Simulation Experimental Study on Mock Circulation System / 医用生物力学

Objective To study the mock circulation system (MCS) which can accurately reproduce the human hemodynamic environment for in vitro test in the development of artificial organs such as ventricular assist devices (VAD) and artificial heart-lung machine.Methods A double-heart MCS including the systemic and pulmonary circulation was established, which basically covered the main physiological characteristics and functions of the cardiovascular system. The simulation of valves and arteries were proposed with a new way made of silicone material. The MCS could simulate a variety of physiological environments such as normal human body, heart failure, valvular diseases, arteriosclerosis and peripheral obstruction changes by adjusting the control system parameters or structural parameters.The sensor and control system were used to realize the real-time display, control and data preservation of pressure and flow.Results The MCS could simulate the hemodynamic environment of normal human body and a variety of diseases, which were basically consistent with the actual human condition. The new valve and artery model reduced pressure fluctuations in a much better way. The HeartCon VAD of RocketHeart was connected to the experimental platform under simulated state of heart failure, and the hemodynamic environment (aortic pressure, left atrial pressure, cardiac output, etc.) could all be recovered to the normal range.Conclusions The MCS can accurately reproduce the hemodynamic environment of body and pulmonary circulation under a variety of physiological states, and provide an effective experimental platform for the performance test and control strategy design of artificial organs such as VAD. At the same time, the simulation method of making valves and arteries with silicone material can also be further improved in MCS.

Assessment of curative effect of sequential type artificial liver with regional citrate anticoagulation in patients with hepatic failure at high risk of bleeding / 中国基层医药

Objective To assess the efficacy and safety of sequential type artificial liver with regional citrate anticoagulation in patients with hepatic failure at high risk of bleeding.Methods Fifteen patients with hepatic failure at high risk of bleeding treated with plasma exchange(PE)plus continuous veno -venous hemofiltration (CVVH)for 4h anticoagulation selected anticoagulant citrate dextrose solution A (ACD -A),blood flow velocity was setted to 100 -120mL/min.In the former,ACD -A solution was delivered pre -filter,with the rate adjusted to maintain a postfilter ionized calcium (iCa2 +)level between 0.35 -0.45mmol/L.Before the extracorporeal blood returned to the patients, 10% calcium gluconate was infused to maintain a systemic iCa2 + level between 0.90 -1.20mmol/L.Hypoxemia and hypocalcemia were correctted before treatment.Acid -base changes,serum sodium,total calcium -ionized calcium ratio were recorded at 2h,4h and 6h during the treatment.Effective therapeutic time (the therapy was completed successfully)also was recorded.Results The total 38 sessions were performed,effective performance was 35 sessions. 3 sessions were stopped because of high transmembrane pressure.Acid -base change,serum sodium had no significant changes.Serum iCa2 + concentration was detected 110 times,16 times were below 0.9mmol/L,the lowest concentration was 0.62mmol/L.Convulsion of the limbs appeared two times because of hypocalcemia.The total calcium -ionized calcium ratio above 2.5 appeared totally 6 times.The events improved after augmented substitution fluid.All events presented in advanced hepatic failure.Conclusion Under closely monitoring and application of preventive measures, regional citrate anticoagulation sequential type artificial liver is safe and efective for patients with hepatic failure at high risk of bleeding.The application in patients with advanced hepatic failure still is cautious.

Síntese e caracterização de derivados de hemoglobina para aplicação terapêutica / Synthesis and characterization of hemoglobin based oxygen carriers for therapeutic application

A transfusão de sangue é uma intervenção terapêutica capaz de salvar muitas vidas. Entretanto, transfusões também apresentam uma alta gama de possíveis eventos adversos, questões logísticas, econômicas e sociais. Dentre as principais preocupações terapêuticas estão a incompatibilidade (principalmente do sistema ABO), a transmissão de microrganismos patogênicos, os distúrbios imunomodulatórios, as reações hemolíticas, o aumento estatístico do risco de morte proporcional ao volume de sangue infundido, dentre outros. Diversas alternativas às transfusões sanguíneas são propostas na literatura científica, dentre elas o desenvolvimento de transportadores de oxigênio que utilizam a hemoglobina, comumente intitulados substitutos sanguíneos. Neste âmbito, o presente estudo teve como objetivo o desenvolvimento de uma rota de síntese e a síntese de partículas de gelatina contendo hemoglobina polimerizada. Para tanto, realizou-se a síntese do polietileno glicol bis-[succinimidil succinato], extraiu-se e polimerizou-se com glutaraldeído ou polietileno glicol bis-[succinimidil succinato] hemoglobina de sangue bovino e, partículas de gelatina coriácea ou óssea contendo hemoglobina polimerizada foram sintetizadas e caracterizadas. A síntese do polietileno glicol bis-[succinimidil succinato] (SSPEG) foi caracterizada por espectroscopia RAMAN, análise diferencial de calorimetria (DSC) e os resultados obtidos indicaram o sucesso das reações. O produto da reação de polimerização da hemoglobina e albumina com o SSPEG foi verificado por SDS-PAGE e os resultados obtidos indicaram a formação com sucesso de polímeros de alta massa molecular. As partículas contendo hemoglobina polimerizada geradas com gelatina coriácea apresentaram diâmetro hidrodinâmico de 1370 nm, dispersividade de 0,029 e potencial zeta de -36,1 mV. As partículas contendo hemoglobina polimerizada geradas com gelatina óssea apresentaram diâmetro hidrodinâmico de 438 nm, dispersividade de 0,563 e potencial zeta de -24,5 mV. Os resultados obtidos sugerem a aplicabilidade da gelatina coriácea para a produção de partículas contendo hemoglobina polimerizada com possível aplicação como transportador de oxigênio

Blood transfusion is a therapeutic intervention that can save many lives. However, transfusion is also related to several possible adverse therapeutic events and logistic, economic and social concerns. Among the major therapeutic concerns are incompatibility (mainly of the ABO group system), pathogenic microorganisms' transmission, immunomodulatory disturbances, hemolytic reactions, death risk increase that is proportional to the infused volume, among others. Several alternatives to blood transfusion are proposed in the scientific literature. Among them is the development of hemoglobin based oxygen carriers, commonly entitle blood substitutes. To this extent, the present work aimed to develop a synthetic route and to synthesize gelatin particles containing polymerized hemoglobin. To this purpose PEG bis(succinimidyl succinate) was synthesized, bovine hemoglobin was extracted and polymerized with glutaraldehyde or PEG and polyhemoglobin contained particles of gelatin from leather or bones were synthesized and characterized. PEG bis(succinimidyl succinate) synthesis was characterized by RAMAN spectroscopy and by differential scanning calorimetry (DSC) and the obtained results indicated the successful synthesis. The reaction product of the polymerization of hemoglobin or albumin with PEG was verified by SDS-PAGE and the results indicated the successful formation of high molecular mass polymers. The particles generated with leather gelatin and polyhemoglobin had a hydrodynamic diameter of 1370 nm, dispersity of 0.029 and zeta potential of -36.1 mV. Particles generated with bone gelatin and polyhemoglobin had hydrodynamic diameter of 438 nm, dispersity of 0.563 and zeta potential of -24.5 mV. The obtained results suggest the applicability of leather gelatin for the production of polyhemoglobin containing particles aiming to the development of a hemoglobin based oxygen carrier

A Study on an Effective Decellularization Technique for a Xenograft Cardiac Valve: the Effect of Osmotic Treatment with Hypotonic Solution / 대한흉부외과학회지

BACKGROUND: Cellular remnants in the bioprosthetic heart valve are known to be related to a host's immunologic response and they can form the nidus for calcification. The extracellular matrix of the decellularized valve tissue can also be used as a biological scaffold for cell attachment, endothelialization and tissue reconstitution. Thus, decellularization is the most important part in making a bioprosthetic valve and biological scaffold. Many protocols and agents have been suggested for decellularization, yet there have been few reports about the effect of a treatment with hypotonic solution prior to chemical or enzymatic treatment. This study investigated the effect of a treatment with hypotonic solution and the appropriate environments such as temperature, the treatment duration and the concentration of sodium dodecylsulfate (SDS) for achieving proper decellularization. MATERIAL AND METHOD: Porcine aortic valves were decellularized with sodium dodecylsulfate at various concentrations (0.25%, 0.5%), time durations (6, 12, 24 hours) and temperatures (4degrees C, 20degrees C)(Group B). Same the number of porcine aortic valves (group A) was treated with hypotonic solution prior to SDS treatment at the same conditions. The duration of exposure to the hypotonic solution was 4, 7 and 14 hours and the temperature was 4degrees C and 20degrees C, respectively. The degree of decellularization was analyzed by performing hematoxylin and eosin staining. RESULT: There were no differences in the degree of decellularization between the two concentrations (0.25% 0.5%) of SDS. Twenty four hours treatment with SDS revealed the best decellularization effect for both groups A and B at the temperature of 4degrees C, but there was no differences between the groups at 20degrees C. Treatment with hypotonic solution (group A) showed a better decellularization effect at all the matched conditions. Fourteen hours treatment at 4degrees C with hypotonic solution prior to SDS treatment revealed the best decellularization effect. The treatment with hypotonic solution at 20degrees C revealed a good decellularization effect, but this showed significant extracellular matrix destruction. CONCLUSION: The exposure of porcine heart valves to hypotonic solution prior to SDS treatment is highly effective for achieving decellularization. Osmotic treatment with hypotonic solution should be considered for achieving decellularization of porcine aortic valves. Further study should be carried out to see whether the treatment with hypotonic solution could reduce the exposure duration and concentration of chemical detergents, and also to evaluate how the structure of the extracellular matrix of the porcine valve is affected by the exposure to hypotonic solution.

Prospect of artificial organs,tissue engineering and biomaterial / 国际生物医学工程杂志

In recent years,implantation medicine and alternative medicine have made great progress.As a resuh.clinical demands of substitutes for damaged organs and tissues have been greatly increased.The artificial organs.the tissue related engineering products,and biomaterials have saved thousands of patient's lives successfully.This article is to prospect for the development of artificial organs,tissue engineering and biomaterials in future vears.It mainlv includes the following aspects:The technical feature,the developing objection,the research direction,as well as a few questions which should be paid attention to in developing the related products.

Study on tissue-engineered esophagus / 第二军医大学学报

Many esophageal diseases need esophageal replacement. Replacement with autograft leads to great damage and complications. The existing artificial esophagus, however, cannot match the demands of esophageal replacement. The study of tissue-engineered esophagus is the hope to solve these problems. This article reviews the progression of tissue-engineered esophagus.