Silvia Galli

Magnesium (Mg) - based alloys are becoming attractive materials for medical applications as temporary bone implants for support of fracture healing, e.g. as a suture anchor. Due to their mechanical properties and biocompatibility, they may replace titanium or stainless-steel implants, commonly used in orthopedic field. Nevertheless, patient safety has to be assured by finding a long-term balance between metal degradation, osseointegration, bone ultrastructure adaptation and element distribution in organs. In order to determine the implant behavior and its influence on bone and tissues, we investigated two Mg alloys with gadolinium contents of 5 and 10 wt percent in comparison to permanent materials titanium and polyether ether ketone. The implants were present in rat tibia for 10, 20 and 32 weeks before sacrifice of the animal. Synchrotron radiation-based micro computed tomography enables the distinction of features like residual metal, degradation layer and bone structure. Additionally, X-ray diffraction and X-ray fluorescence yield information on parameters describing the bone ultrastructure and elemental composition at the bone-to-implant interface. Finally, with element specific mass spectrometry, the elements and their accumulation in the main organs and tissues are traced. The results show that Mg-xGd implants degrade in vivo under the formation of a stable degradation layer with bone remodeling similar to that of Ti after 10 weeks. No accumulation of Mg and Gd was observed in selected organs, except for the interfacial bone after 8 months of healing. Thus, we confirm that Mg-5Gd and Mg-10Gd are suitable material choices for bone implants.

The microstructural architecture of remodeled bone in the peri-implant region of screw implants plays a vital role in the distribution of strain energy and implant stability. We present a study in which screw implants made from titanium, polyetheretherketone and biodegradable magnesium-gadolinium alloys were implanted into rat tibia and subjected to a push-out test four, eight and twelve weeks after implantation. Screws were 4 mm in length and with an M2 thread. The loading experiment was accompanied by simultaneous three-dimensional imaging using synchrotron-radiation microcomputed tomography at 5 μm resolution. Bone deformation and strains were tracked by applying optical flow-based digital volume correlation to the recorded image sequences. Implant stabilities measured for screws of biodegradable alloys were comparable to pins whereas non-degradable biomaterials experienced additional mechanical stabilization. Peri-implant bone morphology and strain transfer from the loaded implant site depended heavily on the biomaterial utilized. Titanium implants stimulated rapid callus formation displaying a consistent monomodal strain profile whereas the bone volume fraction in the vicinity of magnesium-gadolinium alloys exhibited a minimum close to the interface of the implant and less ordered strain transfer. Correlations in our data suggest that implant stability benefits from disparate bone morphological properties depending on the biomaterial utilized. This leaves the choice of biomaterial as situational depending on local tissue properties.

Biodegradable magnesium (Mg) implants are emerging as a potential game changer in implant technology in situations where the implant temporarily supports the bone thereby avoiding secondary surgery for implant removal. However, the consequences of the alteration in the degradation rate to bone healing and the localization of degradation and alloying products in the long term remain unknown. In this study, we present the long-term osseointegration of three different biodegradable Mg alloys, Mg-10Gd, Mg-4Y-3RE and Mg-2Ag, which were implanted into rabbit femur for 6 and 9 months. In addition, we have investigated the effect of blood pre-incubation on the in vivo performance of the aforementioned alloys. Using high-resolution synchrotron radiation based micro computed tomography, the bone implant contact (BIC), bone volume fraction (BV/TV) and implant morphology were studied. The elemental traces have been characterized using micro X-ray fluorescence. Qualitative histological evaluation of the surrounding bone was also performed. Matured bone formed around all three implant types and Ca as well as P which represent parts of the degradation layer were in intimate contact with the bone. Blood pre-incubation prior to implantation significantly improved BIC in Mg-2Ag screws at 9 months. Despite different implant degradation morphologies pointing toward different degradation dynamics, Mg-10Gd, Mg-4Y-3RE and Mg-2Ag induced a similar long-term bone response based on our quantified parameters. Importantly, RE elements Gd and Y used in the alloys remained at the implantation site implying that they might be released later on or might persist in the implantation site forever. As the bone formation was not disturbed by their presence, it might be concluded that Gd and Y are non-deleterious. Consequently, we have shown that short and mid-term in vivo evaluations do not fully represent indicators for long-term osseointegration of Mg-based implants.

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.

Objectives This randomised controlled trial compares the three-year outcomes, i.e. marginal bone level (MBL) changes and clinical parameters, between an abutment level (AL) and implant level (IL) connection for implants with an internal conical connection (ICC) supporting a screw-retained fixed partial denture. Material and methods Fifty patients with 119 implants were randomly allocated to either the AL or IL group. Radiographic and clinical examinations were performed after one, two, and three years. A linear mixed model was used to evaluate the differences between groups. Results The MBL change was not significantly different between the groups at any point. The MBL was 0.12±0.31mm (AL) and 0.23±0.26mm (IL) after one year; 0.15±0.34mm (AL) and 0.17±0.22mm (IL) after two years; 0.18 ± 0.39mm (AL) and 0.15±0.21mm (IL) after three years. The bleeding on probing was 43.44±39.24% (AL) and 58.19±41.20% (IL) after one year; 35.78±39.22% (AL) and 50.43±41.49% (IL) after two years; 51.27±44.63% (AL) and 49.57±37.31% (IL) after three years and was significantly different (p = 0.025) between one- and two- year. The probing depth showed a significant difference at each time point while the plaque was not significant between the group. The overall technical, biological, and prosthetic complication rates were 5.04%, 3.36%, and 16.00%, respectively. Conclusions The MBL change was similar in the groups. The slight differences in the soft tissue complications between the groups are likely not of clinical relevance. An IL connection is considered to be a valid alternative to an AL setup in ICC implants.

The clinical value of ligature-induced experimental peri-implantitis studies has been questioned due to the artificial nature of the model. Despite repeated claims that ligatures of silk, cotton and other materials may not induce bone resorption by themselves; a recent review showed that the tissue reaction toward them has not been investigated. Hence, the current study aimed to explore the hard and soft tissue reactions toward commonly used ligature materials. A total of 60 dental implants were inserted into the femur (n = 20) and tibia (n = 40) of 10 rabbits. The femoral implants were ligated with sterile 3-0 braided silk in one leg and sterile cotton retraction chord in the other leg. The tibial implants were ligated with silk or left as non-ligated controls. All wounds were closed in layers. After a healing time of 8 weeks, femoral (silk versus cotton) and proximal tibial (silk versus non-ligated control) implants were investigated histologically. Distal tibial (silk versus non-ligated control) implants were investigated with real time polymerase chain reaction (qPCR). The distance from the implant-top to first bone contact point was longer for silk ligated implants compared to non-ligated controls (p = 0.007), but did not vary between cotton and silk. The ligatures triggered an immunological reaction with cell infiltrates in close contact with the ligature materials, adjacent soft tissue encapsulation and bone resorption. qPCR further demonstrated an upregulated immune response toward the silk ligatures compared to non-ligated controls. Silk and cotton ligatures provoke foreign body reactions of soft tissue encapsulation type and bone resorption around implants in the absence of plaque.

Osseointegration is likely the result of an immunologically driven bone reaction to materials such as titanium. Osseointegration has resulted in the clinical possibility to anchor oral implants in jaw bone tissue. However, the mechanisms behind bony anchorage are not fully understood and complications over a longer period of time have been reported. The current study aims at exploring possible differences between copper (Cu) and polyetheretherketone (PEEK) materials that do not osseointegrate, with osseointegrating cp titanium as control. The implants were placed in rabbit tibia and selected immune markers were evaluated at 10 and 28 days of follow-up. Cu and PEEK demonstrated at both time points a higher immune activation than cp titanium. Cu demonstrated distance osteogenesis due to a maintained proinflammatory environment over time, and PEEK failed to osseointegrate due to an immunologically defined preferential adipose tissue formation on its surface. The here presented results suggest the description of two different mechanisms for failed osseointegration, both of which are correlated to the immune system.

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.