Double-Network Hydrogel Armored Decellularized Porcine Pericardium as Durable Bioprosthetic Heart Valves.

ABSTRACT

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.