Rabkin-Aikawa Elena, Mayer John E, Schoen Frederick J
Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
Adv Biochem Eng Biotechnol. 2005;94:141-79. doi: 10.1007/b100003.
The valves of the heart cannot regenerate spontaneously. Therefore, heart valve disease generally necessitates surgical repair or replacement of the diseased tissue by mechanical or bioprosthetic valve substitutes in order to avoid potentially fatal cardiac or systemic consequences. Although survival and quality of life is enhanced for many patients treated surgically, currently available valve substitutes remain imperfect. This is especially the case in pediatric applications, where physiologically corrective procedures can be successfully performed, but reoperations are frequently required to replace failed valve substitutes or accommodate growth of the patient. While much work is currently underway to incrementally improve existing valve substitutes, a major impact will require radically new technologies, including tissue engineering or regeneration. The use of engineered tissue offers the potential to create a non-obstructive, non-thrombogenic tissue valve substitute containing living cells capable of providing ongoing remodeling and repair of cumulative injury to the extracellular matrix. Ideally, this would allow growth in maturing recipients. The innovative fabrication of materials and the development of sophisticated methods to repair or regenerate damaged or diseased heart valves requires integration of a diverse array of basic scientific principles and enabling technologies. Thus, heart valve tissue engineering requires an understanding of relationships of structure to function in normal and pathological valves (including mechanisms of embryological development, tissue repair and functional biomechanics), and the ability to control cell and tissue responses to injury, physical stimuli and biomaterial surfaces, through chemical, pharmacological, mechanical and potentially genetic manipulations. These approaches created by advances in cell biology raise exciting possibilities for in situ regeneration and repair of heart valves.
心脏瓣膜无法自发再生。因此，心脏瓣膜疾病通常需要通过机械或生物人工瓣膜替代品对病变组织进行手术修复或置换，以避免潜在的致命心脏或全身后果。尽管许多接受手术治疗的患者的生存率和生活质量得到了提高，但目前可用的瓣膜替代品仍然存在缺陷。在儿科应用中尤其如此，在儿科可以成功进行生理矫正手术，但经常需要再次手术来更换失效的瓣膜替代品或适应患者的生长。虽然目前正在进行大量工作以逐步改进现有的瓣膜替代品，但要产生重大影响则需要全新的技术，包括组织工程或再生技术。使用工程组织有可能创造一种无阻塞、无血栓形成的组织瓣膜替代品，其中含有能够对细胞外基质的累积损伤进行持续重塑和修复的活细胞。理想情况下，这将允许在成长中的受体中生长。创新的材料制造以及修复或再生受损或患病心脏瓣膜的复杂方法的开发需要整合各种基础科学原理和支持技术。因此，心脏瓣膜组织工程需要了解正常和病理瓣膜中结构与功能的关系（包括胚胎发育、组织修复和功能生物力学的机制），以及通过化学、药理学、机械和潜在的基因操作来控制细胞和组织对损伤、物理刺激和生物材料表面的反应的能力。细胞生物学的进展所创造的这些方法为心脏瓣膜的原位再生和修复带来了令人兴奋的可能性。
