温敏型可注射水凝胶的制备研究

为得到应用于软组织重建的新型可注射组织工程支架材料,将经交联合成的HA交联凝胶(XLHA),分别与降解性能不同的两种温敏型材料聚N-异丙基丙烯酰胺(PNIPAAm)凝胶和甲基纤维素(MC),在常温下共混合成XLHA-PNIPAAm与XLHA-MC可注射水凝胶,分析XLHA-PNIPAAm与XLHA-MC水凝胶的可注射性能、耐酶解性能、温敏性能和化学结构,并进行溶血试验与细胞毒性试验评价可注射凝胶的生物相容性。研究获得了XLHA-PNIPAAm的可注射水凝胶的制备条件,并证实了分别将不可降解材料PNIPAAm与可降解材料MC和HA共混均能有效延缓HA的降解,且PNIPAAm延缓HA降解的效果更为显著。辐照剂量为5 kGy,MBAAm/NIPAAm(M/M)=0.015,NIPAAm单体浓度为3%,制备的PNIPAAm与XLHA共混制备的XLHA-PNIPAAm可注射凝胶的耐酶解性能最佳。差示扫描量热仪(DSC)检测显示XLHA-PNIPAAm的温敏性较为稳定。两种复合凝胶的细胞毒性和溶血试验均合格,且XLHA-PNIPAAm水凝胶的生物相容性要好于XLHA-MC凝胶。     

注射用聚乳酸和交联透明质酸钠凝胶的制备及性能研究

本研究对交联透明质酸钠凝胶的交联工艺以及和自制的聚乳酸微球的不同配比进行研究,成功制备了注射用美容凝胶。对不同交联度和不同配比的溶胀度、流变学、渗透压、动力粘度、稳定性等性能指标进行研究,并对本产品的灭菌稳定性进行了考察。结果表明本产品灭菌后较稳定,均匀细腻,其弹性模量、动力粘度和溶胀度均较好,具有很好的临床应用前景。     

可注射水凝胶在心肌梗死治疗中的研究进展

急性心肌梗死后由于大量心肌细胞坏死、纤维瘢痕形成等原因造成心室重构和心功能下降,严重影响心梗患者的远期预后.天然材料或人工合成的水凝胶是一种新兴的生物替代材料,具有良好的亲水性和组织相容性,可模拟心肌细胞微环境的生化和机械特性,目前已广泛地应用于心肌梗死的治疗研究中.水凝胶可单独应用,也可作为细胞/药物运载工具和平台.研究表明:将水凝胶-干细胞-药物复合物进行心肌注射后,可以增加室壁厚度,促进新生血管形成,提高移植干细胞的存活率,并实现生物活性药物的控释,在一定程度上抑制梗死后心室重构,促进心功能的恢复.就目前可注射水凝胶在治疗心肌梗死方面的相关研究进展作一综述.     

透明质酸钠凝胶预防剖宫产后宫腔粘连的临床应用

背景：透明质酸钠具有预防盆、腹腔粘连的作用,但透明质酸钠宫腔停留时间短,难以达到预防宫腔粘连的作用。国外研究对透明质酸钠进行化学修饰形成自交联透明质酸钠凝胶,它对受损的宫内膜具有很强的黏附性,在宫腔内停留时间可达72 h。 目的：评价透明质酸钠凝胶在剖宫产后预防宫腔粘连的效果及安全性。 方法：由第一作者检索PubMed数据库(http://www.ncbi.nlm.nih.gov/PubMed)及维普数据库(http://www.cqvip.com/)有关透明质酸钠凝胶预防剖宫产后宫腔粘连的文献,检索时限为1990-01/2009-12,中文关键词为“透明质酸钠凝胶,剖宫产,粘连,宫腔粘连”,英文关键词为“sodium hyaluronate,cesarean section,adhesion,intrauterine adhesions”,排除重复研究或综述类文章。 结果与结论：共检索到相关文献150余篇,排除内容重复、综述类文章后筛选纳入16篇文献进行评价,其中中文12篇,英文4篇。结果显示,透明质酸钠凝胶是由N-乙酰葡萄糖醛酸反复交替而形成的一种高分子多糖体生物材料,具有高度的黏弹性、可塑性以及良好的生物相容性,在剖宫产后预防宫腔粘连效果明显,特别是能有效减少分离后再粘连的发生。但有一点十分重要,透明质酸钠凝胶是绝对不能用于血管内的,以免引起肺栓塞并发症。注射过程应缓慢,以免回流入静脉系统。     

医用透明质酸钠凝胶生物相容性的比较分析

医用透明质酸钠凝胶被广泛用于眼科手术、骨科疾患治疗及美容等领域。2009年国内生产企业12家共33个产品,进口产品23个。由于生产厂商采用的生产工艺不同,产品性能存在较大差异。本文分别对4种透明质酸钠凝胶产品进行了全面的生物学评价实验。结果显示:除非交联凝胶A出现染色体畸变阳性、交联凝胶C出现亚慢性毒性外,其余试样各实验结果均为阴性。本文为正处于制定过程中的交联透明质酸钠凝胶行业标准以及YY0308-2004的修订提供了参考依据。     

可注射封闭性水凝胶力学性质与其止血性能的相关性

目的探究封闭性水凝胶力学性质与其止血性能之间的关系。方法通过测量透明质酸/明胶水凝胶凝固时间、弹性模量、黏性模量、顶破强度和止血性能,与医用纤维蛋白胶止血剂对比,提出凝固时间和力学参数,用于判断封闭性水凝胶应用于临床止血的可行性。结果凝固时间长以及弹性模量、黏性模量和顶破强度小的水凝胶只可能对小出血量起控制作用,凝固时间短、弹性模量、黏性模量和顶破强度大的水凝胶能有效减少大出血量情况下的血液损失。结论水凝胶的凝固时间、弹性模量、黏性模量以及顶破强度与其止血性能有关,如果水凝胶封闭止血要达到纤维蛋白胶的止血水平,其凝固时间应小于120 s,弹性模量大于600 Pa,黏性模量大于120 Pa;对于直径2 mm的组织模型破损,顶破强度要不低于10.7 kPa,最好高于16.0 kPa。     

透明质酸钠治疗骨性关节炎的临床与实验研究

目的 探讨透明质酸钠关节腔注射对骨性关节炎的临床疗效、安全耐受性及对血清与滑膜液中ＩＬ－１、ＩＬ＿６水平的影响。方法 取３４例有膝关节腔积液的一关节炎患者随机分成两组,分别给予关节腔注身南酸钠与非甾体药治疗,观察治疗前后关节休息痛、活动痛、压痛、肿胀与功能改善程度,并分析其安全耐受性;同时测定前后血清与 膜液中ＩＬ－１、ＩＬ－６水平变化。结果 治疗组关节各种症状均有改善,尤以活动痛与肿胀改善显著,     

关节腔内注射透明质酸钠治疗膝关节骨性关节炎

用积分法观察透明质酸钠膝关节腔内注射治疗骨性关节炎的疗效     

关节腔内注射透明质酸钠治疗膝关节骨性关节炎

用积分法观察透明质酸钠膝关节腔内注射治疗骨性关节炎的疗效.     

Cytodext-3微载体/藻酸钠水凝胶作为可注射性支架构建组织工程软骨的可行性

BACKGROUND: Alginate hydrogel and microcarrier both can be used as injectable scaffolds, but their shortcomings such as poor mechanical property and poor plasticity remain unresolved. OBJIECTIVE: To explore the feasibility of constructing an injectable tissue-engineered cartilage with cytodex-3 microcarrier/alginate hydrogel composite. METHODS: Injectable cytodex-3 microcarrier/alginate hydrogel composite scaffold and injectable alginate hydrogel scaffold were established, and the mechanical properties of the two scaffolds were detected. Chondrocytes-seeded cytodex-3 microcarrier was obtained after incubated in the bioreactor, and then composited with alginate hydrogel as experimental group; chondrocytes were co-cultured with alginate hydrogel as control group. Subsequently, cell viability and ability of DNA and glycosaminoglycan synthesis were detected. RESULTS AND CONCLUSION: The Young’s modulus of the experimental group was significantly higher than that of the control group (P < 0.05). And in the control group, chondrocytes were in a round shape and evenly distributed in the alginate hydrogel; in the experimental group, chondrocytes adhered on the scaffold surface and evenly distributed in the scaffold. After 1 day of culture, both viable and numerous dead chondrocytes could be found in both two scaffolds; and after 14-day culture, there were no dead chondrocytes in both two scaffolds, abundant proliferating chondrocytes maintained a high cell viability, and the number of chondrocytes in the experimental group was significantly higer than that of the control group. What’s more, the contents of DNA and glycosaminoglycans were in a rise with time in both two groups, which were significantly higher in the experimental group than the control group (P < 0.05). These results suggest that the cytodex-3 microcarrier/alginate hydrogel composite is a promising injectable scaffold in cartilage tissue engineering.     

原子荧光光谱法测定注射用透明质酸钠凝胶中砷和汞

目的建立利用原子荧光光谱法检测注射用透明质酸钠凝胶中砷和汞含量的方法。方法首先采用微波消解仪使样品完全消解,将样品消解液定容后,利用原子荧光光谱仪分析样品检验液中砷和汞的含量。通过标准曲线、检出限、精密度和加标回收率证明该方法的有效性。结果此方法中砷和汞的浓度分别在1~50 ng/m L和0.1~10 ng/m L范围内与荧光强度成良好的线性关系,相关系数分别是0.9999%和0.9997%。砷和汞的检出限分别是0.0105 ng/m L和0.0032 ng/m L,精密度RSD均5%,平均加标回收率分别是95.2%和100.2%。此面部注射用透明质酸钠凝胶样品中砷含量低于检出限(0.49 ng/g),汞含量为7.22 ng/g。结论用于测定注射用透明质酸钠凝胶中砷和汞含量的微波消解-原子荧光光谱法具有良好的线性范围、高灵敏度和准确度、重复性好等优点。     

Injectable in situ dual-crosslinking hyaluronic acid and sodium alginate based hydrogels for drug release

A series of injectable in situ dual-crosslinking hydrogels (HA/ALG) based on oxidized sodium alginate (oxi-ALG) and hyaluronic acid modified with thiol and hydrazide (HA-SH/CDH) were prepared via hydrazone bonds and disulfide bonds. The chemical structures, morphologies, rheological properties, gelling time, swelling ratio, degradation rate and drug release behavior of hydrogels were investigated. HA/ALG hydrogels exhibited tunable gelling time, rheological properties, swelling ratio and degradation rate with varying precursor concentrations. The gelling time of HA/ALG hydrogels ranged from 157?s to 955?s, the values of yield stress of HA2/ALG2, HA3/ALG3 and HA4/ALG4 hydrogels were 1724, 4349 and 5306?Pa, and the degradation percentage of HA2/ALG2, HA3/ALG3 and HA4/ALG4 hydrogels were about 64%, 51% and 42% after incubating 35?days, respectively. Bovine serum albumin (BSA) was used as a model drug to investigate the drug controlled release properties, and the in vitro cumulative release percentage of BSA from HA2/ALG2, HA3/ALG3 and HA4/ALG4 drug-loaded hydrogels were about 79%, 72% and 69% after 20?days. The series of injectable in situ dual-crosslinking HA/ALG hydrogels could be an attractive candidate for drug delivery system, tissue engineering and regenerative medicine.     

Injectable and biodegradable sugar beet pectin/gelatin hydrogels for biomedical applications

Abstract

Injectable hydrogels have advantages over pre-formed hydrogels in biomedical applications. In our previous study, we showed usefulness of sugar beet pectin (SBP) as an injectable gel material. However, the in vivo biodegradability of the gels was low because animals lack suitable hydrolytic enzymes of SBP. In this study we developed SBP-based injectable gels with higher in vivo biodegradability than the previous SBP gels by incorporating biodegradable gelatin into the latter. An aqueous solution with dissolved SBP and gelatin rapidly (< 1 min) formed gels through a horseradish peroxidase-catalyzed oxidative coupling reaction between feruloyl moieties on the SBP molecules and phenolic moieties on the gelatin molecules. Gelation time and mechanical properties of the gels were tunable by adjusting the polymer concentrations. The gels containing doxorubicin, an anti-cancer drug, successfully suppressed the growth of a solid tumor created by subcutaneous injection of mouse melanoma B16F1 cells into nude mice. These results indicate that injectable and biodegradable SBP/gelatin gels are useful in biomedical applications.     

Preparation of gelatin hydrogel sponges incorporating bioactive glasses capable for the controlled release of fibroblast growth factor-2

Gelatin hydrogel sponges incorporating bioactive glasses (Gel-BG) were fabricated. We evaluated the characteristics of Gel-BG as scaffolds from the perspective of their mechanical properties and the formation of hydroxyapatite by the incorporation of bioactive glasses (BG). In addition, the Gel-BG degradation and the profile of fibroblast growth factor-2 (FGF-2) release from the Gel-BG were examined. Every Gel-BG showed an interconnected pore structure with the pore size range of 180–200?µm. The compression modulus of sponges incorporating BG increased. The time profiles of degradation for the 72-h crosslinked gelatin hydrogel sponges incorporating 10?wt% BG (Gel-BG(10)) and 50?wt% BG (Gel-BG(50)) were analogous to that of the 24-h crosslinked gelatin hydrogel sponge without BG (Gel-BG(0)). In measuring the release of FGF-2 from Gel-BG, the Gel-BG(10) and Gel-BG(50) showed almost analogous 100% cumulative release within 28?days in vivo. Additionally, a bioactivity evaluation showed that the presence of gelatin does not affect the in vitro bioactivity of Gel-BG. These sponges showed mechanical and chemical functionality as scaffolds, featuring both the controlled release of FGF-2 and the induction of hydroxyapatite crystallization.     

Biodegradable thermosensitive injectable PEG-PCL-PEG hydrogel for bFGF antigen delivery to improve humoral immunity

In this contribution, a biodegradable and injectable thermosensitive poly(ethylene glycol)-poly(ε-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) hydrogel system was successfully prepared for basic fibroblastic growth factor (bFGF) antigen delivery. bFGF encapsulated PECE hydrogel system (bFGF-hydrogel) is an injectable free-flowing sol at ambient temperature, and forms a non-flowing gel at physiological temperature acting as antigen depot. Furthermore, the cytotoxicity results showed that the PECE hydrogel could be regarded as a safe carrier, and bFGF could be released from the hydrogel system in an extended period in vitro. Otherwise, the immunogenicity of bFGF was improved significantly after encapsulated into the hydrogel. Strong humoral immunity created by bFGF-hydrogel was maintained for more than 14 weeks. Therefore, the prepared bFGF loaded PECE hydrogel might have great potential as a novel vaccine adjuvant for protein antigen.     

罗哌卡因和玻璃酸钠在膝关节镜术后镇痛的临床应用

目的：探讨罗哌卡因和玻璃酸钠在膝关节镜治疗半月板损伤术后镇痛的临床效果。方法：将2014年10月至2015年4月在南京军区南京总院骨科关节外科收治的40例半月板损伤患者随机分为2组,每组20人,A组：关节腔内注射罗哌卡因和玻璃酸钠;B组：静脉镇泵给药镇痛和关节腔内注射玻璃酸钠。比较两组疼痛视觉模拟评分(visual analogue scale,VAS)、满意度、辅助口服镇痛药物塞来昔布使用量及不良事件发生率、住院时间。结果：手术后24 h内,在VAS评分、病人满意度、辅助口服止痛药物使用量、不良事件发生率及出院时间方面,A组具有明显优势(P<0.05)。结论：罗哌卡因和玻璃酸钠关节腔内注射可以作为膝关节镜术后镇痛的新选择。     

光疗法联合透明质酸钠治疗膝骨关节炎疗效及安全性的Meta分析

文题释义： 光疗法：是指利用自然光或人工光线用以防治疾病、促进机体功能恢复的一种理疗方法。光疗法最主要的作用是热效应,即通过光照射使局部组织温度升高,扩张周围血管,加速血液循环,抑制神经兴奋性,放松肌肉,其能纠正病变部位微循环障碍,利于炎症的消退,是一种安全且有效的治疗方法。 膝骨关节炎：是一种发病率较高的以关节软骨丧失为主要特征的进行性、关节退化性疾病,临床表现包括膝关节疼痛及功能受损,晚期可致残,严重影响患者身心健康。目前尚没有有效的治疗方法来逆转关节内进行性损害过程,现阶段主要围绕着疼痛减轻和功能改善两大治疗目标。 背景：目前已有大量研究证实光疗法联合透明质酸钠对膝骨关节炎疗效显著,且安全性较高,但仍缺乏循证依据。 目的：对光疗法联合透明质酸钠治疗膝骨关节炎进行Meta分析。 方法：使用计算机对英文数据库(PubMed,OVID,EMBASE)及中文数据库(中国知网、万方、维普、中国生物医学文献数据库)进行检索,查找各数据库建库至2019-07-01发表的光疗法联合透明质酸钠治疗膝骨关节炎的随机对照中英文文献。评价纳入研究的质量并提取文献中相关临床数据,采用专业软件(RevMan 5.3)对结果行Meta分析。 结果与结论：共纳入16篇文献,1 505例患者。实验组采用光疗法联合透明质酸钠治疗,对照组采用透明质酸钠治疗。Meta分析结果显示：实验组临床总有效率优于对照组(OR=4.20,95% CI(2.75,6.39),P < 0.000 01);实验组痊愈率高于对照组[OR=2.62,95%CI(1.78,3.86),P < 0.000 01];实验组治疗膝骨关节炎较对照组目测类比评分降低更为明显[MD=-1.51,95%CI(-2.15,-0.87),P < 0.000 01];实验组治疗膝骨关节炎较对照组Lysholm评分改善更为明显[MD=13.30,95%CI(6.82,19.78),P < 0.000 01];实验组在不良反应发生率方面与对照组无明显差别[OR=0.64,95%CI(0.25,1.63),P=0.35]。结果显示,光疗法联合透明质酸钠治疗膝骨关节炎较单一关节腔注射透明质酸钠具有更大优势,疗效显著,安全性亦较高,但仍需进行更多研究质量高、样本数量大的随机对照研究加以验证。 ORCID: 0000-0003-4306-287X(邓薇) 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

PEG-g-chitosan thermosensitive hydrogel for implant drug delivery: cytotoxicity,in vivo degradation and drug release

Thermosensitive hydrogels based on chitosan are of great interests for injectable implant drug delivery. The poly(ethylene glycol)-grafted-chitosan (PEG-g-CS) hydrogel was reported as a potential thermosensitive system. The objective of the present study is to evaluate the cytotoxicity, in vivo degradation and drug release of PEG-g-CS hydrogel. Cytotoxicity was evaluated using L929 murine fibrosarcoma cell line. Degradation and drug release in vivo were investigated by subcutaneous injection of the hydrogel into Sprague-Dawley rats. PEG-g-CS polymer exhibits no significant cytotoxicity when its concentration is less than 3 mg mL^?1. After being implanted, PEG-g-CS hydrogel maintains its integrity for two weeks and collapses, merging into the tissue, in the third week. It causes moderate inflammatory response but no fibrous encapsulation around the hydrogel is found. The hydrogel presents a three-week sustained release of cyclosporine A with no significant burst release in vitro and produces the effective drug concentration in blood for more than five weeks in vivo, performing almost the same bioavailability to chitosan/glycerophosphate hydrogel. Further modifications of PEG-g-CS hydrogel might be necessary to modulate the degradation and to mitigate the fluctuations in blood drug concentration.     

不同交联密度甲基丙烯酰酯明胶/脱细胞半月板细胞外基质复合水凝胶的性能

文题释义：脱细胞半月板细胞外基质：由新鲜半月板组织通过湿法差速离心方法脱细胞制备而来,在去除了异体半月板的免疫原性的同时,仍保留了组织的大部分成分和组织本身的生物学性能,例如影响细胞的活性、调控细胞的增殖和分化、促进组织再生和修复等。 甲基丙烯酰酯明胶：是一种明胶的衍生物,由甲基丙烯酸酐与明胶合成而来。在加入光引发剂的基础上经紫外线照射,明胶链上的甲基丙烯酰胺和甲基丙烯酸甲酯侧基聚合形成聚合物链,聚合物链交错纵横,最终形成网状结构。 交联密度：通常用来表征交联聚合物里交联键的数量,主要受交联时间和交联光强度的影响,其可明显改变聚合物链的形成情况。 背景：交联后的聚合物链对水凝胶的基本性质和细胞相容性存在显著影响,而交联密度可明显改变聚合物链的形成情况,有关交联密度对水凝胶性能影响的针对性研究较少。 目的：制备一种细胞相容良好性的复合水凝胶,探究交联密度对该水凝胶性能的影响。 方法：配制甲基丙烯酰酯明胶溶液,然后加入脱细胞半月板细胞外基质溶液与LAP溶液,制备预凝胶溶液,采用蓝光对溶液进行交联,交联时间分别为10,30,60 s,检测3种水凝胶的压缩弹性模量、溶胀倍率与降解性能。将半月板纤维软骨细胞加入预凝胶溶液中,采用蓝光对溶液进行交联,交联时间分别为10,30,60 s,检测培养对应时间的细胞活性、形态与聚集。 结果与结论：①交联60 s水凝胶的压缩模明显高于交联10,30 s的水凝胶(P < 0.05);②交联10 s水凝胶的溶胀倍率明显高于交联30,60 s的水凝胶(P < 0.05),交联30,60 s的水凝胶的溶胀倍率比较差异无显著性意义(P > 0.05);③随着交联时间的延长,水凝胶的降解时间延长,交联60 s的水凝胶需要80 min完全降解,交联10 s的水凝胶50 min就可以完全降解;④培养24 h后,3组水凝胶中的细胞活性均在95%以上,各组之间无差异(P > 0.05);⑤培养1 d时,3组水凝胶中的细胞均呈球形且均匀分布;4 d时,3组细胞均开始伸展,交联10 s水凝胶中有较小的细胞团;7 d时,3组细胞树突状伸展更为明显,其中交联10 s水凝胶中形成了较为明显的细胞团;⑥培养1,7,14 d时,交联10 s水凝胶中的细胞活性均在85%以上。培养1 d时,交联10 s水凝胶中的细胞呈球形分布,且分布均匀;培养28 d时,细胞呈树突状伸展,并聚集形成网状结构;⑦结果表明,甲基丙烯酰酯明胶/脱细胞半月板细胞外基质复合水凝胶的性能可通过调整交联密度进行优化。 ORCID: 0000-0002-3606-1097(周建) 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