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Contains fulltext : 291616.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 294433.pdf (Publisher’s version ) (Open Access), Cells continuously sense external forces from their microenvironment, the extracellular matrix (ECM). In turn, they generate contractile forces, which stiffen and remodel this matrix. Although this bidirectional mechanical exchange is crucial for many cell functions, it remains poorly understood. Key challenges are that the majority of available matrices for such studies, either natural or synthetic, are difficult to control or lack biological relevance. Here, we use a synthetic, yet highly biomimetic hydrogel based on polyisocyanide (PIC) polymers to investigate the effects of the fibrous architecture and the nonlinear mechanics on cell-matrix interactions. Live-cell rheology was combined with advanced microscopy-based approaches to understand the mechanisms behind cell-induced matrix stiffening and plastic remodeling. We demonstrate how cell-mediated fiber remodeling and the propagation of fiber displacements are modulated by adjusting the biological and mechanical properties of this material. Moreover, we validate the biological relevance of our results by demonstrating that cellular tractions in PIC gels develop analogously to those in the natural ECM. This study highlights the potential of PIC gels to disentangle complex bidirectional cell-matrix interactions and to improve the design of materials for mechanobiology studies.

Item does not contain fulltext, The aim of this study was to examine the influence of the Young's modulus of the implant material on the bone remodeling in a loaded condition. A combined animal experimental and computational study was set up. The animal experimental group comprised of 16 Saanen goats, each receiving one titanium implant (Young's modulus 110 GPa) and one high-density polyethylene (HDPE) implant (Young's modulus 1 GPa) in the left femoral condyle. Both types of implants received a titanium coating of 100 nm thickness. The implants protruded in the knee joint space and were directly weight bearing. The first group of eight goats was sacrificed after 6 weeks of loading and the second group of eight goats after 6 months of loading. The 16 femoral condyles with the 32 implants were prepared for microfocus computed tomography (micro-CT) scanning and histological sectioning. Three-dimensional trabecular bone parameters were calculated on the micro-CT images for the zones neck, middle, and apex of the implant. The percent of bone contact with the implant was measured on longitudinal histological sections. An axisymmetric finite element (FE) model was created to compare peri-implant bone strains and relative motion between a titanium and a HDPE implant for the experimental loading condition, and to assess the influence of different bone-implant interface (contact) conditions. From the statistical analysis of the 3D bone parameters, the difference between the titanium and HDPE implants was not significantly different (p > 0.05) between the zones (neck, middle, and apex) for both groups of goats. The implants could be considered in their entirety. After 6 weeks of loading, the PE implant presented lower connectivity and smaller marrow spaces in the circular region of 0-500 microm. In the region 500-1500 microm more bone volume was present for the PE implant. After 6 months, the PE implants showed more bone volume and thicker trabeculae than the titanium implants for the entire length of the i