Bone anchored biomaterials have become an indispensable solution for the restoration of lost dental elements and for skeletal joint replacements. However, a thorough understanding is still lacking in terms of the biological mechanisms leading to osseointegration and its contrast, unwanted peri-implant bone loss. We have previously hypothesized on the participation of immune mechanisms in such processes, and later demonstrated enhanced bone immune activation up to 4 weeks around titanium implants. The current experimental study explored and compared in a rabbit tibia model after 10 days of healing time, the bone inflammation/immunological reaction at mRNA level towards titanium, polyether ether ketone (PEEK) and copper compared to a Sham control. Samples from the test and control sites were, after a healing period, processed for gene expression analysis (polymerase chain reaction, (qPCR)) and decalcified histology tissue analysis. All materials displayed immune activation and suppression of bone resorption, when compared to sham. The M1 (inflammatory)/M2 (reparative) -macrophage phenotype balance was correlated to the proximity and volume of bone growth at the implant vicinity, with titanium demonstrating a M2-phenotype at 10 days, whereas copper and PEEK were still dealing with a mixed M1- and M2-phenotype environment. Titanium was the only material showing adequate bone growth and proximity inside the implant threads. There was a consistent upregulation of (T-cell surface glycoprotein CD4) CD4 and downregulation of (T-cell transmembrane glycoprotein CD8) CD8, indicating a CD4-lymphocyte phenotype driven reaction around all materials at 10 days.

Summary Magnesium has a key role in osteoporosis and could enhance implant osseointegration in osteoporotic patients. Titanium implants impregnated with Mg ions were installed in the tibia of ovariectomized rats. The release of Mg induced a significant increase of bone formation and the expression of anabolic markers in the peri-implant bone. Introduction The success of endosseous implants is highly predictable in patients possessing normal bone status, but it may be impaired in patients with osteoporosis. Thus, the application of strategies that adjuvate implant healing in compromized sites is of great interest. Magnesium has a key role in osteoporosis prevention and it is an interesting candidate for this purpose. In this study, the cellular and molecular effects of magnesium release from implants were investigated at the early healing stages of implant integration. Methods Osteoporosis was induced in 24 female rats by means of ovariectomy and low-calcium diet. Titanium mini-screws were coated with mesoporous titania films and were loaded with magnesium (test group) or left as native (control group). The implants were inserted in the tibia and femur of the rats. One, 2 and 7 days after implantation, the implants were retrieved and histologically examined. In addition, expression of genes was evaluated in the peri-implant bone tissue at day 7 by means of quantitative polymerase chain reactions with pathway-oriented arrays. Results The histological evaluation revealed that new bone formation started already during the first week of healing for both groups. However, around the test implants, new bone was significantly more abundant and spread along a larger surface of the implants. In addition, the release of magnesium induced a significantly higher expression of BMP6. Conclusions These results provide evidence that the release of magnesium promoted rapid bone formation and the activation of osteogenic signals in the vicinity of implants placed in osteoporotic bone.

Peer reviewed article authored by (Wennerberg A, Galli S, Albrektsson T). Read article or submit your manuscript for publishing.

Magnesium alloys are increasingly researched as temporary biodegradable metal implants in bone applications due to their mechanical properties which are more similar to bone than conventional implant metals and the fact that Magnesium occurs naturally within the body. However, the degradation processes in vivo and in particular the interaction of the bone with the degrading material need to be further investigated. In this study we are presenting the first quantitative comparison of the bone ultrastructure formed at the interface of biodegradable Mg-5Gd and Mg-10Gd implants and titanium and PEEK implants after 4, 8 and 12 weeks healing time using two-dimensional small angle X-ray scattering and X-ray diffraction. Differences in mineralization, orientation and thickness of the hydroxyapatite are assessed. We find statistically significant (p < 0.05) differences for the lattice spacing of the (310)-reflex of hydroxyapatite between titanium and Mg-xGd materials, as well as for the (310) crystal size between titanium and Mg-5Gd, indicating a possible deposition of Mg within the bone matrix. The (310) lattice spacing and crystallite size further differ significantly between implant degradation layer and surrounding bone (p < 0.001 for Mg-10Gd), suggesting apatite formation with significant amounts of Gd and Mg within the degradation layer. STATEMENT OF SIGNIFICANCE: Biodegradable Magnesium-based alloys are emerging as a viable alternative for temporary bone implant applications. However, in order to understand if the degradation of the implant material influences the bone ultrastructure, it is necessary to study the bone structure using high-resolution techniques. We have therefore employed 2D small angle X-ray scattering and X-ray diffraction to study the bone ultrastructure surrounding Magnesium-Gadolinium alloys as well as Titanium and PEEK alloys at three different healing times. This is the first time, that the bone ultrastructure around these materials is directly compared and that a statistical evaluation is performed. We found differences indicating a possible deposition of Mg within the bone matrix as well as a local deposition of Mg and/or Gd at the implant site. DATA AVAILABILITY STATEMENT: The raw/processed data required to reproduce these findings cannot be shared at this time as the data also forms part of an ongoing study.

Biodegradable magnesium (Mg) alloys can revolutionize osteosynthesis, because they have mechanical properties similar to those of the bone, and degrade over time, avoiding the need of removal surgery. However, they are not yet routinely applied because their degradation behavior is not fully understood.