Jorge-Herrero E, Garcia Paez J M, Del Castillo-Olivares Ramos J L
Unidad de Biomateriales, Servicio de Cirugía Experimental, H.U. Clínica Puerta de Hierro, Madrid - Spain.
J Appl Biomater Biomech. 2005 May-Aug;3(2):67-82.
Attempts to replace diseased human valves with prostheses began more than 30 yrs ago. Heart valve prostheses can be broadly classified into mechanical prostheses (made out of non-biological materials) and bioprostheses made out of biological tissue. Biological valves are made from animal tissue bovine pericardium and porcine valves. The use of these tissues became commercially available after the introduction of the glutaraldehyde (GA) fixation technique. GA reacts with tissue proteins to form inter- and intramolecular crosslinks, resulting in improved durability. The advantage of bioprostheses compared with mechanical valves is the freedom from thromboembolism; and therefore, the avoidance of long-term anticoagulation therapy. These prostheses are preferable in elderly people and in patients who do not tolerate anticoagulants. However, tissular calcification and primary tissue failure (caused by the mechanical stress) are the main unresolved problems. The causes of calcification are numerous and, to date, a satisfactory solution to this question has not been found, although chemical treatments with metal cations, diphosphonates and treatments eliminating phospholipids have proved to mitigate calcification. In addition, alterna-tive approaches to GA chemical treatment fixation are being proposed to provide the tissue with greater resistance to this process. Studies are under way using polyepoxy compounds, derivates of amino oleic acid (AOA), agents such as diphenylphosphorylazide, carbodiimide, amino acids etc. Further improvements in fixation techniques, as well as in bioprosthesis design (stentless valves) are being made to improve the durability and functional characteristics of bioprosthetic heart valves. The development of a biomaterial capable of withstanding calcification and mechanical stress, while being as durable as mechanical prostheses, would convert the bioprostheses into the replacement of choice by eliminating the need for anticoagulation therapy.
30多年前就开始尝试用人工瓣膜替换病变的人体瓣膜。心脏瓣膜假体大致可分为机械假体（由非生物材料制成）和由生物组织制成的生物假体。生物瓣膜由动物组织牛心包和猪瓣膜制成。在引入戊二醛（GA）固定技术后，这些组织的使用开始商业化。GA与组织蛋白反应形成分子间和分子内交联，从而提高了耐用性。与机械瓣膜相比，生物假体的优点是不会发生血栓栓塞；因此，无需长期抗凝治疗。这些假体在老年人和不耐受抗凝剂的患者中更适用。然而，组织钙化和原发性组织衰竭（由机械应力引起）是尚未解决的主要问题。钙化的原因很多，迄今为止，尽管用金属阳离子、双膦酸盐进行化学处理以及消除磷脂的处理已被证明可减轻钙化，但尚未找到令人满意的解决方案。此外，正在提出替代GA化学处理固定的方法，以使组织对这一过程具有更大的抵抗力。正在使用多环氧化合物、氨基油酸（AOA）衍生物、二苯基磷酰叠氮化物、碳二亚胺、氨基酸等试剂进行研究。正在对固定技术以及生物假体设计（无支架瓣膜）进行进一步改进，以提高生物人工心脏瓣膜的耐用性和功能特性。开发一种能够耐受钙化和机械应力，同时又具有与机械假体一样耐用的生物材料，将通过消除抗凝治疗的需要，使生物假体成为首选的替代品。
