oral health impact profile, facial disability index) were used during each of the five postsurgical assessments. Results The pattern of results shows a longitudinal progress of speech intelligibility and acceptability and of the interactive processes underpinning overall speech intelligibility. Vocal quality is normal and resonance is characterized by hypernasality. The phonetic inventory is complete but four phonetic disorders remain. Outcomes pertaining to articulation (formant analysis) show evident progress over time. Lip functions are improving but still decreased. Conclusions Transplantation of the face in this patient has largely restored speech. To what extent resonance, articulation, and lip functions can be enhanced by the permanent use of a palatal obturator, by specialized facial and lip movement exercises in combination with motor-oriented speech therapy, is subject for further research. Learning outcomes Facial transplantation : Readers will be able to (1) describe the relationship between facial transplantation and the impact on speech and oromyofunctional behavior, (2) identify variables that influence the outcome after facial transplantation, (3) define an assessment protocol after facial transplantation, (4) define facial transplantation. [ABSTRACT FROM AUTHOR]

Abstract: Background: Accurate diagnosis of burn depth is essential in selecting the most appropriate treatment. Early assessment of burn depth by clinical means only has been shown to be inaccurate, resulting in unnecessary operations or delay of grafting procedures. Laser Doppler imaging (LDI) was reported as an objective technique to determine the depth of a burn wound, but the accuracy on very early days post burn has never been investigated yet. Methods: In 40 patients with intermediate depth burns, we prospectively evaluated and compared the accuracy of the LDI measurements with the clinical assessments on days 0, 1, 3, 5, 8. Clinical evaluation of the depth of the burn was performed by two observers blinded to the LDI images. Accuracies were assessed by comparison with outcome: healing times longer than 21 days were considered to be equivalent to a biopsy finding of a deep dermal wound. Obviously superficial and full thickness wounds were excluded. LDI flux level was used for LDI prediction of outcome: less than 220PU to predict non-healing at day 21. Results: The accuracies of burn depth assessments on the day of burn and post burn days 0, 1, 3, 5 and 8 using LDI were 54%, 79.5%, 95%, 97% and 100% compared with clinical assessment accuracies of 40.6%, 61.5%, 52.5%, 71.4% and 100%, respectively. LDI accuracy was significantly higher than clinical accuracy on day 3 (p <0.001) and day 5 (p =0.005). Burn depth conversion was also considered. This is the first study to quantify the advantage of LDI scanning over clinical assessments during these important early after burn days. [Copyright &y& Elsevier]

Abstract: The depth of a burn wound and/or its healing potential are the most important determinants of the therapeutic management and of the residual morbidity or scarring. Traditionally, burn surgeons divide burns into superficial which heal by rapid re-epithelialization with minimal scarring and deep burns requiring surgical therapy. Clinical assessment remains the most frequent technique to measure the depth of a burn wound although this has been shown to be accurate in only 60–75% of the cases, even when carried out by an experienced burn surgeon. In this article we review all current modalities useful to provide an objective assessment of the burn wound depth, from simple clinical evaluation to biopsy and histology and to various perfusion measurement techniques such as thermography, vital dyes, video angiography, video microscopy, and laser Doppler techniques. The different needs according to the different diagnostic situations are considered. It is concluded that for the initial emergency assessment, the use of telemetry and simple burn photographs are the best option, that for research purposes a wide range of different techniques can be used but that, most importantly, for the actual treatment decisions, laser Doppler imaging is the only technique that has been shown to accurately predict wound outcome with a large weight of evidence. Moreover this technique has been approved for burn depth assessment by regulatory bodies including the FDA. [Copyright &y& Elsevier]

Background: There is a major clinical need for strategies for adequately reconstructing the soft tissue defects found after deep burns, tumor resection, or trauma. A promising solution is adipose tissue engineering with preadipocytes, stem-cell derived precursors of the adipose tissue, implanted within biomaterials. This pilot study evaluated hyaluronan gels mixed with autologous undifferentiated preadipocytes in a pig model for their potency to generate new fat. Materials and methods: Preadipocytes were isolated from intra-abdominal pig fat by collagenase digestion, plated on fibronectin-coated culture dishes in Dulbecco’s modified Eagle medium/Ham’s F12 (Biochrom, Berlin, Germany) combined with 10% pig serum, expanded, and mixed with hyaluronan gel. Two types of gels with varying degrees of amidation of the carboxyl groups were tested (HYADD3, HYADD4). Cell-loaded gels and unseeded controls were injected subcutaneously into the ears of three pigs, explanted at 6 wk, and analyzed histologically. Results: Both cell-loaded specimens were detected macroscopically. They demonstrated a slight volume effect with limited stability after 6 wk. Unloaded HYADD3 and HYADD4 controls could not be identified at the time of explantation. Histology of HYADD3 revealed islets of mature adipocytes and vessels embedded in fat tissue surrounded by gel. In contrast, no fat formation was found in HYADD4 gels when implanted in the ear. Conclusions: Histological findings demonstrate that HYADD3 is a promising gel for generating adipose tissue. Even though HYADD3 might be a potential material for the reconstruction of small tissue defects, the question remains as to whether the adipose tissue within the gel is attributable to preadipocyte maturation or ingrowth from neighboring tissue. [Copyright &y& Elsevier]

Importance: Since 2005, a total of 50 face transplants have been reported from 18 centers in 11 countries. The overall survival of the grafts has not yet been established., Objective: To assess the survival of the face transplant grafts and evaluate factors potentially influencing it., Design, Setting, and Participants: Data on all the transplants included in this multicenter cohort study were collected at participating transplant centers for updated nonpublished data, supplemented with literature review for nonparticipating centers. Data from 2005 until September 2023, were included. Data were analyzed from November 11, 2005, through September 18, 2023. Patients included the first 50 patients in the world to have received a face transplant., Exposure: Face transplant graft., Main Outcomes and Measures: The primary outcome was the overall survival of the face transplant graft, defined as either transplant loss or patient death. The secondary outcome was the number of acute rejection episodes per year., Results: The 50 transplants were performed on 39 men (81%) and 9 women (19%) with a median age of 35 (range, 19-68) years at the time of the transplant. The median follow-up time was 8.9 (range, 0.2-16.7) years. During the follow-up, 6 transplants were lost with 2 patients retransplanted. There were 10 patients who died, 2 of whom had lost a transplant. The 5- and 10-year survival of the transplants was 85% (SD, 5%) and 74% (SD, 7%), respectively. The sequential number of the transplant in the world was a significant predictor of survival (hazard ratio, 95; 95% CI, 90-100; P < 05). The median number of acute rejection episodes per year was 1.2 (range, 0-5.3) for the transplants that were lost and 0.7 (range, 0-4.6) for the transplants that survived. No correlation with patient and transplant variables was detected for either the transplant survival or the number of rejection episodes., Conclusions and Relevance: In this study, the overall survival of the face transplants is encouraging. These data suggest that the acceptable long-term survival of face transplants makes them a reconstructive option for extensive facial defects.

Adipose tissue engineering (ATE) has been gaining increasing interest over the past decades, offering promise for new and innovative breast reconstructive strategies. Animal-derived gelatin-methacryloyl (Gel-MA) has already been applied in a plethora of TE strategies. However, due to clinical concerns, related to the potential occurrence of immunoglobulin E-mediated immune responses and pathogen transmission, a shift towards defined, reproducible recombinant proteins has occurred. In the present study, a recombinant protein based on human collagen type I, enriched with arginine-glycine-aspartic acid was functionalized with photo-crosslinkable methacryloyl moieties (RCPhC1-MA), processed into 3D scaffolds and compared with frequently applied Gel-MA from animal origin using an indirect printing method applying poly-lactic acid as sacrificial mould. For both materials, similar gel fractions (>65%) and biodegradation times were obtained. In addition, a significantly lower mass swelling ratio (17.6 ± 1.5 versus 24.3 ± 1.4) and mechanical strength (Young's modulus: 1.1 ± 0.2 kPa versus 1.9 ± 0.3 kPa) were observed for RCPhC1-MA compared to Gel-MA scaffolds. In vitro seeding assays showed similar cell viabilities (>80%) and a higher initial cell attachment for the RCPhC1-MA scaffolds. Moreover, the seeded adipose-derived stem cells could be differentiated into the adipogenic lineage for both Gel-MA and RCPhC1-MA scaffolds, showing a trend towards superior differentiation for the RCPhC1-MA scaffolds based on the triglyceride and Bodipy assay. RCPhC1-MA scaffolds could result in a transition towards the exploitation of non-animal-derived biomaterials for ATE, omitting any regulatory concerns related to the use of animal derived products., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

In order to recreate the complexity of human organs, the field of tissue engineering and regenerative medicine has been focusing on methods to build organs from the bottom up by assembling distinct small functional units consisting of a biomaterial and cells. This bottom-up engineering requires bioinks that can be assembled by 3D bioprinting and that permit fast vascularization of the construct to ensure survival of embedded cells. To this end, a small molecular weight alginate (SMWA) gel porogen is presented herein. Alginate is a biocompatible biomaterial, which can be easily converted into small porogen gels with the procedure reported in this article. The SMWA porogen is mixed with photo-crosslinkable hydrogels and leached from the hydrogel post-crosslinking to increase porosity and facilitate vascularization. As a proof of concept, this system is tested with the commonly used biomaterial Gelatin Methacryloyl (GelMA). The SMWA porogen-GelMA blend is proven to be bioprintable. Incubating the blend for 20 min in a low concentration phosphate buffered saline and sodium citrate solution significantly reduces the remaining porogen in the hydrogel . The intent to completely leach the porogen from the hydrogel was abandoned, as longer incubation times and higher concentrations of phosphate and citrate were detrimental to endothelial proliferation. Nonetheless, even with remnants of the porogen left in the hydrogel, the created porosity significantly improves viability, growth factor signaling, vasculogenesis, and angiogenesis in 3D bioprinted structures. This article concludes that the usage of the SMWA porogen can improve the assembly of microvasculature in 3D bioprinted structures. This technology can benefit the bottom-up assembly of large scaffolds with high cell density through 3D bioprinting by improving cell viability and allowing faster vascularization., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Vanlauwe, Dermaux, Shamieva, Vermeiren, Van Vlierberghe and Blondeel.)

The potential of recombinant materials in the field of adipose tissue engineering (ATE) is investigated using a bottom-up tissue engineering (TE) approach. This study explores the synthesis of different photo-crosslinkable gelatin derivatives, including both natural and recombinant materials, with a particular emphasis on chain growth and step growth polymerization. Gelatin type B (Gel-B) and a recombinant collagen peptide (RCPhC1) are used as starting materials. The gel fraction and mass swelling properties of 2D hydrogel films are evaluated, revealing high gel fractions exceeding 94% and high mass swelling ratios >15. In vitro experiments with encapsulated adipose-derived stem cells (ASCs) indicate viable cells (>85%) throughout the experiment with the RCPhC1-based hydrogels showing a higher number of stretched ASCs. Triglyceride assays show the enhanced differentiation potential of RCPhC1 materials. Moreover, the secretome analysis reveal the production of adipose tissue-specific proteins including adiponectin, adipsin, lipocalin-2/NGAL, and PAL-1. RCPhC1-based materials exhibit higher levels of adiponectin and adipsin production, indicating successful differentiation into the adipogenic lineage. Overall, this study highlights the potential of recombinant materials for ATE applications, providing insights into their physico-chemical properties, mechanical strength, and cellular interactions., (© 2024 Wiley‐VCH GmbH.)

Objective: Burn injuries pose a heightened risk of infection, which is primarily responsible for increased morbidity and mortality. Factors such as extensive skin damage and compromised immunity exacerbate this vulnerability. Pseudomonas aeruginosa and Staphylococcus aureus are frequently identified in burns, with Gram-negative Pseudomonas aeruginosa often resistant to antibacterial agents. While Flaminal, an alginate-based wound dressing (Flen Health, Belgium), aids wound healing, its antibacterial effects are limited compared with 1% silver sulfadiazine (1% SSD). In contrast, Prontosan Wound Gel X, a betaine and polyhexanide-based hydrogel (B. Braun Medical AG, Switzerland), has been shown to effectively combat various microbes and promotes wound healing., Method: In this study, two research cohorts were retrospectively established (control group: patients receiving standard of care with the alginate-based wound dressing; intervention group: patients receiving the polyhexanide hydrogel wound dressing), comprising patients admitted to a burn centre between 2019 and 2022. Patients were eligible when continuous wound treatment with either of the two wound dressings was performed. Laser Doppler imaging (LDI) scans were conducted. Regions of interest (ROIs) were selected based on LDI scans and divided into healing time categories. Wound swabs were collected and the presence of Pseudomonas aeruginosa and Staphylococcus aureus was documented. Bacterial load was evaluated using a semiquantitative scale. Wound healing was recorded., Results: The control group consisted of 31 patients with 93 ROIs, while the intervention group had 67 ROIs involving 29 patients. Both groups exhibited similar proportions of healing time categories (p>0.05). The polyhexanide hydrogel dressing outperformed the alginate-based dressing in antiseptic efficacy by significantly reducing the incidence of Pseudomonas aeruginosa - and Staphylococcus aureus -positive cultures in patients' wounds. Wound healing time for conservative treatment was comparable between groups., Conclusion: In this study, the polyhexanide hydrogel dressing minimised Pseudomonas aeruginosa and Staphylococcus aureus colonisation in burn wounds, demonstrating strong antibacterial properties, emphasising its potential to minimise infections in burn injuries.

Background: Facial palsy causes paralytic lagophthalmos, which remarkably deteriorates a patient's quality of life. In cases where denervation time is over 18-24 months (longstanding facial palsy), a free or pedicled muscle transfer is needed to replace the denervated orbicularis oculi muscle., Purpose: The purpose of this systematic review is to investigate the effect of various eye sphincter substitution procedures (free or pedicled muscle transfers) in longstanding facial palsy patients on eye closure and blink., Methods: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we performed a systematic review of the Embase, Medline, Web of Science and Cochrane Library databases and Google Scholar. Our literature search yielded 4322 articles. Following a full-text review, 4 retrospective cohort studies and 21 case series were selected for this review. Meta-analyses using R package meta (version 6.5-0) were conducted., Main Findings: All free and pedicled muscle transfers in this review showed an improvement in the scores and measurements on eye closure and blink. The pedicled temporalis muscle transfer was the procedure most commonly performed as eye reanimation surgery and showed consistent good results. Using the random effects model, the pooled effect of mean difference in lagophthalmos after gentle eye closure post-operatively versus pre-operatively (mm) in patients who received a pedicled (temporalis) muscle transfer was -6.19 (I 2 = 85%, 95% CI: -7.89; -4.49) whereas it was -4.11 (I 2 = 85%, 95% CI: -7.26; -0.95) for free (gracilis or platysma) muscle transfers. The pooled proportion of patients with complete eye closure after surgery was 0.69 (I 2 = 49%, 95% CI: 0.54; 0.82) in patients who received a pedicled (temporalis) muscle transfer and 0.40 (I 2 = 74%, 95% CI: 0.13; 0.74) in patients who received a free (platysma) muscle transfer., Conclusions: Unlike smile reanimation, dynamic eye closure and blink restoration are rather neglected topics in facial reanimation. The pedicled temporalis muscle transfer is often recommended as the first treatment of choice for eye reanimation in longstanding facial palsy patients since it is a reliable, straightforward procedure, that does not require complex microsurgery. However, with the advancements in the field of microsurgery, free muscle transfers are promising therapies, which may regenerate voluntary and spontaneous blinking., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Face transplantation is a viable reconstructive approach for severe craniofacial defects. Despite the evolution witnessed in the field, ethical aspects, clinical and psychosocial implications, public perception, and economic sustainability remain the subject of debate and unanswered questions. Furthermore, poor data reporting and sharing, the absence of standardized metrics for outcome evaluation, and the lack of consensus definitions of success and failure have hampered the development of a "transplantation culture" on a global scale. We completed a 2-round online modified Delphi process with 35 international face transplant stakeholders, including surgeons, clinicians, psychologists, psychiatrists, ethicists, policymakers, and researchers, with a representation of 10 of the 19 face transplant teams that had already performed the procedure and 73% of face transplants. Themes addressed included patient assessment and selection, indications, social support networks, clinical framework, surgical considerations, data on patient progress and outcomes, definitions of success and failure, public image and perception, and financial sustainability. The presented recommendations are the product of a shared commitment of face transplant teams to foster the development of face transplantation and are aimed at providing a gold standard of practice and policy., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Profound variations in facial nerve branching, combined with the severe impact of facial palsy on the patient's quality of life, make surgery in this region challenging. Recent advancements in ultrasound (US) technology, including the improved visualization of small structures, have led to a sharp increase in its medical indications in various medical disciplines. We aimed to prove the feasibility of using ultra-high-frequency (UHF) US to visualize the facial nerve and to guide surgeons during surgery on and around the facial nerve., Methods: A cadaveric study was performed on one hemi-face with a UHF US imaging system and state-of-the-art transducers. Firstly, a transcutaneous US was performed, and the facial nerve branches of interest (zygomatic, buccal, and marginal mandibular branches) were marked using US-guided color-injections of filler mixed with methylene blue. Skin and subcutaneous fat were then removed to simulate the intraoperative field. Secondly, an "intraoperative" US examination was performed, and the same branches were marked by US-guided color-injections of filler mixed with indocyanine green. Anterograde facial nerve dissection was performed, and the distance between the nerve branches and the injected filler was measured., Results: All color-injections (mixed with both methylene blue and indocyanine green) were positioned right next to the nerve branches (<1 mm). The image quality of the US below the skin was observed to be far superior to that of the transcutaneous US., Conclusion: UHF US can be used to visualize the facial nerve with high precision both transcutaneously and intraoperatively (after elevation of the skin flap)., Competing Interests: The authors have no financial interest to declare in relation to the content of this article. Funding for this study was provided internally by the Department of Plastic, Reconstructive and Aesthetic Surgery, UZ Gent., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Background: Nipple-sparing mastectomy (NSM) has evolved as a standard surgical option. The NSM complication rate remains high in large breasts. To reduce the risk of necrosis, several authors have proposed delayed procedures to enhance blood supply to the nipple-areola complex (NAC). The purpose of this study in a porcine model was to show adequate redirection of NAC perfusion by neoangiogenesis through circumareolar scars., Methods: Delayed two-staged NSM was simulated in 52 nipples (six pigs) with a 60-day interval. The nipples underwent a full-thickness, circumareolar incision onto the muscular fascia, with preservation of underlying glandular perforators. After 60 days, NSM was performed through a radial incision. A silicone sheet was introduced in the mastectomy plane to prevent NAC revascularization by wound bed imbibition. Digital color imaging was used to assess necrosis. Near-infrared fluorescence with indocyanine green was used to assess perfusion patterns and perfusion in real time., Results: No NAC necrosis was seen after 60 days' delay in any nipples. In all nipples, indocyanine green angiography showed complete alteration of the NAC vascular perfusion pattern from subjacent gland to a capillary fill following devascularization, exhibiting a predominant arteriolar capillary blush without distinct larger vessels., Conclusions: NAC delay reverses glandular perfusion to adequate dermal neovascularization. Neovascularization through full-thickness scars provides sufficient dermal perfusion after 60 days' delay. Identical staged delay in humans may be a surgically safe NSM option and could broaden therapeutic NSM indications in difficult breasts. Large clinical trials are necessary to provide identical results in human breasts., Clinical Relevance Statement: NAC delay reverses glandular perfusion to adequate dermal neovascularization. Neovascularization through full-thickness scars provides sufficient dermal perfusion after 60 days of delay. Identical staged delay in humans may be a surgically safe NSM option., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Soft tissue defects are a common clinical challenge mostly caused by trauma, congenital anomalies and oncological surgery. Current soft tissue reconstruction options include synthetic materials (fillers and implants) and autologous adipose tissue transplantation through flap surgery and/or lipotransfer. Both reconstructive options hold important disadvantages to which vascularized adipose tissue engineering (VATE) strategies could offer solutions. In this review, we first summarized pivotal characteristics of functional adipose tissue such as the structure, function, cell types, development and extracellular matrix (ECM). Next, we discussed relevant cell sources and how they are applied in different state-of-the-art VATE techniques. Herein, biomaterial scaffolds and hydrogels, ECMs, spheroids, organoids, cell sheets, three dimensional printing and microfluidics are overviewed. Also, we included extracellular vesicles and emphasized their potential role in VATE. Lastly, current challenges and future perspectives in VATE are pointed out to help to pave the road towards clinical applications., (© 2023 IOP Publishing Ltd.)

Background: Absence of almost the entire reticular dermal layer is inherent to the use of autologous split-thickness skin grafting (STSG) to close full-thickness wounds, often resulting in hypertrophic scars and contractures. Many dermal substitutes have been developed, but unfortunately most have varying results in terms of cosmetic and/or functional improvement as well as patient satisfaction, in addition to high costs. Bilayered skin reconstruction using the human-derived glycerolized acellular dermis (Glyaderm®) has been reported to result in significantly improved scar quality using a two-step procedure. Unlike the necessary two-step procedure for most commercially available dermal substitutes, in this study we aimed to investigate the use of Glyaderm® in a more cost-effective single-stage engrafting. This is a method which, if autografts are available, is preferred by the majority of surgeons given the reduction in costs, hospitalization time and infection rate., Methods: A prospective, randomized, controlled, intra-individual, single-blinded study was performed, investigating the simultaneous application of Glyaderm® and STSG vs. STSG alone in full-thickness burns or comparable deep skin defects. During the acute phase, bacterial load, graft take and time to wound closure were assessed and were the primary outcomes. Aesthetic and functional results (secondary outcomes) were evaluated at 3, 6, 9 and 12 months follow-up using subjective and objective scar measurement tools. Biopsies for histological analysis were taken at 3 and 12 months., Results: A total of 66 patients representing 82 wound comparisons were included. Graft take (>95%), pain management and healing time were comparable in both groups. At 1 year follow-up, the overall Patient and Observer Scar Assessment Scale assessed by the patient was significantly in favour of sites where Glyaderm® was used. Not infrequently, patients attributed this difference to improved skin sensation. Histological analysis showed the presence of a well-formed neodermis, with donor elastin present for up to 12 months., Conclusions: A single-stage bilayered reconstruction with Glyaderm® and STSG results in optimal graft take without loss of Glyaderm® nor the overlaying autografts due to infection. The presence of elastin in the neodermis was demonstrated during long-term follow-up in all but one patient, which is a crucial factor contributing to the significantly improved overall scar quality as evaluated by the blinded patients., Trial Registration: The trial was registered on clinicaltrials.gov and received the following registration code: NCT01033604., Competing Interests: None declared., (© The Author(s) 2023. Published by Oxford University Press.)

Facial allograft transplantation can be regarded as a particular and complex type of donation because of its perceptibility and the importance of the face as an identity characteristic. As research on this topic is currently lacking, the objective of this study is to explore the experiences of the family members of the donor in facial allograft donation. In-depth, semi-structured interviews were conducted separately with the donor's family members and analyzed using interpretative phenomenological analysis. Six themes were identified: (1) Contrasting facial donation to that of more commonly donated organs; (2) Consenting to facial donation; (3) Expectations towards the recipient of the facial graft; (4) Expectations and consequences of restoration of the donor's face; (5) Relationship with the medical team during the process; and (6) Media attention. The findings of our study help to better support donor families through the facial donation process and to improve facial transplantation procedures., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

Intra- and transdermal administration of substances via percutaneous injection is effective but considered painful, and inconvenient in addition to bringing forth biohazardous waste material. In contrast to injection, topical drug application, which includes ointments, creams and lotions, increases the local drug load. Moreover, it has reduced side effects compared to systemic administration. However, the epidermis poses a barrier to high molecular weight substances, limiting the delivery efficiency. Dissolving microneedles (DMN) are hydrophilic, mostly polymer-based constructs that are capable of skin penetration and were developed to provide painless and direct dermal drug delivery. This systematic review provides a comprehensive overview of the available clinical evidence for the use of DMN to treat various skin conditions. According to the PRISMA statement, a systematic search for articles on the use of DMN for dermatological indications was conducted on three different databases (Pubmed, Embase, and the Cochrane library). Only human clinical trials were considered. Qualitative assessment was done by two separate reviewers using the Cochrane risk of bias (RoB 2) and Chambers' criteria assessment tools. The search yielded 1090 articles. After deduplication and removal of ineligible records, 889 records were screened on title and abstract. Full text screening was done for 18 articles and ultimately 17 articles were included of which 15 were randomized controlled trials and two were case series. The quality assessment showed that the majority of included studies had low to no risk of bias. Clinical data supports that DMN are an excellent, effective, and pain free drug delivery method for multiple dermatological disorders including skin aging, hyperpigmentation, psoriasis, warts, and keloids by supplying a painless and effective vehicle for intradermal/intralesional drug administration. Microneedle technology provides a promising non- to minimally-invasive alternative to percutaneous injection., (© 2023 Japanese Dermatological Association.)

Hypertrophic scarring (HTS) is frequently observed after deep dermal and full-thickness skin defects. Local drug delivery in HTS has been shown more effective compared to other (minimally) invasive treatments. Disadvantages being operator-dependency and non-uniform drug distribution. Moreover, injections are painful and difficult when confronted with extensive scars or HTS in children. Corticoid-embedded dissolving microneedles (CEDMN) were developed that provide painless skin penetration and direct dermal drug delivery. Hyaluronic acid-based DMN and CEDMN patches were utilized. Structural analysis was performed via nuclear magnetic resonance (NMR) spectroscopy while gel permeation chromatography (GPC) was applied to determine chain length (molar mass) and dispersity of hyaluronic acid. Mechanical properties were evaluated by compression testing. Five burn victims with HTS were included. For each individual, three comparable scars were chosen. One control scar was left untreated. Two scars were treated with either 600 or 800 µm CEDMN patches. Patients were treated monthly for 4 months. Treatment with 800 µm CEDMN was initiated after 8 weeks. Assessor-blinded POSAS was registered. Hydration, evaporation, color and elasticity were recorded. The physico-chemical characterization suggests that the mechanical properties enable skin penetration and adequate drug delivery. Patients experienced the therapy as painless. According to the POSAS, all scars improved over time. However, the scars that were treated with CEDMN patches improved faster and with increased increment. The 800 µm CEDMN ensured the fastest POSAS-decrease. Hyaluronic acid-based CEDMN patches are valuable alternatives to intracicatrical injections, as they offer a painless and effective method for administering corticosteroids in HTS., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Summary: The lumbar artery perforator flap is a valuable alternative in breast reconstruction whenever the deep inferior epigastric perforator flap is not feasible because of insufficient or unavailable abdominal tissue. The advantage is the ideal shape and consistency of the flap, in addition to the option to perform a nerve anastomosis with the cluneal nerve. The anatomy is consistent, but there are some technical issues related to the short perforator and difficult surgical exposure in the lower back region. The inclusion of a vascular interposition graft improved the authors' results and facilitated their technical challenges and final inset of the flap. These videos guide the surgeon through the different steps involved in a breast reconstruction with the lumbar artery perforator flap., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Background: Large and ptotic breasts are considered an anatomical contraindication for nipple sparing mastectomy (NSM). Necrosis rates can be as high as 76%. The authors examined whether targeted preshaping mastopexy/reduction combined with simultaneous two-stage preshaping of the implant pocket prepares for an uneventful implant reconstruction., Methods: Macromastia and ptosis patients opting for risk-reducing NSM or having a peripherally localized carcinoma in situ, were offered a two-stage mastopexy/reduction simultaneously with preshaping of the implant pocket by subpectoral expansion. Only the inferior pedicle bearing the nipple-areola complex (NAC), remained. A delayed secondary NSM and tissue expander-to-implant reconstruction was scheduled 3 months later. The use of an acellular dermal matrix (ADM) was not necessary because the capsule around the expander created a hammock supporting the definite prosthesis. Follow up was at 2 weeks, 3 months, and 6 months., Results: Forty-one procedures were performed in 24 patients. The mean age was 45±12.08 years (range, 22 to 72 years). Patients' mean body mass index (BMI) was 26.79 kg/m 2 (range, 19 to 35 kg/m 2 ). One patient had diabetes and two smoked. One transient epidermolysis of the NAC occurred in each stage. No NAC or skin necrosis occurred; no implant had to be removed., Conclusions: A two-stage mastopexy/reduction, simultaneously with preshaping of the implant pocket by tissue expansion and followed by a 3-month delayed secondary NSM with tissue expander-to-implant reconstruction is a safe technique in large ptotic breasts., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-21-734/coif). The authors have no conflicts of interest to declare., (2022 Gland Surgery. All rights reserved.)

Spheroids are three-dimensional cellular models with widespread basic and translational application across academia and industry. However, methodological transparency and guidelines for spheroid research have not yet been established. The MISpheroID Consortium developed a crowdsourcing knowledgebase that assembles the experimental parameters of 3,058 published spheroid-related experiments. Interrogation of this knowledgebase identified heterogeneity in the methodological setup of spheroids. Empirical evaluation and interlaboratory validation of selected variations in spheroid methodology revealed diverse impacts on spheroid metrics. To facilitate interpretation, stimulate transparency and increase awareness, the Consortium defines the MISpheroID string, a minimum set of experimental parameters required to report spheroid research. Thus, MISpheroID combines a valuable resource and a tool for three-dimensional cellular models to mine experimental parameters and to improve reproducibility., (© 2021. The Author(s).)

Background: Recent evidence confirms that mesenchymal stem cells (MSCs) facilitate angiogenesis mainly through paracrine function. Extracellular vesicles (EVs) are regarded as key components of the cell secretome, possessing functional properties of their source cells. Subsequently, MSC-EVs have emerged as a novel cell-free approach to improve fat graft retention rate., Objectives: The authors sought to provide a systematic review of all studies reporting the utilization of MSC-EVs to improve graft retention rate., Methods: A systematic search was undertaken employing the Embase, PubMed, and Cochrane Central Register of Controlled Trials databases. Outcome measures included donor/receptor organism of the fat graft, study model, intervention groups, evaluation intervals, EV research data, and in vitro and in vivo results., Results: Of the total 1717 articles, 62 full texts were screened. Seven studies reporting on 294 mice were included. Overall, EV-treated groups showed higher graft retention rates compared with untreated groups. Notably, retention rate was similar following EV and MSC treatment. In addition to reduced inflammation, graft enrichment with EVs resulted in early revascularization and better graft integrity. Interestingly, hypoxic preconditioning of MSCs improved their beneficial paracrine effects and led to a more proangiogenic EV population, as observed by both in vitro and in vivo results., Conclusions: MSC-EVs appear to offer an interesting cell-free alternative to improve fat graft survival. Although their clinical relevance remains to be determined, it is clear that not the cells but rather their secretome is essential for graft survival. Thus, a paradigm shift from cell-assisted lipotransfer towards "secretome-assisted lipotransfer" is well on its way., (© 2020 The Aesthetic Society. Reprints and permission: journals.permissions@oup.com.)

Background: Pre-expanded pedicled flaps possess a more flexible transfer pattern and higher tissue utilization than random flaps, but the perfusion is fully dependent on the chosen axial vessels. A precise mapping of the vessels would assist the surgical design and increase the likelihood of success. The application of Infrared thermography (IRT) has been previously reported for perforator location. The aim of this study is to report the use of IRT in mapping the course and distribution of axial vessels in the pre-expanded flap to guide the designing and harvesting., Methods: Patients who underwent head and neck reconstruction using pre-expanded flaps were included. After tissue expansion, IRT was used to mark the vessel distribution along the expanded flap. The results were compared with color Doppler ultrasound (CDU) and/or computed tomographic angiography (CTA). The flap was designed and raised based on the pre-operative marking by IRT. The mark was verified intraoperatively., Results: A total of 26 expanded flaps were performed, including 20 pedicled flaps and 6 free flaps. IRT succeeded to map the vessel distribution in all cases. All marked results were verified by CDU, CTA, and intraoperative dissection (26/26, 100%). IRT showed more comprehensive distribution of vascular branches than CDU or CTA, and could be utilized intraoperatively to identify the arteries., Conclusion: IRT provides accurate and comprehensive mapping of the axial vessel distribution in the pre-expanded flaps, assisting with flap design and harvest. It is easy to use and non-invasive as an important tool pre- or intraoperatively to ensure the safe elevation., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: The number of patients requesting prophylactic mastectomy with immediate reconstruction is rising. The oncological safety of techniques preserving the nipple and/or areola complex is still controversial. Nevertheless, nipple-sparing mastectomy (NSM) and areola-sparing mastectomy (ASM) are becoming increasingly popular. After ASM, traditional nipple reconstruction techniques can be a disappointment and can lead to a deep groove around the new nipple. We describe a technique to overcome these issues and analyzed how three types of mastectomy (skin-sparing mastectomy or SSM, ASM, and NSM) compare to one another by looking into the number of wound infections, extra procedures for the loss of projection, nipple necrosis, and BREAST-Q scores., Methods: We retrospectively analyzed 467 breast reconstructions performed in 351 patients between 2011 and 2017 at the University Hospital of Gent. Patients were asked to fill out the BREAST-Q questionnaire and patient-reported outcomes were analyzed and correlated to demographic information., Results: Patients undergoing a nipple reconstruction after ASM are experiencing similar rates of wound problems, extra surgical procedures for the loss of projection and necrosis, compared to women with a history of SSM. When considering the "satisfaction with breast" and "satisfaction with outcome" modules of the BREAST-Q, we noted that nipple-sparing mastectomy (NSM) patients report lower scores than SSM and ASM patients and ASM patients seem to report a higher "satisfaction with nipple," than the other two treatment groups., Conclusion: An ASM is a valuable alternative to a nipple-sparing mastectomy and leads to a good esthetic result and patient satisfaction., Competing Interests: Declaration of Competing Interest None of the authors have a financial interest in any of the products, devices, or drugs mentioned in this manuscript., (Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.)

Background: Preoperative localization of the perforators allows precise planning of the flap design and improves surgical efficiency. Recently, infrared thermography is introduced as a reliable alternative, where the perforator corresponds to the "hot spot" on the thermogram. This study aims to compare the application of color Doppler ultrasound (CDU) and infrared thermography in preoperative perforator mapping of the anterolateral thigh (ALT) perforator flap., Patients and Methods: From September 2017 to January 2019, CDU and infrared thermography were both applied on 20 patients to locate the perforators originated from lateral circumflex femoral artery preoperatively. The perforators identified using each modality were marked on the anterolateral thigh region. The accuracy of both mapping methods was analyzed according to the intraoperative findings. The relation between location bias and the thickness of subcutaneous tissue was analyzed., Results: A total of 20 ALT flaps were included. Fifty-three perforators were detected by CDU, and 51 "hot spots" were identified by infrared thermography, in which 50 "hot spots" corresponded to CDU, and the consistency test showed that the κ index was 0.712 (P < 0.05), representing high consistency. The infrared thermography has a sensitivity of 94.3% and a specificity of 85.7% compared with CDU. The deviation between thermal imaging and CDU was positively correlated with the thickness of the subcutaneous tissue. The Pearson correlation coefficient was 0.84 (R = 0.84). Forty-four perforators marked by CDU were selected for designing the flap. Anatomical findings showed that the accuracy rate of CDU and infrared thermal was 93.2% (41 of 44) and 86.3% (38 of 44), respectively. There was no statistical difference (P > 0.05)., Conclusions: Compared with CDU, infrared thermography can be used to locate perforators, in this case, the ALT perforators, with a high degree of consistency. It is portable, economical, noninvasive, and easy to operate. It has higher accuracy in patients with thinner subcutaneous tissue. We believe that infrared thermography can be a useful technique for perforator mapping, especially in patients where the subcutaneous tissue is thinner.