L-4-thiazolylalanine (Protinol), a novel non-proteinogenic amino acid, demonstrates epidermal and dermal efficacy with clinically observable benefits.

OBJECTIVE: Facial 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. METHODS: In 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. RESULTS: In 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. CONCLUSION: L4 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.

OBJECTIF: La peau du visage est sujet à des changements majeurs structuraux et fonctionnels dus à des facteurs intrinsèques et extrinsèques. Dans cette étude, nous montrons que l'acide aminé non-protéinogène L-4-thiazolylalanine (L4, Protinol) est une alternative intéressante pour une application topique. MÉTHODES: Des modèles 3D de peaux ont été utilisés pour mesurer les changements d'expressions géniques et protéiques de marqueurs clés du derme à partir d'échantillons traités avec L4 comparés à une condition contrôle. In vivo, après un traitement L4, le renouvellement cutané a été mesuré chez les volontaires et comparé à un traitement au rétinol. Des biopsies de peaux (n = 30) traitées soit à L4 soit au rétinol ont été isolées afin d'évaluer les changements au niveau du derme et de l'épiderme. Pour finir, une étude clinique (n = 28) a été menée pour évaluer l'efficacité de L4 par rapport à une formulation de base en utilisant différents paramètres de vieillissement au sein d'une population de femmes de 46 à 66 ans présentant des rides légères à modérées. RÉSULTATS: Les études in vitro sur tissues 3D ont montré des changements dans la matrice du derme avec une augmentation de la production d'acide hyaluronique et de procollagène I et une diminution d'expression de gènes pro-inflammatoires. Les études menées in vivo sur biopsies ont démontré que L4 et rétinol augmentaient indépendamment tous deux significativement l'épaisseur de l'épiderme et le remodelage du collagène par rapport à leur base seule. Pour finir, une peau plus ferme et plus lisse a été mesurée cliniquement après 28 jours de traitement L4 par rapport au véhicule et cela sans effets indésirables tels que rougeur et irritation. CONCLUSION: L4 est un ingrédient, innovant et multifonctionnel. Il offre une sérieuse alternative aux technologies actuellement disponibles dans les traitements contre le vieillissement de la peau ou le photodommage.

* Gelatin Scaffolds Containing Partially Sulfated Cellulose Promote Mesenchymal Stem Cell Chondrogenesis.

Articular cartilage has a limited capacity to heal after damage from injury or degenerative disease. Tissue engineering constructs that more closely mimic the native cartilage microenvironment can be utilized to promote repair. Glycosaminoglycans (GAGs), a major component of the cartilage extracellular matrix, have the ability to sequester growth factors due to their level and spatial distribution of sulfate groups. This study evaluated the use of a GAG mimetic, cellulose sulfate, as a scaffolding material for cartilage tissue engineering. Cellulose sulfate can be synthesized to have a similar level and spatial distribution of sulfates as chondroitin sulfate C (CSC), the naturally occurring GAG. This partially sulfated cellulose (pSC) was incorporated into a fibrous gelatin construct by the electrospinning process. Scaffolds were characterized for fiber morphology and overall stability over time in an aqueous environment, growth factor interaction, and for supporting mesenchymal stem cell (MSC) chondrogenesis in vitro. All scaffold groups had micron-sized fibers and maintained overall stability in aqueous environments. Increasing concentrations of the transforming growth factor-beta 3 (TGF-ß3) were detected on scaffolds with increasing pSC. MSC chondrogenesis was enhanced on the scaffold with the highest pSC concentration as seen with the highest collagen type II production, collagen type II immunostaining, expression of cartilage-specific genes, and ratio of collagen type II to collagen type I production. These studies demonstrated the potential of pSC sulfate as a scaffolding material for cartilage tissue engineering.