Double-Network Hydrogel Armored Decellularized Porcine Pericardium as Durable Bioprosthetic Heart Valves
Double-Network Hydrogel Armored Decellularized Porcine Pericardium as Durable Bioprosthetic Heart Valves
复制标题
双网络水凝胶铠装脱细胞猪心包膜作为耐用的生物假体心脏瓣膜
DOI：
10.1002/adhm.202102059
复制
发表时间：
2022-01-12
影响因子：
10
通讯作者：
Wang, Jian'an
中科院分区：
文献类型：
--
作者：
Cheng, Si;Liu, Xianbao;Wang, Jian'an
心脏瓣膜具有非凡的抗疲劳性，其一生中跳动约30亿次。在心脏瓣膜置换术中逐渐使用的由固定异质材料制成的生物瓣膜（BHV）由于血栓形成、内皮化不良、炎症、钙化，特别是机械损伤引起的生物相容性变化而无法维持预期的耐久性。长期疲劳试验后，没有有效的策略来保护BHV的生物学特性。在此，引入了双网络坚韧水凝胶，其相互渗透并锚到脱细胞猪心包（dCell-PP）的基质中，以形成坚固且稳定的保形涂层并降低免疫原性。离子交联的透明质酸（HA）网络模拟内皮上的糖萼，其改善抗血栓形成并加速内皮化;化学交联的亲水性聚丙烯酰胺（PAAm）网络进一步增强抗血栓性能并增强屏蔽水凝胶及其与dCell-PP的相互作用。体外和家兔离体分流试验表明聚丙烯酰胺/HA水凝胶杂化PP（P/H-PP）具有良好的血液相容性。细胞实验和大鼠皮下植入证实了令人满意的内皮化，生物相容性和抗钙化性能。在流体力学实验中，P/H-PP在不同流动条件下均获得满分，经过2亿次循环后仍保持良好的生物力学性能和生物学性能。P/H双网络水凝胶铠装dCell-PP是延长BHV耐久性用于临床植入治疗的有希望的进展。
Heart valves have extraordinary fatigue resistance which beat approximate to 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.