Construction of Oriented Structure in Inner Surface of Small-Diameter Artificial Blood Vessels:A Review

There is an urgent need for small-diameter artificial blood vessels in clinic.Physical,chemical and biological factors should be integrated to avoid thrombosis and intimal hyperplasia after implantation and to promote successful fabrication of small-diameter artificial blood vessels.From a physical perspective,the internal oriented structures of natural blood vessels plays an important role in guiding the directional growth of cells,improving the blood flow environment,and promoting the regeneration of vascular tissue.In this review,the effects of the oriented structures on cells,including endothelial cells(ECs),smooth muscle cells(SMCs)and stem cells,as well as the effect of the oriented structures on hemodynamics and vascular tissue remodeling and regeneration are introduced.Various forms of oriented structures(fibers,grooves,channels,etc.)and their construction methods are also reviewed.Conclusions and future perspectives are given.It is expected to give some references to relevant researches.

Influence of Manufacturing Process of Warp-knitted Vascular Prosthesis on the Wall Homogeneity

This paper reports the evolution of textile structure and mechanical properties of vascular prosthesis in the level of the whole prosthesis and the constituent filaments with respect to the manufacturing process. The tubular wall of the prosthesis is divided circumferentially into three zones; basic line (BL), remeshing line ( RL) and guide line ( GL). Some heterogeneity has been observed on the tubular wall in terms of stitch structure of the prosthesis and linear density of the constituent filaments. The breaking position of the prosthesis under circumferential tensile localizes preferentially in remeshing line that is the weakest zone by warp knitting with double needle bed. Furthermore, the statistical differences of the mechanical properties of the filaments of zone RL, GL and BL have been confirmed too. It is predictable that the deterioration of prosthesis, under physiological loads (periodical pulse blood pressure etc.), could happen firstly in the weaker zone in vivo.

3D printed grafts with gradient structures for organized vascular regeneration

Synthetic vascular grafts suitable for small-diameter arteries(<6 mm) are in great need.However,there are still no commercially available small-diameter vascular grafts(SDVGs) in clinical practice due to thrombosis and stenosis after in vivo implantation.When designing SDVGs,many studies emphasized reendothelization but ignored the importance of reconstruction of the smooth muscle layer(SML).To facilitate rapid SML regeneration,a high-resolution 3D printing method was used to create a novel bilayer SDVG with structures and mechanical properties mimicking natural arteries.Bioinspired by the collagen alignment of SML,the inner layer of the grafts had larger pore sizes and high porosity to accelerate the infiltration of cells and their circumferential alignment,which could facilitate SML reconstruction for compliance restoration and spontaneous endothelialization.The outer layer was designed to induce fibroblast recruitment by low porosity and minor pore size and provide SDVG with sufficient mechanical strength.One month after implantation,the arteries regenerated by 3D-printed grafts exhibited better pulsatility than electrospun grafts,with a compliance(8.9%) approaching that of natural arteries(11.36%) and significantly higher than that of electrospun ones(1.9%).The 3D-printed vascular demonstrated a three-layer structure more closely resembling natural arteries while electrospun grafts showed incomplete endothelium and immature SML.Our study shows the importance of SML reconstruction during vascular graft regeneration and provides an effective strategy to reconstruct blood vessels through 3D-printed structures rapidly.

Tailored endothelialization enabled by engineered endothelial cell vesicles accelerates remodeling of small-diameter vascular grafts

Current gold standard for the replacement of small-diameter blood vessel(ID<4 mm)is still to utilize the autologous vessels of patients due to the limitations of small-diameter vascular grafts(SDVG)on weak endothelialization,intimal hyperplasia and low patency.Herein,we create the SDVG with the tailored endothelialization by applying the engineered endothelial cell vesicles to camouflaging vascular grafts for the enhancement of vascular remodeling.The engineered endothelial cell vesicles were modified with azide groups(ECVs-N3)through metabolic glycoengineering to precisely link the vascular graft made of PCL-DBCO via click chemistry,and thus fabricating ECVG(ECVs-N3 modified SDVG),which assists inhibition of platelet adhesion and activation,promotion of ECs adhesion and enhancement of anti-inflammation.Furthermore,In vivo single-cell transcriptome analysis revealed that the proportion of ECs in the cell composition of ECVG surpassed that of PCL,and the tailored endothelialization enabled to convert endothelial cells(ECs)into some specific ECs clusters.One of the specific cluster,Endo_C5 cluster,was only detected in ECVG.Consequently,our study integrates the engineered membrane vesicles of ECVs-N3 from native ECs for tailored endothelialization on SDVG by circumventing the limitations of living cells,and paves a new way to construct the alternative endothelialization in vessel remodeling following injury.

Bioprinting of Small-Diameter Blood Vessels

There has been an increasing demand for bioengineered blood vessels for utilization in both regenerative medicine and drug screening.However,the availability of a true bioengineered vascular graft remains limited.Three-dimensional(3D)bioprinting presents a potential approach for fabricating blood vessels or vascularized tissue constructs of various architectures and sizes for transplantation and regeneration.In this review,we summarize the basic biology of different blood vessels,as well as 3D bioprinting approaches and bioink designs that have been applied to fabricate vascular and vascularized tissue constructs,with a focus on small-diameter blood vessels.

人工血管桥接处理血透通路回流静脉狭窄/闭塞的效果分析

目的探讨人工血管桥接处理血透通路回流静脉狭窄/闭塞病变的效果。方法回顾性分析重庆医科大学附属第一医院2020年1月至2023年1月61例通过人工血管桥接处理回流静脉狭窄/闭塞患者的血透通路基本信息及手术信息、随访术后情况。结果患者住院时间为4~11d,平均(6.27±1.01)d。术后随访6~38个月,平均(19.36±10.30)个月,随访期有4例患者发生与血管通路无关的死亡,进行54例次再干预,11例患者不再使用原通路透析。术后6、12、24、36个月初级通畅率分别为73.8%、58.1%、46.1%、15.4%,次级通畅率分别为91.8%、89.7%、84.8%、56.5%。结论使用人工血管桥接处理血透通路回流静脉病变具有满意的效果,但仍需选择更合适的直径、长度、材质的人工血管来提升术后通畅率。

小口径人工血管的早期血栓形成与预防

背景:小口径人工血管在外周血管疾病治疗中有着广泛的应用价值,但因早期血栓形成导致移植失败的问题亟待解决。目的:总结小口径人工血管早期血栓形成与预防的研究进展。方法:由第一作者检索中国知网、万方、PubMed和Google Scholar数据库2000-2020年发表的相关文献,中文检索词为“小口径人工血管,小口径管状支架,组织工程血管,抗血栓,血栓形成,血液相容性,亲水性,内皮化”,英文检索关键词为“small-caliber vascular graft,vascular tissue engineering applications,endothelialization,hemocompatibility,surface modification”,检索国内外有关小口径人工血管血栓形成的病理生理机制及预防血栓形成的相关文献,就生物材料的表面改性和内皮化研究作为纳入标准,最终选取57篇文献进行综述。结果与结论:预防血栓形成是小口径人工血管研究的热点与难点,从近几年的国内外研究进展来看小口径人工血管早期血栓形成与血浆蛋白吸附、凝血因子的接触激活有关,通过提高表面亲水性、释放抗血栓物质、种植种子细胞、靶向基因诱导等方法,小口径人工血管血栓形成的状况得到一定程度改善,但当前仍处于试验阶段,距离临床应用尚有一定距离,仍需进一步探索或优化一种更适宜的血管材料,为临床应用提供更多选择。

Design and preparation of polyurethane-collagen/ heparin-conjugated polycaprolactone double-layer bionic small-diameter vascular graft and its preliminary animal tests

Background People recently realized that it is important for artificial vascular biodegradable graft to bionically mimic the functions of the native vessel. In order to overcome the high risk of thrombosis and keep the patency in the clinical small-diameter vascular graft （SDVG） transplantation, a double-layer bionic scaffold, which can offer anticoagulation and mechanical strength simultaneously, was designed and fabricated via electrospinning technique. Methods Heparin-conjugated polycaprolactone （hPCL） and polyurethane （PU）-collagen type I composite was used as the inner and outer layers, respectively. The porosity and the burst pressure of SDVG were evaluated. Its biocompatibility was demonstrated by the 3-（4,5-dimethyl-2-thiazol）-2,5-diphenyl-2H tetrazolium bromide （MTT） test in vitro and subcutaneous implants in vivo respectively. The grafts of diameter 2.5 mm and length 4.0 cm were implanted to replace the femoral artery in Beagle dog model. Then, angiography was performed in the Beagle dogs to investigate the patency and aneurysm of grafts at 2, 4, and 8 weeks post-transplantation. After angiography, the patent grafts were explanted for histological analysis. Results The double-layer bionic SDVG meet the clinical mechanical demand. Its good biocompatibility was proven by cytotoxicity experiment （the cell＇s relative growth rates （RGR） of PU-collagen outer layer were 102.8%, 109.2% and 103.5%, while the RGR of hPCL inner layer were 99.0%, 100.0% and 98.0%, on days 1, 3, and 5, respectively） and the subdermal implants experiment in the Beagle dog. Arteriography showed that all the implanted SDVGs were patent without any aneurismal dilatation or obvious anastomotic stenosis at the 2nd, 4th, and 8th week after the operation, except one SDVG that failed at the 2nd week. Histological analysis and SEM showed that the inner layer was covered by new endothelial-like cells. Conclusion The double-layer bionic SDVG is a promising candidate as a replacement of native small-diameter vascular graft.

Bilayer vascular grafts with on-demand NO and H_(2)S release capabilities

Nitric oxide(NO)and hydrogen sulfide(H_(2)S)gasotransmitters exhibit potential therapeutic effects in the car-diovascular system.Herein,biomimicking multilayer structures of biological blood vessels,bilayer smalldiameter vascular grafts(SDVGs)with on-demand NO and H_(2)S release capabilities,were designed and fabri-cated.The keratin-based H_(2)S donor(KTC)with good biocompatibility and high stability was first synthesized and then electrospun with poly(L-lactide-co-caprolactone)(PLCL)to be used as the outer layer of grafts.The elec-trospun poly(ε-caprolactone)(PCL)mats were aminolyzed and further chelated with copper(II)ions to construct glutathione peroxidase(GPx)-like structural surfaces for the catalytic generation of NO,which acted as the inner layer of grafts.The on-demand release of NO and H_(2)S selectively and synergistically promoted the proliferation and migration of human umbilical vein endothelial cells(HUVECs)while inhibiting the proliferation and migration of human umbilical artery smooth muscle cells(HUASMCs).Dual releases of NO and H_(2)S gaso-transmitters could enhance their respective production,resulting in enhanced promotion of HUVECs and inhi-bition of HUASMCs owing to their combined actions.In addition,the bilayer grafts were conducive to forming endothelial cell layers under flow shear stress.In rat abdominal aorta replacement models,the grafts remained patency for 6 months.These grafts were capable of facilitating rapid endothelialization and alleviating neo-intimal hyperplasia without obvious injury,inflammation,or thrombosis.More importantly,the grafts were expected to avoid calcification with the degradation of the grafts.Taken together,these bilayer grafts will be greatly promising candidates for SDVGs with rapid endothelialization and anti-calcification properties.

磷酰胆碱接枝涤纶人工血管的生物相容性

目的通过臭氧活化的方法在涤纶人工血管表面接枝2-甲基丙稀酰氧基乙基磷酰胆碱,进行接枝后人工血管血液相容性研究。方法通过臭氧活化的方法,在涤纶人工血管表面接枝2-甲基丙稀酰氧基乙基磷酰胆碱,接枝后的涤纶人工血管修剪后作兔腹主动脉补片(实验组),并和未接枝涤纶人工血管作对照。术后观察兔腹主动脉人工血管通畅率、吻合口狭窄程度、血流量和吻合口周围BrdU阳性细胞数。结果接枝2-甲基丙稀酰氧基乙基磷酰胆碱的涤纶人工血管补片吻合后,兔腹主动脉通畅率较对照组无明显差异;实验组兔腹主动脉吻合口狭窄程度小于对照组,而吻合口血流量大于对照组,吻合口周围BrdU阳性细胞数明显少于对照组,差异有统计学意义(P<0.05)。结论涤纶人工血管经接枝2-甲基丙稀酰氧基乙基磷酰胆碱后,能有效抑制吻合口内膜和平滑肌增生,减少吻合口狭窄程度,增加血流量。

锁骨下动脉损伤的外科处理

目的探讨锁骨下动脉损伤的外科治疗特点。方法1990年7月～2006年1月,对12例锁骨下动脉损伤患者,取锁骨上下联合切口,充分显露锁骨下动脉全段,分别采用动脉破口修补、包裹修复、血管吻合及人造血管移植修复重建损伤动脉。均为男性,年龄18～36岁,平均22.6岁。损伤部位:锁骨下动脉第1段1例,第2段4例,第3段7例。损伤类型:均为不完全断裂及破损,其中动脉破损区小于动脉周径1/3者4例,小于动脉周径2/3者5例,大于动脉周径2/3者3例。伴全臂丛神经损伤1例,神经干缺损5cm;部分臂丛神经损伤3例,其中2例仅前束损伤,神经缺损分别为4cm和6cm;正中神经完全损伤及尺神经不完全损伤1例,神经缺损4cm。损伤至手术时间3h～1.5个月。结果术后无死亡及肢体坏死。获随访2个月～12年,平均5年2个月。10例桡动脉搏动恢复良好,2例桡动脉搏动不明显,均为动脉直接吻合者。4例合并臂丛神经损伤患者,前束损伤者术后肢体功能基本恢复正常,屈肘肌力级;全臂丛神经完全损伤者术后上肢功能基本无改善。结论锁骨下动脉解剖位置特殊,动脉损伤后显露、修复均较困难。锁骨上下联合切口可在直视下显露动脉全段,修复重建安全可靠。

犬膨体聚四氟乙烯人工血管补片移植后的组织形态学研究

目的 :观察犬膨体聚四氟乙烯人工血管补片移植 ,在不同时期的组织形态学变化。方法 :用e -PTFE补片修补 16条犬的腹主动脉 ,在植入后 2、4、8、12、2 0、2 8周采集标本 ,作光镜、扫描及透射电镜观察。结果 :①内皮细胞 2周已在材料上出现 ,8周时完全覆盖材料面 ;②内膜增生主要是平滑肌细胞和胶原纤维增生 ;③在 8周以前内膜增厚较快 ,12周以后逐趋缓和 ;④补片与血管吻合处增生明显 ;⑤增生的内膜容易与材料分离。结论 :内皮细胞可以覆盖e -PTFE材料表面 ,其内膜增生主要是平滑肌细胞和胶原纤维增生引起 ;主要原因可能是内皮细胞慢性损伤 ,血小板聚集 ,血流动力学改变 ,材料与血管顺应性不一致等。

生物可降解血管内支架研究进展

生物可降解血管内支架具有良好的生物相容性,当所支撑的狭窄段血管恢复畅通、内膜修复完成后即可降解消失,克服了支架自身的血栓原性及异物性,避免了支架引起的远期并发症。本文综述了生物可降解血管内支架的研究进展,重点介绍了生物可降解聚合物血管内支架的选材、制备、设计及临床应用进展。

国产ePTFE人工血管的动物实验研究(英文)

目的研究国产的ePTEE人工血管动物应用可行性。方法以国产ePTEE人工血管移植于狗的股动脉并与进口Dacron人工血管对照,术后通过体检、彩色多普勒、大标标本、光镜、扫描电镜、免疫组化观察ePTEE人工血管通畅程度、内膜与外膜、内皮细胞生长状况。结果体检ePTEE、Dacron人工血管通畅率分别为83%、100%;彩色多普勒示ePTEE人工血管血流速度(0.464±0.041)m/s、管壁压力为(0.83±0.12)mmHg,Dacron人工血管血流速度为(0.461±0.044)m/s、管壁压力为(0.78±0.12)mmHg,两者无显著性差异(P>0.05);大体标本、光镜、扫描电镜、免疫组化示ePTEE人工血管移植90天后可形成完整的新生内膜和外膜,内膜表面为内皮细胞,Ⅷ因子染色弱阳性。结论国产ePTEE人工血管是一种理想的血管替代用品,值得临床推广应用。

丝涤混构小口径人造血管的设计与成型

理想的小口径人造血管产品需要同时具备良好的力学性能和生物相容性,目前尚无理想产品成功应用于临床.以真丝和涤纶长丝为原材料,真丝编织纱为经纱,在经改装的全自动剑杆织机上,成功地制备了丝涤混构小口径人造血管管坯,并对其进行脱胶处理.试验结果表明,制得的人造血管试样结构稳定、形态均匀,脱胶处理后人造血管试样的壁厚在0.3mm内、内直径约4mm、紧度在100%左右.

腔内隔绝术用覆膜支架顺应性的研究意义及进展

小口径人工血管与宿主血管间顺应性不匹配,是导致其植入后远期通畅率低的重要因素;而目前已有文献证明,腔内隔绝术用覆膜支架(SG)与宿主血管间顺应性不匹配,也是引起术后远期滑移、内漏、血流紊乱等并发症的原因。但是,这一领域的研究十分有限。综述SG顺应性的评价方法,包括通过SG体积、压力的变化计算其体积顺应性,或通过脉搏波速和瘤体压力间接反映SG的顺应性。关于SG顺应性的研究主要包括:验证SG的植入对宿主血管的影响,不同结构SG对宿主血管的影响,以及顺应性随疲劳时间推移的可能变化。同时,对改变结构优化SG顺应性进行简要综述。

感染性股动脉假性动脉瘤的外科治疗

目的探讨感染性股动脉假性动脉瘤的外科治疗方法。方法回顾性分析2003年1月至2008年6月期间我院收治的45例感染性股动脉假性动脉瘤行外科治疗患者的资料。43例感染性股动脉假性动脉瘤采用瘤体切除及彻底清创后行人工血管旁路移植治疗；另2例由于感染严重及瘤体巨大被迫采用瘤体切除并行近、远端动脉结扎。结果随访3～12个月，平均7．82个月，人工血管旁路移植病例全部保肢成功，切口均二期愈合，无间歇性跛行；行动脉结扎的2例中，1例因缺血坏疽行膝上高位截肢；另1例保肢成功，但有间歇性跛行。结论动脉瘤切除及彻底清创后行人工血管旁路移植是感染性股动脉假性动脉瘤安全、有效的治疗方法。

血管内支架的研究进展

不凝血材料在小直径血管支架领域具有很大的应用潜力。本文阐述用于血管内支架生物材料的选择 ,用组织工程的方法构建人造血管的研究进展 ,血管支架材料表面修饰的必要性、方法及有效性 ,指出新型不凝血生物医用高分子材料的开拓以及组织工程的发展必然会推动血管医疗技术的创新和发展。

犬Gore-tex人工血管移植后的超微结构观察

目的 扫描及透射电镜下观察犬Gore tex人工血管补片移植后 ,不同时期的材料表面内膜层的超微结构。方法 用Gore tex补片材料修补 14条犬的腹主动脉 ,在植入后 2 4h、1周、2周、4周、8周、12周、2 0周采集标本 ,作扫描、透射电镜观察。结果 (1)术后 2 4h材料表面形成纤维蛋白膜。 (2 )内皮细胞于 1周时已在材料上出现 ,8周时完全覆盖材料面 ,形成光滑的内膜面。 (3) 8周发现内膜增生 ,主要是平滑肌细胞和胶原纤维增生。 (4) 12周仍有内膜增生 ,以吻合口明显仍明显。结论 实验表明Gore tex材料有较好的生物相容性 ,内皮细胞可以覆盖材料表面 ,但材料仍可引起内膜增生 ,主要是平滑肌细胞和胶原纤维增生 ;增生在吻合口较明显 ,小口径Gore

肾下腹主动脉瘤的治疗

目的探讨腹主动脉瘤手术的外科及腔内介入治疗方法,以提高其安全性. 方法回顾性分析1981年1月～2004年12月收治的肾下腹主动脉瘤患者195例,其中男155例,女40例.年龄35～80岁,平均56.5岁.瘤体直径>5 cm 者183例,4～5 cm者12例.动脉瘤破裂行急诊手术者20例;择期手术175例,其中行开腹动脉瘤切除及人工血管置换术139例,行血管腔内修复术36例. 结果择期手术和急诊手术于术后30 d内分别死亡6例;余均获随访1个月～21年,平均8.7年,死亡16例,与血管手术有关的5例.腔内修复术中无手术死亡病例.发生内漏8例,其中Ⅰ型5例,Ⅱ型3例;6个月后CT检查:自行愈合6例,未愈合2例,但动脉瘤腔增大.迟发内漏1例,为Ⅱ型内漏,行介入栓塞后愈合. 结论随着血管外科手术技术的不断改进和血管腔内修复技术的开展,腹主动脉瘤手术的安全性将会不断提高.