玉米醇溶蛋白的物理化学改性

背景：玉米醇溶蛋白作为缓控释材料和生物可降解药用辅料在药剂学领域有着广泛的应用。 目的：对玉米醇溶蛋白的物理化学改性方法进行综合分析。 方法：应用计算机检索CNKI和PubMed数据库中1998-01/2010-10关于玉米醇溶蛋白的文章,在标题和摘要中以“玉米醇溶蛋白,玉米朊,改性,接枝”或“ZEIN,Modification,Graft”为检索词进行检索。选择文章内容与玉米醇溶蛋白改性研究相关,同一领域文献则选择近期发表或发表在权威杂志文章。 结果与结论：对玉米醇溶蛋白的改性研究进行总结有利于指导玉米醇溶蛋白的改性研究,从而增加玉米醇溶蛋白在药物制剂,生物医学工程方面的利用价值。     

生物可降解医用材料的应用和生物相容性

生物可降解医用材料的应用和生物相容性四川省生物医学材料监测中心王定国，吴增树可降解性材料的发展许多聚合生物材料进入机体后，可释放不同分子量和物理化学性质的分子。但这种释放不是真正的降解，而更多是聚合物添加剂的滤出或单体的解聚。早在６０年代，Ｒｏｂｅｒ...     

生物可降解材料在医学领域的应用

生物可降解材料包括天然可降解材料和人工合成可降解材料,由它们制成的产品应用于人体后可逐渐被降解吸收.本文综述了部分已应用于临床的生物可降解材料的特性、种类和应用现状,其中包括甲壳素、胶原蛋白、细菌纤维素、聚羟基丁酸酯、聚乳酸、聚乙醇酸、聚对二氧环己酮和聚丁二酸丁二醇酯及磷酸钙,并对相关的需要解决的问题进行了讨论.总之生物可降解材料所具有的理化结构和降解特性决定其运用于医用产品将会发挥有益的治疗作用,尽管目前只在有限范围应用,在实际应用时也存在一些问题,但生物可降解材料将会有广阔的应用前景.     

生物可降解镁合金植入材料的医用特征

背景：镁及镁合金作为新型医用植入材料是近年来生物可降解材料的一个研究热点,其中合金化、生物相容性、表面改性涂层研究都有了很大进展。 目的：对国内外镁及镁合金医用植入材料的研究现状及新进展作一综述。 方法：应用计算机检索CNKI和Pubmed数据库中1998-01/2010-10关于镁及镁合金的文章,在标题和摘要中以“金属基生物材料; 医用植入材料;镁合金;生物可降解;骨;生物相容性”或“metal matrix biomaterials;medical implant materials;  magnesium alloy; biodegradable;  bone; biocompatibility ”为检索词进行检索。选择关于镁及镁合金的41篇文献进行综述。 结果与结论：镁及镁合金作为新型医用植入材料,具有优异的力学性能和可降解性,正吸引着越来越多研究者的关注。但是由于镁及镁合金较差的耐蚀性能影响到临床上的应用。为了提高镁及镁合金耐蚀性能,研究者们对镁及镁合金进行了表面处理并取得重要进展,镁及镁合金必定会在医用金属植入材料领域得到广泛的应用。     

新型生物可降解支架材料生物特性及在损伤胆道修复中的应用

BACKGROUND:A variety of factors contribute to biliary injury that is difficult to be repaired. Stent implantation is extensively used for bile duct injury, but either scaffolds made by metal or plastics can lead to certain adverse reactions. OBJECTIVE: To explore the biological characteristics of a novel biodegradable scaffold and its repair effects on bile duct injury. METHODS: The biological characteristics of the novel biodegradable scaffold were detected by fresh bile, and its degradation was observed at different time points. Thirty Bama mini pigs were included and were randomly divided into observation group (n=15) and control group (n=15). After bile duct injury models were prepared, the control group was subjected to the bile duct interrupted suture, while the observation group was subjected to the novel biodegradable scaffold combined with omentum majus. The biological properties of the scaffolds were observed. Hepatic enzymes and serum total bilirubin levels were detected, as well as hematoxylin-eosin staining, Masson staining and immunohistochemistry detection of α-smooth muscle actin were performed. RESULTS AND CONCLUSION: Before and 1, 3 and 6 months after surgery, hepatic enzymes and total bilirubin of two groups were detected, and neither intra-group nor intergroup comparisons had significant differences (P > 0.05). Hematoxylin-eosin staining and Masson staining revealed that inflammatory reactions and fiber hyperplasia at the anastomotic site in the observation group were lighter than those in the control group at different time points after surgery. The α-smooth muscle actin-positive scores in both two groups were in a rise at 1 and 3 months after surgery, and peaked at the 3rd month, and then began to decline. Moreover, the α-smooth muscle actin-positive scores in the observation group were significantly lower than those in the control group at 3 and 6 months after surgery (P < 0.05). These results show that the novel biodegradable scaffold has good biological characteristics and can obtain ideal repair effects in the bile duct injury.     

新型生物止血材料--医用生物蛋白胶临床应用的效果观察

通过对术中应用医用生物蛋白胶止血的效果进行比较观察 ,说明医用生物蛋白胶具有良好的止血作用。按照不同专科及病种对应用组与对照组进行止血效果的对比观察。对比后发现应用组的止血效果优于对照组 ,并有促进组织愈合的作用。医用生物蛋白胶是一种新型的、有效的生物止血新材料     

新型生物止血材料——医用生物蛋白胶临床应用的效果观察

通过对术中应用医用生物蛋白胶止血的效果进行比较观察，说明医用生物蛋白胶具有良好的止血作用。按照不同专科及病种对应用组与对照组进行止血效果的对比观察。对比后发现应用组的止血效果优于对照组，并有促进组织愈合的作用。医用生物蛋白胶是一种新型的、有效的生物止血新材料。     

氟处理AZ31B生物可降解镁合金材料的细胞相容性*

背景：镁及镁合金作为新型可降解植入材料,具有优异的生物相容性和综合力学性能,但是由于镁及镁合金较差的耐蚀性能,影响到其在临床上的应用。表面氟化处理的AZ31B镁合金是否具有良好的生物相容性尚不清楚。 目的：以诱导的人骨髓间充质干细胞作为检测细胞,评价不同表面氟处理的镁合金材料的细胞相容性。 方法：以诱导的人骨髓间充质干细胞作为检测细胞,取未经氟处理及不同氟处理时间的镁合金材料浸提液进行体外细胞相容性实验,评价不同氟处理的镁合金AZ31B材料的生物相容性。 结果与结论：经氟处理镁合金AZ31B材料与未经氟处理镁合金AZ31B材料相比能显著提高细胞存活率,细胞毒性分级1级,对细胞生长基本无毒性作用。提示经氟处理镁     

血液相容性抗凝血生物医用高分子材料的制备及其机制

背景:由于生物医用材料要接触人体内环境,甚至必须植入生物体内,因此要求具有无毒性、优良的生物相容性、高化学稳定性、合适的物理机械性能以及易加工成型性。 目的：从生物惰性材料、生物活性表面和白蛋白的结构及其在抗凝血上的应用几个方面分析血液相容性抗凝血生物医用高分子材料的制备及其机制。 方法：由第一作者检索1969/2010 PubMed数据及万方数据库有关血液相容性抗凝血生物医用高分子材料的制备及其机制等方面的文献。 结果与结论：目前抗凝血材料的制备基本上只是采用单独的生物惰性表面或生物活性表面,虽然都获得了较好效果,但不能长期保持其生物相容性尤其是血液相容性,如果能将惰性表面与活性表面结合起来,使材料同时具备两者的长处,并能充分利用人体血液中的天然组分白蛋白或许会是抗凝血材料的一个发展趋势。今后希望通过采用高生物惰性的PEU和具有生物活性的白蛋白识别因子cibacron blue复合,合成具有优良性质的活性改性物,并以此对聚氨酯进行改性。     

可降解血管支架材料的表面性能及生物相容性

BACKGROUND: Biodegradable stent implantation is a commonly used method in the clinical treatment of a variety of cardiovascular diseases. Importantly, the corresponding stent should have good surface properties and biocompatibility. OBJECTIVE: To observe the surface properties of the biodegradable vascular stent material, and to analyze its biocompatibility. METHODS: Artificial plasma was prepared for soaking the biodegradable magnesium alloy stent, and the corrosion of the material was observed by scanning electron microscope. Stent extraction solution was prepared and cytotoxicity test was carried out to observe the toxicity level of human umbilical vein endothelial cells cultured in the culture medium. Platelet adhesion test and hemolysis test were performed to detect cell and blood compatibility of the material. RESULTS AND CONCLUSION: After the 10-day immersion in artificial plasma, the material was scanned and a uniform corrosion layer was found on the surface of the material. During the drying of the material, some cracks appeared on the corrosion layer. After the corrosion products were removed, there were corrosion pits uniformly distributed on the corrosion surface of the material. In the cytotoxicity test, there were no absorbance values in the positive control group, and almost all of the cells died. After cultured in the material extraction, the toxicity level of human umbilical vein endothelial cells was graded 0 or 1. In the adhesion test, platelets on the stent surface were mostly disk-shaped under scanning electron microscope, some of which were deformed and extended pseudopodia, but no platelet aggregation occurred. The hemolysis rate of the material was 3.15%, in accordance with the requirement of the hemolytic rate < 5%. These experimental results show that the biodegradable magnesium alloy stent material has good corrosion resistance and good cell and blood compatibility, which can meet the demand of clinical application.      

Fluoride controlled release tablets for intrabuccal use

We have developed a fluoride controlled release delivering system for intrabuccal use, permitting to reach high enough local concentrations for desirable therapeutic effect with minimal side effects. We have formulated tablets of 160-200mg intended to be fixed on a tooth. The tablets have a granular matrix composed of pure hydroxyapatite, Eudragit((R)) and/or ethylcellulose. NaF is added either by a mechanical mixing or an impregnation method. Profiles of continuous in vitro drug release in saline phosphate buffered solution were recorded by means of a fluoride selective electrode. Linear profiles are observed when ethylcellulose is used. The most reproducible results are obtained when the impregnation method is used. Eudragit((R)) increases the dissolution efficiencies while ethylcellulose decreases it.     

Single-step immunization using a controlled release, biodegradable polymer with sustained adjuvant activity

The use of a biodegradable polymer for antigen delivery based on poly(CTTH-iminocarbonate) (IUPAC nomenclature: poly[oxyimidocarbonyloxy-p-phenylene [2-(hexyloxycarbonyl)ethylene]imino[2-[1-(benzyloxy)formamido]- 1-oxotrimethylene]-p-phenylene]) was investigated. This polymer was selected since its primary degradation product, N-benzyloxycarbonyl-L-tyrosyl-L-tyrosine hexyl ester (CTTH) was found to be as potent an adjuvant as complete Freund's adjuvant and muramyl dipeptide, when measuring the serum antibody response to bovine serum albumin (BSA) in male CD-1 mice over 56 weeks. BSA released from subcutaneously implanted polymeric antigen delivery devices made of poly(CTTH-iminocarbonate) resulted in significantly higher (P less than 0.006) anti-BSA antibody titers than devices made of poly(bisphenol A-iminocarbonate).     

In vivo response to biodegradable controlled antibiotic release systems

In this study, the major goal was to evaluate in vitro and in vivo findings by macroscopy, radiology, and histology to determine the effectiveness of therapy of experimental implant-related osteomyelitis with antibiotic carrier rods constructed of microbial polyesters. The polymers used were poly(3-hydroxybutyrate-co-4-hydroxyvalerate) [P(3-HB-co-4-HB)] and poly(3-hydroxybutyrate-co-3-hydroxy- valerate) [P(3-HB-co-3-HV)]. Both the Sulperazone and the Duocid-P(3-HB-co-4-HB) rods with a drug to polymer ratio of 1:1 (w/w) were effective in treating the bone infection that was experimentally initiated by inoculation of a hemolytic strain of Staphylococcus aureus (coagulase positive; phage type 52/52b) together with metal implants into the medullary area of rabbit tibia. Macroscopical data revealed that the effectiveness of therapy was apparent at week 6 for all categories tested. Radiological findings with Duocid- and Sulperazone-loaded P(3-HB-co-4-HB) rods improved significantly when judged by changes in periosteal elevation, widening of bone shaft, new bone formation, and soft-tissue deformation after 6 weeks of implantation. Histologically the signs of infection were found to subside by weeks 3 and 6. Inflammatory cells were replaced with bone-forming cells upon treatment with Sulperazone-P(3-HB-co-4-HB) and Duocid-P(3-HB-co-4-HB). Osteoblastic activity was prominent. Intramedullary inflammation, although still present, started to be replaced by fibrous or bony tissue. Histological findings presented the subsidence of infection. In summary, the antibiotic-loaded biopolymeric rods appeared to have potential as a new controlled-release system for the treatment of implant related osteomyelitis and chronic osteomyelitis.     

Assessment of biodegradable controlled release rod systems for pain relief applications

Control of chronic, severe pain is a difficult and important clinical problem for most patients, especially those with cancer. Although current applications are insufficient for a satisfactory solution to this problem, the rate of disease incidence is increasing worldwide, thus making the problem more apparent. Based on this fact, this study was designed with the ultimate goal of formulating a controlled release system of pain relievers, mainly opioids, for the local treatment of pain to achieve satisfactory, fast, and less side effect-related relief and to provide a better life status for chronic pain patients. Two copolymers of a biodegradable polymer poly(L-lactide-co-glycolide) (PLGA) were used to prepare an implantable rod type drug release system containing either an analgesic or anesthetic type of pain reliever. In vitro drug release kinetics of these systems were studied. It was observed that release from PLGA 85 : 15 was more zero-order than it was from PLGA 50 : 50. A zero-order release rate was obtained for codeine, hydromorphone, and bupivacaine from PLGA (85 : 15) rods. They, however, were released from PLGA (50 : 50) rods with Higuchi kinetics. The drug solubility was also influential on release rate, as shown by the zero-order morphine release from PLGA (50 : 50) rods. Scanning electron micrographs (SEMs) of the monolithic rods revealed erosion of the rods and the removal of drug crystals from the rod structure.     

A microfabrication method of a biodegradable polymer chip for a controlled release system

A simple microfabrication method for a controlled-release drug-delivery system has been designed using biodegradable polymeric microchips. Microholes were made in a poly(L-lactic acid) plate and dyes were cast in each well. After drying, the wells were sealed with polymers having different biodegradation rates using a mold that had hollows corresponding to the wells. The polymers were prepared by mixing polylactides with the co-polymers. The sealing was confirmed by ultrasonication. The plate was incubated in phosphate-buffered saline and the dye released from the plate as the degradation proceeded was detected spectrophotometrically. The higher the degradation rate of the polymer sealing, the faster the sealed dye was released. This biodegradable biochip is useful for the design of controlled-release drug-delivery systems.     

Preparation of controlled release ophthalmic drops, for glaucoma therapy using thermosensitive poly-N-isopropylacrylamide.

In this study, controlled release ophthalmic agents for glaucoma therapy were developed based on the thermosensitivity of poly-N-isopropylacrylamide (PNIPAAm). The clear solution of PNIPAAm was known to undergo phase transition when the temperature was raised from the room temperature to about 32 degrees C. The drug was entrapped in the tangled polymer chains or encapsulated within the crosslinked polymer hydrogel at room temperature, and released progressively after topical application (i.e., at a higher temperature). Linear PNIPAAm and crosslinked PNIAAm nanoparticles containing epinephrine were prepared. The drug release rate and cytotoxicity were investigated in vitro. Ophthalmic formulations based on either linear PNIPAAm or the mixture of linear PNIPAAm and crosslinked PNIPAAm nanoparticles were administered to rabbits and the intraocular pressure (IOP)-lowering effect was evaluated. The decreased pressure response of the formulation based on linear PNIPAAm lasted six-fold longer than that of the conventional eye drop. Furthermore, for formulation based on the mixture of linear PNIPAAm and crosslinked nanoparticles, the pressure-lowering effect lasted eight times longer. These results suggest the use of thermosensitive polymer solutions or hydrogels is potential in controlled release antiglaucoma ophthalmic drugs.     

A microfabrication method of a biodegradable polymer chip for a controlled release system

A simple microfabrication method for a controlled-release drug-delivery system has been designed using biodegradable polymeric microchips. Microholes were made in a poly(L-lactic acid) plate and dyes were cast in each well. After drying, the wells were sealed with polymers having different biodegradation rates using a mold that had hollows corresponding to the wells. The polymers were prepared by mixing polylactides with the co-polymers. The sealing was confirmed by ultrasonication. The plate was incubated in phosphate-buffered saline and the dye released from the plate as the degradation proceeded was detected spectrophotometrically. The higher the degradation rate of the polymer sealing, the faster the sealed dye was released. This biodegradable biochip is useful for the design of controlled-release drug-delivery systems.     

Stimulation of bone regeneration following the controlled release of water-insoluble oxysterol from biodegradable hydrogel

Recently bone graft substitutes using bone morphogenetic proteins (BMPs) have been heralded as potential alternatives to traditional bone reconstruction procedures. BMP-based products, however, are associated with significant and potentially life-threatening side effects when used in the head and neck region and furthermore, are exorbitantly priced. Oxysterols, products of cholesterol oxidation, represent a class of molecules that are favorable alternatives or adjuncts to BMP therapy due to their low side effect profile and cost. In order to establish the optimal clinical utility of oxysterol, an optimal scaffold must be developed, one that allows the release of oxysterol in a sustained and efficient manner. In this study, we prepare a clinically applicable bone graft substitute engineered for the optimal release of oxysterol. We first solubilized oxysterol in water by making use of polymeric micelles using l-lactic acid oligomer (LAo) grafted gelatin. Then, the water-solubilized oxysterol was incorporated into a biodegradable hydrogel that was enzymatically degraded intracorporeally. In this manner, oxysterol could be released from the hydrogel in a degradation-driven manner. The water-solubilized oxysterol incorporated biodegradable hydrogel was implanted into rat calvarial defects and induced successful bone regeneration. The innovative significance of this study lies in the development of a bone graft substitute that couples the osteogenic activity of oxysterol with a scaffold designed for optimized oxysterol release kinetics, all of which lead to better repair of bone defects.     

In vivo pain relief effectiveness of an analgesic-anesthetic carrying biodegradable controlled release rod systems

Pain is the most common and feared symptom for patients, especially those with cancer. Treatment of chronic pain with conventional ways of medication usually fails with increasing severity of the pain. New approaches enabling the prolonged provision of pain relievers are required. We designed a controlled release system of pain relievers, mainly for opioids (morphine, M, codeine, C, and hydromorphone, HM), and a local anesthetic (bupivacaine, BP) in the form of poly(L-lactide-coglycolide) (PLGA) rods. The efficacy of these rods implanted alone or in combination in relieving chronic pain in rats caused by the ligation of the sciatic nerve of their right hind limbs was studied. The two most common tests for measuring analgesia, i.e. tail-flick tests, that show analgesia at sites other than the site of injury, were used to study the degree of systemic distribution of the drugs and paw-withdrawal tests were used to study the analgesia at the site of injury. Alleviation of this chronic and severe neuropathic pain could be obtained for about 3-4 days when rods for two drugs, 'dual drug' (analgesic-anesthetic), were used. This duration is decreased by half (2 days) with the single-drug rods. Also the dual-drug rods, though at half the dose of each single drug application, enhanced the degree of analgesia of the first day. These in vivo results are also consistent with the previous in vitro results as in the case with codeine which had a higher first-day analgesia than morphine, despite a lower potency due to the faster in vitro release rate. Similarly, slower release of hydromorphone from PLGA (85 :15) rods resulted in less systemic analgesia than the more rapidly eroding PLGA (50 : 50) rods of the same drug.     

Intra-articular controlled release of anti-inflammatory siRNA with biodegradable polymer microparticles ameliorates temporomandibular joint inflammation

We investigated the in vivo therapeutic efficacy of an intra-articular controlled release system consisting of biodegradable poly(dl-lactic-co-glycolic acid) (PLGA) microparticles (MPs) encapsulating anti-inflammatory small interfering RNA (siRNA), together with branched poly(ethylenimine) (PEI) as a transfecting agent, in a rat model of painful temporomandibular joint (TMJ) inflammation. The in vivo effects of PLGA MP dose and siRNA-PEI polyplex delivery were examined via non-invasive meal pattern analysis and by quantifying the protein level of the siRNA target as well as of several downstream inflammatory cytokines. Controlled release of siRNA-PEI from PLGA MPs significantly reduced inflammation-induced changes in meal patterns compared to untreated rats with inflamed TMJs. These changes correlated to decreases in tissue-level protein expression of the siRNA target to 20-50% of the amount present in the corresponding control groups. Similar reductions were also observed in the expression of downstream inflammatory cytokines, e.g. interleukin-6, whose tissue levels in the siRNA-PEI PLGA MP groups were 50% of the values for the corresponding controls. This intra-articular sustained release system has significant implications for the treatment of severe TMJ pain, and also has the potential to be readily adapted and applied to mitigate painful, chronic inflammation in a variety of conditions.