Heart valves have extraordinary fatigue resistance which beat ≈3 billion times in a lifetime. Bioprosthetic heart valves (BHVs) made from fixed heteroplasm that are incrementally used in heart valve replacement fail to sustain the expected durability due to thrombosis, poor endothelialization, inflammation, calcification, and especially mechanical damage induced biocompatibility change. No effective strategy has been reported to conserve the biological properties of BHV after long-term fatigue test. Here, a double-network tough hydrogel is introduced, which interpenetrate and anchor into the matrix of decellularized porcine pericardium (dCell-PP) to form robust and stable conformal coatings and reduce immunogenicity. The ionic crosslinked hyaluronic acid (HA) network mimics the glycocalyx on endothelium which improves antithrombosis and accelerates endothelialization; the chemical crosslinked hydrophilic polyacrylamide (PAAm) network further enhances antifouling properties and strengthens the shielding hydrogels and their interaction with dCell-PP. In vitro and rabbit ex vivo shunt assay demonstrate great hemocompatibility of polyacrylamide/HA hydrogel hybrid PP (P/H-PP). Cell experiments and rat subcutaneous implantation confirm satisfactory endothelialization, biocompatibility, and anticalcification properties. For hydrodynamic experiment, P/H-PP gains full mark at different flow conditions and sustains excellent biomechanical and biological properties after 200 000 000 cycles. P/H double-network hydrogel armoring dCell-PP is a promising progress to extend BHV durability for clinical implantation therapy.
Tissue engineering raised a high requirement to control cell distribution in defined materials and structures. In “ink”-based bioprintings, such as 3D printing and photolithography, cells were associated with inks for spatial orientation; the conditions suitable for one ink are hard to apply on other inks, which increases the obstacle in their universalization. The Magneto-Archimedes effect based (Mag-Arch) strategy can modulate cell locomotion directly without impelling inks. In a paramagnetic medium, cells were repelled from high magnetic strength zones due to their innate diamagnetism, which is independent of substrate properties. However, Mag-Arch has not been developed into a powerful bioprinting strategy as its precision, complexity, and throughput are limited by magnetic field distribution. By controlling the paramagnetic reagent concentration in the medium and the gaps between magnets, which decide the cell repelling scope of magnets, we created simultaneously more than a hundred micrometer scale identical assemblies into designed patterns (such as alphabets) with single/multiple cell types. Cell patterning models for cell migration and immune cell adhesion studies were conveniently created by Mag-Arch. As a proof of concept, we patterned a tumor/endothelial coculture model within a covered microfluidic channel to mimic epithelial-mesenchymal transition (EMT) under shear stress in a cancer pathological environment, which gave a potential solution to pattern multiple cell types in a confined space without any premodification. Overall, our Mag-Arch patterning presents an alternative strategy for the biofabrication and biohybrid assembly of cells with biomaterials featured in controlled distribution and organization, which can be broadly employed in tissue engineering, regenerative medicine, and cell biology research.
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