Clinical and Translational Research
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Feb 6, 2020; 8(3): 504-516
Published online Feb 6, 2020. doi: 10.12998/wjcc.v8.i3.504
Novel zinc alloys for biodegradable surgical staples
Hizuru Amano, Koichi Miyake, Akinari Hinoki, Kazuki Yokota, Fumie Kinoshita, Atsuko Nakazawa, Yujiro Tanaka, Yasuhiro Seto, Hiroo Uchida
Hizuru Amano, Department of Pediatric Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
Koichi Miyake, Yasuhiro Seto, Mitsui Mining and Smelting Co., Ltd., Tokyo 141-0032, Japan
Akinari Hinoki, Kazuki Yokota, Yujiro Tanaka, Hiroo Uchida, Department of Pediatric Surgery, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
Fumie Kinoshita, Department of Advanced Medicine, Nagoya University Hospital, Nagoya 466-8560, Japan
Atsuko Nakazawa, Department of Clinical Research, Saitama Children’s Medical Center, Saitama 330-8777, Japan
Author contributions: Amano H, Miyake K, Hinoki A, Seto Y, and Uchida H designed and coordinated the research; Amano H, Miyake K, Hinoki A, Yokota K, and Uchida H performed the experiments; Amano H, Miyake K, Hinoki A, Kinoshita F, Nakazawa A, Tanaka Y, Seto Y, and Uchida H analyzed the data; Amano H and Miyake K wrote the paper; Amano H, Miyake K, Hinoki A, Yokota K, Tanaka Y, Seto Y, and Uchida H revised this paper critically.
Institutional animal care and use committee statement: This experiment was approved by the Animal Experiment Committee of Nagoya University (Approval ID: 31354).
Conflict-of-interest statement: The authors have no conflict of interest to declare.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Hiroo Uchida MD, PhD, Professor, Chairman, Department of Pediatric Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya 466-8550, Japan. hiro2013@med.nagoya-u.ac.jp
Received: September 3, 2019
Peer-review started: September 3, 2019
First decision: October 14, 2019
Revised: December 14, 2019
Accepted: December 21, 2019
Article in press: December 21, 2019
Published online: February 6, 2020
Processing time: 155 Days and 17.6 Hours
Abstract
BACKGROUND

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.

AIM

To investigate the in vitro mechanical properties and degradation behavior and in vivo safety and feasibility of biodegradable Zn alloy staples.

METHODS

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.

RESULTS

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.

CONCLUSION

Staples made of Zn-1.0Cu-0.2Mn-0.1Ti, Zn-1.0Mn-0.1Ti, and Zn-1.0Cu-0.1Ti exhibit acceptable in vitro mechanical properties, proper degradation behavior, and in vivo safety and feasibility. They are promising candidates for biodegradable staples.

Keywords: Zinc alloy; Surgical staple; Gastric resection; Biodegradability, Biocompatibility; Mechanical Strength

Core tip: Biodegradable Zn alloy can be prepared with adequate strength, ductility, biodegradability, and biocompatibility for use as surgical staples by alloying with ≤1 wt.% Mn or Cu and 0.1 wt.% Ti. Immersion tests reveal no gas evolution or staple fracture. In vivo, none of the Zn alloy staples cause technical failure, and all rabbits survive without complications. The degradation times are sufficient for wound healing. The degradation rate is increased under low pH conditions, suggesting staples used for resection or anastomosis of gastrointestinal tracts would degrade faster, as they are exposed to acidic digestive fluids.