Staff member

Changes in the mechanical properties of the extracellular matrix (ECM) are a hallmark of disease. Due to its relevance, several in vitro models have been developed for the ECM, including cell-derived matrices (CDMs). CDMs are decellularized natural ECMs assembled by cells that closely mimic the in vivo stromal fibre organization and molecular content. Here, we applied atomic force microscopy-force spectroscopy (AFM-FS) to evaluate the nanomechanical properties of CDMs obtained from patients diagnosed with collagen VI-related congenital muscular dystrophies (COL6-RDs). COL6-RDs are a set of neuromuscular conditions caused by pathogenic variants in any of the three major COL6 genes, which result in deficiency or dysfunction of the COL6 incorporated into the ECM of connective tissues. Current diagnosis includes the genetic confirmation of the disease and categorization of the phenotype based on maximum motor ability, as no direct correlation exists between genotype and phenotype of COL6-RDs. We describe differences in the elastic modulus (E) among CDMs from patients with different clinical phenotypes, as well as the restoration of E in CDMs obtained from genetically edited cells. Results anticipate the potential of the nanomechanical analysis of CDMs as a complementary clinical tool, providing phenotypic information about COL6-RDs and their response to gene therapies.

JTD Keywords: Atomic force microscopy-based force spectroscopy, Bethlem myopathy, Cell-derived matrices, Collagen vi-related congenital muscular dystrophies, Elastic modulus, Extracellular matrix, Extracellular-matrix, Fibroblasts, Gene editin, Microenvironment, Migration, Mode, Muscle, Position, Progenitors, Stiffness

Endothelium, the lining in this blood vessel, orchestrates three main critical functions such as protecting blood components, modulating of hemostasis by secreting various inhibitors, and directing clot digestion (fibrinolysis) by activating tissue plasminogen activator. No other surface can perform these tasks; thus, the contact of blood and blood-contacting medical devices inevitably leads to the activation of coagulation, often causing device failure, and thromboembolic complications. This perspective, first, discusses the biological mechanisms of activation of coagulation and highlights the efforts of advanced coatings to recapitulate one characteristic of endothelium, hereafter single functions of endothelium and noting necessity of the synergistic integration of its three main functions. Subsequently, it is emphasized that to overcome the challenges of blood compatibility an endothelium-mimicking system is needed, proposing a synergy of bottom-up synthetic biology, particularly synthetic cells, with passive- and bioactive surface coatings. Such integration holds promise for developing advanced biomaterials capable of recapitulating endothelial functions, thereby enhancing the hemocompatibility and performance of blood-contacting medical devices. The activation of coagulation on the surface of blood-contacting medical devices often leads to thromboembolic complications. A concept for the next generation of hemocompatbile surfaces inspired by endothelium is proposed. This concept not only contribute to the fundamental understanding of hemocompatibility but also offer practical implications for the design and development of biomedical devices with enhanced biocompatibility and functionality. image

JTD Keywords: Animals, Antifouling coatings, Antifouling polymer brushes, Biocompatible materials, Blood coagulation, Coagulation-factor-xii, Coated materials, biocompatible, Endothelium, Endothelium, vascular, Endothelium-inspired, Endothelium‐inspired, Hemocompatibility, Hemocompatible surface coatings, Hemostasis, Heparin-induced thrombocytopenia, Humans, Nitric-oxide release, Of-the-art, Peptide macrocycle inhibitor, Plasma contact system, Protein-adsorption, Self-assembled monolayers, Surface modificatio, Synthetic endotheliu, Synthetic endothelium