Biodegradable Polydioxanone Microspheres for Transcatheter Arterial Embolization: Proof of Principle

PurposeTo evaluate feasibility, embolization success, biodegradability, reperfusion, and biocompatibility of biodegradable microspheres (MS) made from polydioxanone (PDO) for transcatheter arterial embolization.Materials and MethodsUnilateral selective renal embolization of a segmental artery was performed in 16 New Zealand White rabbits with PDO-MS (100–150 μm and 90–315 μm). Animals were randomly assigned to different observation periods and underwent control digital subtraction angiography (DSA) and MR imaging immediately (n = 3), 1 week (n = 2), 4 weeks (n = 2), 8 weeks (n = 2), 12 weeks (n = 5), and 16 weeks (n = 2) after embolization. Kidneys were harvested for macroscopic and histologic analysis of embolization success, biodegradability, and biocompatibility.ResultsEmbolization was technically successful in 15 of 16 animals. One animal died of anesthesia-related circulatory failure. The 100–150 μm MS were injected easily through 3-F catheters; the 90–315 μm MS tended to clog with intermittent catheter obstruction. DSA and MR imaging showed successful target embolization in 13 of 15 animals. In 2 animals, the entire kidney was affected owing to catheter clogging, including a reflux of MS while flushing. Control DSA and MR imaging showed increasing vascular reperfusion with time. Macroscopic and histologic analysis revealed necrosis/infarction in areas in which embolization was achieved. MS were extensively degraded after 16 weeks, and overall inflammatory reaction was mild.ConclusionsBiodegradable PDO-MS induced effective embolization of target vessels while demonstrating good biocompatibility. MS increasingly dissolved at 16 weeks, partial reperfusion started at week 1, and complete reperfusion started at week 8, thus offering possible advantages as a temporary embolic agent.     

软胶囊崩解迟缓现象影响因素研究

目的：研究储存条件以及软胶囊处方对明胶胶片稳定性的影响，探讨软胶囊崩解迟缓的原因。方法：制备明胶胶片模拟软胶囊囊壳，采用溶胀动力学法测定明胶胶片平衡溶胀量(Seq)，同时测定软胶囊内容物溶媒PEG400中甲醛含量。以上述结果为指标，考察不同储存条件与胶囊处方对明胶胶片交联程度的影响。结果：空白明胶胶片在40℃条件下Seq与对照组具有极显著性差异，PEG400中甲醛含量增加。含有甘油、山梨醇、二氧化钛等辅料的胶片浸泡在PEG400中后Seq与对照组具有极显著性差异，PEG400中甲醛含量量著增加。加速条件下含有抗氧剂的胶片Seq与PEG400中甲醛含量变化不大。结论：在考察的储存条件中，温度对软胶囊稳定性影响较大。含有一些常用辅料的明胶胶片易受PEG400中外源性醛类杂质的影响，Seq降低。低沮保存、纯化辅料以及添加抗氧剂有助于缓解软胶囊崩解迟缓现象的发生。     

胶原蛋白海绵在皮肤扩张术中的应用

目的：观察胶原蛋白海绵在皮肤扩张术中的临床应用效果。方法：选择40例（个）皮肤扩张器埋置和50例（个）皮肤扩张器取出及15例自身对照的病例组,应用胶原蛋白海绵术中贴敷于渗血创面,术后观察其吸收、止血效果。结果：术中渗血于2～10min内停止,病例组中无血肿发生,术后引流量明显减少,伤口愈合时间缩短。结论：在皮肤扩张术中胶原蛋白海绵是一种良好的生物止血材料。     

羟乙基淀粉130/0.4对非体外循环冠状动脉搭桥术患者凝血功能的影响

目的比较非体外循环冠状动脉搭桥术(0PCAB)中临床剂量的羟乙基淀粉(HES)130／0．4和琥珀酰明胶对凝血功能的影响。方法选择24例美国麻醉医师协会(ASA)分级Ⅱ～Ⅲ级、择期行OPCAB的患者,随机均分为琥珀酰明胶组(GEL组)和HES组。分别于麻醉诱导前(T0)、术毕即时(T1)和术后24 h(T2)测定血小板计数、凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(Fib)和D-二聚体等凝血功能指标。记录术中失血量、术后24 h内的胸管引流量和输血量。结果两组间手术时间、术中补液量、术中出血量和24 h胸管引流量的差异均无显著性(P值均>0．05)。两组间T0、T1和T2时间点的血小板计数、PT、APTT、Fib及D-二聚体的差异均无显著性(P值均>0．05)。结论临床剂量的HES 130／0．4与琥珀酰明胶对OPCAB患者凝血功能的影响无明显差异,可安全应用于OPCAB的容量治疗。     

Epithelial tissue formation in matrix culture and in histophysiologic gradient culture

Summary Formation of epithelial tissues in culture so that they become facsimiles in their structure of such tissues in nature requires procedures that comply with several spatial imperatives: a) three-dimensional growth; b) histophysiologic conditions that provide, concurrently, gradients of maturation and of diffusion of metabolites; and c) growth as layers of cells without free edges. Many steps have been required in the evolution of these methods. Two systems are described here in sufficient detail to serve as a manual. Three-dimensional growth of masses of epithelial tissue is accomplished in matrix culture using Gelfoam sponge and collagen-coated cellulose sponge. Radial gradient culture, a recent development, provides conditions that comply with the requirements of histophysiologic gradients and of epithelial tissue growth in layers without interruption in their continuity.     

明胶降解物对大鼠真皮成纤维细胞增殖及Ⅰ型胶原蛋白分泌的影响

目的 探讨组织工程心瓣膜常用人工基质材料--明胶发生降解后的产物对大鼠真皮成纤维细胞增殖及Ⅰ型胶原蛋白分泌的影响. 方法 利用酶组合技术制备明胶降解物（gelatin hydrolysate, GH）,采用超滤的方法分离出低分子量明胶降解物组分（gelatin hydrolysate fraction, GHF）,用于5只SD大鼠真皮成纤维细胞的体外培养.采用CCK-8活细胞计数试剂盒（Cell Counting Kit-8）检测细胞的增殖情况,ELISA试剂盒检测细胞I型胶原蛋白的分泌情况. 结果 ①GHF对细胞增殖作用的浓度效应：在0.125～1.0 mg/ml浓度范围内,GHF对细胞的促增殖作用呈现先增强后减弱的趋势,在0.25 mg/ml时,细胞增殖率最大,达到（47.54±16.35）%;②GH与GHF对细胞增殖影响比较：GH与GHF均具有促进细胞增殖的作用,且在浓度为0.25 mg/ml时,促细胞增殖作用无显著差异[（27.04±15.21）% vs （39.22±15.55）%, P=0.177];③GH与GHF对细胞分泌Ⅰ型胶原蛋白影响比较：GHF组第3天时Ⅰ型胶原分泌量为（28.06±5.60）pg/105,与空白对照的（18.24±4.52）pg/105相比,有显著差异（P=0.006）,而GH组直至第6天时Ⅰ型胶原蛋白分泌量,与空白对照相比,无统计学意义（P=0.103）. 结论 分子量大小不同的明胶降解物GH与GHF均具有促进大鼠真皮成纤维细胞增殖的作用,且分子量较小的GHF还具有促进细胞I型胶原分泌的功能.     

Regional gene therapy for full-thickness articular cartilage lesions using naked DNA with a collagen matrix.

A novel gene therapy approach for treating damaged cartilage is proposed that involves placing endotoxin-free cDNA containing the gene for bone morphogenetic protein-2 (BMP-2) in type I collagen sponges and then transferring the naked plasmid DNA construct to the injury site. A full-thickness cartilaginous defect in rabbits implanted with plasmid containing a marker gene (beta-galactosidase) showed expressed protein as detected by immunostaining. At 1 week postimplantation, mesenchymal cells subjacent to the defect had incorporated the implanted naked plasmid DNA and, once transfected, served as local bioreactors, transiently producing the gene product. Plasmids containing the gene for BMP-2 implanted in collagen sponges in cartilage lesions stimulated hyalinelike articular cartilage repair at 12 weeks postimplantation, nearly equivalent in quality to that induced by collagen sponges with recombinant BMP-2 protein. Our approach circumvents the risks of inflammation and immunogenic response associated with the use of viral vectors. Naked plasmid DNA as a vehicle for transferring therapeutic genes has been shown to be effective in a therapeutic model within rabbit articular cartilage and appears to be safe and cost effective.     

明胶海绵替硝唑浸湿剂预防干槽症临床研究

目的　探讨在拔除下颌阻生齿后 ,采用明胶海绵替硝唑浸湿剂置于牙槽窝内是否在预防干槽症中发挥作用。方法　临床上随机选择A、B两组下颌第三磨牙拔除的病人 ,每组 10 0例 ,A组为拔除下颌阻生齿后缝合不做其他处理 ,B组在拔牙后应用明胶海绵替硝唑浸湿剂置于拔牙创内并缝合。结果　A、B两组在拔牙后 4 8～ 72h无显著差异 ,在 72h后发生干槽症上A组明显大于B组 (P <0 .0 5 )。结论　明胶海绵替硝唑浸湿剂有明显的预防拔牙术后发生干槽症的作用。     

Medullary sponge kidneys and unilateral Wilms tumour in a child with Beckwith-Wiedemann syndrome

The occurrence of a Wilms tumour in a 4-year-old girl with bilateral medullary sponge kidney, Beckwith-Wiedemann syndrome and congenital hemihypertrophy demonstrates the close relationship between these disorders. Another six cases from the literature with congenital hemihypertrophy and with medullary sponge kidney are discussed, two of them also developed intra-abdominal neoplasm.     

Transcatheter arterial embolization of abnormal neovessels in a swine model of knee arthritis

BackgroundIn recent years, transcatheter arterial embolization (TAE) using imipenem/cilastatin (IPM/CS) has attracted attention as a treatment for relieving osteoarthritis (OA) pain. However, IPM/CS is not approved by Japanese medical insurance for use as an embolic material. Therefore, it is necessary to develop new embolic materials for TAE to relieve OA pain. The purpose of this study was to develop a swine model of knee arthritis and embolize abnormal neovessels (ANs) using two different embolic materials. We compared the embolic effects and tissue damage in knees.MethodsKnee arthritis was induced by intra-articular injection of papain into 12 knees in six female swine. The swine were divided into two groups of three swine each (six knees per group) for embolization of ANs in the knees with either IPM/CS or soluble gelatin sponge particles (SGSs). Three days after embolization, we compared the embolic effects using angiography and the tissue damage histopathologically.ResultsANs were observed in all 12 knees at 42 days after papain injection. The ANs disappeared and the patent arteries were recanalized 3 days after TAE in all 12 knees. Histopathological evaluation revealed synovitis changes, such as synovial thickening and inflammatory cell infiltration, in all 12 knees. There was no evidence of skin or muscle necrosis in either group. The appearance of ANs, recanalization of the parent arteries, and histopathological outcomes were not significantly different between the two groups.ConclusionSGSs were as safe as IPM/CS for TAE of ANs in this swine model of knee arthritis.