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.     

仿生可降解组织工程纤维环支架的制备与评估

文题释义： 纤维环：是保持椎间盘强度与脊柱稳定性层面的重要组成部分,纤维环的胶原纤维在椎间盘内呈同心圆排列,每层纤维环间呈60°夹角斜行排列,这类特殊的交错网状架构,令纤维环拥有较强的抗拉性能与压缩性,能够预防髓核往外突出,对保持椎间盘的稳定起着重要的作用。 背景：构建既具有仿生结构又具备合适可降解性和良好生物相容性的组织工程纤维环支架仍是难点。 目的：以聚己内酯和聚二恶烷酮为原材料制备仿生可降解支架并评估其作为组织工程纤维环支架的可行性。 方法：通过熔融纺丝技术制备5组不同比例支架(聚己内酯组、聚己内酯/聚二恶烷酮分别为70/30、50/50、30/70组、聚二恶烷酮组)。扫描电子显微镜观察其结构、纤维直径、孔径;测量支架的力学性能和接触角;通过体外模拟和皮下埋植观察支架体外、体内降解情况;检测降解组织周围炎症因子白细胞介素1β和肿瘤坏死因子α的表达情况。接种人脐带间充质干细胞培养7 d,通过CCK-8和死活细胞检测细胞增殖和存活情况。实验于2016-03-02经天津市天津医院医学伦理委员会批准。 结果与结论：①扫描电子显微镜观察显示各组支架纤维粗细均匀,纤维成60°角;②力学性能分析显示单纯聚二恶烷酮支架的拉伸和压缩模量最低,不符合纤维环力学要求;聚己内酯组的力学性能最佳,聚己内酯/聚二恶烷酮为70/30和50/50的支架力学性能适中;③亲水性检测结果表明聚二恶烷酮含量越多,支架亲水性越好;④支架降解情况分析显示,对于组织工程纤维环再生修复来说,单纯聚二恶烷酮和聚己内酯/聚二恶烷酮为30/70支架降解过快,聚己内酯组的降解过慢,聚己内酯/聚二恶烷酮为70/30和50/50的支架降解速率较合适;⑤降解组织周围炎症反应分析显示支架中聚己内酯比例越高炎症反应越严重;⑥CCK-8和死活细胞结果显示人脐带间充质干细胞在聚己内酯/聚二恶烷酮三组混合支架具有良好的增殖活性并且存活率高;⑦结果表明,采用熔融纺丝技术制备的聚己内酯/聚二恶烷酮为70/30和50/50两组支架能够模拟天然纤维环结构,同时具备合适可降解性、优越的力学性能和良好生物相容性,适合用于组织工程纤维环支架的构建。 ORCID: 0000-0001-9088-4222(张维昊) 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     

Tonsillar fossa obliteration and post-operative pain

Fifty consecutive patients over the age of 15 years undergoing tonsillectomy had one tonsillar fossa obliterated by 2/0 Polydioxanone (PDS II) suture. The opposite side was used as a control. Pain was assessed on a visual analogue scale from the first to tenth post-operative day. Although on the initial postoperative days the pain was more on the sutured side, 41 patients subsequently experienced significant pain relief on that side (P= 0.0001). No complications were encountered due to the tonsillar fossa obliteration. On the 10 day review, the 41 patients indicated in their questionnaire that tonsillar fossa obliteration is a useful procedure to reduce the post-operative pain and would have preferred both sides to be obliterated rather than left to heal by secondary intention.     

Raman Spectroscopy as a Novel Method for the Characterization of Polydioxanone Medical Stents Biodegradation

Polydioxanone (PPDX), as an FDA approved polymer in tissue engineering, is an important component of some promising medical devices, e.g., biodegradable stents. The hydrolytic degradation of polydioxanone stents plays a key role in the safety and efficacy of treatment. A new fast and convenient method to quantitatively evaluate the hydrolytic degradation of PPDX stent material was developed. PPDX esophageal stents were degraded in phosphate-buffered saline for 24 weeks. For the first time, the changes in Raman spectra during PPDX biodegradation have been investigated here. The level of PPDX hydrolytic degradation was determined from the Raman spectra by calculating the area under the 1732 cm⁻¹ peak shoulder. Raman spectroscopy, unlike Fourier transform infrared (FT-IR) spectroscopy, is also sensitive enough to monitor the decrease in the dye content in the stents during the degradation. Observation by a scanning electron microscope showed gradually growing cracks, eventually leading to the stent disintegration. The material crystallinity was increasing during the first 16 weeks, suggesting preferential degradation of the amorphous phase. Our results show a new easy and reliable way to evaluate the progression of PPDX hydrolytic degradation. The proposed approach can be useful for further studies on the behavior of PPDX materials, and for clinical practice.     

First-in-Human Study with Eight Patients Using an Absorbable Vena Cava Filter for the Prevention of Pulmonary Embolism

PurposeTo prospectively evaluate the initial human experience with an absorbable vena cava filter designed for transient protection from pulmonary embolism (PE).Materials and MethodsThis was a prospective, single-arm, first-in-human study of 8 patients with elevated risk of venous thromboembolism (VTE). Seven absorbable IVC filters (made of polydioxanone that breaks down into H₂O and CO₂ in 6 mo) were placed prophylactically before orthopedic (n = 5) and gynecologic (n = 2) surgeries, and 1 was placed in a case of deep vein thrombosis. Subjects underwent CT cavography and abdominal radiography before and 5, 11, and 36 weeks after filter placement to assess filter migration, embolization, perforation, and caval thrombosis and/or stenosis. Potential PE was assessed immediately before and 5 weeks after filter placement by pulmonary CT angiography.ResultsNo symptomatic PE was reported throughout the study or detected at the planned 5-week follow-up. No filter migration was detected based on the fixed location of the radiopaque markers (attached to the stent section of the filter) relative to the vertebral bodies. No filter embolization or caval perforation was detected, and no caval stenosis was observed. Throughout the study, no filter-related adverse events were reported.ConclusionsImplantation of an absorbable vena cava filter in a limited number of human subjects resulted in 100% clinical success. One planned deployment was aborted as a result of stenotic pelvic veins, resulting in 89% technical success. No PE or filter-related adverse events were observed.     

PDS血管外支架体外毒性和体内相容性的实验研究

目的观察血管外支架材料聚对二氧环己酮（PDS）的体外毒性和体内生物相容性。方法按照医疗器械生物学评价标准，采用体外细胞培养法、MTT法进行PDS体外细胞毒性试验，并进行体内植入降解实验。结果PDS网状支架材料对细胞形态、生长代谢和增殖不构成损害；PDS在体内12周左右开始加速降解，24周完全降解吸收，炎性反应也减退消失，材料区域被新生纤维组织取代，降解过程中未对周围组织产生不良刺激。结论PDS支架材料元细胞毒性，组织反应轻，可满足体内植入的要求。     

THE RESULTS OF CORACO-CLAVICULAR SLINGS FOR ACROMIO-CLAVICULAR DISLOCATION

Background : Treatment of type 3 acromio-clavicular (A-C) dislocations is controversial. There have been over 60 different surgical procedures as well as a variety of conservative measures used to treat this injury. Methods : The outcome of a coraco-clavicular (C-C) sling for grade 3–4 A-C dislocation was studied. A dissolvable sling of braided 1 polydioxanone (PDS, Ethicon) was used with or without excision of the distal end of the clavicle in six patients. The clinical and radiological outcome of the braid and acromio-clavicular joint were studied by clinical examination, plain and stress radiographs and magnetic resonance imaging (MRI). Results : All patients reported good-excellent results from 6 months after surgery. Radiological examination demonstrated some superior clavicular migration in all patients within 1 month of the procedure, although never more than that seen with a grade 2 dislocation. This migration was clinically evident only in patients with a thin build. At 1 month, the MRI demonstrated partial replacement of the braid by granulation tissue. From 6 months on, the braid was absent and fibrous tissue was noted between the coracoid and the clavicle and the acromion and clavicle. Conclusions : The coraco-clavicular sling did not maintain operative reduction of the dislocated clavicle. This did not diminish the functional result but was a cosmetic complication in patients with a thin build.     

Polydioxanone Biodegradable Stent Placement in a Canine Urethral Model: Analysis of Inflammatory Reaction and Biodegradation

PurposeTo investigate the inflammatory reaction and perform quantitative analysis of biodegradation after placement of a polydioxanone (PDO) biodegradable stent in a canine urethral model.Materials and MethodsPDO biodegradable stents were placed in the proximal and distal urethra of nine male mongrel dogs. The dogs were euthanized 4 weeks (group A; n = 3), 8 weeks (group B; n = 3), or 12 weeks (group C; n = 3) after stent placement. The luminal diameter of the stent-implanted urethra was assessed by follow-up retrograde urethrography, and histologic findings were obtained after the dogs were killed. Stents were removed after euthanasia, and their surface morphology and molecular weight were evaluated. Hematologic examination was performed to evaluate inflammatory reaction.ResultsStent placement was technically successful in all dogs. The average luminal diameter gradually decreased. The average number of epithelial layers (2.93 vs 4.42; P < .001), the average thickness of papillary projection (0.80 mm vs 1.28 mm; P < .001), and the average thickness of submucosal fibrosis (0.34 mm vs 0.49 mm ; P < .001) were significantly increased in group B versus group A. There were no significant differences between group B and group C. The average inflammatory cell infiltration did not differ significantly in the three groups. Molecular weight losses were 54% in group A and 84% in group B. In group C, PDO stents were completely decomposed.ConclusionsAn experimental study in a canine urethral model has demonstrated acceptable inflammatory reaction with gradually increasing granulation tissue but no luminal obstruction within 12 weeks.