While surgical resection is the predominant clinical strategy in the treatment of melanoma, postoperative recurrence and undetectable metastasis are both pernicious drawbacks to this otherwise highly successful approach. Furthermore, the deep cavities result from tumor excision can leave long lasting wounds which are slow to heal and often leave visible scars. These unmet needs are addressed in the present work through the use of a multidimensional strategy, and also promotes wound healing and scar reduction. In the first phase, cell membrane-derived nanovesicles (NVs) are engineered to show PD-1 and dibenzocyclooctyne (DBCO). These are capable of reactivating T cells by blocking the PD-1/PD-L1 pathway. In the second phase, azido (N3) labeled mesenchymal stem cells (MSCs) are cultured into cell sheets using tissue engineering, then apply directly to surgical wounds to enhance tissue repair. Owing to the complementary association between DBCO and N3 groups, PD-1 NVs were accumulated at the site of excision. This strategy can inhibit postoperative tumor recurrence and metastasis, whilst also promoting wound healing and reducing scar formation. The results of this study set a precedent for a new and innovative multidimensional therapeutic strategy in the postoperative treatment of melanoma.

Excessive scar formation such as hypertrophic scars and keloids, resulting from trauma or surgical procedures, present a widespread concern for causing disfigurement, discomfort, and functional limitations. Macrophages play pivotal roles in maintaining tissue homeostasis, orchestrating tissue development, repair, and immune responses, and its transition of function and phenotype plays a critical role in regulating the balance between inflammation and tissue regeneration, which is central to cutaneous scar formation. Recent evidence suggests the involvement of Sonic Hedgehog (SHH) in the induction of anti-inflammatory M2-like macrophage phenotypes within tumor microenvironments. In our study, we observed increased SHH expression in human hypertrophic scars, prompting an investigation into its influence on macrophage polarization, efferocytosis, and cutaneous scar formation. Our findings reveal that SHH can enhance oxidative phosphorylation (OXPHOS) in macrophages, augment macrophage efferocytosis, and promote M2 polarization, finally contributing to the progression of cutaneous scar formation. Notably, targeting SHH signaling with vismodegib exhibited promising potential in mitigating scar formation by reversing the effects of enhanced OXPHOS and M2 polarization in macrophages. In conclusion, this study underscores the critical roles of macrophage metabolism, particularly OXPHOS, efferocytosis and SHH signaling in cutaneous scar formation. Understanding these mechanisms provides new avenues for potential interventions and scar prevention strategies.

OBJECTIVE: Stricture formation is the most common remote complication of caustic ingestion. The aim of this study was evaluation of the efficacy of early topical endoscopic application of mitomycin C (MMC) in prevention of stricture formation after corrosive ingestion in children.
METHODS: We enrolled 78 children with a history of caustic ingestion within 48 h in a prospective, randomised-controlled study. Only 61 children completed the study and were classified into two groups: group A and B. After initial stabilisation, patients in group A (n = 30) received topical application of MMC within the initial 48 h while patients in group B (n = 31) only received conventional management. Follow-up endoscopic dilatation was done every 2 weeks to patients in either group until no need for further dilatation.
RESULTS: The barium study, which was done on the third week, revealed that all the patients (100%) on conservative management (group B) had strictures while only nine patients (30%) in group A had strictures (P < 0.001). The median number of dilatations required for patients in group B was 26 (min. = 23 and max. = 32) while in group A, it was 0 (min. = 0 and max. = 7) (P < 0.001). The success of early MMC application was complete response in 26 patients (86.7%), partial response in 3 patients (10%) and no response in 1 patient (3.3%). On the other side, conventional therapy with endoscopic dilatation achieved complete response in 11 patients (35.5%).
CONCLUSIONS: Early topical MMC application proved its efficacy and safety in prevention of scar and stricture formation in children following caustic ingestion.

The non-neuronal and non-muscular effects of botulinum toxin type A (BTXA) on scar reduction has been discovered. This study was designed to investigate the effects of BTXA on macrophages polarization during the early stage of skin repair. A skin defect model was established on the dorsal skin of SD rats. BTXA was intracutaneous injected into the edge of wound immediately as the model was established. Histological examinations were performed on scar samples. Raw 264.7 was selected as the cell model of recruited circulating macrophages, and was induced for M1 polarization by LPS. Identify the signaling pathways that primarily regulated M1 polarization and respond to BTXA treatment. Application of BTXA at early stage of injury significantly reduced the scar diameter without delaying wound closure. BTXA treatment improved fiber proliferation and arrangement, and inhibited angiogenesis in scar granular tissue. The number of M1 macrophages and the levels of pro-inflammation were decreased after treated with BTXA in scar tissues. LPS activated JAK2/STAT1 and IκB/NFκB pathways were downregulated by BTXA, as well as LPS induced M1 polarization. At early stage of skin wound healing, injection of BTXA effectively reduced the number of M1 macrophages and the levels of pro-inflammatory mediators which contributes to scar alleviation. BTXA resisted the M1 polarization of macrophages induced by LPS via deactivating the JAK2/STAT1 and IκB/NFκB pathways.

UNASSIGNED: To investigate the mechanism by which Qingguang\'an inhibits scar formation in rabbits administered glaucoma filtering surgery (GFS).
UNASSIGNED: Combined trabeculectomy was performed in 100 rabbits diagnosed with glaucoma, which were assigned to five groups, including the no surgery, surgery only, mitomycin C (MMC; positive control), Qingguang\'an (experimental) and PBS (negative control) groups. The animals were followed up at postoperative days 1-28. Ultrastructure was observed under a transmission electron microscope (TEM). Real-Time Polymerase Chain Reaction (RT-PCR), Western blot, Hematoxylin and Eosin (H&E) staining, Masson\'s trichrome staining and Immuno-histochemistry (IHC) were performed to assess the harvested blocks.
UNASSIGNED: In the Qingguang\'an group, intraocular pressure (IOP) on postoperative D28 was significantly lower than values in the no surgery, surgery only and PBS groups (P < 0.05). Its blebs kept better filtering function and less complications in follow-up, which be detected to have less fibroblasts and collagen deposition histologically. Compared with the PBS group, ATG5, Beclin1 and LC3-II mRNA levels were significantly increased while P62 was downregulated in the Qingguang\'an group (P < 0.05). Correspondingly, ATG5 and Beclin1 protein amounts in the Qingguang\'an group were increased while P62 was downregulated. The LC3-II/Ⅰ ratio tended to rise to the process of autophagy. Abundant autophagosomes were captured under TEM in this condition.
UNASSIGNED: Qingguang\'an granules can inhibit scar formation in rabbits after GFS and restrain IOP increase by inducing autophagy in TFs.

Complex fractures present significant challenges in orthopaedic surgery, particularly in terms of postoperative wound healing. Nutritional status plays a crucial role in the recovery process, with early nutritional support potentially influencing wound healing outcomes. This meta-analysis aimed to assess the impact of early nutritional interventions on postoperative wound healing and scar formation in patients with complex fractures. From an initial pool of 1742 articles, 7 studies were selected for analysis. The results revealed that preoperative nutritional support significantly improved early wound healing, as indicated by lower REEDA scores (SMD = -14.06, 95% CI: [-16.79, -11.32], p < 0.01) 1 week post-surgery. Furthermore, there was a notable reduction in scar formation, as demonstrated by lower Manchester Scar Scale scores (SMD = -25.03, 95% CI: [-30.32, -19.74], p < 0.01) 3 months post-surgery. These findings highlight the importance of incorporating nutritional strategies into the management of complex fractures to optimize postoperative recovery.

Skin wound healing often leads to scar formation, presenting physical and psychological challenges for patients. Advancements in messenger RNA (mRNA) modifications offer a potential solution for pulsatile cytokine delivery to create a favorable wound-healing microenvironment, thereby preventing cutaneous fibrosis. This study aimed to investigate the effectiveness of human adipose-derived stem cells (hADSCs) enriched with N 1-methylpseudouridine (m1ψ) modified transforming growth factor-β3 (TGF-β3) and interleukin-10 (IL-10) mRNA in promoting scar-free healing in preclinical models. The results demonstrated that the modified mRNA (modRNA)-loaded hADSCs efficiently and temporarily secreted TGF-β3 and IL-10 proteins. In a dorsal injury model, hADSCs loaded with modRNA TGF-β3 and IL-10 exhibited multidimensional therapeutic effects, including improved collagen deposition, extracellular matrix organization, and neovascularization. In vitro experiments confirmed the ability of these cells to markedly inhibit the proliferation and migration of keloid fibroblasts, and reverse the myofibroblast phenotype. Finally, collagen degradation mediated by matrix metalloproteinase upregulation was observed in an ex vivo keloid explant culture model. In conclusion, the synergistic effects of the modRNA TGF-β3, IL-10, and hADSCs hold promise for establishing a scar-free wound-healing microenvironment, representing a robust foundation for the management of wounds in populations susceptible to scar formation.

Hypertrophic scar formation is influenced by the intricate interplay between fibroblasts and endothelial cells. In this study, we investigated this relationship using in vitro and in vivo models. Clinical observations revealed distinct morphological changes and increased vascularity at pathological scar sites. Further analysis using OCTA, immunohistochemistry, and immunofluorescence confirmed the involvement of angiogenesis in scar formation. Our indirect co-culture systems demonstrated that endothelial cells enhance the proliferation and migration of fibroblasts through the secretion of cytokines including VEGF, PDGF, bFGF, and TGF-β. Additionally, a suspended co-culture multicellular spheroid model revealed molecular-level changes associated with extracellular matrix remodeling, cellular behaviors, inflammatory response, and pro-angiogenic activity. Furthermore, KEGG pathway analysis identified the involvement of TGF-β, IL-17, Wnt, Notch, PI3K-Akt, and MAPK pathways in regulating fibroblasts activity. These findings underscore the critical role of fibroblasts-endothelial cells crosstalk in scar formation and provide potential targets for therapeutic intervention. Understanding the molecular mechanisms underlying this interplay holds promise for the development of innovative approaches to treat tissue injuries and diseases.

In knee osteoarthritis surgery, managing postoperative wound healing and minimizing scar formation are pivotal for patient recovery and satisfaction. These aspects are particularly challenging due to the nature of the surgical procedure and patient demographics. Physiotherapy interventions are increasingly recognized for their role in improving these postoperative outcomes. This meta-analysis sought to evaluate the efficacy of physiotherapy in enhancing wound healing, as measured by REEDA scores, and reducing scar formation, as indicated by Manchester Scar Scale (MSS) scores, following knee osteoarthritis surgery. Analysing data from eight studies, we found that physiotherapy significantly improved wound healing, evidenced by lower REEDA scores (SMD = -19.58, 95% CI: [-22.49, -16.66], p < 0.01), and reduced scar formation, reflected in lower MSS scores (SMD = -24.79, 95% CI: [-30.03, -19.55], p < 0.01). These findings highlight the crucial role of physiotherapy in postoperative care for knee osteoarthritis patients, emphasizing its impact on enhancing recovery and improving surgical outcomes.

Skin injury always results in fibrotic, non-functional scars in adults. Although multiple factors are well-known contributors to scar formation, the precise underlying mechanisms remain elusive. This review aims to elucidate the intricacies of the wound healing process, summarize the known factors driving skin cells in wounds toward a scarring fate, and particularly to discuss the impact of fibroblast heterogeneity on scar formation. To the end, we explore potential therapeutic interventions used in the treatment of scarring wounds.