Calcification of tissue heart valve substitutes: progress toward understanding and prevention

Calcification plays a major role in the failure of bioprosthetic and other tissue heart valve substitutes. Tissue valve calcification is initiated primarily within residual cells that have been devitalized, usually by glutaraldehyde pretreatment. The mechanism involves reaction of calcium-containing extracellular fluid with membrane-associated phosphorus to yield calcium phosphate mineral deposits. Calcification is accelerated by young recipient age, valve factors such as glutaraldehyde fixation, and increased mechanical stress. Recent studies have suggested that pathologic calcification is regulated by inductive and inhibitory factors, similar to the physiologic mineralization of bone. The most promising preventive strategies have included binding of calcification inhibitors to glutaraldehyde fixed tissue, removal or modification of calcifiable components, modification of glutaraldehyde fixation, and use of tissue cross linking agents other than glutaraldehyde. This review summarizes current concepts in the pathophysiology of tissue valve calcification, including emerging concepts of endogenous regulation, progress toward prevention of calcification, and issues related to calcification of the aortic wall of stentless bioprosthetic valves.     

新型复合组织工程瓣膜的构建和体外生物力学研究

目的 构建复合瓣膜进行体外生物力学和脉动流测试.方法 猪主动脉瓣脱细胞处理作为支架,用3-羟基丁酸与3-羟基己酸共聚酯涂层,构建复合瓣膜,用拉伸机进行体外生物力学研究,以新鲜和脱细胞猪瓣作为对照(每组12枚);用脉动流仪进行流体力学研究,以脱细胞猪瓣作为对照(每组6枚).结果 复合瓣膜抗拉强度(12.08±1.72)MPa,与新鲜猪瓣(8.38±0.52)MPa和脱细胞猪瓣(8.16±0.66)MPa比较,差异有统计学意义(P＜0.05);在心输出量2～7L/min时,复合瓣膜与脱细胞猪瓣血流动力学参数差异无统计学意义(P＞0.1).结论 复合瓣膜具有良好的生物力学、流体力学特性.     

Energy loss for evaluating heart valve performance

Energy loss is a well-established engineering concept that when applied to evaluating the performance of native heart valves and valvular prostheses has the potential for providing valuable information about the impact of valve function on myocardial performance. The concept has been understood for many years, but its routine application has been hindered not only by a lack of understanding of its meaning but also because of the lack of investigational tools to easily obtain the data necessary for its estimation. Today the gathering of that information is becoming easier, and thus the time has come to revisit the efficacy of energy loss for evaluating heart valve performance. This review defines what energy loss is, how it is measured, and how it might be applied to clinical situations of heart valve disease to better understand the impact of valvular disease on ventricular function.     

Successful thrombectomy for thrombosis of aortic composite valve graft in pregnancy

Prosthetic heart valve thrombosis in pregnancy is a life-threatening complication whose management remains controversial and particularly difficult because of the additional challenge to save the fetus. Thrombolysis, thrombectomy, or prosthetic replacement are the currently available options. We report the case of a 17-week pregnant patient who was successfully treated by emergency open-heart thrombectomy for thrombosis of an aortic composite valve graft. Pregnancy was carried to term and a healthy baby was vaginally delivered 5 months later.     

应用聚羟基丁酸/聚羟基戊酸共聚物构建组织工程心脏瓣膜的实验研究

目的 探讨应用聚羟基丁酸/聚羟基戊酸共聚物(poly-hydroxybutyrate-co-hydroxyva lerate,PHBV)构建组织工程心脏瓣膜的可行性. 方法应用扫描电子显微镜观察PHBV的结构特点,将PHBV行兔皮下包埋,分别于包埋后2周、4周、6周、8周和10周观察PHBV的生物相容性和降解率.体外培养犬主动脉瓣间质细胞,观察其生长曲线,平滑肌α肌动蛋白表达和透射电子显微镜下特点.将体外培养的犬主动脉瓣间质细胞种植于PHBV上,观察其生长情况并测定细胞合成前列环素的功能. 结果扫描电子显微镜下PHBV呈网孔状泡沫结构,孔径130μm.皮下包埋显示PHBV生物相容性好,体内降解时间约10周.犬主动脉瓣间质细胞平滑肌α肌动蛋白免疫组化染色部分细胞呈阳性表达,细胞内有大量粗面内质网,生长曲线良好.种植实验显示细胞在PHBV上生长良好,并有合成、分泌前列环素的功能. 结论以PHBV为支架构建组织工程心脏瓣膜,种子细胞不仅可以在PHBV上生长,而且可以合成血管活性物质,初步提示应用PHBV及其方法构建组织工程心脏瓣膜是可行的.     

促进组织工程心脏瓣膜细胞黏附力的初步研究

目的探讨纤维连接蛋白(Fn)增强种子细胞与组织工程心脏瓣膜(TEHV)黏附力的可行性,为组织工程心脏瓣膜的构建提供良好的细胞基础。方法取6个规格相同的有P4HB[聚β羟基丁酯]构建的心脏瓣膜,气体消毒后分别置入12孔板中,每2个为1组,前两组分别被Fn及多聚赖氨酸(poly-lysine)包被,第3组空白对照。24 h后分别种植骨髓基质干细胞0．8×10~5个,24h后在瓣膜背面再分别种植0．25×10~5个。2周后分别行MTT检测及扫描电镜检测；取不同数量的MSC,行MTT检测,制作不同细胞个数与MTT吸收光度的曲线。结果经Fn包被的MTT吸光度A值(0．128 96±0．004 896)及poly-lysine包被的MTT吸光度A值(0．12033±0．03991)均明显高于对照组(0．11254±0．006556),P＜0．05,Fn组与poly-lysine组比较有统计学意义,前者高于后者。结论Fn能有效的促进细胞在生物可降解的组织工程心脏瓣膜的黏附及增殖,是发展组织工程心脏瓣膜的一种优良的促细胞黏附剂。     

New vascular graft for assembling the stentless valve composite graft

The use of a new vascular tube with an uncrimped section for assembling the stentless valve composite graft is described. The graft simplifies the fixation of the valve within the tube because no stretching of the crimping is necessary to achieve optimal commissural height of the valve during sewing. Furthermore, this allows the composite construction outside the chest and reduces the cross-clamp time.     

Heart valve tissue engineering

Valvular heart disease is a significant cause of morbidity and mortality world-wide. Classical replacement surgery involves the implantation of mechanical valves or biological valves (xeno- or homografts). Tissue engineering of heart valves represents a new experimental concept to improve current modes of therapy in valvular heart surgery. Various approaches have been developed differing either in the choice of scaffold (synthetic biodegradable polymers, decellularised xeno- or homografts) or cell source for the production of living tissue (vascular derived cells, bone marrow cells or progenitor cells from the peripheral blood). The use of autologous bone marrow cells in combination with synthetic biodegradable scaffolds bears advantages over other tissue engineering approaches: it is safe, it leads to complete autologous prostheses and the cells are more easily obtained in the clinical routine. Even though we demonstrated the feasibility to construct living functional tissue engineered heart valves from human bone marrow cells, so far their general potential to differentiate into non-hematopoietic cell lineages is not fully exploited for tissue engineering applications.     

Ross operation with a tissue-engineered heart valve

BACKGROUND: The Ross procedure has gained increasing acceptance due to excellent hemodynamic results by replacing the diseased aortic valve with the viable autologous pulmonary valve. Consequently, the right ventricular outflow tract (RVOT) has to be reconstructed. In this report a viable heart valve was created from decellularized cryopreserved pulmonary allograft that was seeded with viable autologous vascular endothelial cells (AVEC). METHODS: A 43-year-old patient suffering from aortic valve stenosis underwent a Ross operation on May 20, 2000, using a tissue engineered (TE) pulmonary allograft to reconstruct the RVOT. Four weeks before the operation a piece of forearm vein was harvested to separate, culture, and characterize AVEC. Follow-up was completed at discharge, 3, 6, and 12 months postoperatively by clinical evaluation, transthoracic echocardiography (TTE), and magnetic resonance imaging (MRI). Additionally, at 1-year follow-up a multislice computed tomographic scan was performed. RESULTS: After four weeks of culturing 8.34 x 10(6) AVEC were available to seed a 27-mm decellularized pulmonary allograft. Trypan blue staining confirmed 96.0% viability. Reendothelialization rate after seeding was 9.0 x 10(5) cells/cm2. TTE and MRI revealed excellent hemodynamic function of the TE heart valve and the neoaortic valve as well. Multislice computed tomography revealed no evidence of valvular calcification. CONCLUSIONS: After 1 year of follow-up the patient is in excellent condition without limitation and exhibits normal aortic and pulmonary valve function.     

Transcatheter aortic valve implantation after heart transplantation

Conventional cardiac surgical procedures after orthotopic heart transplantation are generally uncommon. We report the case of a 67-year-old man who had severe symptomatic aortic stenosis develop 9 years after heart transplantation. After joint evaluation of the cardiovascular team, transcatheter aortic valve implantation was preferred due to patient medical conditions. The CoreValve prosthesis (Medtronic, Minneapolis, MN) was inserted percutaneously into the femoral artery. At 4 months postoperatively, the patient is asymptomatic in New York Heart Association functional class II. This case report provides evidence that transcatheter aortic valve implantation is safe and suitable for selected patients with severe aortic stenosis and a history of heart transplantation that must improve allograft function.     

人骨髓基质干细胞构建组织工程心脏瓣膜的研究

目的探讨人骨髓基质干细胞种植在去细胞猪主动脉瓣叶上体外构建组织工程心脏瓣膜的可行性。方法经1%TritonX100、0.01%胰酶0.02%EDTA、DNaseI及RNaseI处理制备去细胞猪主动脉瓣叶支架,测定瓣叶去细胞前、后的生物力学特性;人骨髓基质干细胞体外分离、培养、扩增后种植在去细胞瓣叶表面,观察细胞生长情况。结果猪主动脉瓣叶去细胞后获得完整无细胞的纤维网状支架,瓣叶去细胞前、后的断裂强度和断裂伸长率差异无统计学意义(P>0.05);体外培养的人骨髓基质干细胞(MSCs)在去细胞瓣叶表面形成一层基本连续的细胞层。结论去除细胞成分的猪主动脉瓣叶组织是一种良好的纤维支架,可以用于构建组织工程心脏瓣膜;人骨髓基质干细胞种植在去细胞猪主动脉瓣叶上构建组织工程心脏瓣膜是可行的。     

Outcomes in nonagenarians after heart valve replacement operation

BACKGROUND: Changes in the age profile of the United Kingdom population and improvements in preoperative and postoperative care have resulted in increasing numbers of very elderly patients undergoing heart valve replacement (HVR) operations. Although HVR operations in nonagenarians are relatively uncommon, the demand for cardiac operations in this age group may increase over time. Outcomes after HVR operations in nonagenarians have not been well described yet. Therefore, the aim of this study was to determine outcomes in terms of early mortality and long-term survival in 35 nonagenarians after HVR operation. METHODS: Data from the United Kingdom Heart Valve Registry were analyzed and nonagenarian patients were identified. Additional analyzed data include gender, valve position, valve type, valve size, operative priority, follow-up time, and date and cause of death. Kaplan-Meier actuarial curves were calculated to determine accurate 30-day mortality and long-term survival. RESULTS: On average five HVR operations are performed annually in the United Kingdom in nonagenarians with equal numbers of males and females. Aortic valve replacement with a bioprosthetic valve was the most common operation and 86% were elective admissions. Fourteen patients died within the review period; mean time to death was 402 days. Overall 30-day mortality was 17%, which was higher for males compared with females; females also displayed better long-term survival. CONCLUSIONS: HVR operations in nonagenarians carry a significantly higher risk of early mortality and reduced long-term survival. Despite increases in the age profile of the population, elective HVR operation with patients aged 90 years or older is likely to remain an infrequent surgical procedure reserved for very carefully selected patients.     

Mechanical and structural properties of a novel hybrid heart valve scaffold for tissue engineering

Hybrid heart valve scaffolds were fabricated from decellularized porcine aortic heart valve matrices and enhanced with bioresorbable polymers using different protocols: (i) dip coating of lyophilized decellularized matrices, and (ii) impregnation of wet decellularized matrices. The following polymers were evaluated: poly(4-hydroxybutyrate) and poly(3-hydroxybutyrate-co4-hydroxybutyrate). Tensile tests were conducted to assess the biomechanical behavior of valve leaflet strips. Suture retention strength was evaluated for the adjacent conduit. A pulse duplicator system was used for functional testing of the valves under physiological systemic load conditions. The properties of the hybrid structures were compared with native, decellularized, and glutaraldehyde-fixed specimens. Mechanisms of the polymer impregnation process were studied with IR spectroscopy, fluorescent microscopic imaging, and SEM. Altogether this study demonstrates the feasibility and improved biomechanical function of a novel hybrid heart valve scaffold for an application in tissue engineering.     

静电纺丝纳米纤维在骨组织工程中的应用

静电纺丝纳米纤维技术在生物医学领域有着广泛的应用研究,其在骨组织工程应用中仍未解决的问题是同时满足材料的生物相容性、可降解性、生物活性和力学性能。骨组织工程主要构成要素是支架、细胞和生长因子。静电纺丝复合纳米纤维支架材料具有纳米级别的天然骨分级结构和天然骨的多孔结构,改进复合支架材料可促进细胞的浸润生长、干细胞分化和组织形成。本文重点探讨通过静电纺丝技术改进复合支架的性能,及其在动物实验研究方面的最新进展。