A review on current research status of the surface modification of Zn-based biodegradable metals

Abstract

Recently, zinc and its alloys have been proposed as promising candidates for biodegradable metals (BMs), owning to their preferable corrosion behavior and acceptable biocompatibility in cardiovascular, bone and gastrointestinal environments, together with Mg-based and Fe-based BMs. However, there is the desire for surface treatment for Zn-based BMs to better control their biodegradation behavior. Firstly, the implantation of some Zn-based BMs in cardiovascular environment exhibited intimal activation with mild inflammation. Secondly, for orthopedic applications, the biodegradation rates of Zn-based BMs are relatively slow, resulting in a long-term retention after fulfilling their mission. Meanwhile, excessive Zn²⁺ release during degradation will cause in vitro cytotoxicity and in vivo delayed osseointegration. In this review, we firstly summarized the current surface modification methods of Zn-based alloys for the industrial applications. Then we comprehensively summarized the recent progress of biomedical bulk Zn-based BMs as well as the corresponding surface modification strategies. Last but not least, the future perspectives towards the design of surface bio-functionalized coatings on Zn-based BMs for orthopedic and cardiovascular applications were also briefly proposed.

Keywords: Biocompatibility; Corrosion behavior; Osseointegration; Surface modification; Zn-based biodegradable metals.

Graphical abstract

Fig. 1

The representative surface modification methods of industrial Zn-based alloys. (Reproduced with permissions from Refs. [[13], [14], [15], [16], [17], [18], [19], [20]]).

Fig. 2

(a) Biodegradation mechanism of metals. (Reproduced with permissions from Ref. [97]). (b) The evolution of degradation behavior and mechanical integrity of biodegradable metallic stents during the vascular healing process. (Reproduced with permissions from Ref. [94]). (c) Schema of biodegradable metallic stents over time post-procedure (The left part of the stent in each panel shows the surface layer and right part refers to the internal strut). (Reproduced with permissions from Ref. [98]). (d) The evolution of the degradation behavior and the mechanical integrity of BMs during bone healing process. (Reproduced with permissions from Ref. [94]). (e) Healing process stages in fractured bone. (Reproduced with permissions from Ref. [99]). (f) Healing period for the fixation of autologous bone grafts or bone fracture. (Reproduced with permissions from Ref. [100]).

Fig. 3

(a) Biological roles of Zn. (Reproduced with permissions from Ref. [114]). (b) Comparison of the influence of zinc excess versus deficiency. (Reproduced with permissions from Ref. [131]).

Fig. 4

Summary of reported cell viabilities of MC3T3-E1 cells, MG-63 cells and L929 cells cultured in the 100% extracts of Zn-based BMs for orthopedic applications (The annotation in the bracket shows the working history of the materials and the culturing time of cells. C, E, R, SPS and SLM refer to cast, extruded, rolled, spark plasma sintering and selective laser melting, respectively.) [107,109,132,135,137,138,141,142,[144], [145], [146], [147], [148], [149], [150], [151], [152], [153], [154], [155]].

Fig. 5

Representative in vivo biocompatibility of Zn-based bone implants in the literature: (a) Hard tissue sections of pure Zn, Zn-0.4Li, Zn-0.1Mn, Zn-0.8 Mg, Zn-0.8Ca, Zn-0.1Sr, Zn-0.4Fe, Zn-0.4Cu and Zn–2Ag in metaphysis. The magnified region is marked by red rectangle. NB, new bone; DP, degradation products; FT, fibrous tissue. Scale bar, 0.5 mm in low magnification, 500 μm in high magnification. (Reproduced with permissions from Ref. [109]). (b) Histological sections of mouse distal femoral shaft from Zn–1Mg, Zn–1Ca, Zn–1Sr implanted pins groups and the sham control group observed under fluorescent microscopy at week 8. (Reproduced with permissions from Ref. [132]). (c) Histological section of Zn-0.05 Mg implanted in rabbit tibial shaft for 24 weeks. There are normal cortical bones (blue arrow); implant (white arrow); newly formed bone fractions around the implant (red arrow); bone junction between cortical bone and new bone formation (green arrow). (Reproduced with permissions from Ref. [107]). (d) Hard tissue sections of the Zn-0.1Li alloy after 8 and 12 weeks' implantation in rat femur condyle. (Reproduced with permissions from Ref. [135]). Hard tissue sections of (e) pure Zn (Reproduced with permissions from Ref. [146]), (f) Zn-5HA composite (Reproduced with permissions from Ref. [146]) and (g) Zn–5Mg composite (Reproduced with permissions from Ref. [145]) fabricated by spark plasma sintering after being implanted in the rat femur condyle for 4 and 8 weeks. The red rectangles correspond to the magnified bone-implant interface. The red triangle indicates newly formed bone. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 6

Representative in vivo biocompatibility of Zn-based cardiovascular implants in the literature: (a) hematoxylin-eosin (H&E) stained sections of abdominal aorta after 1, 3, 6 and 12 months' implantation of pure Zn stents. (Reproduced with permissions from Ref. [164]). (b) H&E-stained cross-sections after implantation of Zn-0.8Cu alloy stents in the porcine coronary arteries for 1, 3, 9, 24 months. (Reproduced with permissions from Ref. [165]). (c) Histologic images of representative cross-sections of porcine iliofemoral arteries stented with a Zn–3Ag bioresorbable vascular stent after 3 and 6 months. (Reproduced with permissions from Ref. [166]). (d) H&E staining of 6-months implanted Zn-0.002 Mg, Zn-0.005 Mg, and Zn-0.08 Mg alloy wires through the arterial lumen at different magnifications. 2nd and 3rd rows correspond to green and yellow asterisks respectively at high magnifications. L denotes the luminal opening. (Reproduced with permissions from Ref. [167]). (e) H&E staining of Zn-0.1Li alloy wires after 11months′ implantation in the abdominal aorta of Sprague Dawley rat. Low magnification images show two subsequent areas selected for high magnification. “L” is the luminal opening of the artery. (Reproduced with permissions from Ref. [168]). (f) H&E staining of Zn–xAl alloy (x = 1, 3 and 5) strips after implantation in the wall of the abdominal aorta of adult Sprague-Dawley rats for 1.5–6 months. Black triangles mark the interface between the native adventitial tissue and corroding product/remodeled tissue. (Reproduced with permissions from Ref. [169]). (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 7

The representative surface morphologies of the coatings prepared by different surface modification methods of Zn-based BMs for orthopedic application: (a) Microarc oxidation coating. (Reproduced with permissions from Ref. [137]). (b) Phosphate conversion coating. (Reproduced with permissions from Ref. [136]). (c) Biomimetic deposition. (Reproduced with permissions from Ref. [155]). (d) Collagen coating. (Reproduced with permissions from Ref. [136]). (e) Atomic layer deposition of ZrO₂ coating. (Reproduced with permissions from Ref. [135]).

Fig. 8

The surface morphologies of the coatings prepared by different surface modification methods of Zn-based BMs for cardiovascular applications: (a) Anodization coating. (Reproduced with permissions from Ref. [223]). (b) Electropolished surface (Reproduced with permissions from Ref. [223]). (c) Air oxidation coating (Reproduced with permissions from Ref. [223]). (d) PLLA coating. (Reproduced with permissions from Ref. [222]).

Fig. 9

The future perspectives of surface modification of Zn-based BMs for orthopedic and cardiovascular applications.