烧伤疤痕的发生发展及相应的作用靶点、巨噬细胞、通路、基因

瘢痕是整形外科研究的重点问题，现有瘢痕治疗方法的临床效果存在一定的局限性。自体脂肪移植是经临床证实可有效治疗病理性瘢痕的新方法。自体脂肪移植物中含有脂肪间充质干细胞和多种活性因子，通过免疫调控炎症反应、促血管生成、促细胞分化、重塑细胞外基质、抗氧化应激损伤等机制治疗病理性瘢痕，可有效改善瘢痕外观、质地和局部症状，具有并发症少、治疗效果好等优点，是治疗瘢痕的崭新领域，为瘢痕提供了新的治疗方向。现就自体脂肪移植在瘢痕中的应用及机制作一综述，旨为瘢痕的治疗提供理论基础，归纳其在瘢痕治疗中的应用进展。

目的 探讨脂肪干细胞源性外泌体(ADSC-Exo) 对成纤维细胞增殖、迁移能力以及大鼠深Ⅱ度烧伤创面愈合的影响。 方法 培养人成纤维细胞，采用ADSC-Exos或PBS处理细胞，通过CCK-8和划痕实验观察ADSC-Exo对成纤维细胞增殖能力和迁移能力的影响。选取40只SD大鼠构建深Ⅱ度烧伤模型，分为Exo组 and PBS组，Exo组于烧伤创面周边注射ADSC-Exo溶液，PBS组注射等量PBS溶液。观察2组大鼠创面愈合情况，通过HE染色观察炎症细胞浸润情况，通过免疫组织化学CD31染色观察创面血管新生情况。 结果 CCK-8实验结果显示，ADSC-Exo可促进成纤维细胞增殖，且呈浓度依赖性( P < 0.05)；划痕实验结果显示，ADSC-Exo可增强成纤维细胞的迁移能力( P < 0.000 1)。动物实验发现，创面周边注射ADSC-Exo可促进烧伤创面愈合( P < 0.000 1)。与PBS组比较，Exo组大鼠烧伤创面炎症细胞浸润减少，CD31表达增加( P < 0.01)。 结论 ADSC-Exo可促进成纤维细胞增殖、迁移，并能减轻创面炎症、促进新生血管生成，从而促进烧伤创面愈合。

Hypertrophic Scar (HS) is a common fibrotic disease of the skin, usually caused by injury to the deep dermis due to trauma, burns, or surgical injury. The main feature of HS is the thickening and hardening of the skin, often accompanied by itching and pain, which seriously affects the patient’s quality of life. Macrophages are involved in all stages of HS genesis through phenotypic changes. M1-type macrophages primarily function in the early inflammatory phase by secreting pro-inflammatory factors, while M2-type macrophages actively contribute to tissue repair and fibrosis. Despite advances in understanding HS pathogenesis, the precise mechanisms linking macrophage phenotypic changes to fibrosis remain incompletely elucidated. This review addresses these gaps by discussing the pathological mechanisms of HS formation, the phenotypic changes of macrophages at different stages of HS formation, and the pathways through which macrophages influence HS progression. Furthermore, emerging technologies for HS treatment and novel therapeutic strategies targeting macrophages are highlighted, offering potential avenues for improved prevention and treatment of HS.

Botulinum toxin A (BTXA) is a safe and widely used neurotoxic protein in cosmetic procedures and medical applications. This investigation focuses on the function of BTXA on macrophage phenotype during hypertrophic scar (HS) formation and the underlying functional mechanism. A mouse model of HS was generated, where BTXA treatment reduced dermal thickness, epidermal hyperplasia, and collagen deposition in a dose-dependent manner. Moreover, BTXA reduced fibrosis, proliferation, angiogenesis, and M2 macrophage markers within the scar tissues, with parallel findings obtained in the in vitro co-culture system of induced M2 macrophages (derived from THP-1 monocytes) and human dermal fibroblasts (HDFs). Following bioinformatics and RNA sequencing insights, we identified increased expression of poly (ADP-ribose) polymerase family member 14 (PARP14) and suppressor of cytokine signaling 2 (SOCS2) in wound skin of mice, which were suppressed by BTXA treatment. PARP14 enhanced SOCS2 mRNA stability. Overexpression of PARP14 restored the M2 polarization of macrophages and negated the HS-ameliorating effects of BTXA. However, these effects were counteracted by the additional silencing of SOCS2 in mice or THP-1 cells. In conclusion, this investigation suggests that BTXA inhibits PARP14-mediated SOCS2 RNA stabilization to reduce M2 polarization of macrophages and alleviate hypertrophic scarring.

Antibiotic-resistant bacterial infections in skin wounds can cause persistent inflammatory responses, which may lead to severe hypertrophic scarring. In this study, a pH-responsive antibacterial hydrogel composed of phenylboronic acid-grafted chitosan (PBCS) and tannic acid (TA) was developed to achieve controlled and long-lasting release of baicalein (BA) to address the critical challenges of bacterial infection, wound healing, and scarring. The composite hydrogel (BA@PBCS-TA) not only demonstrates excellent injectability, self-healing properties, and robust mechanical performance but also exhibits favorable biological characteristics. Through pH-responsive release of BA, it effectively eliminates Methicillin-resistant Staphylococcus aureus (MRSA). In vivo experiments further confirm its ability to significantly inhibit fibroblast activation and reduce abnormal collagen deposition, effectively preventing excessive scar formation. Additionally, network pharmacology has identified Glycogen Synthase Kinase 3 Beta (GSK3β) as a key target for BA in inhibiting hypertrophic scar formation. Cellular experiments further demonstrate that the BA@PBCS-TA hydrogel can suppress GSK3β expression, activate the Wnt/β-catenin signaling pathway to repolarize macrophages into the M2 phenotype, and exhibit significant immunomodulatory effects. These results highlight the BA@PBCS-TA hydrogel's ability to harness the excellent properties of biomaterials and optimize BA's pharmacological effects, ultimately promoting wound healing and offering a strategic solution for scar reduction.

Hypertrophic scar (HS) is a fibroproliferative disorder characterized by fibroblast hyperactivation and aberrant extracellular matrix deposition. This study identifies macrophage-derived lactate as a key mediator of fibroblast phenotypic remodeling via monocarboxylate transporter 1 (MCT1)-mediated histone H3 lysine 23 lactylation (H3K23la) in HS. Elevated lactate levels and MCT1 expression were observed in HS tissues, with macrophages in stiff mechanical microenvironments identified as the primary lactate source. Lactate influx through MCT1 upregulated H3K23la, thereby promoting transcriptional activation of profibrotic genes HEY2 and COL11A1. Mechanistically, HEY2 activated YAP1/SMAD2 signaling, while COL11A1 stabilized MCT1 to enhance lactate transport, forming a positive loop that amplified fibrosis. Fibroblast-specific Mct1 deletion or pharmacological inhibition of Mct1 in male mice reduced collagen deposition, accelerated wound healing, and attenuated scar formation. Our findings redefine the macrophage-fibroblast crosstalk in HS and establish the MCT1-H3K23la-HEY2/COL11A1 axis, particularly its self-reinforcing loop, as a novel therapeutic target.

To elucidate the mechanism by which Resveratrol (Res) ameliorates hypertrophic scar (HS) formation by targeting acid-sensing ion channel 3 (ASIC3) to modulate macrophage-fibroblast (FB) crosstalk. A rabbit-ear HS model was established in vivo. Hematoxylin-eosin (H&E) staining, Masson staining, immunofluorescence (IF), Western blot (WB), and quantitative real-time PCR (RT-qPCR) were used to assess the effects of Res on scar hyperplasia, collagen deposition, FB activation, and macrophage polarization. In vitro, FB activation was stimulated by combined treatment with TGF-β1 and lactic acid, and a Transwell co-culture system comprising FB and human monocyte-derived M0 macrophages was established. Scratch assay, FCM, IF, and WB were performed to assess the impacts of Res on FB activation, migration, and macrophage polarization. Additionally, ASIC3 gene knockout experiments were conducted both in vivo and in vitro to confirm the mechanism underlying Res-mediated HS improvement. In vitro, Res significantly inhibited FB migration in a dose-dependent manner and downregulated the protein expression of α-SMA, COL1A1, COL3A1, reduced M-CSF secretion, suppressed macrophage polarization toward the M2 phenotype, and decreased TGF-β1 mRNA expression. It also blocked activation of the PI3K/Akt signaling pathway downstream of ASIC3. These effects were completely abolished after ASIC3 gene knockdown. In vivo, Res significantly reduced the scar elevation index (SEI) in rabbit-ear HS. It improved collagen fiber arrangement and decreased collagen deposition. It markedly inhibited M2 macrophage polarization and TGF-β1 mRNA expression. After ASIC3 knockout, the anti-HS effects of Res, as well as its regulatory effects on macrophage polarization and fibrotic factors, were abrogated. Res ameliorates HS by inhibiting ASIC3 expression. This disrupts the ASIC3-M-CSF-TGF-β1 positive feedback loop. It restores the balance of macrophage polarization, inhibits FB activation, reduces abnormal collagen deposition, and ultimately attenuates HS formation.

Wound healing is a complex, multicellular process that is essential for restoring tissue integrity after injury. In a subset of individuals, however, this process becomes dysregulated, culminating in hypertrophic scars or keloids—fibroproliferative disorders marked by excessive extracellular matrix deposition and prolonged inflammation. Although these lesions differ clinically, both share overlapping molecular mechanisms involving aberrant activation of the TGF‐β, Intergrin‐FAK, and Wnt/β‐catenin pathways. Recent insights from single‐cell and multiomics technologies have revealed profound heterogeneity within scar‐forming fibroblast populations and highlighted the modulatory roles of immune cells, genetic predispositions, and anatomical tension. However, despite increasing mechanistic understanding, current interventions—including surgery, corticosteroids, and laser therapy—are limited by high recurrence rates and variable efficacy. Emerging strategies now target fibroblast plasticity, inflammatory circuits, and biomechanical feedback via tools such as gene editing, immune modulation, and smart biomaterials. This review integrates advances across epidemiology, molecular signaling, and therapeutic innovation, underscoring the need for personalized, multitargeted approaches. Ultimately, transforming pathological scarring from a persistent clinical burden into a regenerative opportunity will depend on interdisciplinary collaboration and the continued translation of benchside discovery into bedside care.

… Hypertrophic scarring is a frequent complication of burn wound healing that compromises … cytokines produced by T helper cells and macrophages entering the ECM from the systemic …

… Methods: We used in vitro hypertrophic scar fibroblast, macrophage–fibroblast coculture and human umbilical vein endothelial cell (HUVEC) assays, RNA sequencing, pathway analysis…

Hypertrophic scar (HS) is a cutaneous fibrotic disorder characterized by persistent myofibroblast activation and excessive extracellular matrix deposition. Elucidating the origin and characteristics of myofibroblasts remains a central focus in the field. This study identifies a novel subtype of scar myofibroblasts originating from macrophage‐myofibroblast transition (MMT). MMT cells constitute a significant proportion of HS myofibroblasts and drive HS progression. Multi‐omics analysis uncovered nicotinamide N‐methyltransferase (NNMT) as a metabolic orchestrator of MMT. Liquid chromatograph mass spectrometer reveals NNMT‐mediated depletion of nicotinamide adenine dinucleotide (NAD+) and S‐adenosyl methionine(SAM), triggering H3K27ac accumulation and H3K27me3 loss. This epigenetic reprogramming facilitated the expression of master transcription factor paired‐related homeobox 1 (Prrx1) and its nuclear co‐condensation with super‐enhancer (SE) components. Inhibition of NNMT disrupted Prrx1‐SE interactions, suppressed MMT in vitro, and reduced scar volume in vivo. This study 1) identifies a new origin of scar‐associated myofibroblasts, 2) establishes metabolite‐guided epigenetic alteration as a regulator of myofibroblasts cellular plasticity, and 3) nominates NNMT as a therapeutic target for HS and related fibrotic disorders.

Burn wound management posed substantial therapeutic challenges due to impaired macrophage polarization dynamics. Metabolic dysfunction in macrophages hindered the transition from glycolysis-driven M1 phenotype to oxidative phosphorylation (OXPHOS)-driven M2 phenotype, result of perpetuating inflammatory reaction to restrain wound healing. Despite all kinds of biomaterials were developed for burn wounds, some critical issues still couldnot be solved, such as limited repair efficacy, strong immunogenicity, and high cost etc. Cellular metabolite α-ketoglutaric acid (AKG) shows good biological activity and can regulate cellular energy metabolism, which is expected to solve the above issues. However, the cellular acid-toxicity of AKG might restrict its wide application in clinic. Therefore, a bioactive electrospinning fiber (PEKUU) was engineered to demonstrate sustained AKG release for modulation of energy metabolism of burn wounds. In vitro assessments confirmed its biocompatibility and effects on keratinocyte and endothelial proliferation, migration and angiogenesis. Meanwhile, PEKUU could attenuated glycolysis-driven M1 polarization, reducing NF-κB-mediated inflammation. While it also could enhance mitochondrial OXPHOS to drive M2 polarization. In vivo experiment showed that PEKUU electrospinning fiber could accelerate epithelialization, collagen remodeling and healing of deep second-degree burn wounds of mice. Finally, proteomics was applied to reveal the underlying mechanism of AKG-mediated metabolic reprogramming, including the coordinated suppression of the glycolytic-NF-κB axes and the potentiation of the OXPHOS and fatty acid oxidation pathways. The dual regulation reshaped macrophage energetics and established a pro-regenerative niche. Overall, PEKUU electrospinning dressing could modulate macrophage polarization state by reprogramming energy metabolism mode, providing a new therapeutic strategy for burn repair.

Abstract Hypertrophic scar (HS) is one of the most common complications of skin injuries, with a lack of effective therapeutic approaches to date. Most current research has focused on the dysfunction of hypertrophic scar fibroblasts (HSFBs) and dermal vascular endothelial cells (HDVECs), neglecting the crucial role of the inflammatory microenvironment that causes them to be abnormal. In this study, we first discovered and validated that the S100A8/9 specific inhibitor Paquinimod could inhibit macrophage polarization toward M1, and further suppress the proliferation, migration, collagen formation, and angiogenesis of HSFBs and HDVECs in vitro. This mechanism has also been validated in a rat model of HS. Then, we developed a good biocompatibility and penetrability Paquinimod‐Hydrogel Hybrid Microneedle Array Patch (PHMAP) for HS treatment. With the advantages of excellent penetrability, surface sealing, sustained release, and precise uniform distribution, PHMAP exhibited superior therapeutic efficacy over intravenous and intradermal injections. These results suggest that PHMAP can be a promising and advanced solution for HS prevention and therapies.

… We have previously studied that timely and sufficient M1 macrophages infiltration and M2 macrophages polarization are necessary for fibrosis during wound healing. In this study, we …

It has been established that inflammatory factors are involved in the formation of pathological scars. Therefore, pathological scars are regarded to be highly associated with chronic inflammation, whereas what factors contribute to this inflammation remains unclear. To confirm that bacterial colonization is involved in the formation of pathological scars, and to reveal that the persistent inflammatory response mediated by macrophages due to bacterial colonization promotes scar formation. This study included 23 normal skin controls and 58 untreated pathological scar samples. To detect the presence of bacteria in surgically-excised scar samples and alterations of histology, as well as bacteria-associated gene levels, histological staining, immunoelectron microscopy, microbiological and cell culture and molecular biology detection methods were employed. The PICRUSt2 tool and BugBase were employed to identify pathways, genes, and phenotypic differences. We found that in pathological scars, bacteria were widely distributed both extracellularly and intracellularly, with intracellular bacteria primarily located in the cytoplasm of macrophages and fibroblasts. A total of 2,260 bacterial species were detected in pathological scars, primarily from the Clostridiales, Burkholderiales, Actinomycetales, and Bacteroidales orders. Moreover, the pathogenicity and motility of colonizing bacteria were positively correlated with the degree of scar hyperplasia and invasiveness. The lysates of four clinically-relevant bacterial species had differential effects on the secretion of inflammatory cytokines from macrophages. When treated macrophage supernatant was added to fibroblasts, collagen secretion was dysregulated, and fibroblast differentiation into myofibroblasts prominently increased. In rat scar model, the expression of inflammatory factors and growth factors in the scar tissue was increased, which activated the TGF-β/Smad signaling pathway, resulting in the increasing of α-SMA. Persistent activation of macrophages by tissue-colonizing bacteria may be a key factor in promoting inflammatory response and dysregulated collagen deposition in pathological scars, offering a potential new strategy for preventing and treating pathological scars.

Chronic scars and pain following burns not only impair patients’ quality of life but also resist current empirical treatments, highlighting an urgent need for mechanism-based therapies. Early studies have characterized key mediators of scar fibrosis and nociception, yet integration of molecular and neural pathways remains limited. Here, we comprehensively review 1 molecular and cellular drivers of burn scar formation—particularly transforming growth factor-β (TGF-β)–induced fibroblast activation and extracellular matrix remodeling; 2 bidirectional interactions between scar tissue and nerve regeneration via neuropeptides (Nerve growth factor, Substance P, calcitonin gene-related peptide); 3 mechanisms underpinning long-term scar pain, including peripheral/central sensitization through TRPV1/Nav channels and neuroinflammation; and 4 emerging treatments—such as laser, extracorporeal shock wave therapy (ESWT), regenerative injections, and transient receptor potential (TRP) antagonists—that target these pathways. We conclude that a detailed understanding of scar–nerve crosstalk at the molecular level is pivotal for developing targeted interventions and improving long-term outcomes.

Objective Human growth hormone (HGH) enhances wound healing by promoting cell proliferation, angiogenesis, and tissue regeneration. This study investigated the effects of HGH-overexpressing Adipose-derived stem cells (HGH-ADSCs) on fibroblast function, ERK pathway activation, and burn wound healing. Methods ADSCs were isolated from adipose tissue, characterized via CD marker expression, and confirmed for multipotency using Oil Red O (adipogenesis), Alizarin Red S (osteogenesis), and Alcian Blue staining (chondrogenesis). ADSCs were then transduced with a lentiviral vector carrying HGH, generating HGH-ADSCs and confirmed by qRT-PCR. Fibroblasts (HDF-a) were co-cultured were co-cultured under HGH-ADSCs-conditioned medium and ADSCs-conditioned medium to assess proliferation (MTT assay), migration and invasion (Transwell), apoptosis (flow cytometry), and G0/G1 cell cycle progression. Western blotting determined ERK activation, and SCH772984 (ERK inhibitor) was used to confirm pathway dependency. A burn rat model was established with three treatment groups: HGH-ADSCs, ADSCs, and saline. and histopathology (H&E, TUNEL staining) analyzed epithelial regeneration and apoptosis. ELISA and biochemical assays quantified TNF-α, IL-1β, IL-6, MDA, SOD, and CAT in wound tissue homogenates. Results HGH-ADSCs significantly enhanced fibroblast proliferation, migration, invasion, and prolonged G0/G1 phase while reducing apoptosis (P < 0.05). ERK inhibition abolished these effects (P < 0.05). In vivo, HGH-ADSCs accelerated wound closure (P < 0.05), enhanced epithelialization, reduced inflammation, and increased collagen formation. Inflammatory cytokines (TNF-α, IL-1β, IL-6) and MDA were lowest, while SOD and CAT were highest in HGH-ADSC-treated wounds (P < 0.05). Conclusion ADSCs overexpressing HGH promote fibroblast activity, activate ERK signaling, and accelerate burn wound healing, demonstrating strong therapeutic potential.

… Burn-induced hypertrophic scarring is driven by persistent inflammation and fibroblast … and fibrotic signaling to promote scarless regeneration of burn wounds. The design was guided by …

Fibrosis, which is characterized by pathological extracellular matrix (ECM) accumulation impairing organ function, is governed primarily by dysregulated transforming growth factor-β (TGF-β)/Smad signalling. TGF-β1 triggers canonical (Smad2/3-dependent) and noncanonical pathways upon receptor binding, driving profibrotic processes such as fibroblast activation, epithelial–mesenchymal transition (EMT), excessive ECM production (e.g., collagen), and the suppression of matrix degradation. This pathway is central to organ-specific fibrogenesis: In liver fibrosis, it activates hepatic stellate cells (HSCs); in renal fibrosis, it promotes tubular injury and ECM deposition; in pulmonary fibrosis, it induces EMT/fibroblast transition in radiation/bleomycin models; in cardiac fibrosis, it mediates fibroblast activation in diabetic cardiomyopathy/atrial fibrillation via NPRC/TGIF1/USP mechanisms; and in skin fibrosis (e.g., scleroderma), it stimulates collagen overproduction, which is suppressed by osthole or mesenchymal stem cells. The TGF-β/Smad axis thus represents a pivotal therapeutic target. Future research should clarify tissue-specific regulatory networks and develop combinatorial antifibrotic strategies.

BACKGROUND Bruceine A(BA) has many pharmacological activities and significantly inhibits fibrosis in keloid fibroblasts. However, the underlying mechanisms have not yet been fully elucidated. OBJECTIVE This study aimed to investigate the effects of BA on pulmonary fibrosis(PF) and explore its underlying mechanisms. METHODS PF models were constructed by BLM-induced C57BL/6 J mice, TGF-β1- induced MRC-5 and HFL-1 cells. Cell proliferation, MMP, apoptosis, and ROS levels were analyzed in vitro. In vivo, experiments were performed to evaluate the therapeutic effect of BA on PF by detecting respiratory function, histopathology, and collagen level. Fibro-associated, ECM, and EMT key proteins were used to assess the degree of PF. To predict the target of BA by molecular docking technology, and verified by DARTS, CETSA, MST,and SPR. Then overexpression gal3-lentivirus, GB1107 gal3 inhibitor, and BA addition were used to verify the TGF-β1/Smad pathway key protein by western blot. RESULTS We found that BA inhibited PF both in vitro and in vivo. The predicted and validated results showed that gal3 was the target of BA, and the binding site was Arg144, His158, and Trp181. Mechanistically, BA disrupts the interaction between gal3 and TGF-β1. BA reduced Smad2/3 and p-Smad2/3 protein content and inhibited TGF-β1/Smad pathway in the overexpressing gal3 HFL-1 cells. After adding GB1107, the inhibitory effect of BA on TGF-β1/Smad pathway disappeared. CONCLUSION This study is the first to demonstrate that BA can target gal3, interfere with the interaction between gal3 and TGF-β1 protein, inhibit the downstream TGF-β1/Smad pathway, and act as a "brake" to reverse the PF process. These findings provide a solid scientific basis for the clinical application of BA in the prevention and treatment of PF.

Keloid is a benign skin disease with excessive growth of fibroblasts, characterized by too much abnormal extracellular matrix deposited in the dermis. It is generally believed that transforming growth factor-β (TGF-β) is the core cytokine that causes keloid. Previously, it was thought that its pathogenic effect was mainly attributed to the classical Smad-dependent pathway. It directly shuttles signals to the nucleus to trigger pro-fibrotic gene transcription. However, accumulating evidence now points to the equally vital role of Smad-independent signaling. Unlike the direct nuclear translocation of Smads, these alternative pathways transmit signals through rapid intracellular kinase cascades. They jointly direct the proliferation, migration, anti-apoptosis, fibrogenesis, and chronic inflammation of fibroblasts in keloids. This review attempts to comprehensively clarify the molecular processes regulated by TGF-β through non-Smad pathways (such as MAPK, PI3K/Akt, Rho GTPase, Wnt/β-catenin, JAK/STAT). Translating these non-Smad insights helps to overcome the high recurrence rates of traditional therapies. Targeting these specific molecular hubs through combination and precision therapies serves to reprogram the fibrotic microenvironment.

在糖尿病患者的创面愈合过程中常出现炎症迁延、血管新生困难及角质形成细胞上皮化能力下降等表现，导致创面愈合过程延缓。细胞自噬是一种细胞内蛋白质的分解代谢途径，有促进细胞存活、维持细胞生物学功能的作用。近年来的研究表明，细胞自噬通过多种机制影响糖尿病创面的愈合。本文综述了细胞自噬在糖尿病创面愈合过程中的潜在机制，即自噬可能通过以下途径延缓创面的愈合：引起巨噬细胞的吞噬能力下降和极化障碍、减弱内皮祖细胞的血管新生能力、降低角质形成细胞迁移和增殖能力以及增加成纤维细胞的凋亡。本综述旨在为探索糖尿病创面愈合的治疗靶点提供新思路。

Fractional carbon dioxide (AFCO2) laser therapy is used for treating pathological scarring, but the clinical outcomes are variable and the mechanisms of scar reduction poorly understood. We investigated the mechanisms underpinning efficacy of AFCO2 laser therapy, performing single-cell RNA sequencing in skin biopsies from patients with hypertrophic scars after AFCO2 laser therapy. Patients with younger scars (Good Responder, GR, <6 years from healing) had better scar reduction than patients with older scars (Poor Responder, PR, >6 years from healing) by various measures of scarring. scRNAseq analysis revealed that genes enriched in GR were associated with extracellular matrix and structure organisation (COL14A1, POSTN, SPARC); whereas genes enriched in PR were related to enhanced immune responses (IL-12, MSTN, HLA-DQA). The groups had distinct intercellular communication networks and differentiation trajectories after AFCO2, with regenerative Mesenchymal fibroblasts associated with a good response and inflammatory Secretory Papillary and Inflammatory Fibroblasts with a poor response.

In this study we have developed, characterized and examined the healing and regenerative potential of gum tragacanth based zinc oxide composite hydrogel (ZnO-GT). ZnO-GT composite is a pliable and soft formulation offering efficient, faster and improved burn wound healing/managements. In this procedure, we generated partial thickness burn wounds in murine model and then applied the wound with ZnO-GT formulation. ZnO-GT showed promising burn wound healing potential in vivo as only 0.48 % of burn residual area was observed in ZnO-GT treatment group compared to11.41 % in positive control group (silver sulfadiazine treatment) and 41.62 % in control group (saline treatment) at the end of 14th day. Two weeks of comparative histopathological study and analysis revealed dermal regeneration along with formation of skin appendages in hydrogel treated groups (p < 0.05). ZnO-GT accelerates inflammatory stage progression and reduces inflammatory responses of wound healing. Further it increases production of fibroblast growth factor and angiogenesis promoting factors such as NOX 4, VEGFR 2, HIF-1α and ANG1 which leads to the formation and differentiation of skin appendages as demonstrated by Western blotting studies. Altogether, ZnO-GT showed good biocompatibility along with substantial wound healing efficacy and regenerative property making it potent therapeutic agent for healing of burn skin wounds.

… Using Nlrp3 −/− mice, multi-omics, and human validation, we demonstrate that NLRP3 activation during the inflammatory phase recruits macrophages and fibroblasts via CCL/CXCL …

Corneal alkali burns are severe ocular injuries characterized by extensive tissue damage, inflammation, oxidative stress, and neovascularization, which often lead to long-term visual impairment and corneal fibrosis. This review comprehensively examines the mechanisms underlying alkali burn injuries, including the roles of inflammatory mediators, oxidative stress, and cellular responses, while highlighting current and emerging therapeutic approaches. Traditional treatments, such as corticosteroids and surgical interventions, often have limited efficacy and significant side effects. Recent advances in innovative therapies, including stem cell-derived exosomes, hydrogel-based drug delivery systems, and herbal components, demonstrate significant potential for improving corneal healing and reducing complications. These novel approaches aim to mitigate inflammation, enhance epithelial repair, and prevent neovascularization, offering promising pathways for scar-free healing and the restoration of corneal transparency. Future research should focus on integrating these therapies into multifunctional treatment strategies to optimize clinical outcomes and improve quality of life for patients suffering from corneal alkali burns.