环氧化合物交联明胶水凝胶的制备及表征

目的明胶水凝胶因其良好的生物相容性而成为一种应用前景很好的组织工程材料。该研究采用不同浓度的明胶,添加了适量的环氧化合物交联剂聚乙二醇二缩水甘油醚(PGDE),制备了不同的明胶水凝胶。红外光谱显示,PGDE以两端开环的方式交联到了明胶分子上。随着明胶和交联剂浓度的增大,水凝胶的溶胀率从1218.19%下降到525.23%,最大压缩应力显著增大,从27.64 kPa增大到113.20 kPa,压缩正切模量也从0.19 kPa增大到0.59 kPa,力学性能得到了明显提高。PGDE交联明胶水凝胶具有优异的弹性回复性能,弹性回复率最高可达98.03%。溶血率试验结果表明,凝胶有良好的血液相容性。     

可注射型纤维蛋白凝胶转化生长因子β1复合骨髓间充质干细胞移植治疗椎间盘退变

背景：纤维蛋白凝胶主体胶与催化剂未混合前为液态,具有可注射的优点,注射混合后凝固成凝胶状,与髓核相似,并且凝固时间可控性强,作为间充质干细胞的载体植入到椎间盘内有诸多优点。 目的：观察可注射型纤维蛋白凝胶转化生长因子β1复合骨髓间充质干细胞移植抑制椎间盘退变的可行性。 方法：将新西兰大白兔随机分为退变模型组、纤维蛋白凝胶组,骨髓干细胞+纤维蛋白凝胶组。3组采用针刺法诱导建立退变模型后,纤维蛋白凝胶组及干细胞+纤维蛋白凝胶组分别移植入纤维蛋白凝胶转化生长因子β1复合物及骨髓间充质干细胞纤维蛋白凝胶转化生长因子β1复合物,于植入后2,6,10周行CR、MRI及病理检查。 结果与结论：退变模型组与纤维蛋白凝胶组椎间隙高度下降明显,并与时间呈正相关,干细胞+纤维蛋白凝胶组下降较缓慢(P < 0.01)。免疫组织化学及组织学检查显示,退变模型组髓核细胞的数量及Ⅱ型胶原含量进行性减少,细胞凋亡率明显增加,纤维蛋白凝胶组与退变模型组相似,干细胞+纤维蛋白凝胶组髓核细胞数量及Ⅱ型胶原含量较退变模型组及纤维蛋白凝胶组明显增多,细胞凋亡率下降。说明骨髓间充质干细胞联合纤维蛋白凝胶转化生长因子β1能很好抑制椎间盘退变,而单纯纤维蛋白凝胶转化生长因子β1移植不能抑制椎间盘退变。     

聚乙烯醇/羟基磷灰石复合水凝胶软骨植入材料的研究

研究了用于人工关节软骨假体的聚乙烯醇水凝胶和羟基磷灰石复合材料的结构与性能，系统讨论了含水量、羟基磷灰石含量等对其拉伸强度，压缩强度，黏弹性、润滑性等生物力学性能的影响，观察和比较了复合材料的徽观形貌。研究表明羟基磷灰石在聚乙烯醇水凝胶中分散均匀，良好相容，使复合材料的力学强度和润滑性能提高。     

纤维蛋白胶存在的问题与相应的解决方法

分析了纤维蛋白胶存在的问题,如蛋白胶不同供体来源、成份来源、应用的简易性与有效性、止血功效局限、机械强度与纤溶抑制剂的选择等,并提出相应的解决方案.     

门静脉高压症猪肝动脉的生物力学特性

目的：建立猪门静脉高压症模型,探讨门静脉高压症对肝动脉的生物力学特性的影响。方法：猪以四氯化碳、苯巴比妥、乙醇,配合高脂、低蛋白、低胆碱饮食进行混合饲养。通过脾静脉插管测压,取肝动脉在生物软组织力学试验机上测定其压力-直径关系,计算机图像分析测量肝动脉两端血管环的张开角及其几何形态学指标。结果：实验组门静脉压(4．17±1．03)kPa明显大于对照组(1．51±0．79)kPa,肝动脉的各向同性增量弹性模量、血管容积弹性模量和血管压力-应变模量均随压力的上升而增大,在相同压力下明显大于对照组。肝动脉的顺应性显著低于对照组,而张开角显著增加。结论：门静脉高压症时,肝动脉的生物力学特性发生了显著变化。     

沉淀法原位复合聚乙烯醇(PVA)/羟基磷灰石(HA)水凝胶的结构与性能研究

研究了制备聚乙烯醇(PVA)，羟基磷灰石(HA)复合水凝胶的沉淀法原位复合技术，对该法制备的复合水凝胶的力学强度、结晶性能和微观形貌进行了分析，并与物理共混法加以比较。结果表明，沉淀法原位复合技术可在PVA水凝胶基体中合成得到粒度细，分散好的晶相HA陶瓷微粒，复合后水凝胶的结晶度和拉伸强度比之基体试样均有大幅度提高。     

纤维蛋白胶在骨科中的应用

背景：纤维蛋白胶是一种生物蛋白制剂,由纤维蛋白原、凝血酶及其他生物活性因子组成,具有止血、趋化及促细胞有丝分裂等特性,有着良好的生物相容性。 目的：对纤维蛋白胶在骨科的应用进行综述。 方法：以“fibrin  glue, biomaterial,application” 为英文检索词,以“纤维蛋白胶,骨科,应用” 为中文检索词,检索PubMed、BP、SD、万方及维普等数据库1995-01/2011-05相关文献,选取纤维蛋白胶在骨科中的应用有关文献30篇进行总结。 结果与结论：纤维蛋白胶是一种具有多向生物活性的生物蛋白,能迅速形成立体网状结构,起到良好的止血作用。在注射部位局部形成凝胶圈,起封闭与粘合作用。具有预防脊柱手术后硬脊膜外腔粘连,抑制局部炎症扩散,减轻水肿压迫,促进术后切口愈合的作用。能充当生物基质,应用于骨或软骨组织工程。关键词：纤维蛋白胶;骨科;应用;生物相容性;综述文献 缩略语注释：BMP：bonemorphogeneticprotein,骨形态发生蛋白 doi:10.3969/j.issn.1673-8225.2012.16.036     

疝补片的微观结构和力学性能研究

目的分析不同品牌疝补片的微观结构及拉伸、顶破强度进而评估不同疝补片的力学性能。方法分别使用天平、显微镜对常见的15种疝补片进行质量和微观结构测试,并分别使用拉伸试验机与顶破试验机来检测疝补片的拉伸性能与顶破性能,并对疝补片进行力学性能分析。结果疝补片的编织结构为菱形、多边形和圆形。腹股沟补片的平均质量为0.08 mg/mm2,腹壁疝补片的平均质量为0.18 mg/mm2。G3~G6疝补片的丝径较大,G12的网孔率较低。在拉伸性能测试中,G15的拉伸强度最大,重量型补片中G12、G14的拉伸强度较小,轻量型补片中G1、G2、G7的拉伸强度较小。在顶破性能测试中,G3、G9、G15疝补片的顶破强度最大,重量型补片中G12、G13、G14的顶破强度较小,轻量型补片中G1、G2、G4的顶破强度较小。结论多边形网孔且大网孔率的疝补片具有更好的力学性能,为优化疝补片提供了实验依据,有望为相关的研究和应用提供更好的支持。     

可吸收止血材料的研究现状及临床应用

简要综述了近年国内外主要的可吸收止血材料包括可吸收纤维蛋白胶、氧化纤维素、氧化再生纤维素、壳聚糖、α-氰基丙烯酸酯类组织胶、可吸收性明胶海绵和明胶纤维网、微纤维胶原和胶原纤维网、海藻酸钙纤维的组成、止血机理、止血性能、研究现状及临床应用,展望了可吸收止血材料未来的发展趋势.对医生了解医用可吸收止血材料的止血特性、掌握正确的使用方法、充分发挥其止血效果,提供了一定的参考价值,同时,对医用材料工作者进一步研究止血材料提供了参考.     

含中药三七的壳聚糖/明胶水凝胶复合止血材料的制备和性能评价

目的制备负载中药三七的壳聚糖/明胶水凝胶复合止血材料(PN/CMC/GMs),并对其性能进行评价。方法利用冷冻干燥法制备PN/CMC/GMs,利用扫描电镜观察其形态,流变仪观察其流变学性能,溶胀测试其吸水膨胀率,细胞毒性实验检测其生物相容性,并利用SD大鼠肝脏出血模型检测其快速止血效果。结果制备了PN/CMC/GMs,呈网格状结构,具有一定的孔隙率。随着三七粉含量的增加,PN/CMC/GMs的模量也相应的增加,机械强度增加。PN/CMC/GMs具有较好的吸水膨胀功能,可形成压迫止血和浓缩血液实现快速止血,且具有良好的生物相容性。止血实验表明,PN/CMC/GMs对大鼠肝脏损伤的止血时间和止血效果均优于空白对照组。结论PN/CMC/GMs具有良好的止血效果和生物相容性,具有进一步研究的价值和临床应用前景。     

Evaluation of a novel hemostatic device in an ovine parenchymal organ bleeding model of normal and impaired hemostasis.

Bleeding is a problem encountered by many surgeons, often complicated by the presence of coagulopathy or anticoagulant. The hemostatic effectiveness of CoStasis Surgical Hemostat (with bovine collagen, bovine thrombin, and autologous plasma) was evaluated and compared to a collagen sponge and to two investigational fibrin-sealant preparations under conditions of normal and impaired coagulation. A liver resection and controlled incisions in spleens and kidneys were made in sheep. Time to complete hemostasis and total blood loss were measured. Tissue response was evaluated at 7, 30, 60, and 75 days. CoStasis-treated sites demonstrated significantly shorter time to hemostasis (all surgical sites combined) compared with fibrin sealant (investigational fibrin sealant 1) (p= .005) or collagen sponge (p=0.013). In anticoagulated animals, CoStasis and fibrin sealant (investigational fibrin sealant 2) had comparable mean times to hemostasis, and CoStasis-treated sites exhibited lowered average blood loss compared to investigational fibrin-sealant-2 treated sites. CoStasis-treated sites demonstrated higher levels of tissue repair (lower inflammation, more extensive tissue repair, and less residual implant) compared to fibrin-sealant- or collagen-sponge-treated sites in Phases I and II. These findings demonstrate that CoStasis is a highly effective hemostatic agent for control of bleeding from parenchymal organs. Furthermore, under conditions of compromised coagulation, treatment with CoStasis demonstrates a reduction in average blood loss when compared to treatment with fibrin sealant.     

Rapidly curable chitosan-PEG hydrogels as tissue adhesives for hemostasis and wound healing

Chitosan–poly(ethylene glycol)–tyramine (CPT) hydrogels were rapidly formed in situ using horseradish peroxidase and hydrogen peroxide to explore their performance as efficient tissue adhesives. A poly(ethylene glycol) modified with tyramine was grafted onto a chitosan backbone to enhance the solubility of the chitosan and to crosslink into three-dimensional networks. The elastic modulus of the hydrogels could be controlled by changing the crosslinking conditions, and the mechanical strength influenced the tissue adhesiveness of the hydrogels. The hydrogels showed the adhesiveness ranging from 3- to 20-fold that of fibrin glue (Greenplast®). The hemostatic ability of the hydrogels was evaluated on the basis that bleeding from liver defects was significantly arrested by the combined effect of the adhesiveness of the hydrogels and the hemostatic property of the chitosan materials. The enzymatic crosslinking method enabled the water-soluble chitosan to rapidly form hydrogels within 5 s of an incision into the skin of rats. Histological results demonstrated that the CPT hydrogels showed superior healing effects in the skin incision when compared to suture, fibrin glue and cyanoacrylate. By 2 weeks post-implantation, the wound was completely recovered, with a newly formed dermis, due to the presence of the CPT hydrogels in the incision. These results suggest that the in situ curable chitosan hydrogels are very interesting and promising tissue adhesive devices for biomedical applications.     

Tetronic®-based composite hydrogel scaffolds seeded with rat bladder smooth muscle cells for urinary bladder tissue engineering applications

Natural hydrogels such as collagen offer desirable properties for tissue engineering, including cell adhesion sites, but their low mechanical strength is not suitable for bladder tissue regeneration. In contrast, synthetic hydrogels such as poly (ethylene glycol) allow tuning of mechanical properties, but do not elicit protein adsorption or cell adhesion. For this reason, we explored the use of composite hydrogel blends composed of Tetronic (BASF) 1107-acrylate (T1107A) in combination with extracellular matrix moieties collagen and hyaluronic acid seeded with bladder smooth muscle cells (BSMC). This composite hydrogel supported BSMC growth and distribution throughout the construct. When compared to the control (acellular) hydrogels, mechanical properties (peak stress, peak strain, and elastic modulus) of the cellular hydrogels were significantly greater. When compared to the 7-day time point after BSMC seeding, results of mechanical testing at the 14-day time point indicated a significant increase in both ultimate tensile stress (4.1–11.6 kPa) and elastic modulus (11.8–42.7 kPa) in cellular hydrogels. The time-dependent improvement in stiffness and strength of the cellular constructs can be attributed to the continuous collagen deposition and reconstruction by BSMC seeded in the matrix. The composite hydrogel provided a biocompatible scaffold for BSMC to thrive and strengthen the matrix; further, this trend could lead to strengthening the construct to match the mechanical properties of the bladder.     

Efficacy of a novel hemostatic agent in animal models of impaired hemostasis

This study evaluated the efficacy of a novel sprayable hemostat under both normal conditions and those of compromised coagulation. CoStasistrade mark Surgical Hemostat ("CoStasis"), containing collagen, thrombin, and autologous plasma, was compared to Instattrade mark collagen sponge, an investigational fibrin sealant, and a no treatment control, for the ability to control bleeding in a rabbit kidney model. Hemostatic performance was determined by time to hemostasis and blood loss in a nonsurvival, randomized, in vivo bleeding rabbit kidney model. Under conditions of normal coagulation, as well as aspirin and heparin treatment, hemostasis was achieved faster with CoStasistrade mark than with Instattrade mark and fibrin sealant. With the exception of the time to hemostasis using Instattrade mark sponge in heparinized rabbits, all differences were statistically significant (p < 0.03, Wilcoxon). Blood loss, where measured, was lower with CoStasistrade mark than with the other hemostats under the three coagulation conditions. Statistical significance, (p < 0.03, Wilcoxon), was achieved with all comparisons except with fibrin sealant in aspirin treated animals. The combination of collagen, thrombin, and autologous plasma used in CoStasis, can achieve significantly faster hemostasis than the conventional atraumatic hemostats, collagen sponge, and fibrin sealant under normal conditions and conditions of impaired hemostasis.     

Reproducibility of the mechanical properties of Vivostat system patient-derived fibrin sealant

Conventional "autologous" fibrin sealants, prepared from fibrinogen concentrates are inconsistent in their physical properties; this reflects the wide variation in the fibrinogen level of the single donor plasma from which they are made. In contrast, the Vivostat System produces a fibrin sealant of reproducible concentration and mechanical properties that are independent of the source plasma fibrinogen concentration. Fibrin solution concentrations prepared with the Vivostat System were 22.0 +/- 0.7 mg/ml (95% CI) with a coefficient of variation [CV] of 10.6% from samples of source plasma with a range of fibrinogen concentration between I and 6 mg/ml (mean 3.28 +/- 0.38 mg/ml (95% CI), 37% CV). Values of viscoelastic and tensile parameters after 11 min and 1 h, respectively, were: storage modulus (G') 891.5 +/- 72.9 Pa, 16.2% CV; loss modulus (G") 98.7 +/- 9.8 Pa, 23.2% CV; loss tangent (tan delta) 0.1093 +/- 0.0054, 9.8% CV; tensile strength 33.2 +/- 2.6kPa, 24.7% CV; extension at break 103 +/- 13%, 22.6% CV; Young's modulus 12.0 +/- 1.0 kPa, 16.6% CV. In the clinical setting this reproducibility provides the surgeon with a patient-derived fibrin sealant that can be expected to perform similarly from patient to patient.     

A fibrinogen-based precision microporous scaffold for tissue engineering

Fibrin has been long used as an effective scaffolding material to grow a variety of cells and tissue constructs. It has been utilized mainly as a hydrogel in varying concentrations to provide an environment in which suspended cells work to rearrange the fibers and lay down their own extracellular matrix. For these fibrin hydrogels to be useful in many tissue-engineering applications, the gels must be cultured for long periods of time in order to increase their mechanical strength to the levels of native tissues. High concentrations of fibrinogen increase the mechanical strength of fibrin hydrogels, but at the same time reduce the ability of cells within the scaffold to spread and survive. We present a method to create a microporous, nanofibriliar fibrin scaffold that has controllable pore size, porosity, and microstructure for applications in tissue engineering. Fibrin has numerous advantages as a scaffolding material as it is normally used by the body as temporary scaffolding for tissue regeneration and healing, and can be autologously sourced. We present here a scaffolding process which enhances the mechanical properties of the fibrin hydrogel by forming it surrounding poly(methyl-methacrylate) beads, then removing the beads with acetone to form an interconnected microporous network. The acetone serves the dual purpose of precipitating and fixing the fibrinogen-based scaffolds as well as adding strength to the network during polymer bead removal. Effects of fibrinogen concentration and time in acetone were examined as well as polymerization with thrombin. A natural crosslinker, genipin, was also used to add strength to the scaffolds, producing a Young's modulus of up to 184+/-5 kPa after 36 h of reaction. Using these methods we were able to produce microporous fibrin scaffolds that support cell growth and have mechanical properties similar to many native tissues.     

An injectable robust denatured albumin hydrogel formed via double equilibrium reactions

Proteins are ideal raw materials for preparing biomaterials with better biocompatibility and larger elastic range than synthetic polymers. Injectable hydrogels are highly desired for minimal invasive strategies. At present, preparation of injectable hydrogels with good comprehensive properties using natural materials receives more and more attention. In this article, BSA was treated with urea and glutathione to prepare bovine serum albumin hydrogel controlled by two dynamic equilibrium bonds (disulfide and hydrogen bonds). The hydrogen bond equilibrium between urea-protein and protein-protein as well as the exchange reaction equilibrium between thiol-disulfide bonds in the system not only facilitated to enhance the mechanical properties, but also to reduce the gelation time to 5?min. Moreover, this novel albumin hydrogel was proved to be of good biocompatibility. Therefore, the albumin hydrogels in this article were injectable within the physiological range and shown low cytotoxicity, good machanical property ( storage modulus could be greater than 10?kPa and compressive stress could reach 0.2?MPa) and good injectability, which exhibited promising prospect.     

Thiol-ene crosslinking polyamidoamine dendrimer-hyaluronic acid hydrogel system for biomedical applications

A series of alkene functionalized polyamidoamine (PAMAM) dendrimers were synthesized to prepare in situ forming hydrogels with varied gelation time and mechanical properties through crosslinking with thiolated hyaluronic acid (HS-HA). By varying the alkenyl groups on the dendrimers, the gelation time displayed a large range from 8 seconds to 18 hours, and the modulus of the hydrogels ranged from 36 to 183 Pa under experimental conditions. Investigation by ¹H-NMR spectroscopy revealed that the gelation time and the stiffness of the hydrogels were governed by the degree of electron deficiency of alkenyl groups on the dendrimers. This research provided a systematic study on the relationship between chemical structures versus gelation time and mechanical properties of hydrogels, which could guide the way to synthesize in situ forming hydrogels with designated gelation time and stiffness for biomedical applications. Further, a RGD peptide was attached to the PAMAM dendrimers to enhance cell attachment and proliferation. Viability assays of Human Umbilical Vein Endothelial Cells (HUVEC) in the synthesized hydrogels demonstrated the biocompatibility of the hydrogels after 48 hours of culturing, and the RGD peptide improved the viability of HUVEC cells in hydrogels. We believe the PAMAM/HA hydrogel system is a tuneable and biocompatible system for diverse biomedical applications.     

超快动态交联的可注射壳聚糖-透明质酸水凝胶及促创伤愈合研究

可注射动态水凝胶是近年研究的热点,而制备无催化剂体系的快速交联的可注射动态水凝胶是研究的难点之一。以甲基丙烯酰化壳聚糖(CHMA)和醛基化透明质酸(ALHA)为原料,利用CHMA分子上的氨基与ALHA分子上的醛基和羧基,分别形成可逆动态席夫碱键和静电相互作用,可快速制备一种水凝胶。通过动态流变分析仪表征其凝胶化速率、剪切变稀行为和自愈合特征,通过体外细胞三维培养实验评估其细胞相容性,并通过急性全层皮肤创伤修复实验对其创伤愈合速率进行评估。结果表明,只需5 s,CHMA和ALHA的混合溶液就能形成凝胶。此外,该凝胶具有剪切变稀和快速自愈合的可注射特征,当扫描频率从10^-1 s^-1增加至10² s^-1时,其复数黏度由0.4 kPa降低至8 Pa;当应变在1%~1000%之间交替变化时,储能模量与损耗模量的大小能够迅速切换,且模量没有显著性地降低。同时,体外细胞三维培养实验表明,该水凝胶还具有优异的细胞相容性(细胞存活率高于95%),并且在雄性ICR小鼠急性全层皮肤缺损模型实验中,水凝胶组的创伤愈合时间相比空白对照组缩短5～7 d,表现出较快的创伤愈合速率。综上可见,这种可注射壳聚糖-透明质酸水凝胶在生物医药、组织功能、临床医学等领域具有广阔的应用前景。     

Bioadhesion and biocompatibility evaluations of gelatin and polyacrylic acid as a crosslinked hydrogel in vitro

This study describes the potentiality of crosslinked hydrogels comprised of gelatin and polyacrylic acid (CHGP) as a biological glue for soft tissues and compares its bonding strength with that of fibrin glue. Water-soluble carbodimide (WSC) was used to crosslink the mixture of gelatin and polyacrylic acid (PAA). An addition of PAA to gelatin increases bonding strength and reduces the gelation time and WSC concentration. Increasing the gelatin, WSC and PAA concentration increases the bonding strength. There is a critical concentration to have a maximum bonding strength. The cured hydrogel exhibited sufficient adhesion to mouse skin with a higher bonding strength than fibrin glue. The in vitro test has been done for evaluating CHGP toxicity.