心脏瓣膜修复材料钙化和抗钙化研究进展

心脏瓣膜生物替代材料发生临床失效的一个主要原因是钙化,其机理非常复杂,涉及一系列决定因素,如含钙细胞外液与膜内磷酸脂反应,形成磷酸钙盐沉积.目前最有效的抗钙化治疗策略有：戊二醛固定组织后加入钙化抑制因子,易钙化位点的剔除或化学修饰,戊二醛固定的改良以及其他化学交联方法.就心脏瓣膜修复材料钙化和抗钙化动物实验研究和临床试验研究进展作一综述.     

外科植入硅橡胶材料钙化及抗钙化研究进展

硅橡胶钙化是材料植入体内后其表面或基质内出现病理性矿化的现象,尚无有效防治方法.钙化的重要过程是材料表面的磷酸根离子与钙离子结合启动成核聚集,缓慢增大、融合,逐渐形成较大的羟基磷灰石钙盐堆积.其研究已发展到细胞和基因水平,如基质Gla蛋白质簇是一种硅橡胶假体周围组织钙化的抑制因子.钙化过程中有机模板对无机晶体的调制作用需理论上的突破.硅橡胶自身局部抗钙化性能受到重视.揭示硅橡胶钙化和钙化抑制的机理,可为构建新型抗钙化功能材料提供依据.     

生物心脏瓣膜钙化前后的应力分析

生物心脏瓣膜钙化前后的应力分析李珏匡震邦（西安交通大学，西安７１００４９）刘维永（西京医院，西安７１００３２）ＳＴＲＥＳＳＡＮＡＬＹＳＩＳＯＦＮＯＲＭＡＬＡＮＤＣＡＬＣＩＦＩＥＤＢＩＯＰＲＯＳＴＨＥＴＩＣＨＥＡＲＴＶＡＬＶＥＳＬｉＪｕｅ，ＫｕａｎｇＺ...     

组织工程化心脏瓣膜的研究进展

心脏瓣膜置换术是外科治疗瓣膜性心脏病的主要方法，但目前临床应用的人工瓣膜的远期效果尚不满意。近年来，随着组织工程学技术的进展，利用培养的自身组织细胞种植于支架材料表面，体外重新构建理想的心脏瓣膜植物日益成为研究热点。本文简述了心脏瓣膜工程的定义，细胞支架材料的选择，种子细胞的培养、种植方法以及组织工程化心脏瓣膜的评估，并指出下一步研究中尚需解决的问题。     

组织工程心脏瓣膜研究进展

目前组织工程心脏瓣膜研究已在支架的选材、种子细胞的选择、种子细胞的种植与瓣膜构建方法三个方面取得进展，并已构建出三种代表性组织工程心脏瓣膜。对它们各自的特点进行综述。     

组织工程心脏瓣膜细胞生物学研究进展

由于现有的机械瓣和生物瓣仍存在种种不足，如不具备生长性、需抗凝、易感染、不能生长和自我修复等。组织工程心脏瓣膜是一新兴的研究领域，涉及多门学科。构建组织工程心脏瓣膜应包括支架的制作、细胞的种植、瓣膜的体外培养和最终移植人人体。其中种植的细胞是组织工程心脏瓣膜的基本要素。就组织工程心脏瓣膜的细胞生物学研究进展做一综述。     

组织工程心脏瓣膜研究进展

目前组织工程心脏瓣膜研究已在支架的选材、种子细胞的选择、种子细胞的种植与瓣膜构建方法三个方面取得进展,并已构建出三种代表性组织工程心脏瓣膜。对它们各自的特点进行综述。     

组织工程心脏瓣膜细胞生物学研究进展

由于现有的机械瓣和生物瓣仍存在种种不足,如不具备生长性、需抗凝、易感染、不能生长和自我修复等。组织工程心脏瓣膜是一新兴的研究领域,涉及多门学科。构建组织工程心脏瓣膜应包括支架的制作、细胞的种植、瓣膜的体外培养和最终移植入人体。其中种植的细胞是组织工程心脏瓣膜的基本要素。就组织工程心脏瓣膜的细胞生物学研究进展做一综述。     

组织工程心脏瓣膜的研究进展

组织工程心脏瓣膜(tissue engineering heart valve,TEHV)理论上能克服机械瓣及生物瓣的不足,具有广阔的发展前景.目前组织工程心脏瓣膜的研究主要集中在瓣膜支架材料的选取及制备、种子细胞的选择和种子细胞的种植及培养等三方面.本文将分别就这三方面研究进展进行介绍,分析目前存在的问题,并对其应用进行展望.     

心肌组织工程生物反应器研究进展

组织工程的研究主要围绕种子细胞、生物材料和组织构建这三个基本要素而展开。组织构建技术是组织工程研究的核心。组织工程生物反应器是一种体外构建人体组织的系统装置。心肌组织工程在替代和维持梗塞的心肌组织功能,并进而治愈疾病以最大限度地挽救病人生命方面可能发挥巨大作用。主要介绍了国内外工程化心肌组织体外构建技术,特别是用于构建工程化心肌组织的心肌组织工程生物反应器研究方面的进展。     

In vivo calcification of glutaraldehyde-fixed cardiac valve and pericardium of Phoca groenlandica

Calcification remains the main reason for failure of bioprosthetic valves. The aim of this study was to evaluate the in vivo calcification response of a new bioprosthetic valve, derived from cardiac tissue of Phoca groenlandica. Aortic and pulmonary leaflets, bovine, and Phoca groenlandica pericardia were fixed in buffered glutaraldehyde solution. Tissues were divided into four groups: group 1, bovine pericardium (BP); group 2, pulmonary leaflets; group 3, seal pericardium; and group 4, aortic leaflets. All samples were implanted subdermally into four sets of eight female 12-day-old Wistar rats for 21 days. The tissues were divided into two parts for calcium measurement, and histology with hematoxylin-eosin, von Kossa, and Weigert Van Gieson staining. All groups experienced significant calcification. Group 1 with 1.39 mg/g (0.34) before and 125.78 mg/g (21.48) after implantation (p < 0.001), group 2 with 1.50 mg/g (0.43) before and 151.85 mg/g (19.1) after (p < 0.001), group 3 with 3.15 mg/g (0.62) before and 116.38 mg/g (33.74) after (p < 0.001), and group 4 with 1.84 mg/g (0.52) before and 126.95 mg/g (13.37) after (p < 0.001). Explant samples showed foreign body response, disorganized collagen, and obvious calcification. The cardiac valve and pericardium of Phoca groenlandica calcify to the same extent as the BP.     

Prevention of tissue calcification on bioprosthetic heart valve by using epoxy compounds: a study of calcification tests in vitro and in vivo.

Calcification is the principal cause of the clinical failures of the bioprosthetic heart valves fabricated from glutaraldehyde pretreated porcine aortic valves or bovine pericardium. In this paper, we compared the calcification on various types of bovine pericardiums pretreated with two hydrophilic epoxy compounds adding GA post-treatment (EP 1 and EP 2), glutaraldehyde (GA)- and nontreated pericardium (Fresh), respectively, by in vitro and in vivo tests. Significant decrease of calcification was found by pretreatment with both epoxy compounds rather than with glutaraldehyde: 0.250 +/- 0.001 (Fresh), 0.276 +/- 0.058 (EP 1), 0.302 +/- 0.071 (EP 2), and 0.478 +/- 0.172 (GA) micrograms (Ca)/mg (dried tissue), respectively, after 20 days dipping in a simulating serum solution in vitro; 115.13 +/- 60.11 (Fresh), 129.84 +/- 51.08 (EP 1), 167.39 +/- 20.81 (EP 2), and 205.19 +/- 16.86 (GA) micrograms/mg, respectively, after 3 months subcutaneous implantation in rabbits. The in vitro method for evaluating calcification designed by us gave the similar order among four samples with that obtained by in vivo test. Because the bovine pericardium pretreated with the epoxy compounds adding GA post-treatment possesses the greater tenacity than that pretreated only with epoxy compounds or GA, meanwhile the calcification is also significantly decreased with this pretreatment, it may be expected that the bovine pericardium with this pretreatment will have the greater anticalcification and durability in dynamic stress.     

Quercetin-crosslinked porcine heart valve matrix: Mechanical properties,stability, anticalcification and cytocompatibility

Bioprosthetic heart valves, prepared by glutaraldehyde (GA) crosslinking, have some limitations due to poor durability, calcification and immunogenic reactions. The aim of this study was to evaluate the crosslinking effect of a natural product, quercetin, on decellularized porcine heart valve extracellular matrix (ECM). After crosslinking, the mechanical properties, stability, anticalcification and cytocompatibility were examined. The results showed that the tensile strength of quercetin-crosslinked ECM was higher than that of GA-crosslinked ECM. After crosslinking with quercetin, the thermal denaturation temperature of ECM was clearly increased. Quercetin-crosslinked ECM could be stored in D-Hanks solution for at least 30 days without any loss of ultimate tensile strength and elasticity. After soaking in D-Hanks solution for 36 days, there was only 11.55% non-crosslinked excess quercetin released and no further release thereafter. Cell culture study shows that no inhibition on proliferation of vascular endothelial cells occurred when the quercetin concentration was lower than 1 μg ml^?1. This non-cytotoxic concentration was 100 times higher than that of GA. The resistibility of quercetin-crosslinked ECM to in vitro enzymatic hydrolysis was comparable to that of GA-crosslinked ECM. An in vitro anticalcification experiment showed that quercetin crosslinking could protect ECM from deposition of minerals in simulated body fluid. The present study demonstrated that quercetin can crosslink porcine heart valve ECM effectively, which suggests that quercetin might be a new crosslinking reagent for the preparation of bioprosthetic heart valve xenografts and scaffolds for heart valve tissue engineering.     

阴茎海绵体组织工程的研究进展

阴茎是男性外生殖器的重要构成部分.先天疾病或外伤可能会导致阴茎发育畸形或缺损,最终需要重建.随着组织工程学的发展,阴茎海绵体组织工程学研究也日益成为阴茎重建的核心内容.目前阴茎海绵体组织工程学研究主要集中在支架制备以及移植细胞(包括血管内皮细胞和平滑肌细胞)的研究.近几年,随着干细胞技术、基因技术以及神经再造技术等的联合发展,将组织工程阴茎海绵体的发展又推上了另一个高度.组织工程的研究为修复阴茎海绵体结构及重建其正常功能提供了可能.拟对近年组织工程在阴茎海绵体重建方面的相关研究进展作一综述.     

The role of glutaraldehyde-induced cross-links in calcification of bovine pericardium used in cardiac valve bioprostheses.

Calcification is the principal cause of failure of tissue-derived cardiac valve replacements pretreated with glutaraldehyde (GLUT). The objective of this study was to determine the role of GLUT-induced cross-links in bovine pericardial tissue calcification. Various levels of 3H-GLUT incorporation were obtained by varying incubation pH, and protein modification was determined by amino acid analysis and resistance to collagenase digestion. Calcification of cross-linked tissue was studied using subdermal implants in rats. Low GLUT uptake (less than 150 nm/mg) resulted in minimal calcification (Ca2+, 12.8 micrograms/mg) and stability (4% residual weight following digestion) due to a limited crosslinking (lysine + hydroxylysine = 26.1 residues/1000 amino acids [AA]). In contrast, higher GLUT uptake induced more cross-links (Lys + Hyl = 8.2 residues/1000 AA) and consequent higher stability (95% residual wt); such tissues calcified severely (Ca2+, 93.5 micrograms/mg). Incorporation of GLUT two to three times beyond a critical level did not further enhance calcification. It is concluded that the amount of GLUT incorporated controls the extent of cross-links, which in turn directly determines tissue stability and calcification.     

Toxic reactions evoked by glutaraldehyde-fixed pericardium and cardiac valve tissue bioprosthesis

Bovine pericardial tissue and tissue-derived bioprosthesis fixed in glutaraldehyde and stored in either glutaraldehyde or formaldehyde can induce cytotoxic reactions even after prolonged washing due to the slow leaching of the chemicals used for crosslinking and sterilizing. Sequential rinsing for up to 60 min was still not sufficient to eliminate cytotoxic effects. On the other hand, satisfactory results were obtained when cardiac valves made from glutaraldehyde fixed pericardium were stored in a solution containing 0.02% of propyl-hydroxy-benzoate and 0.18% methyl-hydroxy-benzoate. The valves stored in this solution and rinsed three times for 1 min in normal saline showed few signs of residual cytotoxicity. Rinsing in a solution containing glycine was partially effective in neutralizing the cytotoxic effect, and this or similar approaches offer good possibilities. The use of Chang cells grown in culture provides an excellent quantitative assay for the assessment of residual cytotoxicity and for evaluating the host response to different methods of fixation, storage, and rinsing of tissue derived bioprosthesis.