In Vitro and In Vivo Biocompatibility of Novel Zwitterionic Poly(Beta Amino)Ester Hydrogels Based on Diacrylate and Glycine for Site‐Specific Controlled Drug Release

New (β‐aminoester) hydrogels (PBAE) based on di(ethylene glycol)diacrylate and glycine are successfully synthesized and characterized for the first time in this work. PBAE macromers are obtained using Michael addition. By changing the diacrylate/amine stoichiometric ratio, but maintaining it >1, samples with different chemical structure containing acrylate end‐groups are obtained. The hydrogels are synthesized from macromers utilizing free radical polymerization. Chemical structure of macromers and hydrogels is confirmed by proton nuclear magnetic resonance, and Fourier transform infra‐red spectroscopy. Swelling and degradation rates in physiological pH range change notably with pH and monomer molar ratio, validating pH sensitivity and zwitterionic behavior, which can be finely tuned by changing any of these parameters. In vitro cytotoxicity and in vivo acute embryotoxicity in zebrafish (Danio rerio) performed to assess the biocompatibility of the novel hydrogel materials and their degradation products reveal that materials are nontoxic and biocompatible. The Cephalexin in vitro drug release study, at pH values 2.20, 5.50, and 7.40, demonstrates pH‐sensitive delivery with the release profiles effectively controlled by pH and the hydrogel composition. PBAE hydrogels exhibit great potential for a variety of biomedical applications, including tissue regeneration and intelligent drug delivery systems.     

应用可降解腔内支架的无缝合吻合术在狗胆肠吻合模型的实验研究

目的 传统的手工缝合行胆肠吻合术操作困难、费时,尤其在小胆管吻合和腹腔镜手术时明显。为简化和改良手术操作,我们设计了一种新的应用可降解腔内支架的无缝合胆肠吻合术。本文拟在狗胆总管十二指肠吻合模型中评估该无缝合方法的可行性和安全性。方法 为无缝合胆总管十二指肠吻合术设计一种腔内吻合支架管,这种专利支架管直径3mm和4mm,材料为可降解聚乳酸。38条毕格犬随机分为支架组（SG n=20）和对照组（CG n=18）。SG组应用无缝合支架法行胆总管十二指肠端侧吻合,CG组行传统可吸收缝线间断一层胆总管十二指肠端侧吻合。动物分术后1、3、6、12月4个亚组,比较两组术中吻合手术时间、术中吻合口耐受压、胆漏发生率、术后吻合口爆破压差异,观察两组术后胆红素和肝酶变化、术后1,3,6,12月取材的吻合口组织病理形态学改变,包括HE染色和Masson染色,比较两组吻合口羟脯氨酸含量,观察两组吻合口疤痕纤维组织增生状况。MRCP了解术后6月,12月两组吻合口状况。结果 手术均顺利完成,支架组吻合时间明显小于对照组(SG19.2±4.3min VS CG29.2±7.1min, P 0.000);两组各有1例胆漏并死亡（SG5.0% VS CG 5.6%,P=0.695)。两组间术中吻合口耐受压、术后胆漏发生率、术后各时期吻合口爆破压、吻合口羟脯氨酸含量、胆红素和肝酶测定均无显著性差异。MRCP检查及病理检查未发现吻合口狭窄和梗阻。结论 在狗胆总管十二指肠吻合模型中,无缝合腔内可降解支架胆吻合方法具有可行性和安全性。     

Multipurpose Degradable Physical Adhesive Based on Poly(d,l‐lactide‐co‐trimethylene Carbonate)

Solutions of amorphous poly(d,l ‐lactide‐co‐trimethylene carbonate)s (PDLTMCs) in ethyl acetate work as solvent‐based physical adhesives through diffusion mechanisms for a variety of aliphatic polyester‐based adherents. The random PDLTMCs with a trimethylene carbonate content of 11, 16, and 20 mol% are synthesized in bulk, achieving high molecular weight, M_n, up to 128 kg mol^?1 and dispersity around 1.7. The PDLTMCs are amorphous and have a glass transition temperature in the range 34.7 to 43.6 °C and in agreement with the theoretical values calculated using the Fox equation. The mechanical and surface properties of the PDLTMCs are tested preparing solvent cast films, which are soft and tough and, although they have a higher contact angle than the parent homopolymer, they show higher water uptake capacity. The potential application as adhesives of the synthesized PDLTMCs is evaluated by preparing a 20 wt% solution in ethyl acetate and testing them by adhering films with different compositions as well as constructs having different geometries and surface roughness. The results demonstrate that the adhesion strength is higher on adherent films having similar chemical compositions as the adhesives and on surfaces having similar compositions to each other but different roughness. The similar chemical nature of the adhesive and adherent probably favors the diffusion mechanism through which adhesion takes place.     

可用于保乳手术瘤床标记物的生物可降解材料的筛选研究

筛选可用于保乳手术瘤床标记物的生物可降解材料。基于文献检索和初选现有材料,选定5种生物可降解材料:PGA、PLLA、Mg1、Mg2、PLA/β-TCP,对这5种材料进行CT及MR图像扫描,评估其成像情况,然后对符合成像要求的材料进行体外降解测试,观察外观、质量及粘度变化。图像扫描测试表明:1)两种镁合金材料(Mg1和Mg2)在CT图像上出现放射状伪影;2)两种高分子材料(PGA和PLLA)及复合材料PLA/β-TCP在CT及MR图像上均没有明显伪影,且能与周围背景明显区分;3)就成像区分度而言,由于密度提高,复合材料PLA/β-TCP在CT图像上和周围背景的对比较PLLA明显提高。体外降解测试表明:1)PGA样品外观上至第8周时完全变成粉末状,粘度变化方面至12周时基本降解为小分子,而质量则至30周时基本降解完全;2)PLA/β-TCP样品至第40周时质量损失率约为10%,且外观无明显变化;3)PLLA样品至第40周时外观无明显变化,且由于亲水性不足降解非常缓慢,在48周的研究周期内粘度变化较小,质量基本不变化;4)进一步观察降解情况,在观察至9个月后,PLLA降解依旧非常缓慢,而PLA/β-TCP已进入加速降解阶段。本研究结合图像扫描及体外降解测试,综合考虑成像区分度和降解周期,最终确定PLA/β-TCP为最佳的生物可降解材料。     

Functional Degradable Polymers via Radical Ring‐Opening Polymerization and Click Chemistry

The use of free‐radical polymerization for the formation of an alkyne‐functionalized polymer with ester units of polycaprolactone type in the backbone is shown. This is done by the copolymerization of a cyclic ketene acetal [2‐methylene‐1,3‐dioxepane (MDO)] with propargyl acrylate using a free radical initiator, azobis(isobutyronitrile). Structural characterization of the copolymers using 1D and 2D NMR techniques shows the random distribution and very high percentage of inclusion of alkyne groups onto the polymer backbone. The exemplary grafting of a biocompatible polymer [poly(ethylene glycol)] via azide‐alkyne “click” chemistry is also shown. Hydrolytic degradation behavior and biocompatibility of the polymers (cytotoxicity) studies are also reported.     

冠脉可降解支架介入的血管力学特性数值模拟与实验研究

目的 探究可降解支架在动态降解过程中,血管应力变化对内皮功能恢复以及血管再狭窄抑制作用的影响.方法 拟合超弹性血管本构关系的材料参数,通过数值模拟计算支架介入前以及动态降解过程中血管内膜应力分布;采用体外培养实验,设置硅胶腔体拉伸率分别为0％、5％、10％、15％,模拟不同降解阶段的力学环境,探究不同拉伸率下对内皮细胞...     

高纯镁在体内定量载荷下的降解行为

目的定量研究力学载荷对高纯镁在体内降解的影响。方法将直径2 mm、长14 mm的圆柱状高纯镁(99. 99 wt.%)试件装配到聚醚醚酮(PEEK)制成的圆环上。PEEK环可使镁试件分别处于3种应力状态:无应力、压应力[(6. 2±0. 6) MPa]和拉应力[(4. 6±0. 1) MPa]。将不同应力状态的试件植入SD大鼠背部皮下4周后取出。通过试件失重、剩余体积、表面形貌和周围软组织染色分析高纯镁的降解行为。结果植入大鼠皮下的高纯镁试件均出现降解,并且被胶原纤维囊包裹。受到压、拉应力的试件与无应力试件在失重和剩余体积上无显著差别。在各应力状态下的试件都趋于均匀腐蚀。结论在体内皮下环境中,PEEK环对高纯镁施加4～6 MPa压、拉应力对高纯镁降解行为无明显影响。研究结果为镁基可降解植入物的设计与临床应用提供理论依据。     

Preparation and Properties of Degradable Shape Memory Material Based on Partial α‐Cyclodextrin–Poly(ε‐caprolactone) Inclusion Complex

A series of supramolecular degradable inclusion complex (IC) films were formed by threading α‐cyclodextrin (α‐CD) molecules over poly(ε‐caprolactone) (PCL) according to the designed ratio of α‐CD–PCL. Due to containing both α‐CD–PCL inclusion crystallites and uncovered PCL crystallites, the resulting supramolecular α‐CD–PCL IC partial films displayed a shape memory effect. The properties of the materials were investigated by ¹H NMR, X‐ray diffraction (XRD), differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), and swelling measurement. It was found that the casting temperature and solvent have great influence on the formation and properties of the α‐CD–PCL partial ICs. The modes of complexes on different conditions were proposed. In addition, the introduction of inclusion structure accelerates the degradation of materials strongly.

     

可降解血管吻合器的结构设计与实验验证

目的 设计一种新型可降解血管吻合器,探究施压距离与吻合口生物力学性能之间的关系,以提高血管端端吻合的效率与质量。方法 设计吻合器的三维结构,并采用挤压态高纯镁为材料进行样机加工;通过建立血管端端吻合的有限元模型,研究在不同施压距离（0.4、0.5、0.6、0.7、0.8 mm）下,血管吻合端面应力分布情况及其变化规律;通过离体组织吻合实验,对有限元结果的合理性及该吻合器的可行性与有效性进行验证。结果 当施压距离为0.6 mm时,吻合口力学性能最优,此时撕脱力为(11.79±0.64) N,爆破压为(39.32±2.99) kPa,满足临床上对组织吻合口强度的要求,同时组织的力学损伤较小。结论 所设计的新型可降解血管吻合器可以通过调节施压距离对组织进行吻合,能够有效提高组织吻合效率,减小组织力学损伤,从而提高吻合质量。研究结果可以为可降解血管吻合器的设计提供重要参考。     

Early metabolic reactivation versus antioxidant therapy after a traumatic spinal cord injury in adult rats

Disability after traumatic spinal cord injury (TSCI) results from physical trauma and from “secondary mechanisms of injury” such as low metabolic energy levels, oxidative damage and lipid peroxidation. In order to prove if early metabolic reactivation is a better therapeutic option than antioxidant therapy in the acute phase of TSCI, spinal cord contusions were performed in adult rats using a well‐characterized weight drop technique at thoracic 9 level. After TSCI, pyrophosphate of thiamine or non‐degradable cocarboxylase (NDC) enzyme was used to maintain energy levels, antioxidants such as superoxide dismutase and catalase (ANT) were used to decrease oxidative damage and methylprednisolone (MP), which has both therapeutic properties, was used as a control. Rats were divided into one sham group and six with TSCI; one of them received no treatment, and the rest were treated with NDC, MP, NDC + MP, NDC + ANT or ANT. The ANT group decreased lactate and creatine phosphokinase levels and increased the amount of preserved tissue (morphometric analysis) as well as functional recovery (Basso, Beattie and Bresnahan or BBB motor scale). In contrast, NDC treatment increased lipid peroxidation, measured through thiobarbituric acid reactive substances (TBARS) levels, as well as spinal cord tissue destruction and functional deficit. Early metabolic reactivation after a TSCI may be deleterious, while natural early metabolic inhibition may not be a “secondary mechanism of injury” but a “secondary neuroprotective response”. While increased antioxidant defence after a TSCI may currently be an ideal therapeutic strategy, the usefulness of metabolic reactivation should be tested in the sub‐acute or chronic phases of TSCI and new strategies must continue to be tested for the early ones.