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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.

Electrospun fiber mats are currently gaining attention as advanced drug delivery systems. Dissolution testing for such systems is generally performed in small vials by immersing the fiber mats in buffered solutions. Defined aliquots of dissolution medium are withdrawn at predefined time points, and the dissolved drug is quantified. However, this procedure is associated with several drawbacks. The method is not automated, and as such requires manual sampling, which potentially leads to inaccuracies particularly in frequent sampling intervals as required for characterization of rapid drug release. Further, the sheet-like fiber mats tend to partially fold upon contact with the dissolution medium, which may potentially affect the release kinetics and reproducibility of the acquired release data.In this study, we investigated the application of a fully automated fiber-optics based dissolution testing system for in situ monitoring of drug release from electrospun fiber mats. Electrospun poly(vinyl alcohol) fibers loaded with lysozyme were used as a model system. To prevent folding of the fiber mats and ensure a fixed position in the dissolution vessel throughout the experiment, a flexible adapter was developed to allow for the attachment of the fiber mats to the vessel walls. Lysozyme release from the fiber mats was compared with the release from cast films with the same composition. Even though the release processes were rather fast and differences in release kinetics of the two systems were marginal, the fiber-optics based dissolution setup allowed for the successful detection of released protein in both cases. The present study, therefore, highlights the potential for the utilization of fully automated fiber-optics based dissolution testing systems for advanced in situ monitoring of drug release from electrospun fibers.

Proteins play a vital role within the human body by regulating various functions and even serving as structural constituent of many body parts. In this context, protein-based therapeutics have attracted a lot of attention in the last few decades as potential treatment of different diseases. Due to the steadily increasing interest in protein-based therapeutics, different dosage forms were investigated for delivering such complex macromolecules to the human body. Here, electrospun fibers hold a great potential for embedding proteins without structural damage and for controlled release of the protein for therapeutic applications. This review provides a comprehensive overview of the current state of protein-based carrier systems using electrospun fibers, with special emphasis on discussing their potential and key challenges in developing such therapeutic strategies, along with a prospective view of anticipated future directions.