Biodegradable Mg-based alloys: biological implications and restorative opportunities

Figures & data

Figure 1. Schematic of the degradation environment of a Mg-based alloy screw in bone tissue.

Figure 2. Schematic of the biomechanical environment of a stent in a blood vessel.

Table 1. Summary of biological processes at cellular and tissue levels that can be mediated by the degradation products of Mg-based alloys.

Degradation products	Biological processes	Ref.
Mg^2+ ions	Bone metabolism homeostasis in bone modelling and remodelling; Osteoblast and osteoclast number in bone; Bone mineralization	[175–180]
	Fibroblast migration	[181,182]
	BMSC proliferation, adhesion, osteogenic differentiation, and ECM mineralization; Proliferation rates and immune responses of MSCs; Adhesion, proliferation, deposition of mineral matrix, the expression of TRPM7 and ALP osteoblasts; Osteoclastogenesis, proliferation and differentiation of osteoclasts	[20,79–83,138,139,183–185]
	Binding interactions between the integrin family on cell surface and their ligand proteins	[87]
	Homeostasis and function of endothelial cells; VEGF expression in BMSCs	[84,138,186–189]
	Inflammation response; Crosstalk behaviour between immune cells and other cells	[86,189–197]
	Local neuronal production of CGRP	[20]
	Smooth muscle cell proliferation; Calcification in vascular smooth muscle cells	[141,198–201]
	Neuronal protection; Injury-induced NPCs death; Differentiation of NPCs towards the neural cell	[202–205]
	Cartilage regeneration and homeostasis; Chondrocyte proliferation, redifferentiation and GAG production; Chondrogenic differentiation of mesenchymal stem cells	[193,197,206–209]
	Oxidation and Apoptosis of cell (as an antagonist of Ca^2+); Pathological calcification of articular cartilage (as an antagonist of Ca^2+)	[210–214]
OH^- ions/Extracellular pH level	Intracellular Ca of vascular smooth-muscle cells and vascular smooth muscle tone; Intracellular pH and intracellular nitric oxide concentration of endothelial and vascular smooth muscle cell; Vasoconstriction of vascular smooth muscle	[215–217]
	Growth and osteogenic differentiation of stem cells; Proliferation, collagen synthesis, ALP activity, and thymidine incorporation of osteoblasts; Osteoclast formation and activity, and osteoclastic beta-glucuronidase release	[91,140,218–224]
	Wound healing and tissue regeneration process; Cell migration rate and DNA synthesis of fibroblasts	[58,89,225]
	Bacterial growth and activity	[95,226,227]
	Inflammation responses	[92–94]
H2 gas	Growth and activity of tumour cells	[228–230]
	Bacterial growth and biofilm formation	[231]
	Oxidative stress of cells, cell apoptosis, and tissue inflammatory response	[98–105,232–234]
	Osteoclastogenesis	[235]

Figure 3. Representative images showing the formation of porosity in the bone near Mg-based alloy implants. (a) Ex vivo micro-CT 2-D images of bone implant complexes after implantation of LAE442 alloy in NZW rabbit tibia for 12 months [21]. T: tibia; F: fibula; E: endosteal bone formation; C: cavities. (b) Micro-CT images of rat femora implanted with pure Mg or SS rod for 2 weeks [20]. (c) Tartrate-resistant acid phosphatase (TRAP)-stained histological slices of mouse femora cortical bone on the 14^th days after implantation with Mg or Ti rods.

Figure 4. Examples of Mg-alloy-based bone-fixation implants. (a) Mg plate and screws for fractured ulna fixation. μCT and toluidine-blue staining of cortical bone after 8 and 16 weeks [376]. (b) Pure-Mg and PLLA screws for femoral intracondylar fracture fixation. μCT scanning of rabbit femur with screws after 4 weeks (red arrows: fracture gap) [277]; (c) SrHPO4-coated JDBM (a Mg–Nd–Zn–Zr alloy) IMNs. Undecalcified sections with Von Gieson staining and μCT 3D reconstruction of rat femurs with IMNs after 8 weeks (red boxes: fracture gap region) [239]; (d) Pure-Mg screw for goat femoral neck fracture fixation, and preoperative and 48-week postoperative μCT 3D reconstruction [380]; (e) Ti/Mg hybrid plate screw system for the fractured tibia fixation (red or blue arrows: Mg screw with PLA coating) [278]; (f) SS/Mg hybrid IMN made by inserting a Mg rod into a hollow stainless steel needle with drilled holes [20].

Figure 5. Spinal cage made of Mg-based alloys. (a) A hybrid cage consisting of the AZ31 alloy and PCL [391]. Left: AZ31 alloy skeleton of the cage, Right: Cage after infiltration and covering with the PCL; (b) A micro-arc oxidation (MAO)-coated Mg–Zn alloy cage [392]; (c) An MAO-coated AZ31 alloy cage [393].

Figure 6. Animal studies and clinical case analysis of Mg-based alloy vascular stents. (a) Haematoxylin-eosin (H&E) staining images and μCT 3D reconstructed images of JDBM (a Mg–Nd–Zn–Zr alloy) stents in rabbit common carotid artery at different time points [407]; (b) Optical coherence tomography 2D images of Magmaris® WE43-alloy-based stent in human coronary artery demonstrated excellent strut apposition with some struts covering the side branch post-implantation; no visible strut remnants exist; and struts initially covering the side branch being resorbed after 12 months [6].

Figure 7. Animal studies of Mg-based surgical instruments for hemostasis and anastomosis. (a) Mg-Zn-Ca-Y alloy clip occluded the proximal and telecentric stump of rat carotid blood vessels (i), and cuts the blood vessel from the middle of the two hemostatic clips (ii) [420]; (b) Pure-Mg staples for anastomose small intestine (i), and no bleeding and intestinal fluid exudation after anastomosis (ii) [421]; (c) Mg–Zn–Sr intestinal anastomosis ring (i) and surgical procedure of intestinal anastomosis(ii) [422].

Figure 8. Mg-based tissue engineering scaffolds for bone defect repair. (a) Digital and scanning electron microscope (SEM) images of Mg/JDBM-MgF₂ scaffold without and with brushite (DCPD) coating. μCT images showing the new bone and vascular formation in the defect area after 4 and 8 weeks (red or white line: bone defect area) [431]; (b) SEM and 2D μCT images of Mg scaffolds; 2D μCT images (red arrows: new bone) and alizarin red S and calcein sequential labels of new bone after 16 weeks [167]; (c) MAO-coated tubular Mg–Zn–Ca scaffold for ulna bone defect repair and X-ray observation after 2, 4, 8 and 12 weeks [433]; (d) A biomimetic-porous Mg material coated with HA/(PEI-SiO₂) hybrid layer for femoropatellar defect repair, and a μCT image of femoropatellar bone and the porous Mg [435]; (e) A biomimetic-Mg scaffold for humerus defect repair and X-ray images at various periods [436]; (f) μCT and SEM images of porous alginate/gelatin hydrogel with Mg powder. μCT images, sequential fluorescence staining, H&E staining, and OSX/CD31 immunofluorescence staining of bone formation in defects after 3 weeks, and μCT images of 3D vasculature in defects after 2 weeks, in Blank, Mg free (−Mg) and Mg containing (+Mg) hydrogel groups [437].

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