Cutaneous chronic wounds remain a major clinical challenge which requires the development of novel wound dressings. Previously, we showed that collagen–silica nanocomposites consisting of polyethyleneimine (PEI)-DNA complexes associated with silica nanoparticles (SiNP), collagen hydrogel and 3T3 fibroblasts, can work as a local “cell factory”. Indeed, the “in-gel” transfection leads to a sustained production and release of biomolecules. Herein, we further explored the possibility for nanocomposites to deliver interleukin-10 (IL-10), a potent anti-inflammatory cytokine, which favors tissue repair. Its anti-inflammatory effect was evaluated in an in vitro inflammation model carried out by LPS (lipopolysaccharide) activation of macrophages embedded in collagen gel. The IL-10 synthesis from nanocomposites was detected over one week in the range of 200–400 pg mL⁻¹ and reached a maximum at day 5 without any observed cytotoxic effects. PEI₁₀-SiNP outperformed free PEI₁₀ and PEI₂₅-SiNP, implying that the introduction of SiNP improved the transfection efficiency of low M_w of PEI. In addition, the structure and mechanical properties of collagen–silica nanocomposites were stable over one week. Subsequently, the ability of nanocomposites to modulate inflammation was tested in a 3D model of inflammation. The decrease of TNF-α and IL-1β gene expression by 20–80% indicated successful inhibition of inflammation by IL-10 released from nanocomposites. Taken together, the nanocomposites are capable of producing effective doses of IL-10 which inhibit the synthesis of pro-inflammatory cytokines and favor the expression of wound healing cytokines. Therefore, the as-constructed 3D gene delivery system represents a promising strategy for the controlled release of therapeutic biomolecules favoring cutaneous wound healing.

中文翻译：

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通过基因传递 从胶原-二氧化硅纳米复合物中释放的IL-10调节皮肤慢性伤口模型中的炎症†

皮肤慢性伤口仍然是主要的临床挑战，需要开发新型伤口敷料。以前，我们证明了胶原-二氧化硅纳米复合材料由聚乙烯亚胺（PEI）-DNA复合物和二氧化硅纳米颗粒（SiNP），胶原水凝胶和3T3成纤维细胞组成，可以作为当地的“细胞工厂”。实际上，“凝胶内”转染导致生物分子的持续产生和释放。在本文中，我们进一步探讨了纳米复合材料递送白细胞介素10（IL-10）（一种有效的消炎细胞因子，有利于组织修复的可能性）的可能性。在体外评估了其抗炎作用通过LPS（脂多糖）激活嵌入胶原蛋白凝胶中的巨噬细胞进行的炎症模型。在一周内检测到了纳米复合物的IL-10合成，范围为200–400 pg mL ^-1，并在第5天达到最大值，而未观察到任何细胞毒性作用。PEI ₁₀ -SiNP优于游离PEI ₁₀和PEI ₂₅ -SiNP，这表明SiNP的引入提高了低M _w的转染效率。PEI。此外，胶原-二氧化硅纳米复合材料的结构和力学性能在一周内稳定。随后，在炎症的3D模型中测试了纳米复合材料调节炎症的能力。TNF-α和IL-1β基因表达降低20-80％，表明纳米复合物释放的IL-10成功抑制了炎​​症。总之，纳米复合物能够产生有效剂量的IL-10，其抑制促炎细胞因子的合成并有利于伤口愈合细胞因子的表达。因此，如此构建的3D基因传递系统代表了一种有希望的策略，可控制释放有利于皮肤伤口愈合的治疗性生物分子。