Department of Chemical, Biological and Bioengineering, North Carolina A&T State University, Greensboro, North Carolina 27411, United States.
Department of Chemistry, North Carolina A&T State University, 1601 E Market St, Greensboro, North Carolina 27411, United States.
ACS Appl Mater Interfaces. 2024 Sep 18;16(37):49197-49217. doi: 10.1021/acsami.4c13458. Epub 2024 Sep 5.
Metal particles incorporated into polymer matrices in various forms and geometries are attractive material platforms for promoting wound healing and preventing infections. However, the fate of these metal particles and their degraded products in the tissue environment are still unknown, as both can produce cytotoxic effects and promote unwanted wound reactions. In this study, we develop biodegradable fibrous biomaterials embedded with metal particles that have an immune activation functions. Initially, biodegradable zinc (Zn) nanoparticles were modified with zein (G), a protein derived from corn. The zein-coated zinc particles (Z-G) were then embedded in polycaprolactone (P) fibers at different weight ratios to create fibrous biomaterials via electrospinning, which were subsequently analyzed for potential wound healing applications. We performed multimodal evaluations of the fibrous scaffolds, examining physicochemical properties such as fiber morphology, mechanical strength, hydrophilicity, degradation, and release of zinc ions (Zn), as well as biological properties, including in vitro cell culture studies. We provide evidence that the integration of 2.4 wt % of Z-G particles in polycaprolactone (PCL) nanofibrous scaffolds improved its physicochemical and biological functions. The in vitro cellular response of the scaffolds was evaluated using a series of cytotoxicity assays and immunocytochemistry analyses with three different cell types: mouse-derived fibroblast cell lines (NIH/3T3), human dermal fibroblasts (HDFn), and human umbilical vein endothelial cells (HUVECs). The composite fibrous scaffold exhibited robust activation and proliferation of NIH/3T3 and HDFn cells, along with a significant angiogenic potential in HUVECs. Immunocytochemistry confirmed elevated expression of vimentin and α-smooth muscle actin (α-SMA), suggesting that NIH/3T3 and Haden cells were highly differentiated into myofibroblasts. Additionally, the increased expression of CD31 and VE-cadherin in HUVECs suggests that the scaffold supports tube formation, thereby enhancing neovascularization and promoting an effective immune response. Overall, our findings demonstrate the regenerative potential of the self-enhanced Zn hemostatic bioscaffolds, which deliver both Zn ions and zein proteins to nourish cells. This capability not only modulates cellular activities but also contributes to tissue repair and remodeling, making the scaffolds suitable for wound repair and various bioengineering applications.
金属颗粒以各种形式和几何形状掺入聚合物基质中,是促进伤口愈合和预防感染的有吸引力的材料平台。然而,这些金属颗粒及其降解产物在组织环境中的命运仍然未知,因为它们都可能产生细胞毒性作用并促进不需要的伤口反应。在这项研究中,我们开发了具有免疫激活功能的可生物降解纤维状生物材料,其中嵌入了金属颗粒。最初,用玉米来源的蛋白质 Zein(G)对可生物降解的锌(Zn)纳米颗粒进行修饰。然后,将 Zein 包覆的锌颗粒(Z-G)以不同的重量比嵌入聚己内酯(P)纤维中,通过静电纺丝创建纤维状生物材料,随后对其进行评估,以确定其在潜在伤口愈合方面的应用。我们对纤维支架进行了多模式评估,研究了纤维形态、机械强度、亲水性、降解和锌离子(Zn)释放等物理化学性质,以及包括体外细胞培养研究在内的生物特性。我们提供的证据表明,将 2.4wt%的 Z-G 颗粒整合到聚己内酯(PCL)纳米纤维支架中可以改善其物理化学和生物学功能。使用一系列细胞毒性测定和免疫细胞化学分析,通过三种不同的细胞类型(鼠源性成纤维细胞系(NIH/3T3)、人真皮成纤维细胞(HDFn)和人脐静脉内皮细胞(HUVECs))评估支架的体外细胞反应。复合纤维支架表现出对 NIH/3T3 和 HDFn 细胞的强大激活和增殖,以及对 HUVECs 的显著血管生成潜力。免疫细胞化学证实了波形蛋白和α-平滑肌肌动蛋白(α-SMA)的表达升高,表明 NIH/3T3 和 Haden 细胞高度分化为肌成纤维细胞。此外,HUVECs 中 CD31 和 VE-钙粘蛋白的表达增加表明支架支持管形成,从而增强血管生成并促进有效的免疫反应。总的来说,我们的研究结果表明,自增强 Zn 止血生物支架具有再生潜力,它既能输送 Zn 离子又能输送 Zein 蛋白来滋养细胞。这种能力不仅调节细胞活动,还有助于组织修复和重塑,使支架适用于伤口修复和各种生物工程应用。