Non-animal derived recombinant collagen-based biomaterials as a promising strategy towards adipose tissue engineering.

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 has already been applied in a plethora of TE strategies. However, due to clinical concerns, related to the potential occurrence of immunoglobulin (IgE)-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 (RGD) was functionalized with photo-crosslinkable methacryloyl moieties (RCPhC1-MA), processed into 3D scaffolds and compared with frequently applied gelatin-methacryloyl (Gel-MA) from animal origin using an indirect printing method applying poly-lactic acid (PLA) 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.

An Update on the Survival of the First 50 Face Transplants Worldwide.

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.

Reconstructing Curves: A Bottom-Up Approach toward Adipose Tissue Regeneration with Recombinant Biomaterials.

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.

Assessing antibacterial efficacy of a polyhexanide hydrogel versus alginate-based wound dressing in burns.

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.

Photo-crosslinkable polyester microneedles as sustained drug release systems toward hypertrophic scar treatment.

Burn injuries can result in a significant inflammatory response, often leading to hypertrophic scarring (HTS). Local drug therapies e.g. corticoid injections are advised to treat HTS, although they are invasive, operator-dependent, extremely painful and do not permit extended drug release. Polymer-based microneedle (MN) arrays can offer a viable alternative to standard care, while allowing for direct, painless dermal drug delivery with tailorable drug release profile. In the current study, we synthesized photo-crosslinkable, acrylate-endcapped urethane-based poly(ε-caprolactone) (AUP-PCL) toward the fabrication of MNs. Physico-chemical characterization (1H-NMR, evaluation of swelling, gel fraction) of the developed polymer was performed and confirmed successful acrylation of PCL-diol. Subsequently, AUP-PCL, and commercially available PCL-based microneedle arrays were fabricated for comparative evaluation of the constructs. Hydrocortisone was chosen as model drug. To enhance the drug release efficiency of the MNs, Brij®35, a nonionic surfactant was exploited. The thermal properties of the MNs were evaluated via differential scanning calorimetry. Compression testing of the arrays confirmed that the MNs stay intact upon applying a load of 7 N, which correlates to the standard dermal insertion force of MNs. The drug release profile of the arrays was evaluated, suggesting that the developed PCL arrays can offer efficient drug delivery for up to two days, while the AUP-PCL arrays can provide a release up to three weeks. Finally, the insertion of MN arrays into skin samples was performed, followed by histological analysis demonstrating the AUP-PCL MNs outperforming the PCL arrays upon providing pyramidical-shaped perforations through the epidermal layer of the skin.

AUP-PCL MN arrays provide long-term transdermal drug delivery of hydrocortisoneAUP-PCL-based MN arrays provide superior drug release profiles compared to PCL MNsEffective skin penetration AUP-PCL-based MNs on skin was achieved.

International consensus recommendations on face transplantation: A 2-step Delphi study.

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.

The effect of various muscle transfer procedures on eye closure and blinking in longstanding facial palsy patients.

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 (I2 = 85%, 95% CI: -7.89; -4.49) whereas it was -4.11 (I2 = 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 (I2 = 49%, 95% CI: 0.54; 0.82) in patients who received a pedicled (temporalis) muscle transfer and 0.40 (I2 = 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.

Visualization of the Facial Nerve with Ultra-high-Frequency Ultrasound.

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).

Influence of Moisturizers on Skin Microcirculation: An Assessment Study Using Laser Speckle Contrast Imaging.

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-ß1) 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.

A single-stage bilayered skin reconstruction using Glyaderm® as an acellular dermal regeneration template results in improved scar quality: an intra-individual randomized controlled trial.

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.

Enzymatic Deglycation of Damaged Skin by Means of Combined Treatment of Fructosamine-3-Kinase and Fructosyl-Amino Acid Oxidase.

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.

Vascularized adipose tissue engineering: moving towards soft tissue reconstruction.

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.

Dermal Nipple-Areola Complex Perfusion through Circumareolar Scars: A Delay Model in Two-Stage Nipple-Sparing Mastectomy.

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.

Pressure therapy for scars: Myth or reality? A systematic review.

BACKGROUND: 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-ß1 (TGF-ß1), 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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).

Facial Allograft Donation: An Interpretative Phenomenological Analysis of the Experiences of Family Members.

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.

Dissolving microneedles for effective and painless intradermal drug delivery in various skin conditions: A systematic review.

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.

Treatment of Hypertrophic Scars with Corticoid-Embedded Dissolving Microneedles.

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 Lumbar Artery Perforator Flap in Breast Reconstruction.

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.

Occlusion and hydration of scars: moisturizers versus silicone gels.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.