Fracture toughness characterizes the ability of a material to maintain a certain level of strength despite the presence of a macroscopic crack. Understanding this tolerance for defects in soft collagenous tissues (SCT) has high relevance for assessing the risks of fracture after cutting, perforation or suturing. Here we investigate the peculiar toughening mechanisms of SCT through dedicated experiments and multi-scale simulations, showing that classical concepts of fracture mechanics are inadequate to quantify and explain the high defect tolerance of these materials. Our results demonstrate that SCT strength is only modestly reduced by defects as large as several millimeters. This defect tolerance is achieved despite a very narrow process zone at the crack tip and even for a network of brittle fibrils. The fracture mechanics concept of tearing energy fails in predicting failure at such defects, and its magnitude is shown to depend on the chemical potential of the liquid environment.

Matrix deposition is essential for wound repair, but when excessive, leads to hypertrophic scars and fibrosis. The factors that control matrix deposition in skin wounds have only partially been identified and the consequences of matrix alterations for the mechanical properties of wounds are largely unknown. Here, we report how a single diffusible factor, activin A, affects the healing process across scales. Bioinformatics analysis of wound fibroblast transcriptome data combined with biochemical and histopathological analyses of wounds and functional in vitro studies identify that activin promotes pro-fibrotic gene expression signatures and processes, including glycoprotein and proteoglycan biosynthesis, collagen deposition, and altered collagen cross-linking. As a consequence, activin strongly reduces the wound and scar deformability, as identified by a non-invasive in vivo method for biomechanical analysis. These results provide mechanistic insight into the roles of activin in wound repair and fibrosis and identify the functional consequences of alterations in the wound matrisome at the biomechanical level.

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Suction experiments have been extensively applied for skin characterization. In these tests the deformation behavior of superficial tissue layers determines the elevation of the skin surface observed when a predefined negative (suction) pressure history is applied. The ability of such measurements to differentiate between skin conditions is limited by the variability of the elevation response observed in repeated experiments. The scatter was shown to be associated with the force exerted by the observer when holding the instrument against the skin. We have developed a novel suction device and a measurement procedure aiming at a tighter control of mechanical boundary conditions during the experiments. The new device weighs only 3.5 g and thus allows to minimize the force applied on the skin during the test. In this way, it is possible to reliably characterize the mechanical response of skin, also in case of low values of suction pressure and deformation. The influence of the contact force is analyzed through experiments on skin and synthetic materials, and rationalized based on corresponding finite element calculations. A comparative study, involving measurements on four body locations in two subjects by three observers, showed the good performance of the new procedure, specific advantages, and limitations with respect to the Cutometer®, i.e. the suction device most widely applied for skin characterization. As a byproduct of the present investigation, a correction procedure is proposed for the Cutometer measurements, which allows to partially compensate for the influence of the contact force. The characteristics of the new suction method are discussed in view of future applications for diagnostic purposes.

Transcatheter aortic valve replacement (TAVR) is being extended to younger patients. However, TAVR-compatible bioprostheses are based on xenogeneic materials with limited durability. Off-the-shelf tissue-engineered heart valves (TEHVs) with remodeling capacity may overcome the shortcomings of current TAVR devices. Here, we develop for the first time a TEHV for TAVR, based on human cell-derived extracellular matrix and integrated into a state-of-the-art stent for TAVR. The TEHVs, characterized by a dense acellular collagenous matrix, demonstrated in vitro functionality under aortic pressure conditions (n = 4). Next, transapical TAVR feasibility and in vivo TEHV functionality were assessed in acute studies (n = 5) in sheep. The valves successfully coped with the aortic environment, showing normal leaflet motion, free coronary flow, and absence of stenosis or paravalvular leak. At explantation, TEHVs presented full structural integrity and initial cell infiltration. Its long-term performance proven, such TEHV could fulfill the need for next-generation lifelong TAVR prostheses.