Skin Replacement Research Articles

Current Trends on Innovative Technologies in Topical Wound Care for Advanced Healing and Management.

To investigate critically traditional and modern techniques for cutaneous wound healing and to provide comprehensive information on these novel techniques to encounter the challenges with the existing wound healing methods. The financial burden and mortality associated with wounds is increasing, so managing wounds is essential. Traditional wound treatments include surgical and non-surgical methods, while modern techniques are advancing rapidly. This review examines the various traditional and modern techniques used for cutaneous wound healing. Traditional wound treatments include surgical techniques such as debridement, skin flaps, and grafts. Non-surgical treatments include skin replacements, topical formulations, scaffold-based skin grafts, and hydrogel-based skin dressings. More modern techniques include using nanoparticles, growth factors, and bioactive substances in wound dressings. Bioengineered skin substitutes using biomaterials, cells, and growth factors are also being developed. Other techniques include stem cell therapy, growth factor/cytokine therapy, vacuum-assisted wound closure, and 3D-printed/bio-printed wound dressings. Traditional wound treatments have been replaced by modern techniques such as stem cell therapy, growth factor/cytokine therapy, vacuum-assisted wound closure, and bioengineered skin substitutes. However, most of these strategies lack effectiveness and thorough evaluation. Therefore, further research is required to develop new techniques for cutaneous wound healing that are effective, cost-efficient, and appealing to patients.

Individualized surgical treatment using decellularized fish skin transplantation after enzymatic debridement: a two years retrospective analysis

Treatment of burn injuries has developed over the past few years with the development of enzymatic debridement and new types of skin replacement materials beyond primary surgical therapy providing complex personalized therapy concepts with the goal of preserving and replacing the dermal layer of the skin.The aim of our study was to develop an individualized treatment algorithm for mixed depth burn wound and to evaluate the outcome of an individualized combined treatment of mixed depth burn wounds with an enzymatic debridement and decellularized fish skin.A total of 18 Patient treated could be analyzed with a mean age of 34.8 years and a mean follow-up of 447,6 days. The mean total burn surface area was 12.3%. All patients received an enzymatic debridement and an average area of ​​247.2 square centimeters decellularized fish skin. Days until complete epithelization was 49,4 ± 25,79. No Patient developed a scar contracture or a keloid. The POSAS Observer Scale showed an overall impression average of 2,2 ± 0,83. The POSAS patient scale showed an overall impression average 2 ± 0,7. The Vancouver Scar Scale showed an average score of 1,89 ± 1,45. In conclusion, a combined treatment of enzymatic debridement and decellularized fish skin, polylactide membrane or split skin grafts allows a more individualized therapy for mixed depth burn wounds. Fish skin was found to provide a satisfying result regarding the overall outcome of the developed scar tissue and could lead to a reduction of the area needed to be autologous transplanted.

A multifunctional polyacrylonitrile fibers/alginate-based hydrogel loaded with chamomile extract and silver sulfadiazine for full-thickness wound healing

Most conventional wound dressings do not meet the clinical requisites owing to their limited multifunctionality. Herein, a bilayer wound dressing containing both hydrogel and fibrous structures with multifunctional features was developed for effective skin rehabilitation. Sodium alginate (SA)/gelatin (Gel) hydrogel comprising Matricaria chamomilla L extract and silver sulfadiazine (AgSD) drug as antibacterial agents was cross-linked using genipin and CaCl2. Then, the surface of the hydrogel was covered by electrospun polyacrylonitrile (PAN) nanofibers to fabricate a bilayer dressing. FESEM images revealed formation of continuous, smooth, and bead-free PAN nanofibers with excellent compatibility between hydrogel and fibers. The bilayer wound dressing exhibited satisfactory mechanical virtues including elastic modulus (2.4 ± 0.2 MPa), tensile strength (6.2 ± 0.5 MPa) and elongation at break (21.8 ± 1 %) as well as suitable swelling ratio. Such bilayer dressing revealed biodegradability, cytocompatibility and effective antibacterial performance against gram positive and gram negative strains. Release kinetics of AgSD drug followed a Fickian diffusion mechanism, ensuring sustained drug release. In vivo studies demonstrated bilayer dressing could promote rate of wound closure, re-epithelialization and collagen deposition, facilitating the replacement of damaged skin with healthy tissue. Such engineered wound dressing has a high potency for inducing skin repair and could be used in skin tissue engineering.

A Comparative Analysis of the Advances in Scar Reduction: Techniques, Technologies, and Efficacy in Plastic Surgery.

The study provides a comprehensive analysis of the latest methodologies and treatments aimed at improving scar management. Scar formation results from the replacement of normal skin with fibroblasts, leading to a structured unidirectional collagen bundle, as opposed to the collagen sheet matrix found in healthy skin. This review categorizes scars into hypertrophic scars and keloids, each with distinct pathophysiological characteristics. It highlights the importance of consistent scar assessment using scales such as the Vancouver Scar Scale and the Patient and Observer Scar Assessment Scale, emphasizing the need for standardized evaluation methods. The study systematically reviews various scar management techniques, ranging from traditional surgical methods to innovative treatments. Conventional approaches such as pressure garments and silicone gel sheeting are explored, noting their roles in maintaining hydration and occlusion. The efficacy of intralesional corticosteroid injections and laser therapies is discussed, with particular attention given to their combined use for optimal outcomes. The review also covers advanced techniques such as microneedling, platelet-rich plasma therapy, and stem cell-based treatments, detailing their mechanisms and potential benefits in scar remodelling. Additionally, the study underscores the emerging role of botulinum toxin A in both preventive and corrective scar treatments, offering promising results in reducing movement-induced scar exaggeration. The systematic review includes a thorough examination of existing literature, clinical trials, and meta-analyses to evaluate the effectiveness of these interventions. It concludes by calling for further research to refine these techniques and enhance their application in clinical practice, aiming to achieve better aesthetic and functional outcomes for patients with scars.

Effects of concurrent optical and magnetic stimulation in hard-to-heal wounds: a real-world evidence case series.

This work explores concurrent optical and magnetic stimulation (COMS) effects on hard-to-heal wounds in real-world settings. In this case series, participants received COMS 1-3 times per week for up to 12 weeks alongside standard wound care. A total of 27 patients (18 female and nine male) were included. Mean age was 72 years. Participants' wounds that were unresponsive to standard wound care included: venous leg ulcers (VLUs, n=13); mixed leg ulcers (MLUs, n=4); diabetic foot ulcers (DFUs, n=1); pressure ulcers (PUs, n=5); and traumatic wounds (TWs, n=4). On average, COMS was applied twice a week, resulting in an overall mean wound area reduction of 69%. In 24 participants, COMS was used primarily to achieve wound closure by the end of the 12-week period, of which: 12 were classified as complete wound closure (50%; VLUs=8, PUs=3 and TW=1); four as likely-to-heal (17%; VLUs=2 and MLUs=2); four as 'improved' (17%; MLU=1, DFU=1 and TWs=2); and four as 'non-responding' (17%; VLUs=3 and MLU=1). The best results were achieved in PUs and VLUs (respectively 100% and 62% categorised as completely healed). When used in participants where its purpose was other than that of achieving wound closure, COMS was successfully used to debride two PUs, and for wound bed preparation in one TW. In this case series, COMS showed positive effects and appeared to be beneficial in healing different types of hard-to-heal wounds in community health and homecare settings. Novel COMS therapy aspects emerged: (1) positive outcomes for PU and VLU treatment; (2) COMS as a potential debridement tool when sharp debridement is unfeasible; and (3) COMS as a promising method to prepare wound beds for subsequent skin grafting or skin replacement procedures.

In-vitro and in-vivo evaluation of angiogenic potential of a novel lithium chloride loaded silk fibroin / alginate 3D porous scaffold with antibacterial activity, for promoting diabetic wound healing

Healing diabetic ulcers with chronic inflammation is a major challenge for researchers and professionals, necessitating new strategies. To rapidly treat diabetic wounds in rat models, we have fabricated a composite scaffold composed of alginate (Alg) and silk fibroin (SF) as a wound dressing that is laden with molecules of lithium chloride (LC). The physicochemical, bioactivity, and biocompatibility properties of Alg-SF-LC scaffolds were investigated in contrast to those of Alg, SF, and Alg-SF ones. Afterward, full-thickness wounds were ulcerated in diabetic rats in order to evaluate the capacity of LC-laden scaffolds to regenerate skin. The characterization findings demonstrated that the composite scaffolds possessed favorable antibacterial properties, cell compatibility, high swelling, controlled degradability, and good uniformity in the interconnected pore microstructure. Additionally, in terms of wound contraction, re-epithelialization, and angiogenesis improvement, LC-laden scaffolds revealed better performance in diabetic wound healing than the other groups. This research indicates that utilizing lithium chloride molecules loaded in biological materials supports the best diabetic ulcer regeneration in vivo, and produces a skin replacement with a cellular structure comparable to native skin.

Use of Fish Skin Grafts for Wound Management: Report of 5 Pediatric Cases

Abstract Background Managing wounds and scars in children presents a significant challenge for surgical and rehabilitation teams. Studies have already explored the potential of fish skin grafts with Omega-3 in hard-to-heal lower extremity chronic ulcers and deep-burn management. Aims The purpose of this study is to assess the safety and outcome of intact fish skin grafts with Omega-3 when used as skin replacement therapy in the pediatric population. Methods This article was conducted in adherence to our hospital's ethical guidelines. Patients enrolled in this study were identified retrospectively. Their medical records were reviewed, and data was collected concerning patient demographics, initial mode of injury, indication for fish skin placement, operative data, postoperative care, complications and outcomes. The acellular dermal matrix was obtained from North Atlantic codfish skin (Gadus morhua) farmed in Isafjordur, Iceland. Results All patients underwent meticulous wound debridement and patch application under general anesthesia and were discharged the same day. Wound surface ranged between 10 and 110 cm2 (mean: 53 cm2). Standard analgesic medications were taken for a maximum period of 48 hours in all patients. Upon follow-up at our outpatient clinic, shrinkage in the wound surface was observed in all patients after a few days, followed by early wound granulation. Two patients underwent subsequent split-thickness grafting to achieve healing. The mean time required to achieve complete epithelialization was 48.6 days (range: 29 – 62 days). No hypersensitivity or allergic reaction was reported. The definitive outcome was satisfactory in all wounds, meaning complete wound coverage. Conclusion The findings from this case series reveal that fish skin grafts with Omega-3 can be an effective and a safe scaffold in the process of repairing damaged tissues in the pediatric population. We have been able to accomplish a quality skin replacement therapy, with no donor site morbidity.

Effects of silver nanoparticle and low-level laser on the immune response and healing of albino mice skin wounds

The structural integrity of the skin, which acts as a barrier to keep harmful external substances out of the body, is compromised by wounds. The process of wound healing is a multifaceted and ever-changing phenomenon that entails the replacement of bodily tissues or damaged skin. It has been demonstrated that nanoparticles, especially silver nanoparticles, have anti-microbial and anti-inflammatory qualities that encourage cell migration and proliferation. Low level laser therapy has the potential to accelerate wound healing by stimulating cell regeneration after injury, reducing pain, and modulating the immune system. The aim of our study is to evaluate the healing process after treatment with silver nanoparticle and/or low level laser by measuring the serum levels of some pro-inflammatory cytokines (IL1b, IL6, and TNF-α), wound healing rate and histological analysis. Wounds were inflicted into 63 adult male albino mice (Mus musculus) and randomly divided into nine groups (7 per each). Control was left to normal healing. Other groups received a different treatment with laser, silver nanoparticle or both for 21 days. Injured skin was sampled for histopathological examination. Quantitative determination of TNFα, IL1 beta and IL6 were carried out using the sandwich enzyme-linked immunosorbent assay (ELISA) twice (day 2 and day 21). One-way and two-way analysis of variance (ANOVA) was used for statistical analysis. The results showed that the groups treated with silver nanoparticles and / or low-level laser promoted wound healing by reducing pro- inflammatory cytokines (IL1β, IL6 and TNFα) and showed significantly better wound closure with a significant reduction in wound size. At day 2 histopathological changes were very similar in different groups. When silver nanoparticles were applied, either alone or in combination with laser exposure, better granulation tissue and fibrosis also necrosis in the canter of the lesion and high score of re-epithelialization with less inflammation observed gradually till day 21. The results of this study suggested that silver nanoparticles and low-level laser have a wound healing potential, since topical treatment with silver nanoparticles and low-level leasers has effectively improved the wound healing process.

Biomedical applications of collagen: A Review

Collagen is an excellent biomaterial. Biological characteristics of collagen including biodegradability and weak antigenicity made it a primary resource in medical application. In biomedical field collagen is mainly used as sponges for wound/burn, supplement in rheumatoid arthritis, drug delivery system, controlling material for transdermal delivery and basic matrices for cell culture system due to its ability to stimulate formation of tissue and organ. Moreover, collagen is also applied in tissue engineering including bone defect, tissue regeneration, skin replacement and artificial blood vessels and valves. The article reviews biomedical application of collagen in wound healing, rheumatoid arthritis, drug delivery system, tissue engineering and lung function improvement in pulmonary fibrosis due to viral infection.

Substituição de pele de frango por óleo de canola em nuggets de frango

ABSTRACT: This study developed chicken nuggets with emulsions with different percentages of canola oil (CO) to replace the chicken skin and evaluating the quality of the final product and the effect of frying. The experiment was set up in a 5x5 factorial scheme with the replacement of skin with different percentages of CO (0, 25, 50, 75, and 100%) and storage periods (0, 45, 90, 135,and 180 days), and parameters such as pH and oxidation were evaluated. It was considered a 5x2 factorial scheme (replacement of skin with CO and different sample conditions (raw and fried in CO)) for the analyses of the centesimal composition, fatty acid profile, atherogenic (AI), and thrombogenic (IT) indices. The sensory analysis evaluated the chicken nuggets at time zero. The pH values ranged from 6.62 to 6.86, as an effect of frying, there was an increase in lipid content with increasing levels of substitution (T0-raw: 5.36% and fried: 12.11%; T100-raw: 7.93% and fried: 15.43%) and a decrease in moisture content in relation to the raw sample. There was a decrease in AI (T0%-raw vs. T100%-fried, 0.39 vs. 0.10) and IT (T0%-raw vs. T100%-fried, 0.61 vs. 0.18) with CO addition and frying, and lipid oxidation increased with storage. The ω6/ω3 ratio decreased and the PUFA/SFA increased with the replacement of chicken skin with CO, but there was no difference in the sensory analysis. Even though chicken nuggets are prone to lipid oxidation, it is possible to improve their nutritional value either by adding CO to the meat mixture or by frying them.

Comparison of combination skin substitutes and skin grafts versus skin grafts only for treating wounds measured by Vancouver Scar Scale: A comprehensive meta-analysis.

Skin is the largest organ in the body and has multiple significant functions. A malformation or injury that compromises its integrity can lead to major issues or even mortality. Wound healing is a vital physiological process of the human skin which facilitates the repair of any damage and the preservation of homeostasis. Possible complications or infections that are fatal may ensue if the patient does not recover within the specified time. Therefore, it is essential to develop biomaterials which facilitate tissue regeneration and exhibit robust biological properties. We conducted a meta-analysis of randomized controlled trials to compare combinations of skin replacements and skin grafts to skin grafts alone for wound treatment, as measured by the Vancouver Scar Scale. This meta-analysis utilized various databases, including as PubMed, ProQuest, Web of Science, Science Direct, Scopus, EBSCOhost, and ClinicalTrials.gov, to conduct a comprehensive search for randomized controlled trials that compared the effectiveness of combined skin substitutes and skin grafts to skin grafts alone in the treatment of wounds. The results primarily consisted of scar features assessed using the Vancouver Scar Scale. Meta-analysis was conducted on a sample of 216 participants from 7 randomized controlled trials. The trials were conducted from 2002 to 2015. The study demonstrated that the use of skin substitutes resulted in a statistically significant improvement in Vancouver Scar Scales ratings compared to skin grafts alone. The mean change was 1.38 (95% CI: 0.13-2.63; p = 0.03). This meta-analysis indicates that the use of skin replacements provides substantial advantages and effectively aids in the closure of wounds. There is no inherent superiority among different skin substitutes. Instead, their suitability for specific patient wound circumstances is the determining factor. A comprehensive and advantageous skin substitute of significant magnitude is needed, rather than relying solely on grafts.

Report of outcomes in burn patients enrolled in the Cultured epidermal autograft prospective Registry

Cultured epidermal autograft (CEA) is a permanent skin replacement indicated for use in adult and pediatric patients with deep dermal or full thickness burns comprising a total body surface area (TBSA) ≥ 30 %. CEA (Epicel®) was approved for use in adults in the United States in 2007 as a Humanitarian Use Device (HUD) under a Humanitarian Device Exemption (HDE) and was approved for pediatric use in 2016. In 2019, a CEA Registry was established with an objective of prospective data collection and analysis of demographic, treatment, and outcome data for the real-world use of CEA. At the time of data cut–off (June 2022), 68 patients (50 adults and 18children) had completed data in the registry, up through hospital discharge, for this analysis. Mean total body surface area (TBSA) of the burn was 58 % in adults and 56 % in pediatric patients, and almost half had inhalation injury in each group. Approximately 74 % of adults and 67 % of pediatric patients had TBSA ≥ 50 %. Overall survival was 87 % (84 % adults, 94 % pediatric). Mean % graft take (engraftment) of CEA was 81 % in adults and 84 % in pediatric patients. Outcomes from this prospective collection of data in severely burned patients treated with CEA demonstrate favorable engraftment and survival rates and are in general agreement with recent literature.

Effect of black jelly mushroom (Auricularia polytricha) and olive oil as fat replacers on the physicochemical and microstructural properties of chicken meat emulsion

Black jelly mushroom (BJM) is particularly low in fat, high in fibre, and packed with many antioxidants, antimicrobials and minerals while having unique soaking characteristics and a gel-like texture, while olive oil (OO) contains high monounsaturated fatty acids where both have the potential to be used as fat replacers in meat products. This study evaluated the effect of the replacement of chicken skin (CS) at various percentages (0%, 25%, 50% and 100%) of black jelly mushroom and olive oil on the physicochemical and microstructural properties of chicken meat emulsion. Emulsions with 100% CS (Control), 50% CS + 50% OO, 50% CS + 50% BJM, 50% CS + 25% OO + 25% BJM, 100% OO and 100% BJM were developed. The pH value, cooking loss, protein content, carbohydrate content, textural properties and shear force of all fat-replaced samples were comparable to the control. The most positive results were demonstrated in the emulsion with 100% BJM, which had lower fat content (1.31±0.84%) and better emulsion stability (%TEF:7.97±4.16%, %EFAT:12.97±6.53%), water-holding capacity (86.67±3.06%), and moisture content (76.69±2.13%). The colour profiles of the BJM-incorporated samples had higher redness and the OO-incorporated sample had higher lightness and yellowness. The micrographs revealed a harmonious distribution of fat droplets and mushroom particles in all samples' protein matrices. In conclusion, the black jelly mushroom is capable to be used as a fat replacer in producing low-fat meat emulsion, and its incorporation at 100% level has the highest potential.

Intraoperative bioprinting of human adipose-derived stem cells and extra-cellular matrix induces hair follicle-like downgrowths and adipose tissue formation during full-thickness craniomaxillofacial skin reconstruction

Craniomaxillofacial (CMF) reconstruction is a challenging clinical dilemma. It often necessitates skin replacement in the form of autologous graft or flap surgery, which differ from one another based on hypodermal/dermal content. Unfortunately, both approaches are plagued by scarring, poor cosmesis, inadequate restoration of native anatomy and hair, alopecia, donor site morbidity, and potential for failure. Therefore, new reconstructive approaches are warranted, and tissue engineered skin represents an exciting alternative. In this study, we demonstrated the reconstruction of CMF full-thickness skin defects using intraoperative bioprinting (IOB), which enabled the repair of defects via direct bioprinting of multiple layers of skin on immunodeficient rats in a surgical setting. Using a newly formulated patient-sourced allogenic bioink consisting of both human adipose-derived extracellular matrix (adECM) and stem cells (ADSCs), skin loss was reconstructed by precise deposition of the hypodermal and dermal components under three different sets of animal studies. adECM, even at a very low concentration such as 2 % or less, has shown to be bioprintable via droplet-based bioprinting and exhibited de novo adipogenic capabilities both in vitro and in vivo. Our findings demonstrate that the combinatorial delivery of adECM and ADSCs facilitated the reconstruction of three full-thickness skin defects, accomplishing near-complete wound closure within two weeks. More importantly, both hypodermal adipogenesis and downgrowth of hair follicle-like structures were achieved in this two-week time frame. Our approach illustrates the translational potential of using human-derived materials and IOB technologies for full-thickness skin loss.

A gyermekkori nagyméretű és óriás festéksejtes anyajegyek eltávolításának szempontjai

The removal of common nevi is necessary only in case of irritation, changes causing complaints, or dermatological recommendations, in addition to regular inspections. In case of the need for surgical removal of special birthmarks (e.g. Spitz nevus, Halo nevus, etc.), a dermatological examination and recommendation are also essential. Congenital melanocytic nevus is a special entity. In 1-3% of newborn cases we encounter the small (<1.5 cm) congenital melanocytic nevus, and less often a giant (≥40 cm) nevus. The number, localization and morphology of congenital melanocytic nevi are more important than size in terms of the probability of melanoma occurrence. The treatment of these nevi varies individually and requires teamwork (e.g. dermatologist, oncologist, surgeon, anesthesiologist, pediatrician). All skin incisions leave a scar, and the characteristics of lifelong scars are influenced by many factors. These include age and surgical technique. For plastic surgery performed in childhood, it is advisable to choose the simplest technique – but the one that leads to the most favorable later results – when possible, to avoid complicated flap plasties and skin replacement procedures. When developing the surgical strategy, it is essential to involve the parent and the child in addition to the allied professions, as well as keeping in mind the characteristics of childhood. In the optimal case, the completion of the reconstruction should carry out before get into community, but at the latest by the teenage years.

Bi-layered photocrosslinkable chitosan-curcumin hydrogel/soy protein nanofibrous mat skin substitute

This study examines the efficacy of a two-layer skin replacement composed of a visible-light photocrosslinkable chitosan hydrogel, either unmodified or incorporating curcumin, and overlaid with soy protein isolate (SPI) nanofibers. In order to achieve this objective, the synthesis of methacrylated chitosan was conducted, followed by the electrospinning of a nanofibrous mat using SPI. The resulting structures were then subjected to characterization using established engineering analyses. Following the utilization of the Taguchi method in experimental design, the optimal quantities of curcumin and riboflavin as a photo-initiator, as well as the curing time, were determined. Subsequently, an optimal hydrogel based on methacrylated chitosan was prepared, and the release rates of curcumin and riboflavin were measured over a specified duration.In order to evaluate the in vivo efficacy of the formulated constructs, four distinct experimental groups were included in the study. These groups consisted of an untreated control group, a group treated with hydrogel alone, a group treated with curcumin-loaded hydrogels, and a group treated with hydrogels coated with SPI electrospun mat. The wound healing potential was assessed through the examination of different histomorphometric parameters at two time points: 10 and 20 days following the surgical procedure. Following a period of 20 days, it was observed that all three treatment groups exhibited the capacity to effectively achieve wound closure, generate a fresh epithelial layer, attract fibroblast cells to the site of injury, and impede the infiltration of inflammatory cells. The success of these outcomes varied depending on the regenerative capabilities inherent to each treatment group. Nevertheless, it has been observed that groups treated with curcumin-loaded and SPI nanofibrous mat substances exhibit noteworthy efficacy in wound healing. This can be attributed to the anti-inflammatory properties of curcumin, which aid in reducing inflammation, as well as the epidermal formation facilitated by SPI. The concurrent application of curcumin loading and SPI nanofibrous mat is anticipated to yield notable beneficial alterations in the wound healing process.

Effects of an Adipose Mesenchymal Stem Cell-Derived Conditioned medium and TGF-β1 on Human Keratinocytes In Vitro.

Human keratinocytes play a crucial role during skin wound healing and in skin replacement therapies. The secretome of adipose-derived stem cells (ASCs) has been shown to secrete pro-healing factors, among which include TGF-β1, which is essential for keratinocyte migration and the re-epithelialization of cutaneous wounds during skin wound healing. The benefits of an ASC conditioned medium (ASC-CM) are primarily orchestrated by trophic factors that mediate autocrine and paracrine effects in keratinocytes. Here, we evaluated the composition and the innate characteristics of the ASC secretome and its biological effects on keratinocyte maturation and wound healing in vitro. In particular, we detected high levels of different growth factors, such as HGF, FGFb, and VEGF, and other factors, such as TIMP1 and 4, IL8, PAI-1, uPA, and IGFBP-3, in the ASC-CM. Further, we investigated, using immunofluorescence and flow cytometry, the distinct effects of a human ASC-CM and/or synthetic TGF-β1 on human keratinocyte proliferation, migration, and cell apoptosis suppression. We demonstrated that the ASC-CM increased keratinocyte proliferation as compared to TGF-β1 treatment. Further, we found that the ASC-CM exerted cell cycle progression in keratinocytes via regulating the phases G1, S, and G2/M. In particular, cells subjected to the ASC-CM demonstrated increased DNA synthesis (S phase) compared to the TGF-β1-treated KCs, which showed a pronounced G0/G1 phase. Furthermore, both the ASC-CM and TGF-β1 conditions resulted in a decreased expression of the late differentiation marker CK10 in human keratinocytes in vitro, whereas both treatments enhanced transglutaminase 3 and loricrin expression. Interestingly, the ASC-CM promoted significantly increased numbers of keratinocytes expressing epidermal basal keratinocyte markers, such DLL1 and Jagged2 Notch ligands, whereas those ligands were significantly decreased in TGF-β1-treated keratinocytes. In conclusion, our findings suggest that the ASC-CM is a potent stimulator of human keratinocyte proliferation in vitro, particularly supporting basal keratinocytes, which are crucial for a successful skin coverage after transplantation. In contrast, TGF-β1 treatment decreased keratinocyte proliferation and specifically increased the expression of differentiation markers in vitro.

3D-printed placental-derived bioinks for skin tissue regeneration with improved angiogenesis and wound healing properties.

Extracellular matrix (ECM)-based bioinks has attracted much attention in recent years for 3D printing of native-like tissue constructs. Due to organ unavailability, human placental ECM can be an alternative source for the construction of 3D print composite scaffolds for the treatment of deep wounds. In this study, we use different concentrations (1.5%, 3% and 5%w/v) of ECM derived from the placenta, sodium-alginate and gelatin to prepare a printable bioink biomimicking natural skin. The printed hydrogels' morphology, physical structure, mechanical behavior, biocompatibility, and angiogenic property are investigated. The optimized ECM (5%w/v) 3D printed scaffold is applied on full-thickness wounds created in a mouse model. Due to their unique native-like structure, the ECM-based scaffolds provide a non-cytotoxic microenvironment for cell adhesion, infiltration, angiogenesis, and proliferation. In contrast, they do not show any sign of immune response to the host. Notably, the biodegradation, swelling rate, mechanical property, cell adhesion and angiogenesis properties increase with the increase of ECM concentrations in the construct. The ECM 3D printed scaffold implanted into deep wounds increases granulation tissue formation, angiogenesis, and re-epithelialization due to the presence of ECM components in the construct, when compared with printed scaffold with no ECM and no treatment wound. Overall, our findings demonstrate that the 5% ECM 3D scaffold supports the best deep wound regeneration in vivo, produces a skin replacement with a cellular structure comparable to native skin.

Functionalised-biomatrix for wound healing and cutaneous regeneration: future impactful medical products in clinical translation and precision medicine.

Skin tissue engineering possesses great promise in providing successful wound injury and tissue loss treatments that current methods cannot treat or achieve a satisfactory clinical outcome. A major field direction is exploring bioscaffolds with multifunctional properties to enhance biological performance and expedite complex skin tissue regeneration. Multifunctional bioscaffolds are three-dimensional (3D) constructs manufactured from natural and synthetic biomaterials using cutting-edge tissue fabrication techniques incorporated with cells, growth factors, secretomes, antibacterial compounds, and bioactive molecules. It offers a physical, chemical, and biological environment with a biomimetic framework to direct cells toward higher-order tissue regeneration during wound healing. Multifunctional bioscaffolds are a promising possibility for skin regeneration because of the variety of structures they provide and the capacity to customise the chemistry of their surfaces, which allows for the regulated distribution of bioactive chemicals or cells. Meanwhile, the current gap is through advanced fabrication techniques such as computational designing, electrospinning, and 3D bioprinting to fabricate multifunctional scaffolds with long-term safety. This review stipulates the wound healing processes used by commercially available engineered skin replacements (ESS), highlighting the demand for a multifunctional, and next-generation ESS replacement as the goals and significance study in tissue engineering and regenerative medicine (TERM). This work also scrutinise the use of multifunctional bioscaffolds in wound healing applications, demonstrating successful biological performance in the in vitro and in vivo animal models. Further, we also provided a comprehensive review in requiring new viewpoints and technological innovations for the clinical application of multifunctional bioscaffolds for wound healing that have been found in the literature in the last 5years.

Hyperpigmentation after sclerotherapy: modern possibilities for prevention and treatment

Sclerotherapy is one of the most popular and most common techniques for the removal of delated reticular veins and telangiectasias on the lower limbs. Despite the vast pooled experience, this procedure can be accompanied by a number of undesirable side effects, of which post-injection hyperpigmentation, which frequency reaches 80%, is the most unpleasant one. The development of postsclerotherapy hyperpigmentation (PSHP) is associated with extravasation and destruction of red blood cells, which results in transformation of haemoglobin into hemosiderin pigment. PSHP is, by definition, a variant of post-traumatic hemosiderin pigmentation. The likelihood of occurrence and persistence of PSHP is determined by a number of hard controllable factors, including the calibre and location of the target veins, the type, concentration and physical form of the sclerosing agent, the sclerotherapy technique, the method and duration of post-procedural compression, patients’ ethnicity, iron metabolism disorders, concomitant use of a number of drugs, a menstrual cycle phase in women, etc. Hyperpigmentation significantly decreases the patients’ quality of life, which determines the need for the prevention and treatment of this undesirable side effect of phlebosclerosing treatment. Recommendations for prevention of PSHP include a detailed history taking aimed at identifying potential risk factors, in the presence of which it is advisable to use various systemic and topical drugs in the post-procedural period in order to prevent the skin hemosiderin deposition, as well as to apply the extended-cycle compression. In the case of PSHP, procedures aimed at the destruction and utilization of hemosiderin, such as Q-Switched laser and IPL therapy, as well as various peeling options intended to speed up the replacement of pigmented skin with normal, can be applied. For the PSHP prevention and treatment, the use of Contractubex containing cepalin onion extract in combination with allantoin and heparin is a matter of interest. Contractubex is a drug originally intended to optimize wound healing and prevent the formation of hypertrophic scars. At the same time, there is ample publications discussing the possible use of this drug for the management of post-traumatic hyperpigmentation due to the combined action of its components. Our clinical experience confirms the effectiveness of Contractubex in the treatment of PSHP, which determines the feasibility of conducting full-fledged clinical trials and accumulating more pooled experience in this area.