Biodegradable magnesium barrier membrane used for guided bone regeneration in dental surgery

Abstract

Barrier membranes are commonly used as part of the dental surgical technique guided bone regeneration (GBR) and are often made of resorbable collagen or non-resorbable materials such as PTFE. While collagen membranes do not provide sufficient mechanical protection of the covered bone defect, titanium reinforced membranes and non-resorbable membranes need to be removed in a second surgery. Thus, biodegradable GBR membranes made of pure magnesium might be an alternative. In this study a biodegradable pure magnesium (99.95%) membrane has been proven to have all of the necessary requirements for an optimal regenerative outcome from both a mechanical and biological perspective. After implantation, the magnesium membrane separates the regenerating bone from the overlying, faster proliferating soft tissue. During the initial healing period, the membrane maintained a barrier function and space provision, whilst retaining the positioning of the bone graft material within the defect space. As the magnesium metal corroded, it formed a salty corrosion layer and local gas cavities, both of which extended the functional lifespan of the membrane barrier capabilities. During the resorption of the magnesium metal and magnesium salts, it was observed that the membrane became surrounded and then replaced by new bone. After the membrane had completely resorbed, only healthy tissue remained. The in vivo performance study demonstrated that the magnesium membrane has a comparable healing response and tissue regeneration to that of a resorbable collagen membrane. Overall, the magnesium membrane demonstrated all of the ideal qualities for a barrier membrane used in GBR treatment.

Keywords: Biodegradable; Bone healing; GBR; GBR, Guided Bone Regeneration; Implant; Magnesium; Soft tissue healing.

Graphical abstract

Fig. 1

The magnesium barrier membrane (NOVAMag® membrane, botiss biomaterials GmbH, Germany) and its insertion protocol. a) The magnesium membrane. b) Before placement of the membrane, the defect sites is prepared for augmentation and filled with an appropriate bone augmentation material. c) The membrane is cut to shape using a pair of scissors (NOVAMag® scissors). d) The membrane is then bent to fit the defect site contours. e) The membrane is fixated from both the buccal and palatial/lingual sides. f) The mucoperiosteal flap is sutured closed over the membrane for closed wound healing.

Fig. 2

Test setups for the mechanical evaluation of the magnesium membrane (colored dark grey in schematics). In the schematics, the light grey colored pieces of equipment move in the direction of the blue arrow, whilst the white colored pieces remain in a fixed position. a) Dogbone shape and tensile test setup for the magnesium membrane. b) Membrane bending test setup, based on the ISO 7438-05 (Metallic materials – Bend test). c) Setup testing for the resistance of the membrane to tensile loads at its anchoring point. This setup is based on the requirements of ASTM F564. d) Test setup for the “Small punch test”, based on the requirements of ASTM F2183-02. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 3

Approximate positions of the defect/implant sites used for the Beagle dog in vivo study. a) In a preparatory surgery, four teeth between the mandibular second premolar to the first molar (PM2 to M1) on each side of the lower jaw and the corresponding teeth of the upper jaw were surgically extracted. b) After a healing period of 12 ± 2 weeks, two independent bone defects were created on each side of the lower jaw. The defects were filled with bone substitute material and covered with a magnesium or collagen membrane fixed with 4 titanium screws (2 on buccal and 2 on lingual side). The left side defect in b) shows the positioning of the magnesium membrane secured with fixation screws and the right side defect demonstrates the position of the defect under the membrane.

Fig. 4

Microstructure of pure Mg membrane (99.95 wt%). Not fully recrystallized structure with an almost homogenous distribution of grains in the range of 1–10 μm (arrow in enlarged insert). Black areas are artifacts from sample preparation.

Fig. 5

Mechanical test data for: a) Tensile testing of the magnesium membrane; b) Bend test of the magnesium membrane; and the Ultimate Load at Anchor Point for c) the magnesium membrane and d) a collagen membrane.

Fig. 6

In vitro immersion corrosion test results: a) the percentage of the membrane corroded in comparison to its initial weight; b) the respective corrosion rate calculated for each time point; and c) is the results of the “small punch test”, with the result of the undegraded collagen membrane shown as a horizontal dashed line at 28.3 ± 1.6 N.

Fig. 7

SRμCT images demonstrating the corrosion kinetics of the magnesium membrane when implanted into Yucatan minipigs after: 1 week (a, b), 2 weeks (c, d), 4 weeks (e, f), and 8 weeks (g, h). The scale bar in each image represents 250 μm. Grey scale images (a, c, e, g) and false colored images (b, d, f, h) are shown to emphasize magnesium membrane location within the surrounding tissue and display magnesium metal corrosion products. In the colorized images: Soft tissue (light blue) and mineralized bone tissue (green) adhere to the surface of the membrane. The magnesium metal (yellow) can be seen to gradually corrode into magnesium salts (orange and red). (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 8

Representable scanned Goldner's Trichrome histology images of GBR performance study on beagles. Dotted Line = edges of the defect site; Asterisks (*) = particles of bone filler material within the defect site; Red Arrow = void/cavity/gas space; (a), (b), (c) and (d) are presenting the magnesium membrane where we can see that is degrading/reabsorbing over time, and by 8 weeks (b), only small residual particles of the magnesium membrane are left, surrounded by new bone and little part of void space. At 16 weeks (c) and 52 weeks (d) the magnesium membrane is completely absorbed and replaced by new bone. (e), (f), (g) and (h) are presenting a collagen membrane at all time points; 1 week (e), 8 weeks (f), 16 weeks (g) and 52 weeks (h). In each image, the scale bar represents 3 mm. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 9

Histology measurements of new bone formation and the soft tissue infiltration. Certain measurements for New Bone Growth show no standard deviation due to uniformity of results at these specific timepoints.

Fig. 10

Histomorphometric measurements for the percentages of bone area, bone substitute total area, soft tissue total area and void area within the defect site of magnesium membrane and collagen membrane treatment groups.