Novel zinc alloys for biodegradable surgical staples

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

Figure 1

Mechanical properties of Zn alloy sheets. A: 0.2% yield strength; B: Elongation.

Figure 2

Weight change of Zn alloy staples after immersion in simulated body fluids. A: Fed-state simulated intestinal fluid; B: Hank's balanced salt solution (+) without phenol red.

Figure 3

Representative scanning electron microscopy images and X-ray diffraction patterns of Zn–1.0Cu–0.2Mn–0.1Ti (Zn alloy 1) staples after 4 wk of immersion in simulated body fluids. A: Fed-state simulated intestinal fluid; B: Hank's balanced salt solution (+) without phenol red.

Figure 4

Staple line using Zn alloy and Ti alloy staples.

Figure 5

Macroscopic appearance and representative scanning electron microscopy images of staples after 12 wks’ implantation.

Figure 6

Representative scanning electron microscopy images and energy dispersive spectrometry elemental maps of staple cross-sections after 12 wks’ implantation.

Figure 7

Histopathological images of rabbit gastric tissues surrounding Zn alloy and Ti alloy staples after hematoxylin–eosin staining. Blue arrows indicate fibrous layers of tissue (observed around both, the Ti alloy and Zn alloy staples), and yellow arrows indicate inflammatory cell infiltrations (localized around Zn alloy staples only).