Xenogeneic scaffolds derived from porcine skin offer a promising alternative due to their structural and biochemical similarities to human skin. However, current decellularization strategies compromise extracellular matrix (ECM) integrity, porosity, or mechanical performance, limiting applicability. Here, we developed a decellularized porcine matrix (DEPOMA) scaffold using an ultrasound-assisted low-detergent strategy designed to achieve effective cellular removal while preserving ECM architecture. Specifically, we focused on combining ultrasonication, hypertonic/hypotonic treatments, and reduced Triton X-100 exposure. Our protocol effectively removed cellular components with over 99% deoxyribonucleic acid (DNA) removal, while preserving key basement membrane and dermal proteins, as seen by quantitative immunohistochemistry (IHC) demonstrating 76% Laminin, approximately 66% Collagen IV, and 889% Elastin retention relative to native tissue. Scanning electron microscopy (SEM) demostrated that DEPOMA maintained native dermal ultrastructure with enhanced and uniformly distributed porosity, quantified using DIGIMIZER image analysis. Uniaxial tensile testing on DEPOMA demonstrated preserved mechanical properties comparable to native skin. The DEPOMA scaffold demonstrated markedly enhanced biocompatibility, supporting a 3.4-fold increase in primary human fibroblast metabolic activity compared to controls. In a porcine full-thickness ex vivo wound model, DEPOMA showed progressive host-derived cellular infiltration reaching a penetration depth of 147 µm after 21 days, consistent with active scaffold integration and remodeling. When benchmarked against a detergent-based decellularized scaffold and a commercial dermal regeneration template, DEPOMA exhibited significantly improved cell viability and proliferative capacity. Collectively, these findings demonstrate that ultrasound-assisted low-detergent decellularization enables superior ECM preservation, structural integrity, and biological performance, supporting DEPOMA as a translationally optimized dermal scaffold for wound healing and regenerative medicine applications.

IntroductionAcellular dermal matrix (ADM) scaffolds support tissue regeneration by providing structural integrity, biological cues, and a permissive microenvironment; optimal ADMs integrate with native tissue while preserving extracellular matrix (ECM) composition, microarchitecture, and biomechanics. Decellularization is a critical step in ADM development, as incomplete cellular removal can induce inflammation, whereas excessive chemical treatment can disrupt ECM structure and impair scaffold biofunctionality.MethodsHere, we optimized human dermal decellularization to develop ADMs that retain ECM instruction while enabling deep host-cell infiltration and effective recellularization. Two low-detergent protocols were evaluated, Protocol A (sequential hypotonic and hypertonic solutions) and Protocol B (0.1% Triton X-100 in a hypotonic solution), both incorporating controlled ultrasonication and benzonase treatment, and compared with a conventional high-detergent method (Protocol C).ResultsAll protocols effectively removed cellular material and nucleic acids, with substantial reductions in residual DNA content; however, Protocols A and B better preserved key ECM proteins, including collagen IV, elastin, and laminin, as confirmed by Raman spectroscopy and scanning electron microscopy. Functional assays demonstrated enhanced fibroblast adhesion and cell proliferation in Protocols A and B, whereas Protocol C showed limited cell growth. In ex vivo human skin wound models, Protocol B supported the highest cell infiltration and ECM deposition by day 21, followed by Protocol A, while Protocol C exhibited minimal integration and remodeling. Histological and immunohistochemical analyses consistently confirmed superior ECM preservation with low-detergent approaches.ConclusionsOverall, combining controlled ultrasonication with minimal non-ionic detergent exposure represents a promising decellularization strategy that preserves ECM architecture, supports recellularization, and enhances scaffold integration potential for tissue engineering applications.

[This corrects the article DOI: 10.1016/j.xjidi.2025.100402.].

The wound-scratch assay is a widely used in vitro model for studying collective cell migration, a fundamental process contributing to wound closure and re-epithelialisation. Owing to its simplicity, low cost, and adaptability, it has become a foundational tool for early-stage wound-healing research and therapeutic screening. The assay involves generating a defined gap in a confluent cell monolayer and monitoring gap closure over time as a surrogate readout of repair. This narrative review examined 199 published studies, identifying 73 relevant to wound healing. A technical hierarchy of wound creation methods was identified across three main categories: mechanical approaches (e.g., pipette tips and cell scrapers), accessible but prone to operator-dependent variability; semi-automated systems (e.g., inserts and wound maker devices), which improve reproducibility; and fully-automated robotic platforms offering high precision and high-throughput capability. While these advances enhance technical consistency, they do not overcome the assay's fundamental biological constraints. Importantly, gap closure in the wound-scratch assay primarily reflects planar collective cell migration and does not recapitulate the integrated inflammatory, vascular, metabolic, and extracellular matrix-dependent processes that govern wound repair in vivo. Consequently, bioactive compounds acting through antioxidant, anti-inflammatory, angiogenic, or matrix-modulating pathways may have their therapeutic potential underestimated or misclassified when assessed using migration-only readouts. Preliminary in-house (unpublished) data are presented to illustrate this limitation, demonstrating modest migration effects for compounds with established wound-healing activity in vivo. Despite these limitations, the wound-scratch assay remains a valuable first-line, hypothesis-generating tool when interpreted appropriately, with future utility dependent on integration with adapted models and complementary assays for translation.

Keloids are a chronic, refractory, wound-triggered fibroproliferative disorder characterized by fibroblast overproduction, excessive extracellular matrix deposition, persistent inflammation, and invasive growth beyond original wound boundaries. Although keloid risk is associated with numerous genetic loci and skin of color, keloid pathogenesis remains incompletely understood. Multiomic technologies have identified cell populations and signaling networks associated with keloid pathogenesis. Emerging evidence highlights adipocyte lipolysis, epigenetic regulation by microRNAs, and disrupted vitamin D signaling as modulators of tissue repair and fibrosis. Genetic studies further implicate heritable risk factors. Integration of these approaches offers insights and therapeutic opportunities for this prevalent, debilitating condition.

Breast augmentation is the most prevalent aesthetic surgical procedure worldwide. While silicone breast implants have evolved in terms of safety and biocompatibility, they inevitably trigger a foreign body response (FBR). This complex process can lead to fibrous encapsulation, capsular contracture, and other complications, often necessitating invasive revision surgeries. This review comprehensively analyzes the molecular and cellular mechanisms underlying FBR, emphasizing the crucial role of implant surface properties. We demonstrate how these properties, including topography, hydrophobicity, and charge, govern the initial protein adsorption patterns, effectively establishing a “molecular fingerprint” that dictates subsequent cellular interactions. This, in turn, orchestrates immune cell activation, notably macrophages, which exhibit plasticity in their polarization into pro-inflammatory (M1) and pro-fibrotic (M2) phenotypes. The balance between these phenotypes influences the extent of fibrosis and capsular contracture. We explored the five distinct phases of FBR: protein adsorption, acute inflammation, chronic inflammation, foreign body giant cell (FBGC) formation, and encapsulation. The impact of implant surface properties on each phase was elucidated, highlighting the dynamic interplay between macrophages, lymphocytes, and matrix. The phenomenon of “frustrated phagocytosis,” where macrophages fail to engulf the implant, leading to FBGC formation and chronic inflammation, is also examined. Finally, we explore promising strategies to modulate FBR and enhance implant biocompatibility, including biomimetic coatings, the use of decellularized matrices, and therapies aimed at disrupting specific molecular pathways involved in fibrosis. This review provides insights into the development of next-generation implants that can harmoniously integrate with the body, minimizing FBR and ensuring long-term clinical success.

Keloid disease (KD) is a common connective tissue disorder of unknown aetiopathogenesis with ill-defined treatment. Keloid scars present as exophytic fibroproliferative reticular lesions postcutaneous injury, and even though KD remains neoplastically benign, keloid lesions behave locally aggressive, invasive and expansive. To date, there is limited understanding and validation of biomarkers identified through combined proteomic and genomic evaluation of KD. Therefore, the aim in this study was to identify putative causative candidates in KD by performing a comprehensive proteomics analysis of subcellular fractions as well as the whole cell, coupled with transcriptomics data analysis of normal compared with KD fibroblasts. We then applied novel integrative bioinformatics analysis to demonstrate that NF-kB-p65 (RELA) from the cytosolic fraction and CAPN2 from the whole-cell lysate were statistically significantly upregulated in KD and associated with alterations in relevant key signaling pathways, including apoptosis. Our findings were further confirmed by showing upregulation of both RELA and CAPN2 in KD using flow cytometry and immunohistochemistry. Moreover, functional evaluation using real-time cell analysis and flow cytometry demonstrated that both omeprazole and dexamethasone inhibited the growth of KD fibroblasts by enhancing the rate of apoptosis. In conclusion, subcellular fractionation and metaproteogenomic analyses have identified, to our knowledge, 2 previously unreported biomarkers of significant relevance to keloid diagnostics and therapeutics.

The skin, the body's largest and most immunologically dynamic organ, functions as both a protective barrier and an active immune interface. Tissue-resident memory T cells (TRMs) are pivotal in orchestrating localized immune responses, enabling rapid antigen-specific reactions, tissue repair, and immune cell recruitment. However, dysregulated TRM activity can drive chronic inflammation and fibrosis, complicating repair processes. This review examines the dual roles of TRMs and innate immune memory in wound healing and pathogen defense, emphasizing their interplay within cutaneous immune memory. This unique memory system integrates adaptive and innate immunity to enhance skin defense and repair but can contribute to pathologies, such as chronic wounds and keloids, when dysregulated. We discuss promising interventions, including cytokine delivery, biomaterial-based scaffolds, and epigenetic modulators, to enhance healing while mitigating pathology. These strategies aim to harness cutaneous immune memory for improved outcomes in conditions such as diabetic ulcers and recurrent infections. A key challenge is balancing protective and pathological immune responses, underscoring the need for personalized, skin-targeted immunotherapies with demonstrated long-term efficacy. By synthesizing recent advances, this review highlights novel therapeutic opportunities to modulate cutaneous immune memory, addressing critical knowledge gaps to guide future research and clinical translation.

Chronic and non-healing wounds are a global health issue with limited effective treatments. Wound care costs continue to rise, highlighting the need for new therapies. Medicinal plants, particularly African species, show promise for enhancing wound healing. This review analysed 93 studies and identified 37 relevant to wound healing, covering 39 plant species. Ten species were identified for their rich phytochemical content, specifically flavonoids, terpenoids, and alkaloids (plant-derived compounds). These compounds act synergistically, enhancing the wound healing process at each stage. Flavonoids reduce inflammation and support tissue turnover, while terpenoids enhance collagen production and wound closure. Alkaloids offer antimicrobial benefits and support wound contraction. Notable plants include Ageratum conyzoides and Aspilia africana (Asteraceae family); promoting haemostasis by lowering plasma fibrinogen and enhancing platelet-derived growth factors; Withania somnifera (Solanaceae); and Entada africana (Fabaceae), effectively regulating inflammation. In the proliferative phase, Ocimum gratissimum (Lamiaceae), Calendula officinalis (Asteraceae), and Centella asiatica (Apiaceae) although C. officinalis is native to Southern Europe, and C. asiatica an Asian-native; they are widely used in African traditional medicine and included here for their relevance in African wound healing practices; Justicia flava (Acanthaceae), Alternanthera sessilis (Amaranthaceae), and Acalypha indica (Euphorbiaceae); play key roles in enhancing collagen production, angiogenesis, and re-epithelialisation. This comprehensive analysis highlights the role of African medicinal plants in wound healing and their potential to improve wound care therapy.

Silicone implants are widely used in medical applications, particularly for breast augmentation and reconstruction. However, ongoing concerns regarding their long-term safety and biocompatibility necessitate comprehensive characterization. This review critically evaluates the chemical, physical, and biological testing approaches currently used to assess silicone implants, and specifically silicone breast implants, biocompatibility, and highlights the limitations of existing ISO 10993-based protocols, which often apply a one-size-fits-all model. We propose an application-specific framework to improve the relevance and precision of biocompatibility assessments. Chemical analyses, including Fourier transform infrared (FTIR) spectroscopy, Raman spectroscopy, and nuclear magnetic resonance (NMR) spectroscopy, provide essential information on polymer structure, integrity, and composition, thereby supporting quality control and market surveillance. Physical characterization methods, such as scanning electron microscopy (SEM), atomic force microscopy (AFM), and contact angle measurements, assess the surface morphology, hydrophobicity, and potential defects that may influence the host response. Mechanical testing, which evaluates properties such as tensile strength and fatigue resistance, simulates in vivo stress conditions to predict the long-term durability. Biological evaluations guided by ISO 10993 use in vitro and in vivo models to assess cytotoxicity, adhesion, inflammation, and tissue integration. However, these are often not tailored to the implant type, surface features, or duration of exposure. Emerging tools, such as organ-on-a-chip platforms and machine learning models, offer new possibilities for predictive and context-specific evaluation. We advocate a standardized, modular strategy that integrates chemical, physical, and biological testing with clinical data to bridge preclinical assessments and real-world outcomes, with a specific focus on silicone breast implants. The aim of this approach is to improve patient safety, regulatory clarity, and device innovation across the global landscape of silicone implant development.

This preliminary study explores the feasibility of identifying novel site-specific biomarkers in keloid disease to enhance understanding of its pathobiology. Keloid scars are clinically and morphologically heterogeneous, showing variable response to therapy. They also differ at the cellular and molecular levels between their actively growing margins and their dormant centers. In addition, keloids behave differently to other fibrous skin tumors, including DSFP and FS. Thus, we performed a high-throughput RNA sequencing and gene/protein analysis on keloid tissue, primary keloid fibroblasts, and keloid-derived immortalized fibroblast cell lines from different sites of the keloid tissue (Extralesional, Peripheral, Middle, and Top). These were compared with normal skin, DFSP, and FS. We identified MTCO1P12 as a common gene transcript exhibiting significantly high expression across all three keloid sites (Peripheral, Middle, and Top), FS, and DFSP compared to the extralesional keloid. Furthermore, three site-specific biomarkers were identified. SLITRK1 was uniquely expressed in the peripheral keloid tissue site and its corresponding fibroblasts. FOXS1 was localized to the middle keloid tissue site and its corresponding fibroblasts. KCNJ6 was exclusively expressed in the top keloid tissue site and its corresponding fibroblasts. It was not found in FS and DFSP. In conclusion, for the first time, we identified and validated three novel site-specific biomarkers within keloid, two of which (SLITRK1 and FOXS1) overlap with more aggressive tumors, while KCNJ6 is unique to keloids. In conclusion, for the first time, we identified and validated three novel site-specific biomarkers in keloids, two of which (SLITRK1 and FOXS1) overlap with more aggressive tumors, while KCNJ6 is unique to keloids. These findings demonstrate the feasibility of identifying spatially distinct molecular signatures in keloids, providing a foundation for future research into targeted therapies.

Keloid disease is a common fibroproliferative skin disorder characterized by excessive scar tissue formation and frequent recurrence. Limited therapies and study models hinder progress in addressing this unmet clinical need. AMA0825, a ROCK (Rho-associated protein kinase) inhibitor, has shown promising antifibrotic and antiproliferative effects in other fibrotic conditions. This study investigated the therapeutic potential of AMA0825 using in vitro, ex vivo, and a 3-dimensional spheroid model of keloid disease, which partially reflects features of the keloid microenvironment. AMA0825 demonstrated potent antiproliferative activity against keloid fibroblasts, with a half-maximal growth inhibitory concentration of 28.19 ± 1.6 nM, significantly outperforming dexamethasone (half-maximal growth inhibitory concentration = 35.35 ± 2.6 μM) and triamcinolone (half-maximal growth inhibitory concentration = 37.84 ± 3 μM). This effect was confirmed by decreased Ki-67 expression and cell cycle arrest at the G1 phase. In the 3-dimensional spheroid model, AMA0825 effectively inhibited cell proliferation at nanomolar concentrations, exceeding the efficacy of dexamethasone. Although AMA0825 did not demonstrate significant antifibrotic activity at lower concentrations, it exhibited antifibrotic effects at higher concentrations. In addition, synergistic effects were observed when combined with dexamethasone. This study highlights the potential of ROCK inhibitors, particularly AMA0825, as an antiproliferative agent for keloid disease and underscores the value of 3-dimensional spheroid models for evaluating alternative therapeutic strategies.

Keloids are a common connective tissue disorder with an ill-understood etiopathogenesis and no effective treatment. This is exacerbated because of the absence of an animal model. Patient-derived primary keloid cells are insufficient as they age through passaging and have a limited supply. Therefore, there is an unmet need for development of a cellular model that can consistently and faithfully represent keloid’s pathognomic features. In view of this, we developed keloid-derived immortalized fibroblast (KDIF) cell lines from primary keloid fibroblasts (PKF) by transfecting the human telomerase reverse transcriptase (hTERT) gene. The TERT gene encodes the catalytic subunit of the telomerase enzyme, which is responsible for maintaining the cellular replicative potential (cellular immortalization). Primary fibroblasts from keloid-specific lesional (peripheral, middle, and top) as well as extralesional sites were isolated and evaluated for cell line development and comparative cellular characteristics by employing qRT-PCR and immunofluorescence staining. Moreover, the immortalized behavior of KDIF cell lines was evaluated by comparing with cutaneous fibrosarcoma and dermatofibrosarcoma protuberans cell lines. Stable KDIF cell lines with elevated expression of hTERT exhibited the cellular characteristics of site-specific keloid fibroblasts. Histochemical staining for β-galactosidase revealed a significantly lower number of β-gal–positive cells in all three KDIF cell lines compared with that in PKFs. The cell growth curve pattern was studied over 10 passages for all three KDIF cell lines and was compared with the control groups. The results showed that all three KDIF cell lines grew significantly faster and obtained a fast growing characteristic as compared to primary keloid and normal fibroblasts. Phenotypic behavior in growth potential is an indication of hTERT-mediated immortalized transformation. Cell migration analysis revealed that the top and middle KDIF cell lines exhibited similar migration trend as site-specific PKFs. Notably, peripheral KDIF cell line showed significantly enhanced cell migration in comparison to the primary peripheral fibroblasts. All KDIF cell lines expressed Collagen I protein as a keloid-associated fibrotic marker. Functional testing with triamcinolone inhibited cell migration in KDIF. ATCC short tandem repeat profiling validated the KDIF as keloid representative cell line. In summary, we provide the first novel KDIF cell lines. These cell lines overcome the limitations related to primary cell passaging and tissue supply due to immortalized features and present an accessible and consistent experimental model for keloid research.

Keloid scars and folliculitis keloidalis nuchae (FKN) are benign fibroproliferative dermal lesions of unknown aetiology and ill-defined treatment, which typically present in genetically susceptible individuals. Their pathognomonic hallmarks include local aggressive invasive behaviour plus high recurrence post-therapy. In view of this, we investigated proliferative and key parameters of bioenergetic cellular characteristics of site-specific keloid-derived fibroblasts (intra(centre)- and peri(margin)-lesional) and FKN compared to normal skin and normal flat non-hypertrophic scar fibroblasts as negative controls. The results showed statistically significant (P < 0.01) and variable growth dynamics with increased proliferation and migration in keloid fibroblasts, while FKN fibroblasts showed a significant (P < 0.001) increase in proliferation but similar migration profile to controls. A statistically significant metabolic switch towards aerobic glycolysis in the fibroblasts from the disease conditions was noted. Furthermore, an increase in basal glycolysis with a concomitant increase in the cellular maximum glycolytic capacity was also demonstrated in perilesional keloid and FKN fibroblasts (P < 0.05). Mitochondrial function parameters showed increased oxidative phosphorylation in the disease conditions (P < 0.05) indicating functional mitochondria. These findings further suggest that Keloids and FKN demonstrate a switch to a metabolic phenotype of aerobic glycolysis. Increased glycolytic flux inhibition is a potential mechanistic basis for future therapy.

Wound healing occurs as a response to disruption of the epidermis and dermis. It is an intricate and well-orchestrated response with the goal to restore skin integrity and function. However, in hundreds of millions of patients, skin wound healing results in abnormal scarring, including keloid lesions or hypertrophic scarring. Although the underlying mechanisms of hypertrophic scars and keloid lesions are not well defined, evidence suggests that the changes in the extracellular matrix are perpetuated by ongoing inflammation in susceptible individuals, resulting in a fibrotic phenotype. The lesions then become established, with ongoing deposition of excess disordered collagen. Not only can abnormal scarring be debilitating and painful, it can also cause functional impairment and profound changes in appearance, thereby substantially affecting patients' lives. Despite the vast demand on patient health and the medical society, very little progress has been made in the care of patients with abnormal scarring. To improve the outcome of pathological scarring, standardized and innovative approaches are required.

Wound healing occurs as a response to disruption of the epidermis and dermis. It is an intricate and well-orchestrated response with the goal to restore skin integrity and function. However, in hundreds of millions of patients, skin wound healing results in abnormal scarring, including keloid lesions or hypertrophic scarring. Although the underlying mechanisms of hypertrophic scars and keloid lesions are not well defined, evidence suggests that the changes in the extracellular matrix are perpetuated by ongoing inflammation in susceptible individuals, resulting in a fibrotic phenotype. The lesions then become established, with ongoing deposition of excess disordered collagen. Not only can abnormal scarring be debilitating and painful, it can also cause functional impairment and profound changes in appearance, thereby substantially affecting patients' lives. Despite the vast demand on patient health and the medical society, very little progress has been made in the care of patients with abnormal scarring. To improve the outcome of pathological scarring, standardized and innovative approaches are required.

Raised dermal scars including hypertrophic, and keloid scars as well as scalp‐associated fibrosing Folliculitis Keloidalis Nuchae (FKN) are a group of fibrotic raised dermal lesions that mostly occur following cutaneous injury. They are characterized by increased extracellular matrix (ECM) deposition, primarily excessive collagen type 1 production by hyperproliferative fibroblasts. The extent of ECM deposition is thought to be proportional to the severity of local skin inflammation leading to excessive fibrosis of the dermis. Due to a lack of suitable study models, therapy for raised dermal scars remains ill‐defined. Immune cells and their associated markers have been strongly associated with dermal fibrosis. Therefore, modulation of the immune system and use of anti‐inflammatory cytokines are of potential interest in the management of dermal fibrosis. In this review, we will discuss the importance of immune factors in the pathogenesis of raised dermal scarring. The aim here is to provide an up‐to‐date comprehensive review of the literature, from PubMed, Scopus, and other relevant search engines in order to describe the known immunological factors associated with raised dermal scarring. The importance of immune cells including mast cells, macrophages, lymphocytes, and relevant molecules such as cytokines, chemokines, and growth factors, antibodies, transcription factors, and other immune‐associated molecules as well as tissue lymphoid aggregates identified within raised dermal scars will be presented. A growing body of evidence points to a shift from proinflammatory Th1 response to regulatory/anti‐inflammatory Th2 response being associated with the development of fibrogenesis in raised dermal scarring. In summary, a better understanding of immune cells and associated molecular markers in dermal fibrosis will likely enable future development of potential immune‐modulated therapeutic, diagnostic, and theranostic targets in raised dermal scarring.

ObjectiveFacial skin undergoes major structural and functional changes as a result of intrinsic and extrinsic factors. The goal of the current work is to demonstrate L-4-thiazolylalaine (L4, Protinol), a non-proteinogenic amino acid shown to stimulate the production of dermal proteins by fibroblasts, is an alternative efficacious topical ingredient for visible signs of ageing.MethodsIn vitro studies using 3D human skin tissue models were performed to show changes in protein and gene expression of key dermal markers in samples treated with 0.3% L4 compared to vehicle control. In vivo evaluation of skin turnover was measured in volunteers after treatment with L4 compared to retinol. Skin biopsies (n = 30) were taken to investigate epidermal and dermal changes in cases treated with L4 and compared to retinol. Finally, a clinical evaluation (n = 28) was conducted to assess the efficacy of L4 over a base formulation using various ageing parameters within a population of women 46-66 years old with mild-to-moderate wrinkles.ResultsIn vitro studies on 3D tissues displayed significant changes in the dermal matrix via an increase in HA and pro-collagen I production and a decrease in the expression of inflammatory genes. In vivo biopsy studies demonstrated that L4 and retinol independently increased epidermal thickness and collagen remodelling significantly more compared with the base formula. Clinical evaluation showed firmer and smoother skin at day 28 post-treatment with L4 over the vehicle control without causing side effects such as redness or irritation.ConclusionL4 is a novel, multi-functional ingredient which offers a superior alternative to currently available technologies for improving epidermal and dermal parameters that change during ageing and photodamage. ObjectifLa peau du visage est sujet a des changements majeurs structuraux et fonctionnels dus a des facteurs intrinseques et extrinseques. Dans cette etude, nous montrons que l'acide amine non-proteinogene L-4-thiazolylalanine (L4, Protinol) est une alternative interessante pour une application topique.Des modeles 3D de peaux ont ete utilises pour mesurer les changements d'expressions geniques et proteiques de marqueurs cles du derme a partir d'echantillons traites avec L4 compares a une condition controle. In vivo, apres un traitement L4, le renouvellement cutane a ete mesure chez les volontaires et compare a un traitement au retinol. Des biopsies de peaux (n = 30) traitees soit a L4 soit au retinol ont ete isolees afin d'evaluer les changements au niveau du derme et de l'epiderme. Pour finir, une etude clinique (n = 28) a ete menee pour evaluer l'efficacite de L4 par rapport a une formulation de base en utilisant differents parametres de vieillissement au sein d'une population de femmes de 46 a 66 ans presentant des rides legeres a moderees.ResultatsLes etudes in vitro sur tissues 3D ont montre des changements dans la matrice du derme avec une augmentation de la production d'acide hyaluronique et de procollagene I et une diminution d'expression de genes pro-inflammatoires. Les etudes menees in vivo sur biopsies ont demontre que L4 et retinol augmentaient independamment tous deux significativement l'epaisseur de l'epiderme et le remodelage du collagene par rapport a leur base seule. Pour finir, une peau plus ferme et plus lisse a ete mesuree cliniquement apres 28 jours de traitement L4 par rapport au vehicule et cela sans effets indesirables tels que rougeur et irritation.L4 est un ingredient, innovant et multifonctionnel. Il offre une serieuse alternative aux technologies actuellement disponibles dans les traitements contre le vieillissement de la peau ou le photodommage. L-4-thiazolyalaine (L4, Protinol) is a non-proteinogenic amino acid shown to stimulate the production of dermal proteins. A series of elegant in vitro and in vivo studies have demonstrated that topical treatments with L4 increase collagen production over vehicle alone; and increase epidermal thickness and collagen remodelling over a base formula after 28 days. Furthermore, L4 delivers clinically observable firming and smoothing of facial skin over base formula without causing redness or irritation after 28 days post-treatment.image