Afghah Ferdows, Altunbek Mine, Zahrabi Mahdiyeh, Koc Bahattin
Sabanci University Nanotechnology Research and Application Center, Istanbul 34956, Turkey.
Sabanci University Faculty of Engineering and Natural Sciences, Istanbul 34956, Turkey.
ACS Appl Bio Mater. 2025 Apr 21;8(4):2875-2887. doi: 10.1021/acsabm.4c01541. Epub 2025 Mar 25.
Engineering thick skin tissue substitutes resembling the physiochemical and mechanical properties of native tissue is a significant challenge. Melt electrowriting (MEW) is a powerful technique with the capability of fabricating highly ordered structures with fine fiber diameters, closely replicating the native extracellular matrix (ECM). In this study, we constructed melt electrowritten porous polycaprolactone (PCL) scaffolds with three different geometries by depositing fibers at 0-90 and 60-120° in a mesh structure and in a honeycomb-like orientation to assess the effects of the microstructure on the mechanical strength of the scaffold and cellular behavior. These scaffolds were subsequently infilled with gelatin hydrogel, encapsulating human skin dermal fibroblasts (HSFs) and human umbilical vein endothelial cells (HUVECs). Mechanical tensile tests revealed that the honeycomb microstructure of the hybrid PCL/gelatin scaffold exhibited greater elongation at failure, along with an acceptable elastic modulus suitable for skin tissue applications. All scaffolds provided a cytocompatible microenvironment that maintained over 90% cell viability and preserved typical cell morphology. HSFs were guided through the PCL fibers to the apical surface, while HUVECs were distributed within the gelatin hydrogel within the hybrid structure. Additionally, HSFs' alignment was regulated by the scaffold geometry. Notably, the expression of CD31 in HUVECs─a key transmembrane protein for capillary formation─increased significantly over a 14 day incubation period. Among those, 0-90° mesh and honeycomb geometries showed the greatest effects on the upregulation of CD31. These findings demonstrate that the microstructural guidance of HSFs and their interaction with HUVECs in hybrid structures play a crucial role in promoting vascularization. In conclusion, the honeycomb MEW-gelatin hybrid scaffold demonstrates significant potential for effectively replicating both the mechanical and physicochemical properties essential for full-thickness skin tissue substitutes.
构建出在物理化学和力学性能上与天然组织相似的厚皮组织替代物是一项重大挑战。熔体静电纺丝（MEW）是一项强大的技术，能够制造出具有精细纤维直径的高度有序结构，紧密复制天然细胞外基质（ECM）。在本研究中，我们通过以0 - 90°和60 - 120°的角度在网状结构和蜂窝状排列中沉积纤维，构建了具有三种不同几何形状的熔体静电纺丝多孔聚己内酯（PCL）支架，以评估微观结构对支架机械强度和细胞行为的影响。随后，这些支架用明胶水凝胶填充，包封人皮肤真皮成纤维细胞（HSFs）和人脐静脉内皮细胞（HUVECs）。机械拉伸试验表明，PCL/明胶混合支架的蜂窝状微观结构在断裂时表现出更大的伸长率，同时具有适合皮肤组织应用的可接受弹性模量。所有支架都提供了一个细胞相容的微环境，保持超过90%的细胞活力并保留典型的细胞形态。HSFs被PCL纤维引导至顶端表面，而HUVECs分布在混合结构内的明胶水凝胶中。此外，HSFs的排列受支架几何形状的调节。值得注意的是，在14天的培养期内，HUVECs中用于毛细血管形成的关键跨膜蛋白CD31的表达显著增加。其中，0 - 90°网状和蜂窝状几何形状对CD31的上调影响最大。这些发现表明，在混合结构中HSFs的微观结构引导及其与HUVECs的相互作用在促进血管生成中起关键作用。总之，蜂窝状MEW - 明胶混合支架在有效复制全层皮肤组织替代物所需的机械和物理化学性质方面显示出巨大潜力。
