Planz Viktoria, Seif Salem, Atchison Jennifer S, Vukosavljevic Branko, Sparenberg Lisa, Kroner Elmar, Windbergs Maike
Department of Biopharmaceutics and Pharmaceutical Technology, Saarland University, Campus Building A 4.1, 66123 Saarbrücken, Germany.
INM - Leibniz Institute for New Materials, Campus Building D 2.2, 66123 Saarbrücken, Germany.
Integr Biol (Camb). 2016 Jul 11;8(7):775-84. doi: 10.1039/c6ib00080k.
The human skin comprises a complex multi-scale layered structure with hierarchical organization of different cells within the extracellular matrix (ECM). This supportive fiber-reinforced structure provides a dynamically changing microenvironment with specific topographical, mechanical and biochemical cell recognition sites to facilitate cell attachment and proliferation. Current advances in developing artificial matrices for cultivation of human cells concentrate on surface functionalizing of biocompatible materials with different biomolecules like growth factors to enhance cell attachment. However, an often neglected aspect for efficient modulation of cell-matrix interactions is posed by the mechanical characteristics of such artificial matrices. To address this issue, we fabricated biocompatible hybrid fibers simulating the complex biomechanical characteristics of native ECM in human skin. Subsequently, we analyzed interactions of such fibers with human skin cells focusing on the identification of key fiber characteristics for optimized cell-matrix interactions. We successfully identified the mediating effect of bio-adaptive elasto-plastic stiffness paired with hydrophilic surface properties as key factors for cell attachment and proliferation, thus elucidating the synergistic role of these parameters to induce cellular responses. Co-cultivation of fibroblasts and keratinocytes on such fiber mats representing the specific cells in dermis and epidermis resulted in a hierarchical organization of dermal and epidermal tissue layers. In addition, terminal differentiation of keratinocytes at the air interface was observed. These findings provide valuable new insights into cell behaviour in three-dimensional structures and cell-material interactions which can be used for rational development of bio-inspired functional materials for advanced biomedical applications.
人体皮肤由一个复杂的多尺度分层结构组成，细胞外基质（ECM）内不同细胞具有层次组织。这种支持性的纤维增强结构提供了一个动态变化的微环境，具有特定的地形、机械和生化细胞识别位点，以促进细胞附着和增殖。目前在开发用于培养人类细胞的人工基质方面的进展集中在使用不同生物分子（如生长因子）对生物相容性材料进行表面功能化，以增强细胞附着。然而，这种人工基质的机械特性对有效调节细胞-基质相互作用来说，往往是一个被忽视的方面。为了解决这个问题，我们制造了模拟人体皮肤天然ECM复杂生物力学特性的生物相容性混合纤维。随后，我们分析了这种纤维与人类皮肤细胞的相互作用，重点是确定优化细胞-基质相互作用的关键纤维特性。我们成功地确定了生物适应性弹塑性刚度与亲水性表面特性的介导作用是细胞附着和增殖的关键因素，从而阐明了这些参数诱导细胞反应的协同作用。在代表真皮和表皮中特定细胞的这种纤维垫上共同培养成纤维细胞和角质形成细胞，导致了真皮和表皮组织层的分层组织。此外，还观察到角质形成细胞在空气界面处发生终末分化。这些发现为三维结构中的细胞行为和细胞-材料相互作用提供了有价值的新见解，可用于合理开发用于先进生物医学应用的仿生功能材料。
