Biomechanical and functional comparison of moulded and 3D printed medical silicones.

Modern 3D printing of implantable devices provides an important opportunity for the development of personalized implants with good anatomical fit. Nevertheless, 3D printing of silicone has been challenging and the recent advances in technology are provided by the systems which can print medical grade silicone via extrusion. However, the potential impacts of the 3D printing process of silicone on its biomechanical properties has not been studied in sufficient detail. Therefore, the present study compares 3D printed and moulded silicone structures for their cytotoxicity, surface roughness, biomechanical properties, and in vivo tissue reaction. The 3D printing process creates increased nanoscale roughness and noticeably changes microscale topography. Neither the presence of these features nor the differences in processes were found to result in an increase in cytotoxicity or tissue reaction for 3D printed structures, exhibiting limited inflammatory reaction and cell viability above the threshold values. On the contrary, the biomechanical properties have demonstrated significant differences in static and dynamic conditions, and in thermal expansion. Our results demonstrate that 3D printing can be used for establishing a better biomechanical microenvironment for the surrounding tissue of the implant particularly for fragile soft tissue like epithelial mucosa without having any negative effect on the cytotoxicity or in vivo reaction to silicone. For engineering of the implants, however, one must consider the differences in mechanical properties to result in correct and personalized geometry and proper physical interaction with tissues.

A composite Gelatin/hyaluronic acid hydrogel as an ECM mimic for developing mesenchymal stem cell-derived epithelial tissue patches.

Here we report fabrication of Gelatin-based biocomposite films and their application in developing epithelial patches. The films were loaded with an epithelial cell growth factor cocktail and used as an extracellular matrix mimic for in vitro regeneration of organized respiratory epithelium using Calu-3 cell line and mesenchymal stem cells (MSCs). Our data show differentiation of Calu-3 cells on composite films as evidenced by tight junction protein expression and barrier formation. The films also supported attachment, migration, and proliferation of alveolar basal epithelial cell line A549. We also show the suitability of the composite films as a biomimetic scaffold and growth factor delivery platform for differentiation of human MSCs to epithelial cells. MSCs differentiation to the epithelial lineage was confirmed by staining for epithelial and stem cell specific markers. Our data show that the MSCs acquire the epithelial characteristics after 2 weeks with significant reduction in vimentin, increase in pan cytokeratin expression, and morphological changes. However, despite the expression of epithelial lineage markers, these cells did not form fully functional tight junctions as evidenced by low expression of junctional protein ZO1. Further optimisation of culture conditions and growth factor cocktail is required to enhance tight junction formation in MSCs-derived epithelial cells on the composite hydrogels. Nevertheless, our data clearly highlight the possibility of using MSCs in epithelial tissue engineering and the applicability of the composite hydrogels as transferrable extracellular matrix mimics and delivery platforms with potential applications in regenerative medicine and in vitro modelling of barrier tissues.