几丁糖和透明质酸钠在产科防粘连应用中的生物相容性比较

背景：几丁糖和透明质酸钠是目前临床常用的预防粘连材料,但目前关于二者在产科患者中预防粘连的相关报道相对较少。 目的：观察几丁糖和透明质酸钠在产科患者中的防粘连效果。 方法：纳入180例剖宫产妇,年龄23-39岁,按照治疗方法分为对照组、几丁糖组、透明质酸钠组,每组60例,对照组剖宫产后常规关闭腹腔,几丁糖组、透明质酸钠组剖宫产后关闭腹腔前,在子宫手术切口表面及手术部位附近肠管和腹膜分别涂抹几丁糖与透明质酸钠。术后1 d,检测3组血清白细胞介素6、白细胞介素10、肿瘤坏死因子α及C-反应蛋白水平;随访1个月,观察3组术后粘连及并发症发生情况。 结果与结论：几丁糖组、透明质酸钠组粘连发生情况及粘连发生率均低于对照组(P < 0.05),血清白细胞介素6、白细胞介素10、肿瘤坏死因子α及C-反应蛋白水平均低于对照组(P < 0.05),术后感染、出血、疼痛等的并发症发生率均低于对照组(P < 0.05);几丁糖组与透明质酸钠组粘连发生情况、血清指标水平及并发症发生情况比较差异均无显著性意义。表明几丁糖和透明质酸钠均可有效抑制剖宫产术后的粘连及炎症反应,减少并发症的发生。 中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

可降解高分子生物材料在整形外科术后防粘连中的应用

目的:探讨可降解高分子生物材料的性能特点及其在整形外科术后防粘连中的应用。方法:由第一作者应用万方数据库(http://www.wanfangdata.com.cn/)检索1999-01/2009-12时限内与可降解高分子生物材料在整形外科术后防粘连的应用有关的文献,关键词为"透明质酸钠及其衍生物;纤维素衍生物;医用几丁糖;聚乳酸及其共聚物;整形外科;防粘连;生物材料"。排除重复研究、综述或Meta分析类文章。结果:依据纳入排除标准共保留文献21篇。可降解高分子生物材料均具有较好的生物相容性、可降解性及可吸收性。透明质酸钠可抑制出血并具有抗炎特性。明质酸钠衍生物可弥补透明质酸钠在组织中易被降解和扩散、体内存留时间较短等缺点。羧甲基纤维素热稳定性、组织黏附性高,易于操作。氧化再生纤维素黏附性强,不需缝合;但用易受血液干扰。医用几丁糖具有一定止血功能,免疫抗原性小、无毒性。聚乳酸及其共聚物机械性能、化学稳定性优良,是最有发展前途的可生物降解的高分子材料。从应用研究的结果来看,透明质酸钠及其衍生物、纤维素衍生物、医用几丁糖和聚乳酸及其共聚物均能有效防止整形外科中术后粘连,具备广阔的发展前景。结论:可降解高分子生物材料性能优越,能有效防止整形外科中的术后粘连,具有临床应用的可能性与可行性。     

医用生物材料在肌腱损伤后粘连修复中的应用

背景：选用何种生物材料预防肌腱粘连,是目前医学界研究的热点。 目的：总结近年生物材料在肌腱损伤术后粘连修复中的应用现状。 方法：由作者应用计算机检索1999-01/2009-10维普数据库,选择生物材料修复肌腱损伤术后粘连的有关文章,共入选相关文献30篇。 结果与结论：几丁糖具有良好的生物学特性,是一种无毒、无刺激性、无抗原性、组织相容性良好、在体内可降解吸收的新型医用生物材料,具有显著预防肌腱粘连作用。医用生物蛋白胶具有优良的止血与封闭作用、良好的生物相容性、生物降解功能,一定的杀菌作用,可减少和控制创伤炎症反应。大量临床研究及动物实验研究显示医用透明质酸钠、明胶海绵、糜蛋白酶等均具有防止术后组织粘连的作用。     

各种防粘连产品对腹壁肌肉愈合的影响

目的评价目前主要防粘连产品对腹壁肌肉愈合的影响,为临床使用防粘连产品提供指导。方法实验使用成年SD大鼠,除假手术组外,对大鼠盲肠及相对腹壁肌肉制造损伤,然后不使用(粘连组)或使用不同防粘连产品覆盖损伤处,手术14 d后,检测大鼠腹壁肌肉力学性质和组织学特征,评价损伤肌肉愈合程度。结果聚乳酸医用膜组和医用聚乙二醇小檗碱液组腹壁肌肉愈合侧的最大抗张力和刚度均与正常侧相近(P0.05);医用几丁糖组和Seprafilm组愈合侧的最大抗张力明显低于正常侧(P0.05),刚度则不存在显著差异(P0.05);粘连组和医用透明质酸钠凝胶组腹壁肌肉愈合侧的力学性质明显小于正常侧(P0.05)。HE染色显示,医用透明质酸钠凝胶、聚乳酸医用膜和医用聚乙二醇小檗碱液组血管增生较多;透明质酸钠凝胶组的纤维结构松散,炎性细胞浸润不均匀,其他产品组炎性细胞浸润充分,且纤维形成致密。结论聚乳酸医用膜和医用聚乙二醇小檗碱液促进腹壁肌肉愈合的能力优于医用透明质酸钠凝胶、医用几丁糖和Seprafilm。     

复合胰岛素样生长因子1壳聚糖胶原支架与人牙周膜细胞的增殖

背景：胰岛素样生长因子1具有促进成纤维细胞有丝分裂的作用,同时具有促进牙周细胞生长、分化及合成细胞外基质的作用。 目的：观察负载胰岛素样生长因子1的壳聚糖胶原支架对于人牙周膜细胞增殖的作用。 方法：将人牙周膜细胞分别接种于负载胰岛素样生长因子1的壳聚糖胶原支架与普通胶原支架上,于接种的1 h、24 h及1周检测重组人转化生长因子β1的释放,于第1,7,28天检测两组细胞的黏附和增殖情况。 结果与结论：负载胰岛素样生长因子1的壳聚糖胶原支架组第1,24小时和第1周的重组人转化生长因子β1释放率明显低于普通胶原支架组(P < 0.01)。两组接种第1天的细胞黏附和增殖检测比较差异无显著性意义  (P > 0.05),负载胰岛素样生长因子1的壳聚糖胶原支架组接种第7,28天的细胞黏附和增殖情况优于普通胶原支架组(P < 0.01)。表明负载胰岛素样生长因子1的壳聚糖胶原支架可显著促进人牙周膜细胞的增殖。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程全文链接：     

透明质酸钠配方材料对术后粘连预防的研究

对不同配方的透明质酸钠膜预防术后粘连的效果进行动物实验研究。实验采用SD雄性大鼠腹壁缺损/盲肠损伤的粘连模型,其中A、B和C实验组分别使用A配方膜(透明质酸钠、壳聚糖)、B配方膜(透明质酸钠)和C配方膜(透明质酸钠、羧甲基壳聚糖),而"空白"手术对照组未放置任何材料。术后7d,参考Phillips和Nair等的5级分类法对大鼠腹腔粘连分别进行分级评分,并获取标本进行组织学观察。结果显示A配方透明质酸钠膜组大鼠的粘连评分与"空白"手术对照组相比无显著性差异(P>0.05),未能预防粘连形成。而B、C配方透明质酸钠膜组大鼠的粘连评分与"空白"手术对照组相比均有显著性差异(P<0.01),显示出预防粘连形成的作用;B配方与C配方透明质酸钠膜间比较无显著性差异。组织学结果显示7d时,A配方透明质酸钠膜组大鼠腹壁和盲肠间的粘连组织中有大量炎性细胞浸润坏死,尤以材料残留区域明显。而B、C配方透明质酸钠膜组大鼠腹壁和盲肠损伤表面为正常修复的疏松结缔组织。实验结果表明,A配方透明质酸钠膜不具有良好的生物相容性,无预防粘连的作用;而B、C配方透明质酸钠膜在本实验模型中表现出预防粘连形成的作用,值得进一步研究。     

生物材料在预防运动损伤致肌腱粘连中的应用前景

背景：高科技生物材料具有良好的防肌腱粘连功能。 目的：评价不同生物材料预防运动损伤修复后肌腱和腱鞘之间粘连的效果,寻找适合生物材料。 方法：以“生物材料,运动,肌腱损伤、预防粘连”为中文关键词,以“biological material, sports, tendon injury, antistick”为英文关键词,采用计算机检索中国期刊全文数据库、PubMed数据库1990年1月至2011年3月相关文章。 结果与结论：几丁糖、壳聚糖/聚乳酸聚乙醇酸共聚物乳化膜、透明质酸钠等高分子化合物胶体及药物薄膜等新型生物材料可有效预防运动肌腱损伤导致的肌腱粘连,各种材料均由优缺点,科学合理的综合运用多种药物或高科技生物材料预防肌腱损伤后粘连将是未来的发展方向。     

几丁糖和透明质酸钠防粘连材料在妇产科的应用

背景：妇产科防粘连材料的应用可避免再次给患者造成痛苦和伤害,减少不孕、肠梗阻等其它相关并发症的发生, 目的：分析在妇产科各种防粘连材料临床应用的效果,为防粘连材料的临床应用选择提供可参考借鉴的理论信息。 方法：对不同防粘连材料妇产科的临床应用效果进行分析,采用动物模型试验和临床病例随访的方法,重点分析几丁糖和透明质酸钠用于多种妇产科疾病防粘连治疗时的选择应用范围及效果。 结果与结论：妇产科临床应用防粘连材料可以获得满意的效果,医用生物膜、玻璃酸钠、聚乳酸凝胶等也可用于妇产科防粘连的应用,但是相比而言,几丁糖和透明质酸钠的防粘连效果更优异。     

椎板切除模型大鼠局部应用绿原酸对硬膜外纤维化及硬脑膜粘连的影响

背景：椎板切除减压能起到有效的脊髓神经减压作用,但该操作也会发生硬膜外纤维增生并突入椎管,致医源性椎管狭窄,发生持续或复发的腰腿疼痛。绿原酸是金银花的有效药理成分之一,主要有抗炎等作用。 目的：观察局部应用绿原酸对椎板切除模型大鼠硬膜外纤维化及硬脑膜粘连的影响。 方法：选用72只健康成年Wistar大白鼠,制备椎板切除模型,随机分成3组(n=24)。绿原酸组皮肤缝合前椎板切除区域给绿原酸溶液2 mL/只;生理盐水组给予等量的生理盐水;空白对照组术后不做任何处理。各组大鼠均于造模后4周被处死,进行实验评估,包括大体评价、组织学分析、羟脯氨酸含量测定及白细胞介素6、转化生长因子β1的表达情况。 结果与结论：3组大白鼠均进入结果分析,解剖并取样。绿原酸组硬膜外胶原纤维增生较少,外观较为正常;生理盐水组和空白对照组硬膜外胶原纤维明显增多,外观可见明显纤维瘢痕组织。组织学评价显示,绿原酸组的组织染色切片中成纤维细胞的密度明显比其他两组的成纤维细胞密度低。绿原酸组硬膜外纤维瘢痕的羟脯氨酸含量显著低于生理盐水组和空白对照组(P < 0.01)。通过RT-PCR方法测得绿原酸组白细胞介素6 和转化生长因子β1的表达低于另外两组。提示椎板切除模型大鼠局部应用绿原酸可以抑制成纤维细胞增殖,同时可以降低白细胞介素6 和转化生长因子β1的表达,防止硬膜外瘢痕粘连。 中国组织工程研究杂志出版内容重点：肾移植;肝移植;移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植;组织工程全文链接：     

灯盏花素对腹膜透析液诱导人腹膜间皮细胞转化生长因子β1的影响

背景：从不同层面了解灯盏花素阻止/延缓腹膜功能衰竭的作用及其机制,从而在临床上推广使用灯盏花素来阻止/延缓腹膜功能衰竭从而延长终末期肾脏病患者腹膜透析时间、提高透析质量、减少透析失败率,提高腹膜透析远期疗效具有广泛的应用前景。 目的：观察灯盏花素对腹膜透析液诱导的人腹膜间皮细胞转化生长因子β1分泌及其增殖活性的影响。 方法：体外培养人腹膜间皮细胞,分为5组：分别为对照组、腹膜透析液组、灯盏花素终浓度为5,10,20 µmol/L组。检测各组上清液中转化生长因子β1的水平以及间皮细胞的增殖活性。 结果与结论：腹膜间皮细胞在腹膜透析液诱导下,转化生长因子β1分泌显著增加、细胞增殖活性显著降低。灯盏花素5 µmol/L组转化生长因子β1分泌低于腹膜透析液组(P < 0.05),细胞增殖活性高于腹膜透析液组(P < 0.05);灯盏花素10,20 µmol/L组转化生长因子β1分泌显著低于腹膜透析液组(P < 0.01),细胞增殖活性显著高于腹膜透析液组(P < 0.01)。结果显示灯盏花素可以抑制腹膜间皮细胞转化生长因子β1分泌,拮抗腹膜透析液对腹膜间皮细胞增殖活性的抑制作用。     

不同壳聚糖材料预防腹膜粘连的动物研究

为探讨不同壳聚糖材料对预防大鼠腹膜粘连的作用及机理,将240只大鼠分成两大组:壳聚糖凝胶组(A组)和壳聚糖/明胶共混膜组(B组)。A组144只随机分成3组,各组再分成对照组和实验组,用不同的方法致腹膜粘连,实验组用壳聚糖凝胶来预防粘连。B组96只,随机分成4组,每组24只,均行创伤法致腹膜粘连处理,其中1组为对照组,其余3组的创面分别用不同明胶含量的壳聚糖膜覆盖。术后2 w、4 w评定粘连程度并取相应组织作病理学检查。实验表明:(1)壳聚糖凝胶对创伤及缺血所致的腹膜粘连有明显的预防作用;(2)壳聚糖膜和壳聚糖/明胶共混膜都可加重腹膜粘连。     

Peritoneal application of chitosan and UV-cross-linkable chitosan

The suitability of chitosan and UV-cross-linkable chitosan for intraperitoneal use, for example as a barrier device for preventing peritoneal adhesions or for drug delivery, was examined. In vitro experiments using two major cell types present in the peritoneal cavity (mesothelial cells and peritoneal macrophages) revealed neither attractive interactions between cross-linked chitosan gels and the cells nor a proliferative effect. However, the same UV-cross-linked chitosan applied in the peritoneal cavity of rabbits caused a granulomatous reaction with adhesion formation within two weeks in all animals, which persisted up to 4 weeks after exposure. Unmodified chitosan also caused adhesions, while UV irradiation did not. UV-cross-linkable chitosan induced significant elevations in MIP-2 and TNF-alpha from peritoneal macrophages, suggesting that soluble mediators could play a role in inducing adhesion formation. These results reinforce the view that the predictive value of in vitro cytotoxicity assays in matters of biocompatibility may not be sufficient, and suggest that other assays such as cytokine levels may be of value in predicting outcomes in situations involving multiple cell types (i.e. in vivo).     

Peritoneal adhesion prevention with an in situ cross-linkable hyaluronan gel containing tissue-type plasminogen activator in a rabbit repeated-injury model

Postoperative peritoneal adhesions can have serious, potentially lethal consequences. Pharmacotherapy and barrier devices can reduce adhesion formation to varying degrees, but their efficacy is limited by rapid clearance from the peritoneum and lack of biological activity, respectively. To overcome these limitations, we have delivered tissue-type plasminogen activator (tPA), which is deficient in the first 2-3 postoperative days, using a highly cross-linked in situ forming hyaluronan gel (HAX(hx)). We demonstrated this formulation's anti-adhesion activity in a rigorous animal model that involved recurrent adhesions. While non-treated or saline-treated animals developed widespread adhesions (frequency, both 100%; median adhesion area, 12.7 and 15.4 cm(2), respectively), tPA delivered by HAX(hx) (tPA-HAX(hx)) was highly effective in preventing recurrent adhesions (frequency, 44%; median adhesion area, 0.1cm(2)). HAX(hx) itself, tPA solution, and inactivated tPA in HAX(hx) did not provide comparable anti-adhesion activity. tPA-HAX(hx) is a system that is easy to use and potentially promising for adhesion prevention.     

Biodegradable and injectable in situ cross-linking chitosan-hyaluronic acid based hydrogels for postoperative adhesion prevention

Postsurgical peritoneal adhesions are very common and serious complication after surgery. Biodegradable and injectable hydrogels derived from natural polysaccharides are ideal biomaterials for prevention of postoperative adhesion. In this work, we report a class of injectable, biodegradable, and non-toxic hydrogel derived from N, O-carboxymethyl chitosan (NOCC) and aldehyde hyaluronic acid (A-HA), without requirement of any chemical linkers or radiant light sources. NOCC was prepared by introducing carboxymethyl groups to the N-position and the O-position of chitosan, and A-HA was prepared using periodate oxidation method. The gelation is attributed to the Schiff base between the amino groups of NOCC and aldehyde groups in A-HA, and the hydrogel precursors cross-linked to form a flexible hydrogel. NOCC, A-HA, and NOCC/A-HA hydrogel extract exhibited very low cytotoxicity and hemolysis, and the acute toxicity tests showed that the hydrogel was non-toxic. Besides, the highly porous three-dimensional hydrogel can supported the growth and proliferation of the cells encapsulated in the hydrogels, but was not favorable for the attachment of fibroblasts to the surface, suggesting that the NOCC/A-HA hydrogel can be developed for adhesion prevention. The hydrogel was susceptible to the lysozyme and can be degraded within 2 weeks in vivo. Furthermore, we employed a rat model of sidewall defect-cecum abrasion to investigate the efficacy of NOCC/A-HA hydrogel in preventing post-operative peritoneal adhesions. A significant reduction of peritoneal adhesion formation was found in the NOCC/A-HA-treated group, compared with commercial hyaluronic acid (HA) hydrogel group and normal saline group. In addition, the potential anti-adhesion mechanism of NOCC/A-HA hydrogel was discussed, which may attribute to the combination of barrier function and bioactivity of NOCC and A-HA.     

A thermosensitive chitosan-based hydrogel barrier for post-operative adhesions' prevention

Post-operative peritoneal adhesions are common and serious complications for surgeons. They can cause pelvic pain, infertility, and potentially lethal bowel obstruction. We synthesized injectable hydrogels that formed by chemical modification through grafted hydrobutyl groups to chitosan chains. Gelation of hydroxybutyl chitosan (HBC) occurs in less than 60 s. Once formed, it can also be recovered completely. The residue time of hydrogels can extend to 4 weeks in Kunming mice. HBC hydrogels showed mild cytotoxicity to mice fibroblast cell (L929) and human vascular endothelial cell (ECV-304) in vitro and were biocompatible in the murine muscles, causing no adhesions for 4 weeks. HBC gels can form a durable barrier between defected cecum and abdominal wall. In a mice sidewall defect-bowel abrasion model, HBC gels showed significant efficacy in reducing adhesion formation.     

Experimental Observation on the Effects of Different Chitosan on Preventing Traumatic Peritoneal Adhesion in Rats

objective： The effects of different chitosan on preventing traumatic peritoneal adhesion in rats was studied in this paper. METHODS ： 96 SD rats with injured vermiform process were randomly divided into 4 groups as follows： group A without any treatment as control, group B treated with chitosan gel, group C treated with pure chitosan film and group D treated with chiston film containing 50% gelatin. 2 and 4 weeks after surgery, 12 rats in each group were respectively belly opened to observe chitosan degradation and evaluate peritoneal adhesion, and the adhesive vermiform processes tissues were histopathologically observed. RESULTS： 1. Degradation in the group D was faster than that in the group C but slower than that in the group B. 2. 2 weeks after surgery the adhesion in the group B was milder than that in the control group（goup A） （P〈0. 05）, but that in the group C and D （both P〈0. 05） were more severe than that in the control group. 3. 4 weeks after surgery , the adhesion in the group B was milder than that in the control group （P〈0. 05）, but that in the group C and D （both P〈0. 05） were more severe than that in the control group , whereas, there was no significant difference between adhesion in the group C and group D （P〉0. 05）. 4. Histopathological examinaiton indicated that： 2 weeks after surgery ,inflammatory cell infiltration and fibroplastic proliferation dominated in local lesion and the response was most severe on the serous coat, furthermore, the response in the control group was more severe than that in the group B, but milder than that in the group C and D; 4 weeks after surgery, fibroplastic proliferation dominated in local lesion in each group , moreover, the response in the control group was more severe than that in the group B but milder than that in the group C and D. What＇s more, integrated fibrous membrane formed around implanted materials in the group C and D, and the fibrous membranes were thinner in the group C than that in the group D. CONCLUSION： 1.Chitosan gel has perfect effect in protecting traumatic peritoneal adhesion in rats. 2. Pure chitosan film could exacerbate peritoneal adhesion and chitosan containing gelatin could exacerbate peritoneal adhesion further.     

Novel Powdered Anti-adhesion Material: Preventing Postoperative Intra-abdominal Adhesions in a Rat Model

Background: Although laparoscopic surgery has decreased postoperative adhesions, complications induced by adhesions are still of great concern. The aim of this study was to investigate the anti-adhesive effects of a novel powdered anti-adhesion material that can be applied during laparoscopic surgery in comparison with other anti-adhesion materials. Methods:Our novel powdered anti-adhesion material is composed of aldehyde dextran and ε-poly(L-lysine). In 40 male rats, a 2.5×2.0-cm abdominal wall resection and cecum abrasion were performed. The rats were randomized into four groups based on the anti-adhesion treatments: normal saline; Seprafilm^®; Interceed^®; and novel powdered anti-adhesion material. The animals were euthanized on days 7 and 28 to evaluate the adhesion severity, area of adhesion formation, gross appearance, and pathological changes. Results: The adhesion severities on both days 7 and 28 were significantly lower for all anti-adhesion material groups compared with the normal saline group (p<0.05). Pathologically, all groups showed inflammatory cell infiltration on day 7 and complete regeneration of the peritoneum on day 28. Conclusions:Our novel powdered anti-adhesion material was found to be effective for reducing postoperative intra-abdominal adhesions and showed equivalent efficacy to commercial anti-adhesion materials.     

Design of high-performance anti-adhesion agent using injectable gel with an anti-oxidative stress function

Postsurgical tissue adhesion formation caused by inflammation and oxidative stress is one of the serious issues because it induces severe clinical disorders. In this study, we designed redox injectable gel (RIG) which covalently possesses nitroxide radicals as a reactive oxygen species (ROS) scavenger for high performance anti-adhesion agent. The redox flower micelles exhibiting gelation under physiological conditions were prepared by a polyion complex (PIC) between polyamine-PEG-polyamine triblock copolymer possessing nitroxide radicals as a side chain of polyamine segments and poly(acrylic acid). RIG showed prolonged local retention in the abdominal cavity of the mice, which was monitored by in vivo imaging system (IVIS). Compared with a commercial anti-adhesion agent (Seprafilm^®, Genzyme, Cambridge, MA), RIG dramatically inhibited the formation of tissue adhesions via a combination of physical separation and biological elimination of generated ROS in talc-induced adhesion model mice. Treatment with RIG suppressed inflammatory cytokines and neutrophil invasion, suppressing the increase in peritoneal membrane thickness. It is also emphasized that RIG suppressed the increase of white blood cells level, indicating that the present RIG treatment effectively prevents diffusion of local inflammation to entire body. These findings indicate that RIG has a great potential as a high performance anti-adhesion agent.