**Fátima García-Villén 1, Rita Sánchez-Espejo 2, Ana Borrego-Sánchez 2, Pilar Cerezo 1, Lucia Cucca 3, Giuseppina Sandri <sup>4</sup> and César Viseras 1,2,\***


Received: 14 August 2020; Accepted: 17 September 2020; Published: 18 September 2020

**Abstract:** Inorganic hydrogels formulated with spring waters and clay minerals are used to treat musculoskeletal disorders and skin affections. Their underlying mechanism of action for skin disorders is not clear, although it is usually ascribed to the chemical composition of the formulation. The aim of this study was to assess the composition and in vitro release of elements with potential wound healing effects from hydrogels prepared with two nanoclays and natural spring water. In vitro Franz cell studies were used and the element concentration was measured by inductively coupled plasma techniques. Biocompatibility studies were used to evaluate the potential toxicity of the formulation against fibroblasts. The studied hydrogels released elements with known therapeutic interest in wound healing. The released ratios of some elements, such as Mg:Ca or Zn:Ca, played a significant role in the final therapeutic activity of the formulation. In particular, the proliferative activity of fibroblasts was ascribed to the release of Mn and the Zn:Ca ratio. Moreover, the importance of formulative studies is highlighted, since it is the optimal combination of the correct ingredients that makes a formulation effective.

**Keywords:** sepiolite; palygorksite; spring water; hydrogel; wound healing; proliferation; Franz cell; bioactive elements
