Heart valve has extraordinary fatigue resistance which beats ∼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, we introduced a double-network tough hydrogel which interpenetrated and anchored 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 mimicked the glycocalyx on endothelium which improved anti-thrombosis and accelerated endothelialization; the chemical crosslinked hydrophilic polyacrylamide (PAAm) network further enhanced anti-fouling properties and strengthened the shielding hydrogels and their interaction with dCell-PP. In-vitro and rabbit ex-vivo shunt assay demonstrated great hemocompatibility of polyacrylamide/HA hydrogel hybrid PP (P/H-PP). Cell experiments and rat subcutaneous implantation confirmed satisfactory endothelialization, biocompatibility and anti-calcification properties. For hydrodynamic experiment, P/H-PP gained full mark at different flow conditions and sustained 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.

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