BackgroundHyaluronic acid (HA), a naturally occurring polysaccharide, is used in the production of dermal fillers for esthetic purposes. As it has a few days of half-life in human tissues, HA-based dermal filler is chemically modified to increase its lifetime in the body. The most common modification used in commercial HA-based filler is the cross-linking of HA chains using 1,4-butanediol diglycidyl ether (BDDE) as cross-linking agent. Residual, or unreacted, BDDE is considered nontoxic when it is <2 parts per million (ppm); therefore, the quantification of residual BDDE in the final dermal filler is mandatory to ensure the safety of the patients.Materials and methodsThe present study describes the detection and characterization of one by-product of the cross-linking reaction between BDDE and HA in alkaline conditions by combining both liquid chromatography and mass spectroscopy (LC–MS).ResultsAfter different analyses, it was found that the alkaline conditions and the high temperatures employed to sterilize the HA–BDDE hydrogel promote the formation of this new by-product, a “propene glicol-like” compound. LC–MS analysis confirmed that this by-product have the same monoisotopic mass as that of BDDE, a different retention time (tR), and also a different UV absorbance (λ=200 nm) pattern. Unlike BDDE, it was observed in the LC–MS analysis that this by-product had a higher detection at 200 nm in the same assay conditions.ConclusionThese results suggest that this new compound does not have an epoxide on its structure. The discussion is open to assess the risk of this new by-product found in the production of HA–BDDE hydrogels (HA dermal fillers) for commercial purposes.

Mesotherapy/biorevitalization with hyaluronic acid (HA) is a treatment approach currently used for skin rejuvenation. Various products with a wide range of polycomponent formulations are available on the market. Most of these formulations contain noncross-linked HA in combination with a biorevitalization cocktail, formed by various amounts of vitamins, minerals, amino acids, nucleotides, coenzymes, and antioxidants. Although ingredients are very similar among the different products, in vitro and clinical effects may vary substantially. There is a real need for better characterization of these products in terms of their action on human skin or in vitro skin models. In this study, we analyzed the effect of the RRS® (Repairs, Refills, Stimulates) HA injectable medical device on human skin fibroblasts in vitro. Skin fibroblast viability and its capacity to induce the production of key extracellular matrix were evaluated in the presence of different concentrations of RRS HA injectable. Viability was evaluated through colorimetric MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay, and key extracellular matrix genes, type I collagen and elastin, were quantified by quantitative polymerase chain reaction. Results demonstrated that RRS HA injectable could promote human skin fibroblast viability (+15%) and increase fibroblast gene expression of type I collagen and elastin by 9.7-fold and 14-fold in vitro, respectively. These results demonstrate that mesotherapy/biorevitalization products can, at least in vitro, effectively modulate human skin fibroblasts.

Clinical and scientific research into new powerful products which could have potential for effective treatment in the periorbital area, and address complex problems such as lymph oedema, dark circles under the eyes and skin atrophy (wrinkles) has been ongoing for many years.The products could be under medicine or medical device registration or license; allowing medical practitioners to perform injections in the tear trough area, palpebral malar groove and upper eyelid. The main medical proposal for this new therapeutic approach is for the final product to be safe, to deliver minimal side effects during long-term treatments, and to be clinically effective.

IntroductionSilanol (organic silicon) has been used for decades in the treatment of skin photoaging as it stabilizes and maintains skin structures through hydrogen bonding electrostatic interaction with extracellular matrix (ECM) proteins or glycosaminoglycans. Organic silicon-based products are often presented as silanol derivatives which are currently associated to other structural molecules such as orthohydroxybenzoate, carboxymethyl theophylline alginate, ascorbate, acetyltyrosine, sodium lactate or mannuronate. Consequently, organic silicon formulations may differ substantially between the medical devices available on the market, which may result in additional effect on the skin. Therefore, there is a real need for a better characterization of the products in terms of their action on human skin and in vitro skin model.Materials and methodsIn this in vitro study, the effect of RRS® Silisorg was analyzed. RRS® Silisorg is a dermal implant (CE Class III medical device) containing monomethylsilanol mannuronate associated to an antioxidant resveratrol. Skin fibroblast viability and capacity to induce the production of key ECM genes were evaluated in the presence of different concentrations of RRS® Silisorg. The key ECM genes selected were collagen type I, elastin and hyaluronan synthase type 2 (HAS2), which is the cellular enzyme responsible for high-molecular weight hyaluronic acid (HA) production. Viability was evaluated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and expression was quantified by quantitative polymerase chain reaction.ResultsRRS® Silisorg increased fibroblast gene expression of HAS2 in the first 24 hours, 25 times in the presence of 1 mg/mL of solution, followed by a collagen type I gene expression (4.7 times) and elastin expression (2.5 times) increase after 48 hours.ConclusionThese results demonstrate that the silanol-based medical device RRS® Silisorg sustains HA, collagen and elastin production in human skin fibroblasts in vitro.

"Introducción. La aplicación de implantes dérmicos, que contienen ácido hialurónico (AH) para la biorrevitalización, corrigen los signos de envejecimiento y la atrofia dérmica al restaurar la hidratación y la fisiología normal de la piel. Dependiendo del grado de fotoenvejecimiento y del estado de la piel, el AH puede proporcionar resultados satisfactorios como tratamiento único y/o como una etapa del tratamiento en sinergias. El objetivo del estudio es evaluar la eficacia de un producto que contiene hialuronato, aminoácidos, antioxidantes y polifenoles para la mejoría del fotoenvejecimiento en los pacientes; así como evaluar su grado de satisfacción y de seguridad de su uso continuado. Material y método. Se incluyeron 51 pacientes, con edad media de 48 años (rango 29‑55). A cada uno se le realizaron 2 sesiones del tratamiento con AH no reticulado asociado a un búfer con propiedades antioxidantes. Resultados. En la visita de control, se observó aumento significativo del parámetro de turgencia de la piel, pasando de una puntuación media de 2,5 antes del tratamiento a 3,6 el día 21. El 90% de los pacientes vieron cumplidas sus expectativas y catalogaron la eficacia del producto como excelente (76%) y buena (14%). Conclusiones. La mesoterapia con AH junto con la solución biorrevitalizante con aminoácidos, polifenoles y antioxidantes, según el protocolo utilizado, puede estar indicada en pacientes con un grado de crono y fotoenvejecimiento de la piel incipiente o avanzado. El resultado es la hidratación y reestructuración de la dermis mejorando su laxitud, grosor, elasticidad y los signos externos de envejecimiento."