Abstract Extracellular vesicles (EVs) have become key mediators of intercellular communication in melanoma cells and significantly affect disease progression by delivering bioactive molecules. EVs are loaded with a wide variety of biomolecule carriers, including proteins, DNA, mRNAs and non‐coding RNAs, which can affect processes such as tumour growth, metastasis, angiogenesis, drug resistance and immune escape. Melanoma‐derived EVs dynamically reshape the tumour microenvironment (TME) by regulating different cellular components, such as cancer‐associated fibroblasts (CAFs), endothelial cells, T cells, macrophages and natural killer (NK) cells. In addition, we emphasize the enormous potential of EVs as minimally invasive biomarkers for diagnosis, prognosis prediction and treatment monitoring. The biocompatibility and targeting characteristics of EVs also make them promising platforms for drug delivery, including as carriers for chemotherapy drugs and immunomodulators. In this review, we emphasized the key role of EVs in melanoma and their dynamic regulation of microenvironment components, providing new diagnostic and therapeutic approaches for the use of EVs in the treatment of invasive malignant tumours. Highlights Melanoma‐derived EVs carry diverse biomolecules that reprogram the tumor microenvironment. EVs mediate immune escape, drug resistance and metastasis via key signaling pathways. EVs serve as minimally invasive liquid biopsy biomarkers for diagnosis, prognosis, and therapy monitoring. Engineered EVs offer promising platforms for targeted drug delivery and immunotherapy in melanoma.

BackgroundIn past three decades, the development of therapeutic vaccines has been a major focus in melanoma research. This strategy seeks to prime the immune system to combat the cancer, ideally leading to the eradication of recurrent disease or a delay in its progression. To date, clinical trials have assessed multiple vaccine methodologies, but the evidence for a clear clinical impact remains ambiguous.Data sourcesWe retrieved relevant clinical trials published as of 1990 through electronic databases, including PubMed, the Cochrane library and ClinicalTrials.gov. The key search terms were “melanoma,” “vaccine,” and “clinical trials”.Study selectionPublications that met the following criteria were included as follows: (i) melanoma patients included; (ii) clinical trial registered; (iii) described the patients’ outcomes; (iv) were full-text articles published in English.ResultsA total of sixteen distinct methodologies have been evaluated in randomized phase III clinical trials. Among these, Talimogene laherparevec (T-VEC) is the sole vaccine that has received approval from the U.S. Food and Drug Administration (FDA) for melanoma treatment. Most vaccine strategies demonstrated acceptable safety profiles and elicited immune responses, but they exhibited limited clinical efficacy. When integrated with other immunomodulatory agents, their therapeutic potential appears significantly enhanced.ConclusionsWithin future therapeutic frameworks, melanoma vaccines are envisioned to play a key role by inducing and amplifying a targeted T-cell response against cancer. This approach is particularly suited for combination with other immunotherapies that neutralize the resistance mechanisms found in the tumor microenvironment.

Diabetic wound (DW), notorious for prolonged healing processes due to the unregulated immune response, neuropathy, and persistent infection, poses a significant challenge to clinical management. Current strategies for treating DW primarily focus on alleviating the inflammatory milieu or promoting angiogenesis, while limited attention has been given to modulating the neuro-immune microenvironment. Thus, we present an electrically conductive hydrogel dressing and identify its neurogenesis influence in a nerve injury animal model initially by encouraging the proliferation and migration of Schwann cells. Further, endowed with the synergizing effect of near-infrared responsive release of curcumin and nature-inspired artificial heterogeneous melanin nanoparticles, it can harmonize the immune microenvironment by restoring the macrophage phenotype and scavenging excessive reactive oxygen species. This in-situ formed hydrogel also exhibits mild photothermal therapy antibacterial efficacy. In the infected DW model, this hydrogel effectively supports nerve regeneration and mitigates the immune microenvironment, thereby expediting the healing progress. The versatile hydrogel exhibits significant therapeutic potential for application in DW healing through fine-tuning the neuro-immune microenvironment.

Tissue-engineered auricular cartilage (TEAC) represents a promising solution for microtia reconstruction. However, current approaches often fail to address the long-term stability and regeneration of the elastic cartilage, which is essential for maintaining the structural integrity and functional properties of the reconstructed tissue over time. In this study, a bionic TEAC scaffold fabricated by 3D bioprinting of thermoplastic polyurethane (TPU) scaffold loaded with GelMA cryogel microspheres and perichondrial stem/progenitor cells (PSPCs) was proposed for microtia reconstruction. The microcarriers (GelMA CM-30) were inspired by the beehive and prepared using a combination of emulsion and cryogel techniques. This design enhanced the interconnection pores that biomimic the lacunar structure of native auricular cartilage. In vitro study indicated that the temporal 3D culture of PSPCs on GelMA CM-30 uniquely promoted chondrogenic differentiation and extracellular matrix (ECM) remodeling, which promoted regeneration of elastic cartilage in response to mechanical restraint of the pores. Transcriptome analyses further revealed a remarkable upregulation of relevant genes related to collagen synthesis and elastic cartilage ECM and a downregulation of genes related to matrix metalloproteinases (MMPs). In vivo results indicated that the TPU@CM-30@PSPCs scaffold exhibited favorable cytocompatibility and promoted the formation of elastic neocartilage from PSPCs. This strategy combining scaffold reinforcement with potent tissue-specific stem cells and mechanical cues shows good potential for the development of clinically applicable TEACs for microtia reconstruction.

Keloids, pathological scars resulting from skin trauma, have traditionally posed significant clinical management challenges due to their persistence and high recurrence rates. Our research elucidates the pivotal roles of lipids and their derivatives in keloid development, driven by underlying mechanisms of abnormal cell proliferation, apoptosis, and extracellular matrix deposition. Key findings suggest that abnormalities in arachidonic acid (AA) synthesis and non-essential fatty acid synthesis are integral to keloid formation. Further, a complex interplay exists between lipid derivatives, notably butyric acid (BA), prostaglandin E2 (PGE2), prostaglandin D2 (PGD2), and the regulation of hyperfibrosis. Additionally, combinations of docosahexaenoic acid (DHA) with BA and 15-deoxy-Δ12,14-Prostaglandin J2 have exhibited pronounced cytotoxic effects. Among sphingolipids, ceramide (Cer) displayed limited pro-apoptotic effects in keloid fibroblasts (KFBs), whereas sphingosine 1-phosphate (S1P) was found to promote keloid hyperfibrosis, with its analogue, FTY720, demonstrating contrasting benefits. Both Vitamin D and hexadecylphosphorylcholine (HePC) showed potential antifibrotic and antiproliferative properties, suggesting their utility in keloid management. While keloids remain a prevalent concern in clinical practice, this study underscores the promising potential of targeting specific lipid molecules for the advancement of keloid therapeutic strategies.

Abdominoplasty is increasingly sought after by patients for aesthetic rejuvenation or functional improvement. However, no previous study has comprehensively evaluated the impact of diabetes on post-abdominoplasty complications. This systematic review aimed to investigate the impact of diabetes on outcomes following abdominoplasty. A comprehensive literature search was conducted systematically on MEDLINE Ovid, PubMed, Web of Science, and the Cochrane CENTRAL databases from inception to January 2023. The primary outcomes of interest were overall complications. The secondary outcomes included major complications and minor complications. A meta-analysis was performed in accordance with PRISMA guidelines to examine the impact of diabetes on post-abdominoplasty complications. A total of fifteen studies involving 79724 patients, 5483 of whom had diabetes, met our inclusion criteria. Patients with diabetes were more likely to suffer from overall complications (OR = 1.63, 95 www.springer.com/00266 .

Schematic illustration of roles and targets of immunoregulatory cells and hydrogel design strategies to promote wound healing.

Objective: Anoikis is a kind of programmed cell death that is triggered when cells lose contact with each other or with the matrix. However, the potential value of anoikis-related genes (ARGs) in keloid (KD) has not been investigated.Approach: We downloaded three keloid fibroblast (KF) RNA sequencing (RNA-seq) datasets from the Gene Expression Omnibus (GEO) and obtained 338 ARGs from a search of the GeneCards database and PubMed articles. Weighted correlation network analysis was used to construct the coexpression network and obtain the KF-related ARGs. The LASSO-Cox method was used to screen the hub ARGs and construct the best prediction model. Then, GEO single-cell sequencing datasets were used to verify the expression of hub genes. We used whole RNA-seq for gene-level validation and the correlation between KD immune infiltration and anoikis.Results: Our study comprehensively analyzed the role of ARGs in KD for the first time. The least absolute shrinkage and selection operator (LASSO) regression analysis identified six hub ARGs (HIF1A, SEMA7A, SESN1, CASP3, LAMA3, and SIK2). A large number of miRNAs participate in the regulation of hub ARGs. In addition, correlation analysis revealed that ARGs were significantly correlated with the infiltration levels of multiple immune cells in patients with KD.Innovation: We explored the expression characteristics of ARGs in KD, which is extremely important for determining the molecular pathways and mechanisms underlying KD.Conclusions: This study provides a useful reference for revealing the characteristics of ARGs in the pathogenesis of KD. The identified hub genes may provide potential therapeutic targets for patients. This study provides new ideas for individualized therapy and immunotherapy.

Introduction Several systematic reviews and meta-analyses have confirmed that percutaneous vertebroplasty and percutaneous kyphoplasty showed safety and beneficial efficacy in patients with osteoporotic vertebral compression fractures. Whereas, there is wide variation among results, which are not conducive to the evaluation and use of clinicians. This study will investigate the efficacy and safety of percutaneous vertebroplasty and percutaneous kyphoplasty for the treatment of osteoporotic vertebral compression fractures, aiming to provide a more reliable evidence base for clinical practice in treating osteoporotic vertebral compression fractures.Methods and analysis We will retrieve the relevant articles using the five databases(PubMed, Scopus, EMBASE, Cochrane Library and Web of Science) from inception to March 2023 for systematic review and meta-analysis comparing the overall safety and efficacy of percutaneous vertebroplasty and percutaneous kyphoplasty in patients with osteoporotic vertebral compression fractures. Three reviewers will screen citation titles, abstracts and evaluate the full text of each relevant citation based on prespecified eligibility criteria. Any discrepancies in decisions between reviewers will be resolved through discussion. We will assess the methodological quality of the included studies according to A MeaSurement Tool to Assess systematic Reviews 2 checklist.Ethics and dissemination This umbrella review will inform clinical and policy decisions regarding the benefits and harms of percutaneous vertebroplasty versus percutaneous kyphoplasty for osteoporotic vertebral compression fractures. Neither primary data nor individual patient information will be collected, thus ethics approval is not required. Findings will be reported through a peer-reviewed publication, conference presentations and the popular press.PROSPERO registration number CRD42021268141.

Objective To explore the complex mechanisms of keloid, new approaches have been developed by different strategies. However, conventional treatment did not significantly reduce the recurrence rate. This study aimed to identify new biomarkers and mechanisms for keloid progression through bioinformatics analyses. Methods In our study, microarray datasets for keloid were downloaded from the GEO database. Differentially expressed genes (DEGs) were identified by R software. Multiple bioinformatics tools were used to identify hub genes, and reverse predict upstream miRNAs and lncRNA molecules of target hub genes. Finally, the total RNA-sequencing technique and miRNA microarray were combined to validate the identified genes. Results Thirty-one DEGs were screened out and the upregulated hub gene SPP1 was finally identified, which was consistent with our RNA-sequencing analysis results and validation dataset. In addition, a ceRNA network of mRNA (SPP1)-miRNA (miR-181a-5p)-lncRNA (NEAT1, MALAT1, LINC00667, NORAD, XIST and MIR4458HG) was identified by the bioinformatics databases. The results of our miRNA microarray showed that miR-181a-5p was upregulated in keloid, also we found that the lncRNA NEAT1 could affect keloid progression by retrieving the relevant literature. Conclusions We speculate that SPP1 is a potential candidate biomarker and therapeutic target for patients with keloid, and NEAT1/miR-181a-5p/SPP1 might be the RNA regulatory pathway that regulates keloid formation.

At present,the clinical reconstruction of the auricle usually adopts the strategy of taking autologous costal cartilage.This method has great trauma to patients,poor plasticity and inaccurate shaping.Three-dimensional(3D)printing technology has made a great breakthrough in the clinical application of orthopedic implants.This study explored the combination of 3D printing and tissue engineering to precisely reconstruct the auricle.First,a polylactic acid(PLA)polymer scaffold with a precisely customized patient appearance was fabricated,and then auricle cartilage fragments were loaded into the 3D-printed porous PLA scaffold to promote auricle reconstruction.In vitro,gelatin methacrylamide(GelMA)hydrogels loaded with different sizes of rabbit ear cartilage fragments were studied to assess the regenerative activity of various autologous cartilage fragments.In vivo,rat ear cartilage fragments were placed in an accurately designed porous PLA polymer ear scaffold to promote auricle reconstruction.The results indicated that the chondrocytes in the cartilage fragments could maintain the morphological phenotype in vitro.After three months of implantation observation,it was conducive to promoting the subsequent regeneration of cartilage in vivo.The autologous cartilage fragments combined with 3D printing technology show promising potential in auricle reconstruction.

The delayed healing of diabetic wounds is directly affected by the disturbance of wound microenvironment, resulting from persistent inflammation, insufficient angiogenesis, and impaired cell functions. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) showed considerable therapeutic potential in diabetic wound healing. However, the low retention rate of MSC-EVs at wound sites hampers their efficacy. For skin wounds exposed to the outer environment, using a hydrogel with tissue adhesiveness under a moist wound condition is a promising strategy for wound healing. In this study, we modified methacryloyl-modified gelatin (GelMA) hydrogel with catechol motifs of dopamine to fabricate a GelMA-dopamine hydrogel. EVs isolated from MSCs were applied in the synthesized GelMA-dopamine hydrogel to prepare a GelMA-dopamine-EV hydrogel. The results demonstrated that the newly formed GelMA-dopamine hydrogel possessed improved properties of softness, adhesiveness, and absorptive capacity, as well as high biocompatibility in the working concentration (15% w/v). In addition, MSC-EVs were verified to promote cell migration and angiogenesis in vitro. In the skin wound model of diabetic rats, the GelMA-dopamine-EV hydrogel exerted prominent wound healing efficacy estimated by collagen deposition, skin appendage regeneration, and the expression of IL-6, CD31, and TGF-β. In conclusion, this combination of MSC-EVs and the modified hydrogel not only accelerates wound closure but also promotes skin structure normalization by rescuing the homeostasis of the healing microenvironment of diabetic wounds, which provides a potential approach for the treatment of diabetic wounds.

HBO treatment decreased the recurrence rate of pathological scars after surgery and radiotherapy, increased patient satisfaction, and reduced the VSS score, thus providing a new way to treat pathological scar hyperplasia. However, evaluation of the longer-term effects of HBO treatment requires further comprehensive studies, including more RCTs.

Cartilage absorption and calcification are prone to occur after the implantation of diced cartilage wrapped with autologous materials, as well as prolong the operation time, aggravate surgical trauma and postoperative pain during the acquisition process. Small intestinal submucosa (SIS) has suitable toughness and excellent degradability, which has been widely used in the clinic. Urine-derived stem cells (USCs), as a new type of stem cells, have multi-directional differentiation potential. In this study, we attempt to create the tissue engineering membrane material, termed USCs-SIS (U-SIS), and wrap the diced cartilage with it, assuming that they can promote the survival and regeneration of cartilage. In this study, after co-culture with the SIS and U-SIS, the proliferation, migration and chondrogenesis ability of the auricular-derived chondrocyte cells (ACs) were significantly improved. Further, the expression levels of chondrocyte phenotype-related genes were up-regulated, whilst that of dedifferentiated genes was down-regulated. The signal pathway proteins (Wnt3a and Wnt5a) were also participated in regulation of chondrogenesis. In vivo, compared with perichondrium, the diced cartilage wrapped with the SIS and U-SIS attained higher survival rate, less calcification and absorption in both short and long terms. Particularly, USCs promoted chondrogenesis and modulated local immune responses via paracrine pathways. In conclusion, SIS have the potential to be a new choice of membrane material for diced cartilage graft. U-SIS can enhance survival and regeneration of diced cartilage as a bioactive membrane material.

Wound healing is a sophisticated process consisting of serial phases with overlaps, including hemostasis, inflammation, proliferation, and remodeling. The inflammation response is an early response that plays a crucial role in eliminating microbes and clearing damaged cell debris. However, in some pathological circumstances, such as diabetes mellitus, ischemia, trauma, deep burn, etc., abnormal inflammation can cause impaired wound healing. Adipose-derived stem cells (ADSCs) belong to the mesenchymal stem cell (MSC) family and exhibit prospective applications in tissue regeneration and dermatological repairs. ADSC-secreted extracellular vesicles (ADSC-EVs) mimic the functions of ADSCs without the concerns of cell survival, immune response, or ethical issues. Studies have revealed that ADSC-EVs can inhibit abnormal inflammation responses and accelerate wound healing through various mechanisms. Moreover, some studies explored modifications in the cargo components of ADSC-EVs to enhance their therapeutic efficacy. Given the increasing studies focusing on the potential of ADSC-EVs in wound healing, how they interfere with different phases of this process has been investigated in pieces. In this review, we summarized all up-to-date evidence to map a clearer picture of the underlying mechanisms of ADSC-EVs in inflammation response. The applications of ADSC-EVs aiming at inflammation in the healing process were also reviewed to provide therapeutic strategies for future investigators.

Objective Botulinum toxin (Btx) therapy has emerged as a potential treatment for patients with Raynaud phenomenon (RP) in recent years. This study aimed to investigate the efficacy and safety of Btx treatment for RP. Methods Databases of PubMed, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from their inception up to August 2022. Studies that reported Btx use for the treatment of RP were included. A meta-analysis was conducted for the Shortened version of the Disabilities of the Arm, Shoulder, and Hand (Quick DASH) score and visual analog scale pain score using a random-effects model. Results Thirteen full-text studies were included. The pooled standard mean changes for the visual analog scale pain score and QuickDASH score were −3.82 (95% confidence interval, −6.62 to −1.02) and 0.83 (95% confidence interval, −1.47 to −0.19), respectively. The 2 most common complications were injection site pain and intrinsic hand weakness. Conclusions The effect of Btx treatment on RP is promising based on current evidence. Nevertheless, more studies and randomized clinical trials with larger sample sizes are needed to confirm the current results.

Objective:To investigate effectiveness of transconjunctival lower eyelid blepharoplasty with "super released" orbital fat in correction of lower eyelid pouch protrusion and tear trough and palpebromalar groove depression. Methods:A clinical data of 82 patients (164 sides) with lower eyelid pouch protrusion and tear trough and palpebromalar groove depression, who met the selection criteria between September 2021 and May 2022, was retrospectively analyzed. Of the included patients, 3 were males and 79 were females, with an average age of 34.5 years (range, 22-46 years). All patients had varying degrees of eyelid pouch protrusion and tear trough and palpebromalar groove depression. The deformities were graded by the Barton grading system as gradeⅠ in 64 sides, grade Ⅱ in 72 sides, and grade Ⅲ in 28 sides. The orbital fat transpositions were performed through the lower eyelid conjunctival approach. The membrane surrounding the orbital fat was completely released, allowing the orbital fat to fully herniate until the herniated orbital fat did not retract significantly in a resting and relaxed state, which is regarded as the "super released" standard. The released fat strip was spread into the anterior zygomatic space and the anterior maxillary space, and percutaneous fixed to the middle face. The suture that penetrates the skin was externally fixed by adhesive tape pasting without knotted. Results:There were 3 sides with chemosis after operation, 1 side with facial skin numbness, 1 side with mild lower eyelid retraction at the early stage after operation, and 5 sides with slight pouch residue. No hematoma, infection, or diplopia occurred. All patients were followed up 4-8 months, with an average of 6.2 months. The eyelid pouch protrusion, tear trough, and palpebromalar groove depression were significantly corrected. At last follow-up, the deformity was graded by Barton grading system as grade 0 in 158 sides and grade Ⅰ in 6 sides, with a significant difference compared to the preoperative score ( P<0.001). Patient's self-evaluation satisfaction reached very satisfied in 67 cases (81.7%), satisfied in 10 cases (12.2%), generally satisfied in 4 cases (4.8%), and dissatisfied in 1 case (1.2%). Conclusion:The "super released" orbital fat can effectively prevent the retraction of orbital fat, reduce the probability of residual or recurrence of eyelid pouches, and improve the correction effect.