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BACKGROUND: Micronized purified flavonoid fraction (MPFF) is a widely prescribed and extensively investigated venoactive drug (VAD). The standard dosage for MPFF is 500 mg administered twice daily. However, a new daily dose of 1000 mg has just been introduced. OBJECTIVE: This study investigated whether a daily dose of 1000 mg MPFF could be implemented and embraced by the public and still has the same therapeutic effects as conventional pharmaceuticals. METHODS: For this meta-analysis, we searched MEDLINE, Embase, Science of Web, Cochrane, and PubMed databases and forward and backward citations for studies published between database inception and March 2023. Three randomized controlled trials (RCTs) of comparison of different dosages of MPFF to evaluate whether there is a significant difference between them were included, without language or date restrictions. Due to the small sample size of the study included, we conducted a simple sensitivity test using a one-by-one exclusion method, and the results showed that the study did not affect the final consolidation conclusion. The quality of the evidence was assessed using the Cochrane risk-of-bias tool. RESULTS: Out of 232 studies, 99 were eligible and 39 RCTs had data, all with low to moderate bias. Overall, 1924 patients (experimental group: 967, control group: 957) in 3 RCTs met the criteria. There is no significant difference in patient compliance, efficacy, clinical adverse events, and quality of life scores between MPFF 1000 mg once daily and MPFF 500 mg twice daily (standardized mean difference [SMD]: 0.049 [0.048, 0.145], p=0.321, risk ratio [RR]: 0.981 [0.855, 1.125], p=0.904, and SMD: 0.063 [0.034, 0.160], p=0.203). INTERPRETATION: In symptomatic chronic venous disease patients, MPFF 1000 mg once daily and MPFF 500 mg twice daily improve patient compliance, lower limb discomfort, clinical adverse events, and quality of life scores similarly. Regular medical care should recommend MPFF 1000 mg daily more often. CLINICAL IMPACT: Micronized purified flavonoid fraction (MPFF) is a popular venoactive medication (VAD) in modern medicine.MPFF is effective in treating lower extremity venous problems.Currently, besides conventional 500 mg tablets, there exist alternative dosage forms such as solutions, chewable tablets, and other novel formulations for MPFF.The excessive frequency and amount of medication may have a negative impact on patient adherence.
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This review aimed to explore the therapeutic effect of bioabsorbable stents in the inferior genicular artery, from the emergence of absorbable bare metal stents to the latest technology in polymer and anti-proliferative eluting drugs mixed with coated bioresorbable vascular stents (BVSs). Currently, there are conflicting data regarding the safety and effectiveness of BVSs in infrapopliteal artery interventions, especially compared to the current generation of drug-eluting stents (DESs). This review will cover the existing data on BVSs in reconstructing the infrapopliteal arterial blood flow and active clinical trials for future iterations of BVSs. In terms of primary patency rate and target lesion revascularization rate, the available research on the effectiveness of BVSs in reconstructing the infrapopliteal arterial blood flow suggests that a BVS is compatible with current DESs within 3-12 months; long-term data have not yet been reported. The ABSORB BVS is the most studied BVS in cardiovascular disease (CAD). Initially, the ABSORB BVS showed promising results. Managing intricate regions in peripheral artery disorders, such as branching or lengthy lesions, continues to be a formidable undertaking. In contrast to the advanced narrowing of arteries seen in standard permanent stent procedures, bioabsorbable stents have the potential to promote the expansion and beneficial merging of blood channels in the latter stages. Furthermore, incorporating stents and re-establishing the endothelial function can diminish the probability of restenosis or thrombosis. Nevertheless, the extent to which bioabsorbable stents may simultaneously preserve arterial patency and guarantee their structural integrity remains uncertain. The powerful and intricate mechanical stresses exerted by the blood in the superficial femoral artery and popliteal artery can cause negative consequences on any implant inserted into the vessel, regardless of its composition, even metal. Furthermore, incorporating stents is advantageous for treating persistent occlusive lesions since it does not impact later treatments, including corrective bypass operations. Evidence is scarce about the use of bioabsorbable stents in treating infrapopliteal lesions. Utilizing bioabsorbable stents in minor infrapopliteal lesions can successfully maintain the patency of the blood vessel lumen, whereas balloon angioplasty cannot offer this benefit. The primary focus of testing these materials is determining whether bioabsorbable scaffolds can provide adequate radial force in highly calcified elongated lesions. Indeed, using "-limus" medication elution technology in conjunction with bioabsorbable stents has previously offered clinical benefits in treating the popliteal artery, as evidenced by limited trials.BVSs for peripheral arterial disease (PAD) show promise and have the potential to offer a less inflammatory and more vessel-friendly option compared to permanent metallic stents. However, current evidence does not yet allow for a universal recommendation for their use. Thus, ongoing, and future studies, such as those examining the newer generation of bioresorbable scaffolds (BRSs) with improved mechanical properties and resorption profiles, will be crucial in defining the role of BRSs in managing PAD.
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OBJECTIVE: The study aimed to compare the effectiveness of drug-coated balloon (DCB) and drug-eluting stents (DESs) to standard endovascular techniques like percutaneous transluminal angioplasty (PTA) and bare metal stent (BMS) for treating infrapopliteal artery disease. METHODS: Including 8 DCB trials and 4 DES trials, this meta-analysis of 12 recent randomized controlled trials (RCTs) is comprehensive. We searched MEDLINE, EMBASE, Science of Web, Cochrane, and PubMed for this meta-analysis. We searched these databases for papers from their inception to February 2023. We also analyzed the references given in the listed studies and any future study that cited them. No language or publication date restrictions were applied to the 12 RCTs. The experimental group includes 8 DCB studies and 4 DES investigations, the DCB group is primarily concerned with the paclitaxel devices, whereas the DES group is preoccupied with the "-limus" devices. Key clinical outcomes in this study were primary patency and binary restenosis rates. This study's secondary outcomes are late lumen loss (LLL), clinically-driven target lesion revascularization (CD-TLR), limb amputation, and all-cause mortality. The evidence quality was assessed using Cochrane risk-of-bias. The PROSPERO registration number for this study is CRD42023462038. FINDINGS: Only 108 of 1152 publications found satisfied qualifying criteria and contained data. All 13 RCTs have low to moderate bias. Drug-coated balloons and DESs were compared in the excluded study. The analysis comprised 2055 participants from 12 RCTs that met the inclusion criteria, including 1417 DCB patients and 638 DES patients. Drug-coated balloons outperform traditional methods in short-term monitoring of primary patency, binary restenosis, and CD-TLR. The benefits fade over time, and the 2 techniques had similar major amputation rates, mortality rates, and LLL. Drug-eluting stents outperform conventional procedures in primary patency, binary restenosis, and CD-TLR during medium-term to short-term follow-up. Comparing the 2 methods, major and minor amputations, death rate, and LLL were similar. CONCLUSION: Comparison of DES and DCB with PTA or BMS shows that DES had better follow-up results. DCB has positive short-term results, but long-term effects differ, however, more research is needed to determine when DES and DCB should be used in medical procedures. CLINICAL IMPACT: The provision of additional evidence to substantiate the advancement of drug-coated balloon (DCB) therapy in the treatment of lower limb arteriosclerosis obliterans, particularly in the below-the-knee area characterized by high calcium load and significant occlusion, is comparable in efficacy to conventional procedures. This finding is advantageous for the progress of interventional revascularization. The advancement and efficacy of DCB have resulted in improved treatment outcomes for medical practitioners in clinical settings. Our research incorporates the most recent randomized experiments.
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BACKGROUND: Subclavian aneurysms are rare in clinic; right subclavian artery aneurysms (SAAs) are more common than left SAAs in clinical practice. Although the causes and methods of treating subclavian aneurysms have been studied, it is still unknown how they form naturally. OBJECTIVE: While describing the uncommon subclavian aneurysm, examine the pertinent literature to discuss its etiology and treatment outcomes, and offer some recommendations for this patient's treatment plan. METHODS: In this case report, we describe a man patient who had a right subclavian proximal aneurysm that was discovered by accident. No clear clinical symptoms or signs were present in the patient. Upon admittance, an examination revealed an aneurysm in the vertebral artery but no peripheral embolization or compression symptoms. The patient refused operation, so we opted for follow-up instead. RESULT: The patient took an ultrasound examination at our first follow-up appointment 3 months after discharge, and the results showed no thrombosis or appreciable aneurysm enlargement. Follow-up appointments for 6 months and a year have begun. CONCLUSION: Follow-up is a good method to monitor the course of subclavian aneurysms without a clear indication for surgery when there is a clear operation mode and risk.
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OBJECTIVE: To evaluate the efficacy of deep vein thrombosis (DVT) prevention among real-world surgical inpatients who received panax notoginseng saponins (PNS) combined with low-molecular-weight heparin (LMWH). METHODS: A prospective cohort study was conducted among surgical patients between January 2016 and November 2018 in Xuanwu Hospital, Capital Medical University, Beijing, China. Participants received LMWH alone or PNS combined with LMWH for preventing DVT. The primary outcome was incidence of lower extremity DVT, which was screened once a week. Participants in the LMWH group were given LMWH (enoxaparin) via hypodermic injection, 4000-8000 AxalU once daily. Participants in the exposure group received PNS (Xuesaitong oral tablets, 100 mg, 3 times daily) combined with LMWH given the same as LMWH group. RESULTS: Of the 325 patients screened for the study, 281 participants were included in the final analysis. The cohort was divided into PNS + LMWH group and LMWH group with 134 and 147 participants, respectively. There was a significant difference of DVT incidence between two groups (P=0.01), with 21 (15.7%) incident DVT in the PNS + LMWH group, and 41 (27.9%) incident DVT in the LMWH group. Compared with participants without DVT, the participants diagnosed with DVT were older and had higher D-dimer level. The multivariate logistic regression model showed a significant lower risk of incident DVT among participants in the PNS + LMWH group compared with the LMWH group (odds ratio 0.46, 95% confidence interval, 0.25-0.86). There were no significant differences in thromboelaslography values (including R, K, Angle, and MA) and differences in severe bleeding between two groups. No symptomatic pulmonary embolism occurred during the study. CONCLUSION: Combined application of PNS and LMWH can effectively reduce the incidence of DVT among surgical inpatients compared with LMWH monotherapy, without increased risk of bleeding.
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Panax notoginseng , Saponinas , Trombose Venosa , Anticoagulantes/uso terapêutico , Hemorragia , Heparina de Baixo Peso Molecular/efeitos adversos , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Estudos Prospectivos , Saponinas/uso terapêutico , Trombose Venosa/induzido quimicamente , Trombose Venosa/tratamento farmacológico , Trombose Venosa/prevenção & controleRESUMO
BACKGROUND: Tracheobronchial tuberculosis (TBTB) is a common subtype of pulmonary tuberculosis. Concomitant diseases often obscure the diagnosis of senile TBTB. AIM: To characterize senile patients with TBTB and to identify the potential causes of misdiagnosis. METHODS: One hundred twenty patients with senile TBTB who were admitted to the Anhui Chest hospital between May 2017 and May 2019 were retrospectively analyzed. Patients were classified as diagnosed group (n = 58) and misdiagnosed group (n = 62). Clinical manifestations, laboratory results, radiographic data, and endoscopic findings were compared between the two groups. RESULTS: Patients in the misdiagnosed group were most commonly diagnosed as pulmonary tuberculosis (non-TBTB, 29/62, 46.8%), general pneumonia (9/62, 14.5%), chronic obstructive pulmonary disease (8/62, 12.9%), and tracheobronchial carcinoma (7/62, 11.3%). The time elapsed between disease onset and confirmation of diagnosis was significantly longer in the misdiagnosed group [median (first quartile, third quartile): 6.32 (4.94, 16.02) mo vs 3.73 (2.37, 8.52) mo]. The misdiagnosed group had lower proportion of patients who underwent bronchoscopy [33.87% (21/62) vs 87.93% (51/58)], chest computed tomography (CT) scan [69.35% (43/62) vs 98.28% (57/58)], and those who showed CT signs of tuberculosis [27.91% (12/62) vs 50% (29/58)] as compared to that in the diagnosed group (P < 0.05). There were no significant between-group differences with respect to age, gender, occupation, clinical manifestations, or prevalence of comorbid chronic diseases (P > 0.05). CONCLUSION: Insufficient or inaccurate radiographic or bronchoscopic assessment was the predominant cause of delayed diagnosis of TBTB. Increased implementation and better interpretation of CT scan and early implementation of bronchoscopy can help reduce misdiagnosis of senile TBTB.
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OBJECTIVE: To explore the management strategies of pyogenic vascular prosthetic graft infection. METHODS: The clinical data of 5 cases of prosthetic vascular graft infection in lower extremity between 2003 and 2010 were retrospectively analyzed. RESULTS: All of them were treated by antibiotics, debridement and drainage. One patient died from acute myocardial infarction and septic shock. Two patients were cured by extra-anatomic arterial bypass and removal of infected graft after a basic control of infections. And another two patients had the diseased limb amputated after the removal of infected vascular graft without blood reconstruction. CONCLUSION: Pyogenic infection of vascular graft is hard to treat with conservative measures. Revascularization prior to removal of infected graft is recommended for a better outcome.
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Implante de Prótese Vascular/efeitos adversos , Prótese Vascular/microbiologia , Infecções Relacionadas à Prótese/terapia , Adulto , Idoso , Humanos , Extremidade Inferior/irrigação sanguínea , Masculino , Estudos RetrospectivosRESUMO
A 68-year-old female patient was treated for unhealed ulcer in the fourth toe of the left foot. Clinical examinations identified severe stenosis of the proximal segment and occlusion of the distal segment of the left anterior tibial artery, and occlusion of the left posterior tibial artery and the peroneal artery. The proximal stenotic segment of the left anterior tibial artery was dilated, but the distal occlusive part failed to be re-canalized. Left anterior tibial artery to dorsal pedal artery bypass was performed on the patient with an epoxide-crosslinked, special radicals antigen-sealed, porcine-derived biological graft; debridement of the left 4th digiti pedis was also performed. Postoperation course was uneventful. The pulse of the left dorsal pedal artery was strong. The ankle brachial index (ABI) increased from 0.60 to 1.09. Warfarin and two antiplatelet drugs were given after the operation. Six months after operation, computed tomographic angiogram (CTA) identified the patent graft.
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Prótese Vascular , Pé Diabético/cirurgia , Isquemia/cirurgia , Perna (Membro)/irrigação sanguínea , Idoso , Feminino , HumanosRESUMO
OBJECTIVE: To explore the feasibility and efficacy of carotid endarterectomy (CEA) in the treatment of atherosclerotic carotid artery stenosis (ACAS). METHODS: From January 2002 to December 2010, 126 ACAS patients undergoing carotid endarterectomy at our hospital were retrospectively analyzed. There were 92 males and 34 females with an average age of 65.5 years old (range: 48 - 75). Among them, 25 had sequelae of cerebral infarction, 69 symptomatic cerebral ischemia and 32 asymptomatic. Sixty-two patients were monitored intra-operatively with transcranial Doppler (TCD). Among them, 5 patients underwent arterial shunt due to a reduced of blood flow in middle cerebral artery for over 50%. The other 64 patients without TCD monitoring underwent intra-operative arterial shunt. And 22 patients underwent patch angioplasty with autologous or prosthetic vascular patch. Intracranial hyperperfusion was prevented by a compression of common carotid artery or control was successful without perioperative mortality. All patients with cerebral ischemic symptoms and some patients with cerebral infarction sequelae had much post-operative improvement. Deviated tongue protrusion occurred in 10 patients and 8 of them recovered at Week 2 post-operation. And 118 patients were followed up for a mean period of 46.5 months (range: 6 - 96). Two patients with deviated tongue protrusion had slight improvements; 2 patients with severe carotid artery stenosis underwent stent angioplasty; 4 patients with moderate carotid artery stenosis received conservative treatment; among 7 deceased patients, two died of cerebral infarction. CONCLUSION: CEA is effective in the treatment of carotid artery stenosis with a high success rate. TCD monitoring during CEA is valuable for preventing cerebral ischemia and intracranial hyperperfusion. Arterial shunt and arterial patch angioplasty should be considered according to certain conditions during CEA.
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Estenose das Carótidas/cirurgia , Endarterectomia das Carótidas , Idoso , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/cirurgia , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória , Estudos Retrospectivos , Ultrassonografia Doppler TranscranianaRESUMO
OBJECTIVE: To evaluate medium-long term patency of below-knee bypass on patients who suffered from diabetic lower limb ischemia. METHODS: Clinical and follow-up data of 51 patients was retrospectively analyzed who underwent 56 below-knee bypass because of diabetes from November 2001 to December 2006. There were 35 male and 16 female with an average age of 68 years. They endured 26 months ischemic time lag in average, and had suffered from diabetes for 11 years. All of the patients were performed bypass to below-knee (posterior tibial, anterior tibial or peroneal) arteries. Kaplan-meier method was applied. The subgroups of different operative methods and different out-flow vessels were compared by Log-rank tests. RESULTS: An average follow-up time of 23 months was achieved, and lost-follow-up rate was 15%. The total 1- and 5-year primary patent rates were 68% and 54% respectively, secondary patent rate were 70% and 60% respectively, limb salvage rates were 69% and 65%, survival rates were 82% and 60%. One year (3 years) of patent rate(s) of operative method subgroups of femoral-popliteal-infrageniculate bypass with composite grafts, femoral/popliteal-infrageniculate bypass with artificial grafts and femoral/popliteal-infrageniculate bypass with autologous veins were 70% (50%), 33% (33%) and 70% (70%) respectively. One year (4 years) of patent rate(s) of out-flow vessel subgroups of posterior tibial artery, anterior tibial artery and peroneal artery were 65% (60%), 80% (53%) and 77% (66%) respectively. However, both subgroups did not show any statistic differences by log-rank tests. CONCLUSIONS: Partial or whole autologous veins as bypass grafts should be chosen when infrageniculate bypass is considered in diabetic patients. Considerable patent rates are acceptable no matter what kinds of out-flow vessels are chosen.
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Angiopatias Diabéticas/cirurgia , Isquemia/cirurgia , Extremidade Inferior/irrigação sanguínea , Idoso , Feminino , Artéria Femoral/cirurgia , Seguimentos , Humanos , Isquemia/etiologia , Masculino , Pessoa de Meia-Idade , Artéria Poplítea/cirurgia , Estudos Retrospectivos , Veia Safena/transplante , Artérias da Tíbia/cirurgia , Procedimentos Cirúrgicos Vasculares/métodosRESUMO
OBJECTIVE: To evaluate the effect of surgical bypass and to explore the role of transcranial doppler (TCD) during the bypass operation. METHODS: From March 2003 to February 2008, sixteen patients (4 male and 12 female) with mean age of 32 years old and mean disease course of 7.5 years were treated by surgical procedures. The main clinical presentations were dizziness, headache, vertigo, and visional dysfunction. Variated degree of artery stenoses in the 4 arteries (bilateral carotid and vertebral arteries) were revealed by color doppler ultrasonography and DSA. Eight patients underwent aorto-bi-subclavian arteries prosthetic graft bypass. Three patients underwent aorto-bi-subclavian artery prosthetic graft bypass and graft-unilateral carotid artery bypass with autologous great saphenous vein. Three patients underwent aorta-unilateral subclavian artery-unilateral carotid artery prosthetic graft bypass. Two patients underwent aorta carotid artery bypass with autologous great saphenous vein, of which one patient underwent aortocoronary artery bypass simultaneously. Cerebral blood supply was monitored in 14 patients with transcranial doppler. Unilateral subclavian carotid and femoral carotid artery shunt was used respectively to avoid cerebral ischemia during operation in 2 patients. RESULTS: Symptoms and signs of cerebral ischemia improved in all patients with effective rate of 100% apart from deflected tongue-protrusion in 3 patients which recovered in 2 weeks after operation. All patients survived and no symptoms recurred at the end of a 2.2 year's follow-up. Unfortunately, two patients developed aneurysm at the anastomosis within 4 years after operation. CONCLUSIONS: Arterial reconstruction is an effective method for Takayasu's disease with severe cerebral ischemia. TCD monitoring plays an important role during the bypass operation. It can help to determine the revision of blood pressure and prevent postoperative brain reperfusion injury.
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Isquemia Encefálica/cirurgia , Revascularização Cerebral/métodos , Arterite de Takayasu/cirurgia , Adulto , Encéfalo/irrigação sanguínea , Isquemia Encefálica/etiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória , Fluxo Sanguíneo Regional , Arterite de Takayasu/complicações , Resultado do Tratamento , Ultrassonografia Doppler Transcraniana , Adulto JovemRESUMO
This study investigated the effect of resistance testing quantified through a genotypic sensitivity score (GSS) on virologic, immunologic, and clinical responses among patients with late stage HIV-1 disease receiving supervised highly active antiretroviral therapy (HAART). Newly admitted patients received drug resistance testing (n = 198) and then HAART supervised by residential health-care facilities nurses. After initiating a resistance testing-informed HAART regimen, patients were followed for HIV-1 RNA suppression (<50 copies/ml), mean change in CD4(+) T-cells, new AIDS defining category C opportunistic conditions and death. GSS was constructed using the HAART regimen prescribed after resistance testing and data derived from IAS-USA consensus mutations table with modification. Regressions with generalized estimating equations for robust estimation of standard errors and Cox proportional hazards regression estimated independent associations between GSS and treatment responses. After adjusting for adherence, initial log(10) HIV-1 RNA levels, and other covariates, patients with a GSS > or =3 had significantly greater HIV-1 RNA suppression (adjusted odds ratio (AOR) 2.32; 95% CI 1.14, 4.75). HIV-1 RNA levels were lower among patients with > or =95% adherence, but the effect of GSS on viral suppression was not modified by adherence. Self-rated health status, and baseline CD4(+) T-cell counts independently predicted HIV-1 RNA suppression. GSS did not predict mean change in CD4(+) cells/mm(3) (236 vs. 233, P = 0.92), occurrence of new AIDS defining category C conditions or death. These data support resistance testing-guided therapy as an independent predictive factor to improve virologic responses in treatment-experienced patients.
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Terapia Antirretroviral de Alta Atividade/métodos , Farmacorresistência Viral , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/genética , HIV-1/isolamento & purificação , Adulto , Contagem de Linfócito CD4 , Feminino , Infecções por HIV/imunologia , Infecções por HIV/mortalidade , HIV-1/efeitos dos fármacos , Humanos , Masculino , Resultado do Tratamento , Estados Unidos , Carga ViralRESUMO
OBJECTIVE: To explore the method and effectiveness of treatment for severe acute deep venous thrombosis (DVT) in lower extremity. METHODS: Eighteen patients with severe acute DVT treated in our hospital from January 1, 2002 to December 31, 2008 were retrospectively analysed. All the patients had limb edema and pain, sixteen had limb cyanochroia(one had calf skin ulcer and foot gangrene), two had limb pallor, ten had weakened dorsalis pedis artery pulsation, eight had silent dorsalis pedis artery pulsation. Colour Doppler ultrasonography revealed DVT and superficial venous thrombosis in all diseased limbs. One patient underwent above knee amputation for limb gangrene. Seventeen underwent surgical thrombectomy, of which three were simple thrombectomy, five were supplemented with suprapubic saphenous vein bypass, six with suprapubic PTFE graft bypass, three with iliac vein lysis angioplasty. RESULTS: One patient died (5.6%) on the third day after surgery. Limb edema relieved in seven patients (41.2%), reduced in ten patients (58.8%). All diseased limbs regained normal artery pulsation and skin appearance except for one limb amputated. Sixteen patients (94.1%) were followed up by a mean of 34 months. Limb edema disappeared in five patients (31.3%), reduced in eight patients (50%), recurrent in three patients (18.7%). Among three recurrent patients, one died of malignant tumor 9 months after operation, two had their graft occluded resulting from intimal hyperplasia. CONCLUSIONS: Surgical thrombectomy is an effective method for treating severe acute DVT in lower extremity.
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Trombectomia , Trombose Venosa/cirurgia , Doença Aguda , Adulto , Idoso , Estado Terminal , Feminino , Humanos , Extremidade Inferior/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the method of constructing small-diameter vascular grafts from xenogenic decellularized arterial matrices and mesenchymal stem cells (MSCs). METHODS: Porcine iliac arteries were decellularized by detergent and trypsin treatment. Histology, mechanical strength and porosity experiments were performed to evaluate the properties of decellularized matrices. MSCs were isolated from bone marrow of dogs and expanded ex vivo. Decellularized matrices were seeded with MSCs and further cultured in a pulsatile bioreactor. Morphological features of the tissue engineered grafts were assayed by HE staining and scanning electron microscopy. RESULTS: After cell extraction, absence of cellular components and preservation of extracellular matrix were verified. Mechanical strength of decellularized matrices was slightly reduced compared with native arteries. Porosity of decellularized matrices was 94.9%. Decellularized matrices were successfully seeded with MSCs, which grew to a near-confluent monolayer under flow conditions and MSCs were highly elongated and oriented to the flow direction. CONCLUSION: Small-diameter vascular grafts can be constructed by seeding MSCs onto xenogenic decellularized arterial matrices and culturing in a pulsatile bioreactor.
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Células-Tronco Mesenquimais , Engenharia Tecidual , Animais , Artérias , Prótese Vascular , Células Cultivadas , Matriz ExtracelularRESUMO
PURPOSE: Uniform and tubular surface seeding is a prerequisite for tissue-engineered blood vessels to mature properly in a bioreactor. Our objective was to investigate reendothelialization of tubular scaffolds by the synergistic forces of sedimentation and rotation, so as to fabricate tissue-engineered venous grafts in vitro. MATERIALS AND METHODS: Canine bone-marrow-derived endothelial progenitor cells were expanded in vitro. By means of a homemade horizontally rotative device, enzymatically decellularized porcine aortic scaffolds were tubularly seeded with the cells by precoating different matrices, under different rotation speeds, culture durations, and seeding techniques. Incorporation of lipoprotein and antiplatelet aggregation functions of seeded cells were evaluated. The seeding efficacies of various methods were compared by histology and scanning electronic microscopy. RESULTS: Uniform distribution and a larger area of cell coverage were demonstrated by precoating with fibronectin (Fn) and a rotation speed of 2.5 revolutions per hour (rph). The efficacy of rotative seeding was comparable to its static counterpart at 4 h, but decreased at 72 h. The result of single-spin seeding was not different from that of three-spin seeding. The seeded cells showed their natural functions of lipoprotein uptake and antiplatelet aggregative properties. Based on these, we constructed 12 tissue-engineered venous grafts with a cell coverage area of 87.4+/-6.2%. CONCLUSIONS: Efficient and reproducible endothelialization was demonstrated by precoating scaffolds with Fn and by performing single-spin seeding at a speed of 2.5 rph.
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Bioprótese , Prótese Vascular , Células da Medula Óssea/fisiologia , Proliferação de Células , Células Endoteliais/fisiologia , Células-Tronco/fisiologia , Engenharia Tecidual , Alicerces Teciduais , Veias/citologia , Animais , Aorta/citologia , Reatores Biológicos , Células da Medula Óssea/metabolismo , Células da Medula Óssea/ultraestrutura , Adesão Celular , Células Cultivadas , Cães , Células Endoteliais/metabolismo , Células Endoteliais/ultraestrutura , Fibronectinas/metabolismo , Lipoproteínas/metabolismo , Agregação Plaquetária , Desenho de Prótese , Reprodutibilidade dos Testes , Rotação , Células-Tronco/metabolismo , Células-Tronco/ultraestrutura , Estresse Mecânico , Suínos , Fatores de TempoRESUMO
OBJECTIVE: To explore the feasibility of the tissue engineered venous grafts (TEVGs) constructed in vitro based on canine autologous bone marrow-derived endothelial progenitor cells (EPCs) and porcine decellularized aortic scaffolds implanted into the canine inferior vena cava. METHODS: To draw out a volume of 8 - 12 ml of bone marrow from the canine (n = 8), to culture and expand EPCs in vitro using conditioned medium. After labeled with a red fluorescent dye PKH26-GL, the cells were seeded onto the luminal surface of decellularized porcine scaffolds with single, rotative method for 4 h. Following static culture for 24 - 72 h, the hybrids were implanted to replace autologous canine inferior vena cava about 4 cm long. Meantime one femoral artery-venous shunt about 1 cm long was performed. The non-seeded decellularized scaffolds (n = 4) were performed the same as control. Angiography was performed and the hybrids were explanted for morphology and labeled cells' immuno-fluorescence examinations at postoperative 10 d, 4 weeks and 12 weeks, respectively. RESULTS: The patent number of experiment (control) group were 7/7 (2/4), 6/6 (2/2) and 4/4 (1/2) at postoperative 10 d, 4 weeks and 12 weeks, respectively. At 12 weeks, tightly confluence endothelial cells which covered the whole inner luminal surface of the explants were detected by immunohistochemistry of factor VIII and scanning electron microscopy, while fibrin-based pseudo-intima was detected on the inner luminal surface of matrix in the solo patent dog from the control group. Meanwhile, fibroblasts and alpha-actin positive cells in the matrices were found by transmission electron microscopy and alpha-actin immunohistochemistry. PKH26-GL labeled EPCs sustained on the luminal surface at a rather proportion accompanied by newly formed endothelial cells. However, the explants in both groups showed partial stenosis. CONCLUSIONS: Such constructed tissue engineered venous graft based on canine autologous bone marrow-derived endothelial progenitor cells and porcine decellularized aortic matrices is promising and deserve to further improvement and testing.