Santos-Vizcaino Edorta, Salvador Aiala, Vairo Claudia, Igartua Manoli, Hernandez Rosa Maria, Correa Luis, Villullas Silvia, Gainza Garazi
NanoBioCel Group, Laboratory of Pharmaceutics, University of the Basque Country (UPV/EHU), School of Pharmacy, Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain.
Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), 01006 Vitoria-Gasteiz, Spain.
Nanomaterials (Basel). 2020 Jun 3;10(6):1108. doi: 10.3390/nano10061108.
Negatively charged microspheres (NCMs) represent a new therapeutic approach for wound healing since recent clinical trials have shown NCM efficacy in the recovery of hard-to-heal wounds that tend to stay in the inflammatory phase, unlocking the healing process. The aim of this study was to elucidate the NCM mechanism of action. NCMs were extracted from a commercial microsphere formulation (PolyHeal Micro) and cytotoxicity, attachment, proliferation and viability assays were performed in keratinocytes and dermal fibroblasts, while macrophages were used for the phagocytosis and polarization assays. We demonstrated that cells tend to attach to the microsphere surface, and that NCMs are biocompatible and promote cell proliferation at specific concentrations (50 and 10 NCM/cell) by a minimum of 3 fold compared to the control group. Furthermore, NCM internalization by macrophages seemed to drive these cells to a noninflammatory condition, as demonstrated by the over-expression of CD206 and the under-expression of CD64, M2 and M1 markers, respectively. NCMs are an effective approach for reverting the chronic inflammatory state of stagnant wounds (such as diabetic wounds) and thus for improving wound healing.
带负电荷的微球（NCMs）代表了一种伤口愈合的新治疗方法，因为最近的临床试验表明，NCMs在愈合倾向于停留在炎症阶段的难愈合伤口方面具有疗效，从而开启愈合过程。本研究的目的是阐明NCMs的作用机制。从商业微球制剂（PolyHeal Micro）中提取NCMs，并在角质形成细胞和真皮成纤维细胞中进行细胞毒性、附着、增殖和活力测定，同时将巨噬细胞用于吞噬作用和极化测定。我们证明细胞倾向于附着在微球表面，并且NCMs具有生物相容性，在特定浓度（50和10个NCM/细胞）下促进细胞增殖，与对照组相比至少增加3倍。此外，巨噬细胞对NCMs的内化似乎使这些细胞转变为非炎症状态，分别通过CD206的过表达和CD64、M2和M1标记物的低表达得以证明。NCMs是一种有效的方法，可逆转停滞伤口（如糖尿病伤口）的慢性炎症状态，从而促进伤口愈合。
