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Microneedle (MN) patches are gaining increasing attention as a cost-effective technology for delivering drugs directly into the skin. In the present study, two different 3D printing processes were utilized to produce coated MNs, namely, digital light processing (DLP) and semisolid extrusion (SSE). Donepezil (DN), a cholinesterase inhibitor administered for the treatment of Alzheimer's disease, was incorporated into the coating material. Physiochemical characterization of the coated MNs confirmed the successful incorporation of donepezil as well as the stability and suitability of the materials for transdermal delivery. Optical microscopy and SEM studies validated the uniform weight distribution and precise dimensions of the MN arrays, while mechanical testing ensured the MNs' robustness, ensuring efficient skin penetration. In vitro studies were conducted to evaluate the produced transdermal patches, indicating their potential use in clinical treatment. Permeation studies revealed a significant increase in DN permeation compared to plain coating material, affirming the effectiveness of the MNs in enhancing transdermal drug delivery. Confocal laser scanning microscopy (CLSM) elucidated the distribution of the API, within skin layers, demonstrating sustained drug release and transcellular transport pathways. Finally, cell studies were also conducted on NIH3T3 fibroblasts to evaluate the biocompatibility and safety of the printed objects for transdermal applications.

Background: The use of sentinel lymph node biopsy (SLNB) for high-risk cutaneous squamous cell carcinoma (CSCC) is not yet clearly documented, especially for the head and neck area, due to its rich and cross-branching lymphatic system. We present the first prospective randomized study on the use of SLNB in high-risk CSCCs of the head and neck., Methods: Seventy-six patients with high-risk CSCCs of the head and neck were randomly divided into two groups: A (n = 38) and B (n = 38). In group A, SLNB was performed additionally to the excision of squamous cell carcinoma, whereas in group B, only excision of the lesion was performed. The patients were followed up for 5 years postoperatively, and local recurrences, regional metastases (regional lymph nodes), and mortality were documented., Results: One patient of group A, who never attended any follow-up, was excluded. Both groups had similar characteristics regarding Breslow thickness, perineurial invasion, peripheral limits, differentiation, size, previous incomplete excision, age, sex, education, sun exposure, Fitzpatrick score, previous incomplete excision, previous skin cancer, and smoking. Two patients had a positive sentinel lymph node and were submitted to regional lymphadenectomy. We documented deaths (three in group A and two in group B; P = 0.674), local recurrence (seven in group A and six in group B; P = 0.768), and regional metastasis (zero in group A and two in group B; P = 0.159)., Conclusion: There is no clear benefit on the use of SLNB in high-risk CSCCs of the head and neck regarding metastasis, mortality, or local recurrence control., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Keloids are complex fibroproliferative disorders with diverse clinical presentations. Spontaneous keloids (SKs) represent a rare subtype that emerges without any known preceding traumatic event. This report presents a case of familial spontaneous keloids appearing on the thoracic region in two brothers with no prior history of trauma or keloid occurrence in other family members. The lesions exhibited progressive growth over several years but responded to cycles of triamcinolone treatment. This case underscores an unusual spontaneous occurrence of keloids in the thoracic region of two siblings, highlighting the potential genetic predisposition in the aetiology of these lesions. Additionally, this instance reinforces the concept that keloids can develop spontaneously without any apparent trauma in the affected area., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kyriazidis et al.)

Introduction: Total nose reconstruction is demanding as it is a 3-dimensional structure that needs lining, support and external coverage. Usually, several stages are needed to achieve a satisfactory result. The authors present 2 cases of prelaminated radial forearm and 2 prelaminated forehead nose reconstructions and compare both methods. According to our review of the literature, this is the first report of prelaminated forehead for total nose reconstruction., Materials and Methods: The last 5 years the authors have treated 4 patients with prelaminated flaps for total nose reconstruction. The age ranged from 50 to 75 years. There were 3 male patients and one female. Three patients underwent total nose amputation due to squamous cell carcinoma and one due to melanoma., Results: Two patients were treated with prelaminated radial forearm reconstruction and 2 with prelaminated forehead reconstruction. Both patients that were treated with prelaminated radial forearm reconstruction had the collapse of the nasal pyramid and had salvage procedures with replacement of the cartilaginous framework with iliac bone graft framework., Conclusions: Prelaminated nose reconstruction with either the radial forearm or forehead flap needs several stages. There is the possibility of infection-collapse of the cartilage framework, therefore, the authors recommend reconstruction of the nasal skeleton with an iliac bone graft. The flaps are stiff and difficult to handle. The authors don't think that prelaminated nose reconstruction with the radial forearm flap has advantage compared with the classic several stages nose reconstruction with radial forearm flap. Possibly, prelaminated forehead reconstruction can be applied for aged patients who cannot undergo microsurgical reconstruction., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Hand injuries typically present with localized symptoms. However, we report an unusual case of a 32-year-old female who experienced a transient complete loss of sensation and motor function in her entire left nondominant hand after sustaining a minor 1 cm stab wound between the third and fourth metacarpals. Wound exploration under local anesthesia revealed no tendon, vascular, neural, or bony injury. Remarkably, she spontaneously regained full hand sensation and function within 120 minutes of the injury. Extensive neurological evaluation, including magnetic resonance imaging (MRI), electromyography (EMG), nerve conduction studies (NCS), and somatosensory evoked potentials (SSEPs), ruled out organic pathology and supported a diagnosis of functional neurological disorder (FND), specifically functional movement disorder (FMD). Close collaboration between hand surgeons, neurologists, and occupational therapists is essential for accurate diagnosis and appropriate multidisciplinary management. Further research is needed to elucidate the mechanisms underlying FND and optimize evidence-based treatment for FND in the context of hand trauma. The increased awareness of this condition across specialties involved in hand injury management is crucial to facilitate timely diagnosis and avoid unnecessary interventions., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kyriazidis et al.)

In the current study, coated microneedle arrays were fabricated by means of digital light processing (DLP) printing. Three different shapes were designed, printed, and coated with PLGA particles containing two different actives. Rivastigmine (RIV) and N-acetyl-cysteine (NAC) were coformulated via electrohydrodynamic atomization (EHDA), and they were incorporated into the PLGA particles. The two actives are administered as a combined therapy for Alzheimer's disease. The printed arrays were evaluated regarding their ability to penetrate skin and their mechanical properties. Optical microscopy and scanning electron microscopy (SEM) were employed to further characterize the microneedle structure. Confocal laser microscopy studies were conducted to construct 3D imaging of the coating and to simulate the diffusion of the particles through artificial skin samples. Permeation studies were performed to investigate the transport of the drugs across human skin ex vivo . Subsequently, a series of tape strippings were performed in an attempt to examine the deposition of the APIs on and within the skin. Light microscopy and histological studies revealed no drastic effects on the membrane integrity of the stratum corneum. Finally, the cytocompatibility of the microneedles and their precursors was evaluated by measuring cell viability (MTT assay and live/dead staining) and membrane damages followed by LDH release.

Background: Indocyanine green (ICG) lymphography, a key diagnostic tool for lymphedema, is influenced by the dilution process of ICG dye, impacting patient experience. Methods and Results: In our study, we assessed three different ICG diluents-water for injection (WFI), normal saline (NS), and Dextrose ® plus human albumin-in five healthy volunteer individuals undergoing superficial lymphography of the upper limb over 3 weeks. Results indicated that NS, as a diluent for ICG, caused the least discomfort during injection, in contrast to WFI, which led to the highest levels of discomfort. Transport time of ICG from the injection site to the axillary lymph nodes was notably shorter in intradermal injections than in subdermal injections. Conclusion: Our findings advocate for using NS as the optimal and cost-effective diluent for ICG, enhancing patient experience.

Background:  The aim of our study was to evaluate a new propeller vascularized lymphatic tissue flap (pVLNT) combined with aligned nanofibrillar collagen scaffolds (CS) (BioBridge) in reducing lymphedema in the rat lymphedema model., Methods:  Unilateral left hindlimb lymphedema was created in 15 female Sprague-Dawley rats following inguinal and popliteal lymph nodes (LN) resection and radiation. An inguinal pVLNT was elevated from the contralateral groin and transferred through a skin tunnel to the affected groin. Four collagen threads were attached to the flap and inserted in the hindlimb at the subcutaneous level in a fan shape. The three study groups consisted of group A (control), group B (pVLNT), and group C (pVLNT + CS). Volumetric analysis of both hindlimbs was performed using micro-computed tomography imaging before the surgery (at initial time point) and then at 1 and 4 months, postoperatively, and the relative volume difference (excess volume) was measured for each animal. Lymphatic drainage was assessed by indocyanine green (ICG) fluoroscopy for number and morphology of new collectors and the time required for ICG to move from injection point to the midline., Results:  Four months after the induction of lymphedema, an increased relative volume difference remained in group A (5.32 ± 4.74%), while there was a significant relative volume reduction in group B (-13.39 ± 8.55%) and an even greater reduction in group C (-14.56 ± 5.04%). ICG fluoroscopy proved the functional restoration of lymphatic vessels and viability of pVLNT in both B and C groups. Notably, only group C demonstrated statistically significant improvements in lymphatic pattern/morphology and in the number of lymphatic collectors as compared with the control group A., Conclusion:  The pedicle lymphatic tissue flap combined with SC is an effective procedure for the treatment of lymphedema in rats. It can be easily translated into treatment of humans' lower and upper limb lymphedema and further clinical studies are warranted., Competing Interests: None declared., (Thieme. All rights reserved.)

The combined use of a deep inferior epigastric perforator (DIEP) flap coupled with vascularized inguinal lymph nodes (VILNs) for simultaneous breast and lymphedema reconstruction has already been well established, and promising results have been reported. However, a standardized approach for the planning and shaping of this combined flap is still lacking. We aimed to propose a comprehensive algorithmic approach for delayed unilateral breast and lymphedema reconstruction using a predesigned abdominal flap associated with inguinal lymph node transfer. We present in detail the preoperative measurements and surgical technique of the chimeric flap, which combines a predesigned DIEP template and a preselected inguinal lymph node flap, based on the preoperative computed tomography angiography and SPEC-CT findings, respectively; four different flap types are described according to the location of the pedicles of the two flap components. Our results of a series of 34 consecutive female patients with unilateral mastectomy and arm lymphedema, who underwent this combined predesigned reconstructive procedure, are retrospectively analyzed and reported. We recorded a high survival rate of the chimeric flaps in our series, with only one case of partial ischemic loss of a DIEP skin island. In the majority of our patients, the pedicles of the combined flaps were located in opposite positions. After a mean 35-month follow-up, we recorded a 47% mean volume difference reduction of the lymphedematous compared to the unaffected arm; no donor-site lymphedema was documented. Self-evaluation questionnaires showed high patient satisfaction rates regarding breast reconstruction. This algorithmic approach provides standardized guidance for accurate design and transfer of the DIEP-VILN chimeric flap while achieving highly satisfactory outcomes for both breast and lymphedema reconstruction., Competing Interests: None., (© 2024 The Authors.)

Competing Interests: None declared.

Because lipofilling is often associated with various reconstructive procedures, especially breast reconstructions, improving fat-graft retention remains a major concern for plastic surgeons. We conducted an experimental protocol in a rat model simulating an autologous breast reconstruction method using the fat-augmented latissimus dorsi myocutaneous (LDM) flap. This study aimed to compare the survival rates of autologous adipocytes when injected subcutaneously and intramuscularly and to evaluate the role of recipient host tissue, volume of the injected fat, and postoperative radiation on fat-graft retention. Thirty rats were divided into five groups (A, B, C, D, and E), of six rats each. All animals underwent a pedicled LDM flap transfer to the anterior thoracic wall, and different volumes of autologous fat were injected into three recipient areas, namely, the pectoralis major and latissimus dorsi muscles and the subcutaneous tissue of the flap's skin island, as follows: 1 mL of fat was injected in total in group A, 2 mL in groups B and D, and 5 mL in group C. Group D animals received postoperative radiation (24 Gy), whereas group E animals (controls) did not undergo any fat grafting procedure. Eight weeks after surgery, adipocyte survival was assessed in all groups using histological and immunochemistry techniques. The results showed that the pectoralis major muscle was the substrate with the highest adipocyte survival rates, which were proportional to the amount of fat injected, followed by the latissimus dorsi muscle and the subcutaneous tissue. Increased volumes of transplanted fat into the subcutaneous tissue did not correspond to increased adipocyte survival. Irradiation of host tissues resulted in a statistically significant decrease in surviving adipocytes in all three recipient sites (p<0.001). Our study strongly suggests that muscle ensures optimal fat-graft retention, whereas postoperative radiation negatively affects adipocyte survival following fat transplantation., Competing Interests: None., (© 2023 The Author(s).)

Background: Lymphedema is a debilitating and progressive clinical entity characterized by abnormal accumulation of lymph and fluid in the extracellular space. Most of the cases in western population are related to cancer treatment. Research on cancer-related lymphedema (CRL) is mounting for potential risk factors associated to disease, treatment, or patient. However, only a few cancer survivors with the same risk factors will develop lymphedema, giving rise to the hypothesis that inherited genetic susceptibility may play a role in CRL pathophysiology. This systematic review aimed to identify, critically appraise, and summarize the results of individual studies that have examined the genetic predisposition to CRL. Methods and Results: A comprehensive literature search in MEDLINE, Cochrane, and Scopus was conducted from inception to February 2021. Screening of available studies and quality of the included studies were carried out by two reviewers independently. Eight studies fulfilled eligibility criteria, involving 573 women with breast-cancer related lymphedema (BCRL) among 1,481 participants. Associations between the development of CRL and genetic factors were observed for variations in 23 genes in patients with BCRL. Conclusions: The present systematic review is the first examining specifically the genetic predisposition in CRL. Statistically significant genetic variations were found in 23 genes in patients with BCRL. These preliminary findings highlight the importance of genetic susceptibility in the development of CRL, altering the traditional perception of its iatrogenic etiology. Additional well-designed research, aiming toward the confirmation of previously performed genetic analyses and functional assessment of the genetic variations, is required.

Background: In this experimental study, the authors investigated whether fat placement in the pocket during implant insertion affects capsule formation., Methods: Twenty albino Wistar rats, 400 g each, were used. The rats were divided into two groups, A and B, of 10 rats each. At the dorsum of each rat, four pockets (2 × 2 cm each) were dissected, two left and two right of the midline. In each pocket, a 1 × 1 × 1.5-cm silicone implant was inserted. In the two left pockets, only silicone implants were placed (control). In the two right pockets, 0.4 ml of fat was injected around the implant. Animals in group A were killed 2 months postoperatively, and those in group B were killed 4 months postoperatively. The implants were dissected with the capsule and sent for histopathologic examination., Results: The data of the fat transfer group was compared with control in groups A and B. Capsule thickness, neovascularization, myofibroblast layer thickness, and mast cell population demonstrated no statistically significant difference in either group A (p = 0.385, p = 0.862, p = 0.874, and p = 0.210, respectively) or group B (p = 0.338, p = 1.000, p = 0.288, and p = 0.344, respectively). Inflammation was statistically significantly less (p = 0.07) at 4 months (group B) in the fat transfer group compared to the control group. Likewise, cellularity was statistically significantly less (p = 0.019) at 4 months for the fat transfer group compared with the control group., Conclusion: Fat injection in the pocket during implant placement may reduce inflammation and cellularity of capsules and predispose to faster capsule maturation., Clinical Relevance Statement: Fat transfer around implants may positively affect implant-based breast reconstruction and/or breast augmentation., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Currently, there is a lack of models representing the skin dermal heterogeneity for relevant research and skin engineering applications. This is the first study reporting production of dermal equivalents reproducing features of papillary and reticular dermal compartments. Inspired from our current knowledge on the architecture and composition differences between the papillary and reticular dermis, we evaluated different collagen-based porous materials to serve as scaffolds for the three-dimensional expansion of freshly isolated papillary and/or reticular fibroblasts. The scaffolds, composed of either collagen I or collagen I and III mixtures, were prepared by lyophilization. Pore size and hydrolytic stability were controlled by crosslinking with 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) or EDC/NHS with covalently bound heparin. The evaluation of the resultant "papillary" and "reticular" dermal equivalents was based on the analysis of characteristic features of each dermal compartment, such as cell density and deposition of newly synthetized extracellular matrix components in histological sections. Crosslinking supported cell growth during dermal tissue formation independent on the fibroblast subpopulation. The presence of collagen III seemed to have some positive but non-specific effect only on the maintenance of the mechanical strength of the scaffolds during dermal formation. Histological analyses demonstrated a significant and specific effect of heparin on generating dermal equivalents reproducing the respective higher papillary than reticular cell densities and supporting distinct extracellular matrix components deposition (three to five times more carbohydrate material deposited by papillary fibroblasts in all scaffolds containing heparin, while higher collagen production was observed only in the presence of heparin)., (© 2021 Wiley Periodicals LLC.)

Background: This retrospective study aimed to assess the impact of certain flap characteristics on long-term outcomes following microsurgical treatment in Breast Cancer-Related Lymphedema (BCRL) patients., Methods: Sixty-four out of 65 BCRL patients, guided by the "Selected Lymph Node" ("SeLyN") technique, underwent Vascularized Lymph Node Transfer (VLNT) between 2012 and 2018. According to their surface size, flaps were divided into small (<25 cm 2 , n = 32) and large (>25 cm 2 , n = 32). Twelve large and six small flaps were combined with free abdominally based breast reconstruction procedures. Lymphedema stage, flap size, vascular pedicle and number of lymph nodes (LNs) were analyzed in correlation with long-term Volume Differential Reduction (VDR)., Results: At 36-month follow-up, no major complication was recorded in 64 cases; one flap failure was excluded from the study. Mean flap size was 27.4 cm 2 , mean LNs/flap 3.3 and mean VDR 55.7%. Small and large flaps had 2.8 vs. 3.8 LNs/flap ( p = 0.001), resulting in 49.6% vs. 61.8% VDR ( p = 0.032), respectively. Lymphedema stage and vascular pedicle (SIEA or SCIA/SCIP) had no significant impact on VDR., Conclusion: In our series, larger flaps included a higher number of functional LNs, directly associated with better outcomes as quantified by improved VDR.

Purpose: The genomic status of non-malignant tissues from carriers of pathogenic germline BRCA1/2 (gBRCA1/2) variants may reveal information towards individualized prophylaxis. We performed spatiotemporal tissue genotype comparisons in a real-life cohort of gBRCA1/2 carriers of Greek origin, who underwent multiple risk-reducing/prophylactic surgeries at various time points., Methods: Fifty-three women (median age 36 years) within cancer families were observed for up to 37.5 years; 43 were cancer carriers and 10 were healthy carriers. Histology review and genotyping were performed for 187 paraffin tissues (average: 3.5 per carrier) including 46 carcinomas (40 breast) and 141 non-malignant breast and gynecological samples., Results: High allelic imbalance (AI) and somatic pathogenic TP53 variants were present in cancer carriers only (p values < 0.0001). High AI was associated with gBRCA1/2 indels (p < 0.0001) and gBRCA2 alterations (p = 0.0109). Somatic (pathogenic) variants were infrequently shared between non-malignant tissues and matched carcinomas. Aberrations of gBRCA1 variant heterozygosity were noticed in tissues from cancer carriers only (13/43, 30.2%). These pertained to classic LOH (neoplastic lesions in 9/43 carriers, 20.9%) and under-representation of the germline variants (5 samples, 4 non-malignant, all in the breast). Both aberrations coexisted in matched samples in one case. Over time, germline variant heterozygosity prevailed in non-malignant tissues; intra-carrier genomic alterations were aggravated (21.1%), ameliorated (26.3%) or remained stable., Conclusion: This real-life case study supports the need to address tissue genotypes from prophylactic surgeries in combination with polygenic scores towards personalized prophylaxis. To this end, knowing the traditionally classified pathogenic potential of a gBRCA1/2 variant may not be enough., (© 2021. The Japanese Breast Cancer Society.)

Hybrid composites of synthetic and natural polymers represent materials of choice for bone tissue engineering. Ulvan, a biologically active marine sulfated polysaccharide, is attracting great interest in the development of novel biomedical scaffolds due to recent reports on its osteoinductive properties. Herein, a series of hybrid polycaprolactone scaffolds containing ulvan either alone or in blends with κ-carrageenan and chondroitin sulfate was prepared and characterized. The impact of the preparation methodology and the polysaccharide composition on their morphology, as well as on their mechanical, thermal, water uptake and porosity properties was determined, while their osteoinductive potential was investigated through the evaluation of cell adhesion, viability, and osteogenic differentiation of seeded human adipose-derived mesenchymal stem cells. The results verified the osteoinductive ability of ulvan, showing that its incorporation into the polycaprolactone matrix efficiently promoted cell attachment and viability, thus confirming its potential in the development of biomedical scaffolds for bone tissue regeneration applications.

The present study aimed to fabricate a hollow microneedle device consisting of an array and a reservoir by means of 3D printing technology for transdermal peptide delivery. Hollow microneedles (HMNs) were fabricated using a biocompatible resin material, while PLA filament was used for the reservoirs. The fabricated microdevice was characterized by means of optical microscopy, scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), contact angle measurements and leakage inspection studies to ensure the passageway of liquid formulations. Mechanical failure and penetration tests were carried out and supported by Finite Element Analysis (FEA). The cytocompatibility of the microneedle arrays was assessed to human keratinocytes (HaCaT). Finally, the transport of the model peptide octreotide acetate across artificial membranes was assessed in Franz cells using the aforementioned HMN design., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A novel High-Performance Liquid Chromatography-Tandem Mass Spectrometry (HPLC-MS/MS) method was developed for the simultaneous determination of the in vitro skin permeation profile of four UV filters. The sunscreen products contained the following components: octocrylene (OC), ethylhexyl methoxycinnamate (EHMC), diethylamino hydroxybenzoyl hexyl benzonate (DHHB) and ethylhexyl salicylate (EHS). The target compounds were analyzed by HPLC-MS/MS method in positive ionization electrospray (ESI) in Multiple Reaction Monitoring (MRM) mode. The proposed method was validated in terms of the detection (LOD) and quantification limits (LOQ), linearity range, intra- and inter- day precision and accuracy of the analysis. The stability of the target compounds in solutions was also studied. All tests provided satisfactory results illustrating acceptable method performance. Samples were analyzed with simple pretreatment procedure, necessary to achieve solvent change and preconcentration. To evaluate matrix effect, the slopes of the standard regression curves with those of the matrix-matched calibration curves were compared using the Student's t-test. Quantitative evaluation of the test samples was performed using external methanolic calibration curves. Accuracy was found within the range 94.37-108.76%. The method was successfully applied to the analysis of UV filters in samples after permeability studies, in Franz's cells, for 24 h, using human skin. Concentration of sunscreens in the acceptor phase at the timescale of 24 h was very low implying the safety of the products., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Soft tissue defects to the dorsum of fingers are quite demanding for the reconstructive surgeon especially in the cases that bone and extensor tendons are exposed. The purpose of our study was to describe a new adipofascial island flap by a single dorsal digital perforator (dorsal adipofascial digital artery perforator, DADAP)., Materials: Methods: In 8 patients (7 male, 1 female), 12 soft tissue defects to the dorsum of the fingers (3 index, 6 middle, 2 ring, 1 little finger), ranging from 1 × 2 cm to 2 × 4 cm, were reconstructed using the DADAP flap., Results: The flaps sizes ranged from 2.5 × 1.5 cm to 8 × 3 cm. The defects were covered in 9 cases by a propeller-rotation type flap and in 3 by a turn-over flap. In 4 cases a tendon graft was used to cover the tendon defect and in 3 cases an open joint was reconstructed. In all cases a splint thickness skin graft (SSG) covered the flaps. Mean follow-up was 18 months. One patient developed distal tip flap necrosis and was treated conservatively. Delayed wound healing with partial SSG failure due to haematoma was observed in 3 fingers, but the underlying flap was viable and complete healing was achieved by secondary intention., Conclusions: The use of DADAP flap is a fast, safe and reliable solution to cover the defects of the dorsum of fingers and can be performed under local anaesthesia as a day surgery., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020. Published by Elsevier Ltd.)

Introduction Reverse neurocutaneous and propeller perforator flaps are both used to reconstruct diabetic distal lower limb defects. Our study aims to compare outcomes between these two groups of flaps with an emphasis on indications and complication rates. Method A retrospective analysis was conducted, reviewing data from 54 diabetic patients who underwent reconstruction of acute or chronic wounds of the foot and ankle between 2005-2018. Thirty-four patients (Group A) had a reverse neurocutaneous flap (NCF): nineteen sural and fifteen lateral supramalleolar flaps. Twenty patients (Group B) had a propeller flap (PF) based on peroneal (n = 13) or posterior tibial artery perforators (n = 7). All patients had a preoperative Doppler examination to identify the nutrient artery of the flap. In both groups, we recorded patients' demographics, characteristics of the defect, postoperative complications and time to heal. Follow-up ranged from 6 to 59 months. Student's t-test and chi-squared test were used for statistical analysis. Results Mean patients' age was 59.1 and 50.8 years for Group A and B, respectively. Defects were located at the Achilles zone (n = 16), posterior heel (n = 14), foot dorsum (n = 9), lateral and medial malleolar areas (n = 8), anterior ankle (n = 5) and lateral foot (n = 2). Mean size of the defect was 42.8 cm 2 in Group A and 23 cm 2 in Group B. Uneventful healing was recorded in 20/34 neurocutaneous flaps and in 12/20 propeller flaps; complications included two complete flap losses (one NCF, one PF), seventeen distal flap necroses (10 NCFs, 7 PFs), fifteen delayed wound healing events over the donor or recipient site (12 NCFs, 3 PFs). Secondary surgeries were required in 15 NCF and 8 PF patients. Mean healing time was 48.1 and 40.7 days for Group A and B, respectively. All patients, except one NCF case, which resulted in leg amputation, returned to previous levels of ambulation. Conclusion Reverse neurocutaneous and propeller flaps may provide stable reconstruction of diabetic lower limb defects; neurocutaneous flaps are specially indicated for larger and more distally located defects, although they might be associated with longer healing time and additional revision surgeries. Propeller flaps were more frequently used in younger patients for smaller and more proximally located defects., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020. Published by Elsevier Ltd.)

Introduction: Concepts of beauty are different amongst different cultures and civilizations. The objective of this study was to evaluate beauty perceptions through cosmetic advertisements in an effort to further appreciate beauty understanding amongst lay people in various parts of the world. To achieve these objectives, we reviewed cosmetics' advertisements to study whether the concept of beauty varies amongst different countries., Materials and Methods: We used the keywords "cosmetics" and "advertisements" in YouTube search engine in all existing languages in Google translator and came up with advertisements from 18 countries. The faces of the models were compared against Marquardt ® beauty mask template in order to have a mean to objectively test symmetry with a mathematical computer model. The weak point of our study is that we can present no model photographs due to General Data Protection Regulation., Results: Advertisements retrieved in total were 257. Characteristics with no statistically significant difference (SSD) amongst models in different parts of the world were: symmetry (p = 0.187), high cheek bones (p = 0.325), small noses (p = 0.72), thin jaws (p = 0.98), lush hair (p = 0.54), clean and smooth skin (p = 0.367), and white toothed smile (p = 0.235). Characteristics with SSD were: in Latin America, USA, and Australia tanned models and fuller lips were preferred (p < 0.001), whilst in Asia milky white skin models and small mouth were preferred. Age ratio (p = 0.022) was lower amongst models in Southeast Asia compared to American, European, Indian, Australian, and Arab models. Arab and Southeast Asia women had intense eyebrows (p < 0.001) and used artificial eyelashes., Conclusions: All the common characteristics noted by the two independent surgeons (GAS and LP) referred to symmetry, youthfulness, and health. Differences noticed reflected cultural influences in the perception of beauty., Level of Evidence V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Cell adhesion on 3D-scaffolds is a challenging task to succeed high cell densities and even cell distribution. We aimed to design a 3D-cell Culture Device (3D-CD) for static seeding and cultivation, to be used with any kind of scaffold, limiting cell loss and facilitating nutrient supply. 3D printing technology was used for both scaffold and device fabrication. Apart from testing the device, the purpose of this study was to assess and compare static and dynamic seeding and cultivation methods, of wet and dry scaffolds, under normoxic and hypoxic conditions and their effects on parameters such as cell seeding efficiency, cell distribution and cell proliferation. Human adipose tissue was harvested and cultured in 3D-printed poly(epsilon-caprolactone) scaffolds. Micro-CT scans were performed and projection images were reconstructed into cross section images. We created 3D images to visualize cell distribution and orientation inside the scaffolds. The group of prewetted scaffolds was the most favorable to cell attachment. The 3D-cell Culture Device (3D-CD) enhanced cell seeding efficiency with almost no cell loss. We suggest that the most favorable outcome can be produced with static seeding in the device for 24 h, followed either by static cultivation in the same device or by dynamic cultivation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Capsular contracture is one of the most distressing complications of breast implant use in both aesthetic and reconstructive plastic surgery procedures. This systematic review was performed to assess the effectiveness of all nonsurgical treatments for established capsular contracture.

Ulvan, a bioactive natural sulfated polysaccharide, and gelatin, a collagen-derived biopolymer, have attracted interest for the preparation of biomaterials for different biomedical applications, due to their demonstrated compatibility for cell attachment and proliferation. Both ulvan and gelatin have exhibited osteoinductive potential, either alone or in combination with other materials. In the current work, a series of novel hybrid scaffolds based on crosslinked ulvan and gelatin was designed, prepared and characterized. Their mechanical performance, thermal stability, porosity, water-uptake and in vitro degradation ability were assessed, while their morphology was analyzed through scanning electron microscopy. The prepared hybrid ulvan/gelatin scaffolds were characterized by a highly porous and interconnected structure. Human adipose-derived mesenchymal stem cells (hADMSCs) were seeded in selected ulvan/gelatin hybrid scaffolds and their adhesion, survival, proliferation, and osteogenic differentiation efficiency was evaluated. Overall, it was found that the prepared hybrid sponge-like scaffolds could efficiently support mesenchymal stem cells' adhesion and proliferation, suggesting that such scaffolds could have potential uses in bone tissue engineering.

One of the most severe complications in aesthetic and reconstructive surgeries is the partial or total necrosis of a skin flap. In our experimental study, we demonstrated the use of adipose-derived stem cells in the increase of skin flap survival rates. Stem cells were isolated from the fat of Wistar rats and genetically modified to permanently produce a green fluorescent protein (GFP). Two random-pattern skin flaps (2 cm × 8 cm) were elevated on the dorsal area of the spine, and after being separated from the surgical wounds with a thin silicone sheet, they were placed back onto their original location. Then, the autologous GFP-producing cells were injected intradermally into the dorsal area of the rats. At the seventh day, after the implantation of the stem cells, a clinical and immunohistochemical control was performed. The fluorescence microscopy revealed green vascular formations, suggesting that autologous GFP stromal cells were converted into endothelial cells through neovascularization. In the control skin flaps, where no stromal cells were used, no fluorescence was observed. The statistical analysis showed significantly lower necrosis rates in the right-sided flaps (i.e., the flaps where adipose-derived stromal cells were injected) compared with the left-sided ones. Findings from our study demonstrate that adipose-derived stem cells play an important role in the improvement of skin flap survival. Neovascularization is an effective way of achieving it., (© 2019 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Background: A new technique named "Selected Lymph Node" ("SeLyN") was evaluated, aiming to identify the most functional groin lymph nodes (LNs) for an effective LN transplantation., Methods: Bilateral lower-limb SPECT-CT was performed in the upper-limb lymphedema patients, to select the most radioactive inguinal LN. Recorded data included demographics, stage, etiology of lymphedema, flap consistency in accordance to preoperative findings, flap size, number of LN, and harvesting time. Infection episodes per year and volume changes of the upper limbs were documented. Donor-site complications were recorded and lower-limb evaluation was performed through clinical examination, volume analysis, and lymphoscintigraphy., Results: A total of 41 patients underwent a "SeLyN" transfer technique. The mean flap size was 28.34 cm 2 containing a mean of 3.4 LNs. The mean time spent on flap harvest was 39 minutes. A mean 56.5% volume reduction (P < .001) and a mean 1.41 to 0.29 infection episodes per patient per year (P < .001) were recorded. Clinical evaluation and lymphography of the donor site advocated no major complications for a mean follow-up period of 42.5 months., Conclusions: "SeLyN" is a safe and effective technique in selecting the most suitable LNs, minimizing the donor-site morbidity, and decreasing the overall operating time., (© 2019 Wiley Periodicals, Inc.)

Efforts on bioengineering are directed towards the construction of biocompatible scaffolds and the determination of the most favorable microenvironment, which will better support cell proliferation and differentiation. Perfusion bioreactors are attracting growing attention as an effective, modern tool in tissue engineering. A natural biomaterial extensively used in regenerative medicine with outstanding biocompatibility, biodegradability and non-toxic characteristics, is collagen, a structural protein with undisputed beneficial characteristics. This is a study designed according to the above considerations. 3D printed polycaprolactone (PCL) scaffolds with rectangular pores were coated with collagen either as a coating on the scaffold's trabeculae, or as a gel-cell solution penetrating scaffolds' pores. We employed histological, molecular and imaging techniques to analyze colonization, proliferation and chondrogenic differentiation of Adipose Derived Mesenchymal Stem Cells (ADMSCs). Two different differentiation culture media were employed to test chondrogenic differentiation on gelated and non gelated PCL scaffolds in static and in perfusion bioreactors dynamic culture conditions. In dynamic culture, non gelated scaffolds combined with our in house TGF-β 2 based medium, augmented chondrogenic differentiation performance, which overall was significantly less favorable compared to StemPro™ propriety medium. The beneficial mechanical stimulus of dynamic culture, appears to outgrow the disadvantage of the "weaker" TGF-β 2 medium used for chondrogenic differentiation. Even though cells in static culture grew well on the scaffold, there was limited penetration inside the construct, so the purpose of the 3D culture was not fully served. In contrast dynamic culture achieved better penetration and uniform distribution of the cells within the scaffold., (Copyright © 2019 Elsevier B.V. All rights reserved.)

This research aimed to manufacture and evaluate in vitro 3D printed microneedles for transdermal drug delivery. Firstly, microneedle arrays were fabricated using a polymer-based material. Subsequently, these arrays were tested for their mechanical strength applying axial load along their length, while prediction of the buckling load was performed using widely known arithmetic models. Additionally, the force required to pierce human skin was calculated in order to verify that microneedles insert human skin without buckling or fracturing. Finite Element Analysis (FEA) was used to simulate the insertion process and complement the experimental findings. Furthermore, permeation studies were carried out in order to compare diffusion of two model dyes with different molecular weight namely; FITC-Dextran (M.W.:4000 Da) and calcein (M.W.:622.54 Da) across full thickness human skin in vitro before and after skin treatment with microneedles. Finally, visualization studies enabled illustration of microneedle perforation sites. The results showed that the manufactured 3D printed microneedle arrays penetrate sufficiently human skin and can significantly enhance the transport of the dyes across human skin., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: Limited data exist regarding the correlation between adipose-derived stromal vascular fraction (SVF) and wound healing. The aim of this study was to investigate the direct effect of intradermally injected SVF on full-thickness cutaneous wounds in a murine model., Method: Wistar rats were divided into three groups (A, B and C) according to their day of euthanasia (day 7, 16 and 21). Inguinal fat pad was excised and SVF enzymatically extracted. Full-thickness cutaneous wounds were created on each side of the dorsum; SVF injected intradermally at one side while the contralateral wound served as control receiving normal saline. Postoperatively, evaluation of wound healing was performed by planimetry (percentages of wound contraction, epithelialisation and total wound healing) on days 0, 3, 5, 7, 10, 13, 16 and 21, and histology and immunochemistry (cellular infiltration score, collagen production score, neoangiogenesis and epithelial thickness) on days 7, 16 and 21., Results: Despite the high rate of wound contraction, it was significantly lower in the SVF-treated wounds on day 21 (p=0.037). On days 13, 16 and 21, the percentages of epithelialisation were higher in the SVF-treated wounds compared with control wounds (p=0.026, p=0.048 and p=0.05, respectively). Histologically, the number of new vessels was significantly higher in the SVF-treated wounds compared with controls on days seven (p=0.028) and 16 (p=0.027). This was also confirmed by immunohistochemistry. No significant differences were found between treated and control wounds regarding cellular infiltration score, collagen production score and epithelial thickness., Conclusion: Data indicate that intradermally injected SVF increases angiogenesis and enhances epithelialisation in full-thickness cutaneous wounds in rats.

Abstracts Background: Among current surgical options used for treating breast cancer-related lymphedema (BCRL), autologous lymph node transfer (ALNT) is shown to provide favorable results. However, postoperative donor-site lymphedema (DSL), following the lymphatic flap harvesting from the groin area, has already been reported. Our aim is to summarize the recent literature for evidence of DSL following an ALNT for BCRL., Methods and Results: A PubMed bibliographic search was performed for published studies evaluating donor-site complications following LNT in BCRL patients. We recorded demographic data of the patients, the type of flap used, the follow-up, the donor-site morbidity, and the diagnostic tests performed pre- and postoperatively. Statistical analysis was conducted to document any correlation between the incidence of DSL and the abovementioned recorded parameters. According to our results, 11 studies met the inclusion criteria. From a total of 189 patients, three cases with DSL of the lower limb were reported (1.6%). No statistically significant correlations were found., Conclusion: ALNT has become increasingly popular and is considered an effective surgical option for treating BCRL of the upper limb. Although the incidence of postoperative DSL is low, insufficient data on patients' demographics, surgical details, and postoperative assessment do not allow extracting significant correlations. Meticulous technique of lymph node harvesting should be seriously considered to further minimize this infrequent but debilitating complication.

Aim: To report our initial experience and preliminary results of autologous free fat transfer to improve speech and hypernasality in patients with velopharyngeal insufficiency (VPI) as a sequela of cleft lip and palate repair., Material and Methods: To date 2 patients with a mean age of 25 years were treated with this method. Both had initially received multiple procedures elsewhere for cleft lip and palate repair. We recorded the number of free fat transfer sessions, anatomical places of placement and volumes injected in-patient stay, occurrence or absence of complications and effectiveness of this operation in terms of clinical speech evaluation, functional velopharyngeal closure measurements and speech improvement percentage by an Ear, Nose and Throat (ENT) specialist., Results: Two autologous free fat transfer sessions per patient were performed. Mean hospitalization time was 1 day per operation. Following liposuction, autologous free fat was transferred to the following anatomical areas: a) Passavant's ridge, b) uvula, c) palatopharyngeal and palatoglossal folds. The volume of fat injected varied from 6.5 cc to 8 cc per session. Postoperative periods were uneventful for both cases in each session. On clinical examination, improvement in speech was noted as well as a reduction in hypernasality with an improvement in articulation and audibility of consonant words, which were also reported by the patients' relatives. This was confirmed by objective nasendoscopy velopharyngeal closure measurements, both during speech and deglutition., Conclusion: Augmentation pharyngoveloplasty with autologous free fat transfer in patients with velopharyngeal insufficiency is a safe and innovative alternative, particularly for small to medium degrees of structural velophayngeal dysfunction.