Utilisation des implants biodégradables dans le traitement chirurgical des fractures et au cours des ostéotomies

Résumé L'utilisation de matériaux d'ostéosynthèse biodégradables a l'avantage d'éviter la réintervention pour extraire le matériel. Les biomatériaux de polymères polyglycolides ont été expérimentés sur plus de 3 600 animaux de laboratoire avant leur introduction en pratique clinique. Depuis 1984 nous les avons utilisés comme matériau d'ostéosynthèse dans près de 1 700 cas parmi lesquels 880 cas de fracture malléolaire, 226 cas d'ostéotomie en chevron pour hallux valgus, 65 cas de fracture de la tête radiale et 54 cas de fracture de l'olécrane. Parmi les 800 premiers cas traités par broches biodégradables nous avons obtenu des résultats favorables et sans incidents dans 91 pour cent des cas. Il y eut 7 cas de fixation défaillante nécessitant une réintervention. Il y a eu 7 cas d'infection superficielle et 3 cas d'infection profonde. Nous avons observé la formation d'une collection séreuse sous-cutanée sans influence sur le résultat radiologique ou clinique dans 52 cas (6,5 %). Au vue de ces résultats et compte tenu des avantages économiques et psychologiques des matériaux biodégradables (pas de réintervention), on peut penser que l'usage de biomatériaux rivalise favorablement avec l'usage de matériaux conventionnels dans certains types d'ostéosynthèse.

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Utilization of biodegradable implants in the surgical treatment of fractures and osteotomies

Summary The utilization of biodegradable implants instead of metals in orthopaedic surgery abolishes the need to remove the fixation material. For this study biodegradable rods and screws of self-reinforced polyglycolide, polylactide and lactide-glycolide copolymer were developed and manufactured. The clinical introduction of these implants was preceded by thorough experimental studies with 3 600 animals. From November 1984 the developed biodegradable method of osteofixation was used in 1 700 operations. These included 880 displaced malleolar fractures, 226 chevron-osteotomy for hallux valgus, 65 displaced fracture of the radial head, 54 displaced frature of the olecranon and other fresh fractures or orthopaedic operations. In the first 800 cases operated on using self-reinforced polyglycolide rods the postoperative course was uneventful (91%). Because of failure in the fixation reoperation was needed in 7 cases. A superficial wound infection was observed in 7 cases, deep infection in 3 and transient fluid accumulation in 52 cases (6,5%). Fluid accumulation did not influence the radiological or clinical end-result. The advantages of biodegradable fixation are many-sided. There is a costbenefit and clinical capacity is free for other use, and psychological advantages must be emphasised because removal of implants is not needed. The over all results of this study were considered favourable.

     

几丁糖-聚乳酸复合生物材料神经导管的预构

目的:神经导管修复周围神经损伤,作为一种新的周围神经损伤修复方法显示出广阔的应用前景.本实验将几丁糖、聚乳酸两种材料结合,试图研制出一种理化性质、生物相容性俱佳的神经导管材料.材料和方法:第一部分:几丁糖-聚乳酸复合生物材料的研制及其物理性能测试.将2%几丁糖与0.5%聚乳酸以不同的比例化合反应后制成导管.力学实验检测不同比例制成导管的强度和韧性,根据实验结果选择最佳比例,并进一步测定该复合材料的其它物理性能.第二部分:几丁糖-聚乳酸复合生物材料的生物相容性检测.用细胞增殖度实验评价新材料的细胞毒性.用最大剂量法豚鼠致敏实验测试新材料致敏性.结果:2%几丁糖与0.5%聚乳酸以5∶1(体积比)比例混合反应制成的新材料,其各项物理性能符合制备神经导管要求.在细胞毒性实验中,复合材料浸提液培养2天后及5天后,细胞相对增殖度(RGR)为83.67%,96.41%.致敏实验显示新复合材料浸提液致敏率为0级.实验证明新复合材料无细胞毒性、无致敏性.结论:几丁糖、聚乳酸通过适当比例结合制作的复合生物材料具有良的物理性能及生物相容性,符合制备神经导管的理化要求.     

Controlled release of sugar and toxicant from a novel device for controlling pest insects

A novel biodegradable device, designed for long-lasting residual effectiveness of feeding stimulant (sugar) and insecticide (dimethoate) against apple maggot flies and other insects, was formulated. The device is an 8-cm diameter fruit-mimicking sphere, consisting of 42–50% sugar entrapped in a mixture of gelatinized corn flour and wheat flour in the presence of glycerin, and coated with a layer of latex paint containing dimethoate and sugar. We found that the outer layer of paint prevents cracking of the sphere upon drying and creates a barrier to control the release of both sugar and dimethoate. Releases of each ingredient were screened first by chemical analysis and then by bioassays in the laboratory and in field cages against apple maggot flies. Chemical analysis demonstrated strong potential for controlled release of water-soluble feeding stimulant and water-insoluble insecticide measured as a function of the amount of rainfall and duration of exposure time. Field results showed greater than 70% insecticidal activity after 11 weeks of sphere exposure in an orchard. This device has the potential to be used for a variety of insect-control applications through manipulating its shape, color and texture into forms known to be attractive to target insects, and by employing various toxicants designed to be effective against such insects.     

载药纳米微球的制备和评价

含有有效药物的载药纳米粒子是一种新型的缓释系统,可改变常规的给药方式,有极广阔的发展前景。我们用超声的方法结合了不同的药物制成作用不同的纳米粒子,验证了纳米粒子对局部给药治疗的有效性,建立了良好的动物动脉摄取模型,为继续研究奠定了坚实的基础。     

骨髓基质细胞和内皮细胞联合种植构建组织工程化骨的初步研究

为阐明骨髓基质细胞和内皮细胞联合种植在生物复合材料上构建组织工程化骨 ,在促进成骨过程、加速局部血管生成中的作用 ,将大鼠骨髓基质细胞和人脐静脉内皮细胞联合种植在左旋聚乳酸 /β-磷酸三钙 (PL L A/β- TCP)多孔复合支架材料上作为实验组 ,仅种植骨髓基质细胞在该材料上作为对照组。将此种有活细胞的复合材料种植于裸鼠大腿后侧肌袋内 ,分别于种植后 1、4、8、12、16周处死动物 ,取出复合材料 ,行组织学检测 ,并用图像处理技术计算实验组和对照组的成骨面积百分比和材料面积百分比 ,观察其变化规律。结果显示 :实验组成骨面积百分比增加比对照组明显加快 ,而材料面积百分比减少比对照组迅速 ;其内毛细血管网形成情况也要明显优于对照组。表明骨髓基质细胞和内皮细胞联合种植于支架材料构建组织工程化骨不仅有利于成骨作用 ,促进新生骨区内部血管网形成 ,还有利于复合材料的降解吸收 ,这在构造组织工程化骨过程中具有重要意义。     

疝环充填式无张力疝修补40例的疗效观察

目的 观察聚丙烯锥形网塞、网片为疝修补材料行疝修补术的效果。方法 作疝环充填式无张力疝修补４０例,其中单侧斜疝２９例,单侧直疝６例,膀胱滑动疝１例,骑跨疝１例,双侧斜疝２例,双侧直疝１便。４０例中１１例首次复发、１例第４次复发。手术采用美国巴德公司提供的聚丙烯锥形网塞、网片作修补材料。结果 患者伤口均一期愈合,４０一部得到随访,随访时间１￣１５个月,无１例复发,均恢复下沉工作与生活结论 近期疗效满     

Nano-engineered microcapsules boost the treatment of persistent pain

Persistent pain remains a major health issue: common treatments relying on either repeated local injections or systemic drug administration are prone to concomitant side-effects. It is thought that an alternative could be a multifunctional cargo system to deliver medicine to the target site and release it over a prolonged time window. We nano-engineered microcapsules equipped with adjustable cargo release properties and encapsulated the sodium-channel blocker QX-314 using the layer-by-layer (LbL) technology. First, we employed single-cell electrophysiology to establish in vitro that microcapsule application can dampen neuronal excitability in a controlled fashion. Secondly, we used two-photon excitation imaging to monitor and adjust long-lasting release of encapsulated cargo in target tissue in situ. Finally, we explored an established peripheral inflammation model in rodents to find that a single local injection of QX-314-containing microcapsules could provide robust pain relief lasting for over a week. This was accompanied by a recovery of the locomotive deficit and the amelioration of anxiety in animals with persistent inflammation. Post hoc immunohistology confirmed biodegradation of microcapsules over a period of several weeks. The overall remedial effect lasted 10–20 times longer than that of a single focal drug injection. It depended on the QX-314 encapsulation levels, involved TRPV1-channel-dependent cell permeability of QX-314, and showed no detectable side-effects. Our data suggest that nano-engineered encapsulation provides local drug delivery suitable for prolonged pain relief, which could be highly advantageous compared to existing treatments.     

A Phase II Study of Biodegradable Stents Plus Palliative Radiotherapy in Oesophageal Cancer

AimsSelf-expanding metal stents provide rapid improvement of dysphagia in oesophageal cancer but are associated with complications. The aim of the present study was to test the effectiveness of an alternative treatment of combining biodegradable stents with radiotherapy.Materials and methodsA Simon two-stage single-arm prospective phase II trial design was used to determine the efficacy of biodegradable stents plus radiotherapy in patients with dysphagia caused by oesophagus cancer who were unsuitable for radical treatment. Fourteen patients were recruited and data from 12 were included in the final analyses.ResultsFive of 12 patients met the primary end point: one stent-related patient death; four further interventions for dysphagia within 16 weeks of stenting (41.7%, 95% confidence interval 15.2–72.3%). The median time to a 10-point deterioration of quality of life was 2.7 weeks. Nine patients died within 52 weeks of registration. The median time to death from any cause was 15.0 weeks (95% confidence interval 9.6–not reached).ConclusionThe high re-intervention observed, which met the pre-defined early stopping criteria, meant that the suggested alternative treatment was not sufficiently effective to be considered for a larger scale trial design. Further work is needed to define the place of biodegradable stents in the management of malignant oesophageal strictures.     

In vivo toxicological evaluation of polymeric nanocapsules after intradermal administration

Polymeric nanocarriers have shown great promise as delivery systems. An alternative strategy has been to explore new delivery routes, such as intradermal (i.d.), that can be used for vaccines and patch-based drug delivery. Despite their many advantages, there are few toxicity studies, especially in vivo. We report a safety assessment of biodegradable poly(ɛ-caprolactone) lipid-core nanocapsules (LNC) with a mean size of 245 ± 10 nm following single and repeated intradermal injections to Wistar rats. Suspensions were prepared by interfacial deposition of polymer. The animals (n = 6/group) received a single-dose of saline solution (1.2 ml/kg) or LNC (7.2 × 10¹² LNC/kg), or repeated-doses of two controls, saline solution or Tween 80 (0.9 ml/kg), or three different concentrations of LNC (1.8, 3.6, and 5.4 × 10¹² LNC/kg) for 28 consecutive days. Clinical and physiological signs and mortality were observed. Samples of urine, blood, and tissue were used to perform toxicological evaluation. There were no clinical signs of toxicity or mortality, but there was a slight decrease in the relative body weights in the Tween 80–treated group (p < 0.01) after repeated administration. No histopathological alterations were observed in tissues or significant changes in blood and urinary biomarkers for tissue damage. Mild alterations in white blood cells count with increases in granulocytes in the Tween-80 group (p < 0.05) were found. Genotoxicity was evaluated through the comet assay, and no statistical difference was observed among the groups. Therefore, we conclude that, under the conditions of these experiments, biodegradable LNC did not present appreciable toxicity after 28 consecutive days of intradermal administration and is promising for its future application in vaccines and patch-based devices for enhancing the delivery of drugs.     

New hydrophilic polyesters and related polymers as bioerodible polymeric matrices

A survey is reported on our activity performed in the last few years on the preparation of new synthetic and semisynthetic polymeric materials endowed with bioerodible-biodegradable characteristics and designed for applications in the practice of controlled release of active principles of pharmaceutical and agrochemical significance. The presentation of the results will be arranged into the following sections: (1) hydroxyl containing polyesters, that comprise polymerization products based on racemic and optically active glyceric acid, or attained by polyaddition reactions among cyclic anhydrides, including also carbon dioxide, with monoglycidyl ethers of reversibly protected polyols. In this class are also presented the related polyhydroxylated systems obtained by selective grafting functional epoxides on cyclodextrins. (2) Bioerodible carboxyl containing plolymeric systems as derived from the alternating copolymerization of maleic anhydride with alkyl vinyl ethers followed by partial esterification of maleic anhydride groups. (3) Linear and cross-linked functional polymers of synthetic and semisynthetic origin with hydrogel forming capability. Typical examples of their applications in the release of drugs and phytodrugs are also presented.