A Polyvinyl Alcohol/Acrylamide Hydrogel with Enhanced Mechanical Properties Promotes Full-Thickness Skin Defect Healing by Regulating Immunomodulation and Angiogenesis Through Paracrine Secretion

Hydrogel-based tissue-engineered skin has attracted increased attention due to its potential to restore the structural integrity and functionality of skin.However,the mechanical properties of hydrogel scaffolds and natural skin are substantially different.Here,we developed a polyvinyl alcohol(PVA)/acrylamide based interpenetrating network(IPN)hydrogel that was surface modified with polydopamine(PDA)and termed Dopa-gel.The Dopa-gel exhibited mechanical properties similar to native skin tissue and a superior ability to modulate paracrine functions.Furthermore,a tough scaffold with tensile resistance was fabricated using this hydrogel by three-dimensional printing.The results showed that the interpenetration of PVA,alginate,and polyacrylamide networks notably enhanced the mechanical properties of the hydrogel.Surface modification with PDA endowed the hydrogels with increased secretion of immunomodulatory and proangiogenic factors.In an in vivo model,Dopa-gel treatment accelerated wound closure,increased vascularization,and promoted a shift in macrophages from a proinflammatory M1 phenotype to a prohealing and anti-inflammatory M2 phenotype within the wound area.Mechanistically,the focal adhesion kinase(FAK)/extracellular signal-related kinase(ERK)signaling pathway may mediate the promotion of skin defect healing by increasing paracrine secretion via the Dopa-gel.Additionally,proangiogenic factors can be induced through Rho-associated kinase-2(ROCK-2)/vascular endothelial growth factor(VEGF)-mediated paracrine secretion under tensile stress conditions.Taken together,these findings suggest that the multifunctional Dopa-gel,which has good mechanical properties similar to those of native skin tissue and enhanced immunomodulatory and angiogenic properties,is a promising scaffold for skin tissue regeneration.

Oxygen Penetration Through Full-Thickness Skin by Oxygen-Releasing Sutures for Skin Graft Transplantation

The transplantation of full-thickness skin grafts(FTSGs)is important for reconstructing skin barrier and promoting wound healing.Sufficient oxygen supply is closely related to the success of skin grafting.However,full-thickness oxygen delivery is limited by the poor oxygen permeability of skin.Oxygen-releasing sutures(O_(2)sutures)were developed to facilitate oxygen penetration through full-thickness skin.The O_(2)sutures delivered 100 times more oxygen than topical gaseous oxygen therapy at a 15 mm depth in the skin model.Under extreme hypoxia(<0.5%O_(2),v/v),O_(2)sutures could also promote endothelial cell proliferation.After the transplantation of FTSGs in mice,O_(2)sutures accelerated blood re-perfusion and increased the survival area of the skin graft.It is expected that O_(2)sutures will be adopted in clinical applications to increase the success rate of full-thickness skin transplantation.

Effects of hyperbaric oxygen therapy on 32 cases of full-thickness skin grafting for the repair of defects on the hand and foot

Full-thickness skin grafting is one of the most commonly used repair methods for skin defects. It has the advantage of wear-resistant with less scar hyperplasia and less difficult to operate with no symptoms. Hyperbaric oxygen was used in this study after full-thickness skin grafting from September 2012 to August 2016 to achieve the best effect of skin survival after surgery.

3-D bioprinted human-derived skin organoids accelerate full-thickness skin defects repair

The healing of large skin defects remains a significant challenge in clinical settings.The lack of epidermal sources,such as autologous skin grafting,limits full-thickness skin defect repair and leads to excessive scar formation.Skin organoids have the potential to generate a complete skin layer,supporting in-situ skin regeneration in the defect area.In this study,skin organoid spheres,created with human keratinocytes,fibroblasts,and endothelial cells,showed a specific structure with a stromal core surrounded by surface keratinocytes.We selected an appropriate bioink and innovatively combined an extrusion-based bioprinting technique with dual-photo source cross-linking technology to ensure the overall mechanical properties of the 3D bioprinted skin organoid.Moreover,the 3D bioprinted skin organoid was customized to match the size and shape of the wound site,facilitating convenient implantation.When applied to full-thickness skin defects in immunodeficient mice,the 3D bioprinted human-derived skin organoid significantly accelerated wound healing through in-situ regeneration,epithelialization,vascularization,and inhibition of excessive inflammation.The combination of skin organoid and 3D bioprinting technology can overcome the limitations of current skin substitutes,offering a novel treatment strategy to address large-area skin defects.

Double-nylon purse-string suture technique: Another addition to the endoscopist's toolbox for full-thickness defect closure

Iatrogenic perforation is the most feared adverse event in endoscopy.With the expansion of interventional endoscopy in favor of traditional surgery,it is now more crucial than ever to develop effective defect closure techniques.This has culminated in the dissemination of multiple novel closure technologies,including through-the-scope clips,over-the-scope clips,through-the-scope suturing and over-the-scope suturing devices.In this editorial,we comment on the recent publication by Wang and colleagues discussing the performance of the double-nylon purse-string suture technique in the closure of large(>3 cm)gastric full-thickness defects.This technique offers a promising,practical and cost-effective approach to closure of large full-thickness defects that can be readily imple-mented across diverse healthcare settings.

Effect of endoscopic full-thickness resection assisted by distal serosal turnover with floss traction for gastric submucosal masses

BACKGROUND Complex and high-risk surgical complications pose pressing challenges in the clinical implementation and advancement of endoscopic full-thickness resection(EFTR).Successful perforation repair under endoscopy,thereby avoiding surgical intervention and postoperative complications such as peritonitis,are pivotal for effective EFTR.AIM To investigate the effectiveness and safety of EFTR assisted by distal serosal inversion under floss traction in gastric submucosal tumors.METHODS A retrospective analysis of patients with gastric and duodenal submucosal tumors treated with EFTR assisted by the distal serosa inversion under dental floss traction from January 2023 to January 2024 was conducted.The total operation time,tumor dissection time,wound closure time,intraoperative bleeding volume,length of hospital stay and incidence of complications were analyzed.RESULTS There were 93 patients,aged 55.1±12.1 years.Complete tumor resection was achieved in all cases,resulting in a 100% success rate.The average total operation time was 67.4±27.0 min,with tumor dissection taking 43.6±20.4 min.Wound closure times varied,with gastric body closure time of 24.5±14.1 min and gastric fundus closure time of 16.6±8.7 min,showing a significant difference(P<0.05).Intraoperative blood loss was 2.3±4.0 mL,and average length of hospital stay was 5.7±1.9 d.There was no secondary perforation after suturing in all cases.The incidence of delayed bleeding was 2.2%,and the incidence of abdominal infection was 3.2%.No patient required other surgical intervention during and after the operation.CONCLUSION Distal serosal inversion under dental-floss-assisted EFTR significantly reduced wound closure time and intraoperative blood loss,making it a viable approach for gastric submucosal tumors.

Postoperative encapsulated hemoperitoneum in a patient with gastric stromal tumor treated by exposed endoscopic full-thickness resection: A case report

BACKGROUND Gastric stromal tumors,originating from mesenchymal tissues,are one of the most common tumors of the digestive tract.For stromal tumors originating from the muscularis propria,compared with conventional endoscopic submucosal dissection(ESD),endoscopic full-thickness resection(EFTR)can remove deep lesions and digestive tract wall tumors completely.However,this technique has major limitations such as perforation,postoperative bleeding,and post-polypectomy syndrome.Herein,we report a case of postoperative serous surface bleeding which formed an encapsulated hemoperitoneum in a patient with gastric stromal tumor that was treated with exposed EFTR.Feasible treatment options to address this complication are described.CASE SUMMARY A 47-year-old male patient had a hemispherical protrusion found during gastric endoscopic ultrasonography,located at the upper gastric curvature adjacent to the stomach fundus,with a smooth surface mucosa and poor mobility.The lesion was 19.3 mm×16.1 mm in size and originated from the fourth ultrasound layer.Computed tomography(CT)revealed no significant evidence of lymph node enlargement or distant metastasis.Using conventional ESD technology for mucosal pre-resection,exposed EFTR was performed to resect the intact tumor in order to achieve a definitive histopathological diagnosis.Based on its morphology and immunohistochemical expression of CD117 and DOG-1,the lesion was proven to be consistent with a gastric stromal tumor.Six days after exposed EFTR,CT showed a large amount of encapsulated fluid and gas accumulation around the stomach.In addition,gastroscopy suggested intracavitary bleeding and abdominal puncture drainage indicated serosal bleeding.Based on these findings,the patient was diagnosed with serosal bleeding resulting in encapsulated abdominal hemorrhage after exposed EFTR for a gastric stromal tumor.The patient received combined treatments,such as hemostasis under gastroscopy,gastrointestinal decompression,and abdominal drainage.All examinations were normal within six months of follow-up.CONCLUSION This patient developed serous surface bleeding in the gastric cavity following exposed EFTR.Serosal bleeding resulting in an encapsulated hemoperitoneum is rare in clinical practice.The combined treatment may replace certain surgical techniques.

A CS-based composite scaffold with excellent photothermal effect and its application in full-thickness skin wound healing

The development of natural polymer-based scaffolds with excellent biocompatibility,antibacterial activity,and blood compatibility,able to facilitate full-thickness skin wound healing,remains challenging.In this study,we have developed three chitosan(CS)-based porous scaffolds,including CS,CS/CNT(carbon nanotubes)and CS/CNT/HA(nano-hydroxyapatite,n-HA)using a freeze-drying method.All three scaffolds have a high swelling ratio,excellent antibacterial activity,outstanding cytocompatibility and blood compatibility in vitro.The introduction of CNTs exhibited an obvious increase in mechanical properties and exerts excellent photothermal response,which displays excellent healing performance as a wound dressing in mouse full-thickness skin wound model when compared to CS scaffolds.CS/CNT/HA composite scaffolds present the strongest ability to promote full-thickness cutaneous wound closure and skin regeneration,which might be ascribed to the synergistic effect of photothermal response from CNT and excellent bioactivity from n-HA.Overall,the present study indicated that CNT and n-HA can be engineered as effective constituents in wound dressings to facilitate full-thickness skin regeneration.

One-step approach for full-thickness skin defect reconstruction in rats using minced split-thickness skin grafts with Pelnac overlay

Background:Split-thickness skin grafting is the current gold standard for the treatment of traumatic skin loss.However,for patients with extensive burns,split-thickness skin grafting is limited by donor skin availability.Grafting split-thickness skin minced into micrografts increases the expansion ratio but may reduce wound repair quality.Dermal substitutes such as Pelnac can enhance the healing of full-thickness skin wounds,but their application currently requires two surgeries.The present study investigated whether it is possible to repair full-thickness skin defects and improve wound healing quality in a single surgery using Pelnac as an overlay of minced split-thickness skin grafts in a rat model.Methods:A full-thickness skin defect model was established using male Sprague-Dawley rats of 10 weeks old.The animals were randomly divided into control and experimental groups in which Vaseline gauze and Pelnac,respectively,were overlaid on minced split-thickness skin grafts to repair the defects.Wound healing rate and quality were compared between the two groups.For better illustration of the quality of wound healing,some results were compared with those obtained for normal skin of rats.Results:We found that using Pelnac as an overlay for minced split-thickness skin grafts accelerated wound closure and stimulated cell proliferation and tissue angiogenesis.In addition,this approach enhanced collagen synthesis and increased the formation of basement membrane and dermis as well as the expression of growth factors related to wound healing while reducing scar formation.Conclusions:Using minced split-thickness skin grafts overlaid with Pelnac enables the reconstruction of fullthickness skin defects in a single step and can increase the healing rate while improving the quality of wound healing.

Ultraconformable Integrated Wireless Charging Micro-Supercapacitor Skin

Conformable and wire-less charging energy storage devices play important roles in enabling the fast development of wearable,non-contact soft electronics.However,current wire-less charging power sources are still restricted by limited flexural angles and fragile connection of components,resulting in the failure expression of performance and constraining their fur-ther applications in health monitoring wearables and moveable artificial limbs.Herein,we present an ultracompatible skin-like integrated wireless charging micro-supercapacitor,which building blocks(including electrolyte,electrode and substrate)are all evaporated by liquid precursor.Owing to the infiltration and permeation of the liquid,each part of the integrated device attached firmly with each other,forming a compact and all-in-one configuration.In addition,benefitting from the controllable volume of electrode solution precursor,the electrode thickness is easily regulated varying from 11.7 to 112.5μm.This prepared thin IWC-MSC skin can fit well with curving human body,and could be wireless charged to store electricity into high capacitive micro-supercapacitors(11.39 F cm-3)of the integrated device.We believe this work will shed light on the construction of skin-attachable electronics and irregular sensing microrobots.

Recent advances and current challenges in endoscopic resection with the full-thickness resection device

Endoscopic full-thickness resection(EFTR)has emerged as a viable technique in the management of mucosal and subepithelial lesions of the gastrointestinal tract(GIT)not amenable to conventional therapeutic approaches.While various devices and techniques have been described for EFTR,a single,combined fullthickness resection and closure device(full-thickness resection device,FTRD system,Ovesco Endoscopy AG,Tuebingen,Germany)has become commercially available in recent years.Initially,the FTRD system was limited to use in the colorectum only.Recently,a modified version of the FTRD has been released for EFTR in the upper GIT as well.This review provides a broad summary of the FTRD,highlighting recent advances and current challenges.

Extensively infarcted giant solitary hamartomatous polyp treated with endoscopic full-thickness resection:A case report

BACKGROUND Solitary hamartomatous polyps(SHPs)are rare lesions.Endoscopic full-thickness resection(EFTR)is a highly efficient and minimally invasive endoscopic procedure that benefits from complete lesion removal and high safety.CASE SUMMARY A 47-year-old man was admitted to our hospital after experiencing hypogastric pain and constipation for over fifteen days.Computed tomography and endoscopy revealed a giant pedunculated polyp(approximately 18 cm long)in the descending and sigmoid colon.This is the largest SHP reported to date.Having considered the condition of the patient and mass growth,the polyp was removed using EFTR.CONCLUSION On the basis of clinical and pathological evaluations,the mass was considered an SHP.

Use of autologous tissue engineered skin to treat porcine full-thickness skin defects

Objective. To explore a feasible method to repair full-thickness skin defects utilizing tissue engineered techniques. Methods： The Changfeng hybrid swines were used and the skin specimens were cut from the posterior limb girdle region, from which the keratinocytes and fibroblasts were isolated and harvested by trypsin, EDTA, and type II collagenase. The cells were seeded in Petri dishes for primary culture. When the cells were in logarithmic growth phase, they were treated with trypsin to separate them from the floor of the tissue culture dishes. A biodegradable material, Pluronic F-127, was prefabricated and mixed with these cells, and then the cell-Pluronic compounds were seeded evenly into a polyglycolic acid （PGA）. Then the constructs were replanted to the autologous animals to repair the full-thickness skin defects. Histology and immunohistochemistry of the neotissue were observed in 1, 2, 4, and 8 postoperative weeks. Results. The cell-Pluronic F-127-PGA compounds repaired autologous full-thickness skin defects 1 week after implantation. Histologically, the tissue engineered skin was similar to the normal skin with stratified epidermis overlying a moderately thick collageneous dermis. Three of the structural proteins in the epidermal basement membrane zone, type IV collagen, laminin, and type VII collagen were detected using immunohistochemicai methods. Conclusions ： By studying the histology and immunohistochemistry of the neotissue, the bioengineered skin graft holds great promise for improving healing of the skin defects.

The efficacy of full-thickness endoscopic resection of subepithelial tumors in the gastric cardia

BACKGROUND Gastric subepithelial tumors(SETs)may harbor potential malignancy.Although it is well recognized that large SETs should be resected,the precise treatment strategy remains controversial.Compared to surgical resection,endoscopic resection(ER)has many advantages;however,ER of SETs in the cardia is challenging.AIM To evaluate the safety and efficacy of endoscopic full-thickness resection(EFTR)for the treatment of gastric cardia SETs.METHODS We retrospectively reviewed data from all patients with SETs originating from the muscularis propria layer in the gastric cardia that were treated by EFTR or submucosal tunneling ER(STER)at Zhongshan Hospital Fudan University between November 2014 and May 2022.Baseline characteristics and clinical outcomes,including procedure times and complications rates,were compared between groups of patients receiving EFTR and STER.RESULTS A total of 171 tumors were successfully removed[71(41.5%)tumors in the EFTR and 100(58.5%)tumors in the STER group].Gastrointestinal stromal tumors(GISTs)were the most common SET.The en bloc resection rate was 100%in the EFTR group vs 97.0%in STER group(P>0.05).Overall,the EFTR group had a higher complete resection rate than the STER group(98.6%vs 91.0%,P<0.05).The procedure time was also shorter in the EFTR group(44.63±28.66 min vs 53.36±27.34,P<0.05).The most common major complication in both groups was electrocoagulation syndrome.There was no significant difference in total complications between the two groups(21.1%vs 22.0%,P=0.89).CONCLUSION EFTR of gastric cardia SETs is a very promising method to facilitate complete resection with similar complications and reduced operative times compared to STER.In cases of suspected GISTs or an unclear diagnosis,EFTR should be recommended to ensure complete resection.

Bioengineered skin organoids:from development to applications

Signifcant advancements have been made in recent years in the development of highly sophisticated skin organoids.Serving as three-dimensional(3D)models that mimic human skin,these organoids have evolved into complex structures and are increasingly recognized as efective alternatives to traditional culture models and human skin due to their ability to overcome the limitations of two-dimensional(2D)systems and ethical concerns.The inherent plasticity of skin organoids allows for their construction into physiological and pathological models,enabling the study of skin development and dynamic changes.This review provides an overview of the pivotal work in the progression from 3D layered epidermis to cyst-like skin organoids with appendages.Furthermore,it highlights the latest advancements in organoid construction facilitated by state-of-the-art engineering techniques,such as 3D printing and microfuidic devices.The review also summarizes and discusses the diverse applications of skin organoids in developmental biology,disease modelling,regenerative medicine,and personalized medicine,while considering their prospects and limitations.

A Comprehensive Systematic Review: Advancements in Skin Cancer Classification and Segmentation Using the ISIC Dataset

The International Skin Imaging Collaboration(ISIC)datasets are pivotal resources for researchers in machine learning for medical image analysis,especially in skin cancer detection.These datasets contain tens of thousands of dermoscopic photographs,each accompanied by gold-standard lesion diagnosis metadata.Annual challenges associated with ISIC datasets have spurred significant advancements,with research papers reporting metrics surpassing those of human experts.Skin cancers are categorized into melanoma and non-melanoma types,with melanoma posing a greater threat due to its rapid potential for metastasis if left untreated.This paper aims to address challenges in skin cancer detection via visual inspection and manual examination of skin lesion images,processes historically known for their laboriousness.Despite notable advancements in machine learning and deep learning models,persistent challenges remain,largely due to the intricate nature of skin lesion images.We review research on convolutional neural networks(CNNs)in skin cancer classification and segmentation,identifying issues like data duplication and augmentation problems.We explore the efficacy of Vision Transformers(ViTs)in overcoming these challenges within ISIC dataset processing.ViTs leverage their capabilities to capture both global and local relationships within images,reducing data duplication and enhancing model generalization.Additionally,ViTs alleviate augmentation issues by effectively leveraging original data.Through a thorough examination of ViT-based methodologies,we illustrate their pivotal role in enhancing ISIC image classification and segmentation.This study offers valuable insights for researchers and practitioners looking to utilize ViTs for improved analysis of dermatological images.Furthermore,this paper emphasizes the crucial role of mathematical and computational modeling processes in advancing skin cancer detection methodologies,highlighting their significance in improving algorithmic performance and interpretability.

Regulatory T cells in skin regeneration and wound healing

As the body’s integumentary system,the skin is vulnerable to injuries.The subsequent wound healing processes aim to restore dermal and epidermal integrity and functionality.To this end,multiple tissue-resident cells and recruited immune cells cooperate to efficiently repair the injured tissue.Such temporally-and spatially-coordinated interplay necessitates tight regulation to prevent collateral damage such as overshooting immune responses and excessive inflammation.In this context,regulatory T cells(Tregs)hold a key role in balancing immune homeostasis and mediating cutaneous wound healing.A comprehensive understanding of Tregs’multifaceted field of activity may help decipher wound pathologies and,ultimately,establish new treatment modalities.Herein,we review the role of Tregs in orchestrating the regeneration of skin adnexa and catalyzing healthy wound repair.Further,we discuss how Tregs operate during fibrosis,keloidosis,and scarring.

Atmospheric Particulate Matter 2.5(PM_(2.5))Induces Cell Damage and Pruritus in Human Skin

With the accelerated rate of urbanization in recent years,air pollution has become an environmental problem that requires urgent resolution,almost all of the world’s population exposed to pollution on a daily basis.Among the various air pollutants,the excessive dispersion and suspension of particulate matter(PM)in the air.

Anti-skin aging effects and bioavailability of collagen tripeptide and elastin peptide formulations in young and middle-aged women

Background:Collagen peptides(CP),including tripeptides and elastin peptides(EP),are known for their in vitro and in vivo anti-skin aging effects.Despite positive results in animal models,the combination effects of CP and EP and the bioavailability of CP in human studies,particularly in young and middle-aged women,remain underexplored.Objective:To evaluate the effects of an orally administered collagen drink combining CP and EP on the skin health of young and middle-aged women.Materials and Methods:A single-center,randomized,double-blind,parallel-controlled trial was conducted,utilizing the WONDERLABR fish collagen tripeptide beverage.Participants consumed the drink over an 8-week period.Results:Compared to the placebo group,the collagen drink group showed significant improvements in skin hydration(39.19%increase),transepidermal water loss(33.45%decrease),skin elasticity(25.37%increase),dermal collagen content(21.64%increase),pore size(7.94%decrease),wrinkle length(18.09%decrease),skin smoothness(2.85%improvement),and skin roughness(15.32%decrease).Overall pore volume decreased by 60%,and visual assessments indicated a decrease in skin luminosity by 15.20%and smoothness index by 22.55%.Mass spectrometry demonstrated a significant increase in collagen efficacy components,including blood pH and GPH levels(P<0.05).Conclusion:The study confirmed the combination nourishing and anti-skin aging effects of EP and CP on the skin of young and middle-aged women,demonstrating significant improvements in various skin parameters and good bioavailability of collagen peptides.

Nanozyme‑Engineered Hydrogels for Anti‑Inflammation and Skin Regeneration

Inflammatory skin disorders can cause chronic scarring and functional impairments,posing a significant burden on patients and the healthcare system.Conventional therapies,such as corticosteroids and nonsteroidal anti-inflammatory drugs,are limited in efficacy and associated with adverse effects.Recently,nanozyme(NZ)-based hydrogels have shown great promise in addressing these challenges.NZ-based hydrogels possess unique therapeutic abilities by combining the therapeutic benefits of redox nanomaterials with enzymatic activity and the water-retaining capacity of hydrogels.The multifaceted therapeutic effects of these hydrogels include scavenging reactive oxygen species and other inflammatory mediators modulating immune responses toward a pro-regenerative environment and enhancing regenerative potential by triggering cell migration and differentiation.This review highlights the current state of the art in NZ-engineered hydrogels(NZ@hydrogels)for anti-inflammatory and skin regeneration applications.It also discusses the underlying chemo-mechano-biological mechanisms behind their effectiveness.Additionally,the challenges and future directions in this ground,particularly their clinical translation,are addressed.The insights provided in this review can aid in the design and engineering of novel NZ-based hydrogels,offering new possibilities for targeted and personalized skin-care therapies.