Amano Hizuru, Miyake Koichi, Hinoki Akinari, Yokota Kazuki, Kinoshita Fumie, Nakazawa Atsuko, Tanaka Yujiro, Seto Yasuhiro, Uchida Hiroo
Department of Pediatric Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
Mitsui Mining and Smelting Co., Ltd., Tokyo 141-0032, Japan.
World J Clin Cases. 2020 Feb 6;8(3):504-516. doi: 10.12998/wjcc.v8.i3.504.
The development of biodegradable surgical staples is desirable as non-biodegradable Ti alloy staples reside in the human body long after wound healing, which can cause allergic/foreign-body reactions, adhesion, or other adverse effects. In order to develop a biodegradable alloy suitable for the fabrication of surgical staples, we hypothesized that Zn, a known biodegradable metal, could be alloyed with various elements to improve the mechanical properties while retaining biodegradability and biocompatibility. Considering their biocompatibility, Mg, Ca, Mn, and Cu were selected as candidate alloying elements, alongside Ti, the main material of clinically available surgical staples.
To investigate the mechanical properties and degradation behavior and safety and feasibility of biodegradable Zn alloy staples.
Tensile and bending tests were conducted to evaluate the mechanical properties of binary Zn alloys with 0.1-6 wt.% Mg, Ca, Mn, Cu, or Ti. Based on the results, three promising Zn alloy compositions were devised for staple applications (wt.%): Zn-1.0Cu-0.2Mn-0.1Ti (Zn alloy 1), Zn-1.0Mn-0.1Ti (Zn alloy 2), and Zn-1.0Cu-0.1Ti (Zn alloy 3). Immersion tests were performed at 37 °C for 4 wk using fed-state simulated intestinal fluid (FeSSIF) and Hank's balanced salt solution (HBSS). The corrosion rate was estimated from the weight loss of staples during immersion. Nine rabbits were subjected to gastric resection using each Zn alloy staple, and a clinically available Ti staple was used for another group of nine rabbits. Three in each group were sacrificed at 1, 4, and 12 wk post-operation.
Additions of ≤1 wt.% Mn or Cu and 0.1 wt.% Ti improved the yield strength without excessive deterioration of elongation or bendability. Immersion tests revealed no gas evolution or staple fracture in any of the Zn alloy staples. The corrosion rates of Zn alloy staples 1, 2, and 3 were 0.02 mm/year in HBSS and 0.12, 0.11, and 0.13 mm/year, respectively, in FeSSIF. These degradation times are sufficient for wound healing. The degradation rate is notably increased under low pH conditions. Scanning electron microscopy and energy dispersive spectrometry surface analyses of the staples after immersion indicated that the component elements eluted as ions in FeSSIF, whereas corrosion products were produced in HBSS, inhibiting Zn dissolution. In the animal study, none of the Zn alloy staples caused technical failure, and all rabbits survived without complications. Histopathological analysis revealed no severe inflammatory reaction around the Zn alloy staples.
Staples made of Zn-1.0Cu-0.2Mn-0.1Ti, Zn-1.0Mn-0.1Ti, and Zn-1.0Cu-0.1Ti exhibit acceptable mechanical properties, proper degradation behavior, and safety and feasibility. They are promising candidates for biodegradable staples.
可生物降解手术吻合钉的研发很有必要，因为不可生物降解的钛合金吻合钉在伤口愈合后仍会长期留存于人体内，这可能会引发过敏/异物反应、粘连或其他不良反应。为了研发一种适合制造手术吻合钉的可生物降解合金，我们推测，已知的可生物降解金属锌可以与各种元素形成合金，在保持生物降解性和生物相容性的同时改善机械性能。考虑到它们的生物相容性，选择镁、钙、锰和铜作为候选合金元素，同时选择临床上可用手术吻合钉的主要材料钛。
研究可生物降解锌合金吻合钉的机械性能、降解行为以及安全性和可行性。
对含0.1-6 wt.%镁、钙、锰、铜或钛的二元锌合金进行拉伸和弯曲试验，以评估其机械性能。基于这些结果，设计了三种有前景的锌合金成分用于吻合钉应用（wt.%）：锌-1.0铜-0.2锰-0.1钛（锌合金1）、锌-1.0锰-0.1钛（锌合金2）和锌-1.0铜-0.1钛（锌合金3）。使用进食状态模拟肠液（FeSSIF）和汉克斯平衡盐溶液（HBSS）在37°C下进行4周的浸泡试验。通过浸泡期间吻合钉的重量损失估算腐蚀速率。每组9只兔子使用每种锌合金吻合钉进行胃切除术，另一组9只兔子使用临床上可用的钛吻合钉。每组中的3只兔子在术后1、4和12周处死。
添加≤1 wt.%的锰或铜以及0.1 wt.%的钛可提高屈服强度，而不会过度降低伸长率或弯曲性。浸泡试验表明，任何锌合金吻合钉均未出现气体逸出或吻合钉断裂。锌合金吻合钉1、2和3在HBSS中的腐蚀速率为0.02毫米/年，在FeSSIF中的腐蚀速率分别为0.12、0.11和0.13毫米/年。这些降解时间足以实现伤口愈合。在低pH条件下，降解速率显著增加。浸泡后吻合钉的扫描电子显微镜和能量色散光谱表面分析表明，组成元素在FeSSIF中以离子形式洗脱，而在HBSS中产生腐蚀产物，抑制了锌的溶解。在动物研究中，没有一种锌合金吻合钉导致技术失败，所有兔子均存活且无并发症。组织病理学分析显示，锌合金吻合钉周围没有严重的炎症反应。
由锌-1.0铜-0.2锰-0.1钛、锌-1.0锰-0.1钛和锌-1.0铜-0.1钛制成的吻合钉具有可接受的机械性能、适当 的降解行为以及安全性和可行性。它们是可生物降解吻合钉的有前景的候选材料。
