Long-term clinical study and multiscale analysis of in vivo biodegradation mechanism of Mg alloy

Abstract

There has been a tremendous amount of research in the past decade to optimize the mechanical properties and degradation behavior of the biodegradable Mg alloy for orthopedic implant. Despite the feasibility of degrading implant, the lack of fundamental understanding about biocompatibility and underlying bone formation mechanism is currently limiting the use in clinical applications. Herein, we report the result of long-term clinical study and systematic investigation of bone formation mechanism of the biodegradable Mg-5wt%Ca-1wt%Zn alloy implant through simultaneous observation of changes in element composition and crystallinity within degrading interface at hierarchical levels. Controlled degradation of Mg-5wt%Ca-1wt%Zn alloy results in the formation of biomimicking calcification matrix at the degrading interface to initiate the bone formation process. This process facilitates early bone healing and allows the complete replacement of biodegradable Mg implant by the new bone within 1 y of implantation, as demonstrated in 53 cases of successful long-term clinical study.

Keywords: biodegradable implant; bone formation; clinical application.

Fig. 1.

Histological and SEM analysis of rabbit femoral condyle after 8 wk of implantation of Ø 2 × 6-mm cylindrical Mg alloy implant. (A) Implant–bone interface at low magnification, the degradation of the Mg alloy implant is evidenced by drawing the original surface line. Magnified image of bone formation region observed by (B) light microscopy, (C) fluorescence microscopy, and (D) SEM.

Fig. 2.

Hierarchical multiscale analysis of Mg alloy–implant interface. (A) Separation of regions in Mg alloy–implant interface: (i) merged image of the fluorescence and SEM images and (ii) SEM/EDX line profile. (B) Changes in the microstructure of the key regions; TEM images and SAD pattern (Inset) of (i) region I (Mg, O-rich: red arrowhead of A, i), (ii) region II (Ca, P-rich: blue arrowhead), (iii) region II′ (Ca, P-rich: sky-blue arrowhead), (iv) region III (bone: orange arrowhead). (C) TEM/EDX change of (Mg + Ca)/P ratio, Mg (%), Ca (%), and P (%) throughout regions I, II, II′, and III.

Fig. 3.

Gradual degradation of the Mg alloy interface and bone formation stained with Villanueva stain method at (A) 8 wk, (B) 16 wk, and (C) 26 wk postimplantation. (A, i) Mg alloy degradation observed under fluorescence light in low magnification at 8 wk, (B, i) 16 wk, and (C, i) 26 wk postimplantation. (A, ii) Bone formation observed in fluorescence light at high magnification at 8 wk, (B, ii) 16 wk, and (C, ii) 26 wk postimplantation. (A, iii) Bone formation observed in natural light at high magnification of 8 wk, (B, iii) 16 wk, and (C, iii) 26 wk postimplantation. Straight line in A, i, B, i, and C, i, indicates original implant surface line; dotted line refers to the center of implants at the time of implantation.

Fig. 4.

Clinical observation of complete degradation and bone healing of Mg alloy screw over a 1-y period. (A) A 1-y follow-up X-ray of patient that received Mg alloy implant (D 2.3 mm × L 14 mm) for the distal radius fracture and stainless steel conventional implant (CI) for the scaphoid nonunion. (B) X-ray images of (i) the distal radius fracture and the scaphoid nonunion before the surgical intervention, (ii) implantation site immediately taken after the surgical procedures to fix the distal radius fracture with Mg alloy implant and the scaphoid nonunion with CI, (iii) 6-mo follow-up, and (iv) complete degradation and bone healing after 1 y postoperation. (C) Schematic diagram showing implantation site and the change of Mg alloy over time: immediately, 6 mo, and 1 y after implantation. Red arrow shows the distal radius fracture, and white arrow is pointing at the scaphoid nonunion. Yellow arrow shows the Mg alloy implant.