title: Three-dimensional hierarchical cultivation of human skin cells on bio-adaptive hybrid fibers.
abstract: 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.
authors.affiliation: Department of Biopharmaceutics and Pharmaceutical Technology, Saarland University, Campus Building A 4.1, 66123 Saarbrücken, Germany. m.windbergs@mx.uni-saarland.de.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Planz
authors.affiliation: Department of Biopharmaceutics and Pharmaceutical Technology, Saarland University, Campus Building A 4.1, 66123 Saarbrücken, Germany. m.windbergs@mx.uni-saarland.de and PharmBioTec GmbH, Science Park 1, 66123 Saarbrücken, Germany.
authors.forename: Salem
authors.initials: S
authors.lastname: Seif
authors.affiliation: INM - Leibniz Institute for New Materials, Campus Building D 2.2, 66123 Saarbrücken, Germany.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Atchison
authors.affiliation: Helmholtz Centre for Infection Research (HZI) and Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Department of Drug Delivery (DDEL), Campus Building E 8.1, 66123 Saarbrücken, Germany.
authors.forename: Branko
authors.initials: B
authors.lastname: Vukosavljevic
authors.affiliation: Department of Biopharmaceutics and Pharmaceutical Technology, Saarland University, Campus Building A 4.1, 66123 Saarbrücken, Germany. m.windbergs@mx.uni-saarland.de.
authors.forename: Lisa
authors.initials: L
authors.lastname: Sparenberg
authors.affiliation: INM - Leibniz Institute for New Materials, Campus Building D 2.2, 66123 Saarbrücken, Germany.
authors.forename: Elmar
authors.initials: E
authors.lastname: Kroner
authors.affiliation: Department of Biopharmaceutics and Pharmaceutical Technology, Saarland University, Campus Building A 4.1, 66123 Saarbrücken, Germany. m.windbergs@mx.uni-saarland.de and PharmBioTec GmbH, Science Park 1, 66123 Saarbrücken, Germany and Helmholtz Centre for Infection Research (HZI) and Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Department of Drug Delivery (DDEL), Campus Building E 8.1, 66123 Saarbrücken, Germany.
authors.forename: Maike
authors.initials: M
authors.lastname: Windbergs
mesh_terms: D000222:Adaptation, Physiological; D061249:Batch Cell Culture Techniques; D040761:Biomimetic Materials / Q000737:chemistry*; D002448:Cell Adhesion / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000737:chemistry*; D005347:Fibroblasts / Q000166:cytology* / Q000502:physiology; D006801:Humans; D021621:Imaging, Three-Dimensional; D015603:Keratinocytes / Q000166:cytology* / Q000502:physiology; D008422:Materials Testing; D009924:Organ Culture Techniques / Q000379:methods*; D012867:Skin / Q000166:cytology / Q000254:growth & development; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds