Scar Formation Research Articles

Updates on the controversial roles of regulatory lymphoid cells in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is the most common and severe form of pulmonary fibrosis, characterized by scar formation in the lung interstitium. Transforming growth factor beta (TGF-β) is known as a key mediator in the fibrotic process, acting on fibroblasts and mediating their proliferation and differentiation into myofibroblasts. Although the immune system is not considered responsible for the initiation of IPF, markers of tolerogenic immunity define the pro-fibrotic microenvironment in the lungs. In homeostatic conditions, regulatory T cells (Tregs) constitute the main lymphoid population responsible for maintaining peripheral tolerance. Similar to Tregs, regulatory B cells (Bregs) represent a recently described subset of B lymphocytes with immunosuppressive functions. In the context of IPF, numerous studies have suggested a role for Tregs in enhancing fibrosis, mainly via the secretion of TGF-β. In humans, most studies show increased percentages of Tregs associated with the severity of IPF, although their exact role remains unclear. In mice, the most commonly used model involves triggering acute lung inflammation with bleomycin, leading to a subsequent fibrotic process. Consequently, data are still conflicting, as Tregs may play a protective role during the inflammatory phase and a deleterious role during the fibrotic phase. Bregs have been less studied in the context of IPF, but their role appears to be protective in experimental models of lung fibrosis. This review presents the latest updates on studies exploring the implication of regulatory lymphoid cells in IPF and compares the different approaches to better understand the origins of conflicting findings.

Exosomes and microRNAs: insights into their roles in thermal-induced skin injury, wound healing and scarring.

A burn is a type of injury to the skin or other tissues caused by heat, chemicals, electricity, sunlight, or radiation. Burn injuries have been proven to have the potential for long-term detrimental effects on the human body. The conventional therapeutic approaches are not able to effectively and easily heal these burn wounds completely. The main potential drawbacks of these treatments include hypertrophic scarring, contracture, infection, necrosis, allergic reactions, prolonged healing times, and unsatisfactory cosmetic results. The existence of these drawbacks and limitations in current treatment approaches necessitates the need to search for and develop better, more efficient therapies. The regenerative potential of microRNAs (miRNAs) and the exosomal miRNAs derived from various cell types, especially stem cells, offer advantages that outweigh traditional burn wound healing treatment procedures. The use of multiple types of stem cells is gaining interest due to their improved healing efficiency for various applications. Stem cells have several key distinguishing characteristics, including the ability to promote more effective and rapid healing of burn wounds, reduced inflammation levels at the wound site, and less scar tissue formation and fibrosis. In this review, we have discussed the stages of wound healing, the role of exosomes and miRNAs in improving thermal-induced wounds, and the impact of miRNAs in preventing the formation of hypertrophic scars. Research studies, pre-clinical and clinical, on the use of different cell-derived exosomal miRNAs and miRNAs for the treatment of thermal burns have been documented from the year 2000 up to the current time. Studies show that the use of different cell-derived exosomal miRNAs and miRNAs can improve the healing of burn wounds. The migration of exosomal miRNAs to the site of a wound leads to inhibition of apoptosis, induction of autophagy, re-epithelialization, granulation, regeneration of skin appendages, and angiogenesis. In conclusion, this study underscores the importance of integrating miRNA and exosome research into treatment strategies for burn injuries, paving the way for novel therapeutic approaches that could significantly improve patient outcomes and recovery times.

Losartan in Situ Forming Gel as a New Treatment for Hypertrophic Scars.

Hypertrophic scars are defined as visible lesions formed by excessive wound healing that cause cosmetic and, in some cases, functional challenges in patients. This study aimed to assess the efficacy of intralesional injections of losartan-loaded in situ forming gel and compare it with the common treatment (triamcinolone) in preventing scar formation. The formulation was prepared using a thermosensitive PLGA-PEG-PLGA triblock copolymer. Ear scar tissue in rabbits represented the hypertrophic scar, and the animals were treated with three treatments in three groups. Nine weeks following the single treatment, images of the scars were obtained and quantitatively analyzed using ImageJ and light microscopy was used to evaluate the fibroblast cell number, vascularization, inflammation and collagen deposition and fibrosis in H&E-stained sample tissue. According to the results based on the ImageJ and the Vancouver criteria, the losartan in situ forming gel (F-LG) indicated significantly higher improving effects on decreased vascularity and pigmentation in comparison with triamcinolone (F-TA) and placebo as a control (F-Ctl), although the effect F-LG was almost similar to F-TA on pliability and scar height, and they were better than the control. Histological findings showed F-LG and F-TA have less inflammatory and fibroblast cells compared to F-Ctl. Also, results indicated the dermal layers of the F-TA and F-LG groups' scar were thinner, and the deposition of collagens was reduced compared to the control. Consequently, F-LG was found to be an effective treatment in reducing scarring and promoting wound healing.No Level Assigned This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Liposomal nano-encapsulation of bFGF combined with injectable BSA hydrogel for efficient burn wound healing

Rapid and scar-free healing of burn wounds is an urgent clinical issue. Basic fibroblast growth factor (bFGF) has been proven to promote the healing of burn wounds by accelerating ECM remodeling and angiogenesis. However, exudates from burn wounds can accelerate bFGF degradation, thereby affecting its bioactivity. This study proposes an effective protection strategy for bFGF that involves encapsulating bFGF in nanoliposomes (bFGF-NLip) and then incorporating bFGF-NLip into a bovine serum albumin (BSA) hydrogel. This hybrid hydrogel system (bFGF-NLip@B) could maintain the activity of bFGF, achieve sustained release, and allow phospholipids and cholesterol to penetrate the skin, thereby enabling bFGF to function in the dermis. The experimental results showed that the hydrogel was injectable with good mechanical properties and biocompatibility. In a mouse scald wound model, owing to the sustained release of bFGF and skin permeation function of the nanoliposomes, the hydrogel promoted granulation formation, collagen deposition, vascular regeneration, and re-epithelialisation, ultimately accelerating wound healing. In addition, the hydrogel effectively inhibited scar formation. This system provides novel insights into the delivery of bFGF and scar-free healing of burn wounds.

Electrographic flow mapping of atrial fibrillation.

A low ceiling of efficacy exists for the treatment of persistent atrial fibrillation via pulmonary vein isolation without adjunctive ablations, which is likely because they do not target an individual patient's specific underlying disease mechanisms. Electrographic flow (EGF) mapping is the first system that reliably displays wavefront propagation through the atria. It is a promising tool for localizing sources of atrial fibrillation, guiding targeted ablation, and visualizing conduction through the atrial substrate. We describe EGF mapping with emphasis on contemporary studies examining map reproducibility and use cases in the preclinical and clinical environment. Animal experiments demonstrated that maps were interpretable across increasingly complex rhythms with pacing during spontaneously persistent atrial fibrillation reliably simulating EGF sources. The FLOW-AF randomized controlled trial showed that source ablation improved outcomes and that EGF map properties may be used to phenotype patients based on their atrial fibrillation mechanisms and recurrence likelihoods. Targeted ablation strategies balance the risks of insufficiently ablating atrial fibrillation triggers with exacerbating disease through additional scar formation. EGF mapping leverages spatiotemporal relationships in voltage to localize sources and quantify substrate health. Further research is needed to optimize phenotyping and treatment efforts.

A Strategy Involving Microporous Microneedles Integrated with CAR-TREM2-Macrophages for Scar Management by Regulating Fibrotic Microenvironment.

Dipeptidyl peptidase 4 (DPP4) positive fibroblasts play a pivotal role in scar development following skin injury. Heterogeneous vascular endothelial cells (ECs) within scarred areas retain the capacity to drive tissue regeneration and repair. Simultaneously, TREM2 macrophages play a crucial role in the progression and resolution of fibrosis by engaging in mutual regulation with ECs. However, effective strategies to inhibit scar formation through multi-factor regulation of the scar microenvironment remain a challenge. Here, CAR-TREM2-macrophages (CAR-TREM2-Ms) capable of targeting DPP4+ fibroblasts and modulating ECs subtype within the scar microenvironment are engineered to effectively prevent scarring. Hydrogel microporous microneedles (mMNs) are employed to deliver CAR-TREM2-Ms, which can effectively alleviate scar. Single-cell transcriptome sequencing (scRNA-seq) analysis reveals that CAR-TREM2-Ms can modify ECs fibrotic phenotype and regulate fibrosis by suppressing the profibrotic gene leucine-rich-alpha-2-glycoprotein 1 (Lrg1). In vitro experiments further demonstrate that CAR-TREM2-Ms improve the scar microenvironment by phagocytosing DPP4+ fibroblasts and suppressing TGFβ secretion. This, in turn, inhibits the phenotypic conversion of LRG1 ECs and provides multifactorial way of alleviating scars. This study uncovers the evidence that mMNs attached to CAR-TREM2-Ms may exert vital influences on skin scarring through the regulation of the skin scar microenvironment, providing a promising approach for treating posttraumatic scarring.

Bioactive Curcuma aromatica-stabilized silver nanoparticles embedded chitosan dressing with improved antibacterial, anti-inflammatory, and wound healing properties

Chronic wounds, particularly those infected with multidrug-resistant (MDR) pathogens, present significant challenges for effective healing. Silver nanoparticles (CAAgNPs) were synthsized using aqueous rhizome extract of Curcuma aromatica (CA), known for its wound-healing properties. CAAgNPs were incorporated in a chitosan (CS) dressing (CAAgNPs/CS) and tested for their wound healing potential, expecting synergistic action of AgNPs and phytochemicals capped on it. The porous nature of the CAAgNPs was confirmed using Field emission scanning electron microscopy. Fourier-transform infrared spectroscopy demonstrated a shift in peak intensity from 1589.06 to 1575.54 cm-1 for CAAgNPs/CS dressing confirming crosslinking with glutaraldehyde. Antibacterial activity of the dressings was cofirmed against isolates of Pseudomonas aeruginosa and Staphylococcus aureus. Wound healing studies were carried out using Wistar rats (six groups)- wound control, CS, CAAgNPs256/CS, CAAgNPs512/CS, CAAgNPs1024/CS, and commercial dressings. Histological examination and direct red-80 staining demonstrated maximum epithelization and collagen deposition (58.02%) within CAAgNPs1024/CS groups on day 10. Increased hydroxyproline levels (76.51 µg/mL) on day 7 for CAAgNPs1024/CS indicated maximum collagen formation. Reduced levels of inflammatory cytokines IL-6 (17.38 pg/mL) and TNF-α (80.38 pg/mL) on day 10 indicated quick wound healing without scar formation and damaging effects. The present study highlights the antibacterial and anti-inflammatory properties of CAAgNPs1024/CS dressings with a potential for wound healing applications.

A novel model of post-burn hypertrophic scarring in rat tail with a high success rate and simple methodology

BackgroundHypertrophic scars present a serious concern after surgeries and trauma, particularly with the highest risk following burn injury. The current modeling methods usually involve relatively complicated surgical operations and special equipment, and have unstable reproducibility and reliability. This study aimed to establish a simple and reliable model of post-burn hypertrophic scarring in the rat tail. MethodsWet gauze saturated with hot water (94–98 °C) was applied to the dorsal side of the rat tail for varying durations to induce burn injury. Wounds were left exposed until completely healed, and the optimal duration for scalding treatment was determined based on gross examination. Thereafter, the optimal scalding duration was used again to evaluate scar formation over time, which was tracked through hematoxylin-eosin (HE) and Masson staining, immunohistochemistry of scar-related proteins and number/distribution of vascular endothelial cells, and picrosirius red staining to measure the quantities and proportion of type I and III collagen. ResultsThe scalding duration which led to optimal post-burn scarring was 15 s, with an overall success rate of 87.5 %. Complete healing of the wound occurred after roughly 30 days, leading to the formation of scars grossly red in appearance, tough to the touch and raised compared to the surrounding skin. Microscopically, the epidermis and dermis of the scar were significantly thicker than normal rat tail skin, and the dermis of scar contained a large number of disorganized bundles of fine filamentous collagen. We also observed a significant increase in the number of TGF-β1-positive cells and capillaries in the dermis (p < 0.05). Picrosirius red staining showed that compared to type III collagen, the expression of type I collagen was more dominant in scar tissue, and was more finely distributed than in normal rat tail skin. ConclusionWe successfully established a model for post-burn hypertrophic scarring, utilizing reliable and simple techniques and materials, which could simulate the biological characteristics of post-burn scarring. Our innovative model has the potential to facilitate the study of post-burn wound healing and scar formation.

Unlocking the Potential of Collagenases: Structures, Functions, and Emerging Therapeutic Horizons.

Collagenases, a class of enzymes that are specifically responsible for collagen degradation, have garnered substantial attention because of their pivotal roles in tissue repair, remodeling, and medical interventions. This comprehensive review investigates the diversity, structures, and mechanisms of collagenases and highlights their therapeutic potential. First, it provides an overview of the biochemical properties of collagen and highlights its importance in extracellular matrix function. Subsequently, it meticulously analyzes the sources of collagenases and their applications in tissue engineering and food processing. Notably, this review emphasizes the predominant role played by microbial collagenases in commercial settings while discussing their production and screening methods. Furthermore, this study elucidates the methodology employed for determining collagenase activity and underscores the importance of an accurate evaluation for both research purposes and clinical applications. Finally, this review highlights the future research prospects for collagenases, with a particular focus on promoting wound healing and treating scar tissue formation and fibrotic diseases.

A rare case report of endobronchial neurofibroma treated with transbronchial endoscopic resection and literature review.

Endobronchial neurofibroma is an extremely rare neoplastic disease. The majority of endobronchial neurofibroma are symptomatic, but nonspecific. The treatment of endobronchial neurofibroma is controversial that surgery is previously considered to be the main option. With the development of bronchoscopic intervention, most endobronchial neurofibroma can be treated with transbronchial endoscopic resection with few complications. Here we reported a case of diagnosed endobronchial neurofibroma that was successfully resected with transbronchial electrical snaring and laser coagulation. Moreover, the relevant literature was reviewed to raise awareness of this disease. A 57-year-old man presented to our hospital with cough, sputum, and shortness of breath for 2 days. Physical examination was normal. Laboratory tests revealed moderately increased C-reactive protein. Chest computed tomography showed a 10 × 8 mm round, polypoid-shaped nodule located in the left main bronchus, which was heterogeneous after contrast enhancement. It demonstrated a smooth, round, hypervascularized neoplasma obstructing most of the lumen of the upper left main bronchus under bronchoscopy. The tumor was removed with electrical snaring and laser coagulation completely instead of surgical resection, without any complications. Pathologically, it was confirmed of endobronchial neurofibroma. Repeated bronchoscopy showed no recurrence of the tumor, and the procedure site healed with a little of fibrotic scar formation. Endobronchial neurofibroma is rare. Although the standard treatment for endobronchial neurofibroma is surgery, transbronchial endoscopic resection (electrical snaring and laser coagulation) is an applicable option, especially for those lesions strictly in the lumen.

Dynamics of changes in the representation of mesenchymal cells in the forming glial scar during dexamethasone application

Mesenchymal stem cells are involved in cellular responses in the injured brain after a stroke. The formation of a glial scar is a local response in the brain to damage, and mesenchymal stem cells may be involved in the processes of scar formation. Mesenchymal stem cells express a range of membrane markers, the expression profile of which obviously changes as they differentiate and depends on the microenvironment in which these cells are located. However, it is still unclear where the stem cells in the damaged brain originate from – whether they come from a resident source or from the bone marrow, although an increase in CD34+ cells in the blood of stroke patients is a well-known fact. In this study, we consider the hypothesis regarding the appearance of mesenchymal stem cells in the brain during a stroke and their potential involvement in the formation of a glial scar. The aim of the study is to investigate the involvement of CD44+, CD68+, CD90+, and CD146+ cells in the formation of a glial scar during hemorrhagic stroke and the changes in their representation under the effect of dexamethasone. To achieve this goal, we simulated hemorrhagic stroke in rats and compared the results of immunohistochemical detection of CD44+, CD68+, CD90+, and CD146+ cells in the area of glial scar formation against the dexamethasone administration. We obtained convincing results of differences in the activity and timing of migration of cells expressing CD44 compared to cells expressing CD68, CD90, and CD146. There is a tendency indicating a dependence between the detection of CD44+ cells and the extent of the damage, while the detection of CD68+, CD90+, and CD146+ cells is strongly correlated and increases under the effect of dexamethasone. Cells expressing CD44 were the main participants in the infiltrating pool of cells in the acute phase, but dexamethasone delayed the peak accumulation of CD44+ cells in the forming scar. There were some changes in the detection of these cells around the hemorrhage during dexamethasone treatment, which may indicate its modulating effect on mesenchymal stem cells during glial scar formation. The more frequent detection of CD68+, CD90+, and CD146+ cells can be considered a manifestation of the potential modification by dexamethasone of cellular reactions involved in glial scar formation in the brain after a stroke. The study of the roles of specific immunophenotypes of mesenchymal stem cells in the areas of glial scar formation following hemorrhagic stroke opens new perspectives in the study of brain recovery processes.

Corneal scarring after epithelium-off collagen cross-linking

Abstract Collagen cross-linking (CXL) is considered as a successful therapeutic approach for corneal conditions like keratoconus and corneal ectasia. Despite its efficacy in stabilizing these conditions, the occurrence of post-CXL scars remains a concern. Keratoconus and other corneal ectasias are characterized by structural weaknesses in the cornea. This weakness contributes to the vulnerability of corneal scar formation. In addition, corneal biomechanics and tissue properties play a significant role in scar development. Procedural factors during CXL, including duration and intensity of ultraviolet light exposure, the concentration and type of riboflavin, and the precise application of treatment, have been identified as potential causes of scar formation. Individual patient factors such as variations in healing response and genetic predispositions, associated ocular allergy, and chronic contact lens wear can also impact scar development post-CXL. Understanding these variables is essential for risk stratification and personalized treatment approaches, ultimately optimizing patient outcomes. In addition, regular follow-up visits and patient education are essential to ensure optimal healing and minimize scar related complications. We have tried to explain the numerous reasons of scarring following epithelium-off CXL by conducting a thorough Medline search and reviewing our clinical images. This review serves as a concise overview of the causes and risk factors associated with scar formation after epithelium-off CXL.

The Combination of Proteolytic Enzyme Supplementation, Acupuncture, and Osseous Manipulation for the Treatment of Traumatic Peripheral Nerve Injury: A Case Report

This report describes the treatment of peripheral nerve injury in a 43-year-old woman using a combination of proteolytic enzymes, acupuncture, and osseous manipulation as alternatives to conventional care. Her presenting symptoms include complete loss of sensation in the superolateral left thigh and a mass of fibrotic scar tissue in the area of injury. A holistic treatment plan was created to address the underlying mechanisms of the injury. Plant-based proteolytic enzymes, bromelain and papain, were used to address tissue inflammation and reduce scar tissue formation around the nerve, acupuncture was used to regenerate the superficial nerves, and osseous manipulations were provided for structural re-alignment. After 8 weeks of treatment, the patient reported significant reduction in the size of the fibrotic mass and complete resolution of sensory loss. The fibrotic mass of tissue reduced from 6 cm to 1 cm during the treatment course. Proteolytic enzymes have wide-ranging indications; however, they have not been well studied for peripheral nerve injury, which makes this a novel indication for this natural health product. This case report found the use of proteolytic enzymes, and acupuncture, effective in treating peripheral nerve injury and provides grounds for research to treat nerve-related injuries.

Repeated intrathecal injections of peripheral nerve-derived stem cell spheroids improve outcomes in a rat model of traumatic brain injury

BackgroundTraumatic brain injury (TBI) is a major cause of disability and mortality worldwide. However, existing treatments still face numerous clinical challenges. Building on our prior research showing peripheral nerve-derived stem cell (PNSC) spheroids with Schwann cell-like phenotypes can secrete neurotrophic factors to aid in neural tissue regeneration, we hypothesized that repeated intrathecal injections of PNSC spheroids would improve the delivery of neurotrophic factors, thereby facilitating the restoration of neurological function and brain tissue repair post-TBI.MethodsWe generated PNSC spheroids from human peripheral nerve tissue using suspension culture techniques. These spheroids were characterized using flow cytometry, immunofluorescence, and reverse-transcription polymerase chain reaction. The conditioned media were evaluated in SH-SY5Y and RAW264.7 cell lines to assess their effects on neurogenesis and inflammation. To simulate TBI, we established a controlled cortical impact (CCI) model in rats. The animals were administered intrathecal injections of PNSC spheroids on three occasions, with each injection spaced at a 3-day interval. Recovery of sensory and motor function was assessed using the modified neurological severity score (mNSS) and rotarod tests, while histological (hematoxylin and eosin, Luxol fast blue staining) and T2-weighted magnetic resonance imaging analyses, alongside immunofluorescence, were conducted to evaluate the recovery of neural structures and pathophysiology.ResultsPNSC spheroids expressed high levels of Schwann cell markers and neurotrophic factors, such as neurotrophin-3 and Ephrin B3. Their conditioned medium was found to promote neurite outgrowth, reduce reactive oxygen species-mediated cell death and inflammation, and influence M1-M2 macrophage polarization. In the CCI rat model, rats receiving repeated triple intrathecal injections of PNSC spheroids showed significant improvements in sensory and motor function, with considerable neural tissue recovery in damaged areas. Notably, this treatment promoted nerve regeneration, axon regrowth, and remyelination. It also reduced glial scar formation and inflammation, while encouraging angiogenesis.ConclusionOur findings suggest that repeated intrathecal injections of PNSC spheroids can significantly enhance neural recovery after TBI. This effect is mediated by the diverse neurotrophic factors secreted by PNSC spheroids. Thus, the strategy of combining therapeutic cell delivery with multiple intrathecal injections holds promise as a novel clinical treatment for TBI recovery.

Investigating the Influence of Natural Compounds on the Healing Process of Wounds

Advancements in modern medicine have not fully resolved the complexities associated with wound healing, particularly for chronic wounds, such as diabetic ulcers and burn injuries. Effective wound management necessitates not only the regeneration of damaged tissue but also minimizing scar formation. In this context, natural compounds derived from plants have emerged as promising candidates for enhancing wound healing. Ethnobotanical research has demonstrated that various herbal extracts possess properties that could significantly improve wound healing outcomes. This review explores the potential of these natural compounds, focusing on their mechanisms of action, efficacy in clinical and preclinical studies, and the challenges that still need to be addressed. By synthesizing findings from traditional medicinal practices and contemporary scientific research, this review aims to provide a comprehensive understanding of how natural compounds can contribute to more effective wound healing strategies. In this review, widely used and studied plants are discussed, along with their ability to induce wound healing through all the phase and their mechanism of action.

Multifunctional Nanofiber Membranes Constructed by Microfluidic Blow-Spinning to Inhibit Scar Formation at Early Intervention Stage.

Pathological scarring has been a challenge in skin injury repair since ancient times, and prophylactic treatment in the early stages of wound healing usually results in delayed wound healing. In this study, poly(ethylene oxide) (PEO) and chitosan (CTS) were used as carrier materials to construct multifunctional pirfenidone (PFD)/CTS/PEO (PCP) nanofiber membranes (NFMs) loaded with PFD by microfluidic blow-spinning (MBS). MBS is a good method for quickly, safely, and greenly constructing large-area manufacturing of inexpensive NFMs. PCP NFMs were uniform in external morphology, with diameters ranging from 200 to 500 nm. The encapsulation efficiency of the drug-loaded PCP NFMs was above 80%, which had a good slow release, visualization, water absorption, and biocompatibility. The inhibitory effect of PCP NFMs on normal human dermal fibroblasts was dose-dependent and inhibited the expression of the transforming growth factor-β1/SMAD family member 3 (TGF-β1/SMAD3) signaling pathway. PCP NFMs showed significant antibacterial effects against both Staphylococcus aureus and Escherichia coli. In the rabbit ear scar experiment, the wound healed about 70% on day 5 and almost completely on day 10 after PCP-3 NFMs treatment, with the thinnest scar tissue, skin color, tenderness close to normal tissue, and a Vancouver scar scale score of less than 5. PCP-3 NFMs had good effects on anti-inflammatory, wound healing, and collagen-I deposition reducing effects. In conclusion, PCP-3 NFMs can both promote wound healing and intervene to inhibit pathological scarring in advance, making them a potential multifunctional wound dressing for early prevention and treatment of pathological scarring.

Scar Formation, Healing Stages, and Advanced Treatment Strategies – Review

Introduction and Aim of the Study: Scarring is a major concern in clinical dermatology, affecting individuals' quality of life due to both physical and psychological impacts. This review aims to explore the pathophysiology of various scar types—hypertrophic, keloid, and atrophic—and evaluate the effectiveness of current and emerging treatments to inform better clinical practices and therapeutic strategies. Description of the State of Knowledge: Scar formation involves complex biological processes: inflammation, proliferation, and remodeling. The nature of the scar varies with the underlying cause and biological response, influenced by genetic factors, skin tension, and environmental elements such as UV exposure. Recent advances in treatments range from surgical techniques to laser therapy and biological agents like cytokines. Conclusion: The studies reviewed underscore the complexity of scar management, influenced by diverse genetic, biological, and environmental factors. No single treatment is universally effective, but a combination of preventative and therapeutic strategies shows the best promise.

Endogenous opioid signalling regulates spinal ependymal cell proliferation.

After injury, mammalian spinal cords develop scars to confine the lesion and prevent further damage. However, excessive scarring can hinder neural regeneration and functional recovery1,2. These competing actions underscore the importance of developing therapeutic strategies to dynamically modulate scar progression. Previous research on scarring has primarily focused on astrocytes, but recent evidence has suggested that ependymal cells also participate. Ependymal cells normally form the epithelial layer encasing the central canal, but they undergo massive proliferation and differentiation into astroglia following certain injuries, becoming a core scar component3-7. However, the mechanisms regulating ependymal proliferation in vivo remain unclear. Here we uncover an endogenous κ-opioid signalling pathway that controls ependymal proliferation. Specifically, we detect expression of the κ-opioid receptor, OPRK1, in a functionally under-characterized cell type known as cerebrospinal fluid-contacting neuron (CSF-cN). We also discover a neighbouring cell population that expresses the cognate ligand prodynorphin (PDYN). Whereas κ-opioids are typically considered inhibitory, they excite CSF-cNs to inhibit ependymal proliferation. Systemic administration of a κ-antagonist enhances ependymal proliferation in uninjured spinal cords in a CSF-cN-dependent manner. Moreover, a κ-agonist impairs ependymal proliferation, scar formation and motor function following injury. Together, our data suggest a paracrine signalling pathway in which PDYN+ cells tonically release κ-opioids to stimulate CSF-cNs and suppress ependymal proliferation, revealing an endogenous mechanism and potential pharmacological strategy for modulating scarring after spinal cord injury.

Poison Turned Panacea: Arsenic Trioxide Loaded Hydrogel for Inhibiting Scar Formation in Wound Healing.

Without intervention, the natural wound healing process can often result in scarring, which can have detrimental effects on both the physical and mental well-being of patients. Therefore, it is crucial to develop biomaterials that can promote healing without scarring. Regulating the Yes-associated protein-1/PDZ-binding motif (YAP/TAZ) signaling pathway is possible to reduce excessive fibrosis of fibroblasts and proliferation of vascular endothelial cells, ultimately impacting scar formation. Arsenic trioxide (ATO), an ancient drug with medicinal and toxic properties, has shown promise in regulating this pathway. An ATO-loaded hydrogel dressing (ATO@CS/SA) was created to facilitate scarless wound healing, utilizing chitosan (CS) and sodium alginate (SA) to prevent direct contact of ATO with the wound tissue and minimize potential side effects. In vitro studies demonstrated that low concentrations of ATO did not impact cell viability and even promoted proliferation and migration. Co-culturing the hydrogel with fibroblasts and vascular endothelial cells led to decreased expression levels of YAP and TAZ. Animal studies over a 90-day period revealed significant inhibition of scar formation with this system. Histological experiments further confirmed that the decreased expression of YAP and TAZ was responsible for this outcome. In conclusion, when administered at the appropriate dose, ATO can be repurposed from a traditional poison to a therapeutic agent, effectively suppressing excessive cell fibrosis and blood vessel proliferation and offering a novel approach to scar-free treatment.

A Skin Stress Shielding Platform Based on Body Temperature-Induced Shrinking of Hydrogel for Promoting Scar-Less Wound Healing.

Stress concentration surrounding wounds drives fibroblasts into a state of high mechanical tension, leading to the delay of wound healing, exacerbating pathological fibrosis, and even causing tissue dysfunction. Here, an innovative skin stress-shielding hydrogel wound dressing is reported that makes the wound sites shrink as a response to body temperature and then remolds the stress micro-environment of wound sites to reduce the formation of skin scars. Composed of a modified natural temperature-sensitive polymer cross-linked with polyacrylic acid networks, this hydrogel wound dressing has demonstrated a substantial decrease in scar area for full-thickness wounds in rat models. The physical forces exerted by the wound dressing are instrumental in attenuating the activation and transduction of fibroblasts within the wound sites, thereby mitigating the excessive deposition of the extracellular matrix (ECM). Notably, the wound dressing significantly down-regulates the expression of transforming growth factor-β1(TGF-β1) and collagen I, while concurrently exerting a dramatic inhibitory effect on the integrin-focal adhesion kinase (FAK)/phosphorylated-FAK (p-FAK) signaling pathway. Collectively, the fabrication of functional hydrogels with a stress-shielding profile is a new route for achieving scar-less wound healing, thus offering immense potential for improving clinical outcomes and restoring tissue integrity.