Clinical, radiographic, and histological/histomorphometric analysis of maxillary sinus grafting with deproteinized porcine or bovine bone mineral: A randomized clinical trial.

OBJECTIVE: The present study aimed to compare histomorphometrically evaluated new bone formation, radiographically measured graft stability, and clinical implant outcome between maxillary sinus grafting with either deproteinized porcine bone mineral (DPBM) or deproteinized bovine bone mineral (DBBM). MATERIALS AND METHODS: Thirty maxillary sinuses were initially included and randomly assigned to the test group (TG; DPBM, n = 15) or control group (CG; DBBM, n = 15). After a healing period (6 months), axially retrieved bone biopsies of the molar region were used for histological/histomorphometric analysis of new bone formations. Additionally, radiographically measured graft stability and clinical implant outcome were assessed. RESULTS: Twenty-three sinus sites with 10 sinuses of the TG and 13 of the CG were ultimately available for data and statistical analysis. In the TG, a slightly, but yet significantly (p = .040) higher proportion of new bone formation (TG: 27.7 ± 5.6% vs. CG: 22.9 ± 5.1%) and a lesser (p = .019) amount of connective (non-mineralized) tissue (TG: 47.5 ± 9.5% vs. CG: 56.1 ± 9.5%) was found than in the CG. However, both xenografts showed comparable (n.s.) residual bone graft (TG: 23.7 ± 7.2% vs. CG: 21.1 ± 9.85.6%), bone-to-graft contacts (TG: 26.2 ± 9.8% vs. CG: 30.8 ± 13.8%), similar graft height reduction over time (TG: 12.9 ± 6.7% CG: 12.4 ± 5.8%) and implant survival/success rate (100%). At the 3-year post-loading evaluation, the peri-implant marginal bone loss (TG: 0.52 ± 0.19 mm; CG: 0.48 ± 0.15 mm) and the peri-implant health conditions (TG: 87.5%/CG: 81.2%) did not differ between implants inserted in both xenografts used. CONCLUSIONS: The use of DPBM or DBBM for maxillary sinus augmentation is associated with comparable bone formation providing stable graft dimension combined with healthy peri-implant conditions.

Mg-Zn-Ca Alloy (ZX00) Screws Are Resorbed at a Mean of 2.5 Years After Medial Malleolar Fracture Fixation: Follow-up of a First-in-humans Application and Insights From a Sheep Model.

BACKGROUND: In the ongoing development of bioresorbable implants, there has been a particular focus on magnesium (Mg)-based alloys. Several Mg alloys have shown promising properties, including a lean, bioresorbable magnesium-zinc-calcium (Mg-Zn-Ca) alloy designated as ZX00. To our knowledge, this is the first clinically tested Mg-based alloy free from rare-earth elements or other elements. Its use in medial malleolar fractures has allowed for bone healing without requiring surgical removal. It is thus of interest to assess the resorption behavior of this novel bioresorbable implant. QUESTIONS/PURPOSES: (1) What is the behavior of implanted Mg-alloy (ZX00) screws in terms of resorption (implant volume, implant surface, and gas volume) and bone response (histologic evaluation) in a sheep model after 13 months and 25 months? (2) What are the radiographic changes and clinical outcomes, including patient-reported outcome measures, at a mean of 2.5 years after Mg-alloy (ZX00) screw fixation in patients with medial malleolar fractures? METHODS: A sheep model was used to assess 18 Mg-alloy (ZX00) different-length screws (29 mm, 24 mm, and 16 mm) implanted in the tibiae and compared with six titanium-alloy screws. Micro-CT was performed at 13 and 25 months to quantify the implant volume, implant surface, and gas volume at the implant sites, as well as histology at both timepoints. Between July 2018 and October 2019, we treated 20 patients with ZX00 screws for medial malleolar fractures in a first-in-humans study. We considered isolated, bimalleolar, or trimalleolar fractures potentially eligible. Thus, 20 patients were eligible for follow-up. However, 5% (one patient) of patients were excluded from the analysis because of an unplanned surgery for a pre-existing osteochondral lesion of the talus performed 17 months after ZX00 implantation. Additionally, another 5% (one patient) of patients were lost before reaching the minimum study follow-up period. Our required minimum follow-up period was 18 months to ensure sufficient time to observe the outcomes of interest. At this timepoint, 10% (two patients) of patients were either missing or lost to follow-up. The follow-up time was a mean of 2.5 ± 0.6 years and a median of 2.4 years (range 18 to 43 months). RESULTS: In this sheep model, after 13 months, the 29-mm screws (initial volume: 198 ± 1 mm3) degraded by 41% (116 ± 6 mm3, mean difference 82 [95% CI 71 to 92]; p < 0.001), and after 25 months by 65% (69 ± 7 mm3, mean difference 130 [95% CI 117 to 142]; p < 0.001). After 13 months, the 24-mm screws (initial volume: 174 ± 0.2 mm3) degraded by 51% (86 ± 21 mm3, mean difference 88 [95% CI 52 to 123]; p = 0.004), and after 25 months by 72% (49 ± 25 mm3, mean difference 125 [95% CI 83 to 167]; p = 0.003). After 13 months, the 16-mm screws (initial volume: 112 ± 5 mm3) degraded by 57% (49 ± 8 mm3, mean difference 63 [95% CI 50 to 76]; p < 0.001), and after 25 months by 61% (45 ± 10 mm3, mean difference 67 [95% CI 52 to 82]; p < 0.001). Histologic evaluation qualitatively showed ongoing resorption with new bone formation closely connected to the resorbing screw without an inflammatory reaction. In patients treated with Mg-alloy screws after a mean of 2.5 years, the implants were radiographically not visible in 17 of 18 patients and the bone had homogenous texture in 15 of 18 patients. No clinical or patient-reported complications were observed. CONCLUSION: In this sheep model, Mg-alloy (ZX00) screws showed a resorption to one-third of the original volume after 25 months, without eliciting adverse immunologic reactions, supporting biocompatibility during this period. Mg-alloy (ZX00) implants were not detectable on radiographs after a mean of 2.5 years, suggesting full resorption, but further studies are needed to assess environmental changes regarding bone quality at the implantation site after implant resorption. CLINICAL RELEVANCE: The study demonstrated successful healing of medial malleolar fractures using bioresorbable Mg-alloy screws without clinical complications or revision surgery, resulting in pain-free ankle function after 2.5 years. Future prospective studies with larger samples and extended follow-up periods are necessary to comprehensively assess the long-term effectiveness and safety of ZX00 screws, including an exploration of limitations when there is altered bone integrity, such as in those with osteoporosis. Additional use of advanced imaging techniques, such as high-resolution CT, can enhance evaluation accuracy.

Caspase inhibitor attenuates the shape changes in the alveolar ridge following tooth extraction: A pilot study in rats.

OBJECTIVE: The aim of the study was to determine whether the inhibition of apoptosis via pan-caspase inhibitors can attenuate the changes in the alveolar ridge upon tooth extraction. BACKGROUND: Cells undergoing apoptosis might play a central role in the onset of alveolar bone resorption and the ensuing bone atrophy following tooth extraction. Caspases are proteases that regulate apoptotic cell death. It is, therefore, reasonable to hypothesize that blocking apoptosis with pan-caspase inhibitors attenuates the changes in the alveolar ridge following tooth extraction. METHODS: In 16 inbred rats, the mandibular first (M1) and second (M2) molars of one side were extracted. Following random allocation, the rats received either a cell-permeable pan-caspase inhibitor or diluent. After a healing period of 10 days, changes in shape and height of the alveolar ridge were examined using geometric morphometrics and linear measurements based on micro-computed tomography. RESULTS: Geometric morphometric analysis revealed that the pan-caspase inhibitor prevented major shape changes of the alveolar ridge following M1 tooth extraction (P < .05). Furthermore, linear measurements confirmed that the pan-caspase inhibitor significantly prevented the atrophy of the alveolar ridge height following M1 tooth extraction compared to the diluent controls (-0.53 mm vs -0.24 mm; P = .012). M2 tooth extraction caused no shape changes of the alveolar ridge, and thus, the pan-caspase inhibitor group did not differ from the control group (-0.14 mm vs -0.05 mm; P = .931). CONCLUSIONS: These findings suggest that the inhibition of apoptosis may attenuate shape changes of the alveolar ridge following M1 tooth extraction in rodents.

Impaired periodontium and temporomandibular joints in tumour necrosis factor-α transgenic mice.

AIM: Tumour necrosis factor (TNF)-α is a pathological factor causing the characteristic symptoms of periodontal disease and rheumatoid arthritis. In this study, we describe the phenotypes of human TNF-α transgenic mice (hTNFtg) with respect to their periodontium and the temporomandibular joint (TMJ). MATERIAL AND METHODS: Periodontal structures, TMJ and skull shape of hTNFtg mice and wild-type (WT) littermates were assessed by microcomputed tomography, automated segmentation, geometric morphometrics and histologic ground sections. RESULTS: We show that hTNFtg mice have an eroded lamina dura and reduced periodontal ligament space compared to (WT) littermates. Transgenic mice further exhibit severe destruction of the TMJ. Geometric morphometrics revealed that hTNFtg mice have a more laterally positioned TMJ with a concomitantly enlarged zygomatic process. Mandibular and maxillary teeth occluded properly. CONCLUSIONS: Our findings suggest that chronic inflammation in hTNFtg mice causes destructive changes of the periodontium and the TMJ.

Comparison of marginal fit of cemented zirconia copings manufactured after digital impression with lava™ C.O.S and conventional impression technique.

BACKGROUND: Evaluation of the marginal fit of cemented zirconia copings manufactured after digital impression with Lava™ Chairside Oral Scanner in comparison to that of zirconia copings manufactured after conventional impressions with polyvinyl siloxane. METHODS: A prepared typodont tooth #36, was replicated 40 times with a vinyl silicone and precise model resin. The dies were randomly divided into two groups according to the impression taking technique. Digital impressions with Lava™ C.O.S. and conventional impressions were taken according to the group. Subsequently zirconia copings were manufactured and cemented on their respective dies with zinc oxide phosphate cement. After embedding in resin, mesio-distal section of each coping was performed with a diamond saw in order to obtain two slices. One half of the specimen was used for evaluation with an optical microscope (OM) and the other half for evaluation with a scanning electron microscope (SEM). Marginal gap (MG) and absolute marginal discrepancy (AMD) were measured mesial and distal on each slice. RESULTS: No significant difference of the marginal parameters between the digital and the conventional group was found. The mean values for MG in the digital group were 96.28 µm (+/-43.21 µm) measured with the OM and 99.26 µm (+/-48.73 µm) measured with the SEM, respectively. AMD mean values were 191.54 µm (+/-85.42 µm) measured with the optical microscope and 211.6 µm (+/-96.55 µm) with the SEM. For the conventional group the mean MG values were 94.84 µm (+/-50.77 µm) measured with the OM and 83.37 µm (+/-44.38 µm) measured with the SEM, respectively. AMD mean values were 158.60 µm (+/-69.14 µm) for the OM and 152.72 µm (+/-72.36) for the SEM. CONCLUSIONS: Copings manufactured after digital impression with Lava™ C.O.S. show comparable marginal parameters with the copings manufactured after conventional impression with polyvinyl syloxane. The mean MG values of both groups fit in the clinically acceptable range.

Alveolar bone regeneration in response to local application of calcitriol in vitamin D deficient rats.

AIM: Vitamin D deficiency is considered to diminish bone regeneration. Yet, raising the serum levels takes months. A topic application of the active vitamin D metabolite, calcitriol, may be an effective approach. Thus, it becomes important to know the effect of vitamin D deficiency and local application on alveolar bone regeneration. MATERIAL AND METHODS: Sixty rats were divided into three groups; two vitamin depletion groups and a control group. Identical single defects (2 mm diameter) were created in the maxilla and mandible treated with calcitriol soaked collagen in one deficiency group while in the other two groups not. Histomorphometric analysis and micro CTs were performed after 1 and 3 weeks. Serum levels of 25(OH)D3 and PTH were determined. RESULTS: Bone formation rate significantly increased within the observation period in all groups. Bone regeneration was higher in the maxilla than in the mandible. However, bone regeneration was lower in the control group compared to vitamin depletion groups, with no significant effects by local administration of calcitriol (micro CT mandible p = 0.003, maxilla p < 0.001; histomorphometry maxilla p = 0.035, mandible p = 0.18). CONCLUSION: Vitamin D deficiency not necessarily impairs bone regeneration in the rat jaw and a single local calcitriol application does not enhance healing.

Morphometric characteristics of cortical and trabecular bone in atrophic edentulous mandibles.

OBJECTIVES: Adaptations of the alveolar ridge after tooth loss have been well described. However, studies on the morphometric characteristics of cortical bone are rare; hence, this study of human atrophic edentulous mandibles was undertaken. MATERIAL AND METHODS: Total cortical area, porosity, and thickness, and the percentage of cortical area in the complete mandibular area as well as in an area (height, 10 mm) starting at the most caudal point of the trabecular compartment and extending in the coronal direction were determined in 185 thin ground sections of edentulous mandibles (incisor region, 49; premolar region, 76; molar region, 60; 95 from females and 90 from males; mean age, 78.2 years, SD ± 7.8 years; Caucasian donors; cause of death: cardiovascular disease). Further, mandibular height and width and degree of residual ridge resorption (RRR) were recorded. RESULTS: The percentage of cortical area in the complete mandibular area increased with increasing RRR. Yet, evaluation of the 10-mm caudal portion corresponding to the basal part of the mandibular body did not confirm these changes in cortical bone. Cortical porosity and thickness decreased from the mesial to the distal region. Cortical porosity was unaffected by RRR, while cortical thickness increased, mainly at lingual aspects. CONCLUSIONS: In conclusion, cortical bone remained stable in different degrees of RRR except for some modulations in the lingual aspects. Changes in the relative composition between cortical and trabecular bone are due to loss of height and total area, mainly at expense of trabecular bone area, but not to adaptations of the cortical bone.

Dimethyloxalylglycine lyophilized onto bone substitutes increase vessel area in rat calvarial defects.

AIM: Pharmacological inhibitors of prolyl hydroxylases, also termed hypoxia-mimetic agents (HMAs), when repeatedly injected can support angiogenesis and bone regeneration. However, the possible role of HMA loaded onto bone substitutes to support angiogenesis and bone regeneration under diabetic condition is unknown. The capacity of HMA loaded onto deproteinized bovine bone mineral (DBBM) to support angiogenesis and bone formation was examined in diabetic Wistar rats. METHODS: Diabetes was induced by intraperitoneal injection of streptozotocin. The HMA dimethyloxalylglycine (DMOG) and desferrioxamine (DFO) were lyophilized onto DBBM. Calvarial defects were created with a trephine drill and filled with the respective bone substitutes. After 4 weeks of healing, the animals were subjected to histological and histomorphometric analysis. RESULTS: In this report, we provide evidence that DMOG loaded onto DBBM can support angiogenesis in vivo. Specifically, we show that DMOG increased the vessel area in the defect site to 2.4% ± 1.3% compared with controls 1.1% ± 0.48% (P = 0.012). There was a trend toward an increased vessel number in the defect site with 38.6 ± 17.4 and 31.0 ± 10.3 in the DMOG and the control group (P = 0.231). The increase in angiogenesis, however, did not translate into enhanced bone formation in the defect area with 9.2% ± 7.1% and 8.4% ± 5.6% in DMOG and control group, respectively. No significant changes were caused by DFO. CONCLUSIONS: The results suggest that DMOG loaded onto DBBM can support angiogenesis, but bone formation does not increase accordingly in a type 1 diabetic rat calvarial defect model at the indicated time point.

Efficacy of fosfomycin compared to vancomycin in treatment of implant-associated chronic methicillin-resistant Staphylococcus aureus osteomyelitis in rats.

Fosfomycin monotherapy was compared to therapy with vancomycin for the treatment of implant-associated methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis in an experimental rat model. The proximal tibiae were inoculated with 15 µl of a suspension containing 1×10(8) to 5×10(8) CFU/ml of a clinical isolate of MRSA with simultaneous insertion of a titanium wire. Four weeks later, treatment was started for 28 days with either 50 mg/kg of body weight vancomycin intraperitoneally twice daily (n=11) or 75 mg/kg fosfomycin intraperitoneally once daily (n=10). Eleven animals were left untreated. After treatment, quantitative cultures from bone were found to be positive for MRSA in all animals in the untreated group (median, 3.29×10(6) CFU/g of bone) and the vancomycin group (median, 3.03×10(5) CFU/g of bone). In the fosfomycin group, MRSA was detectable in 2 out of 10 (20%) animals (3.42×10(2) and 1.51×10(3) CFU/g of bone). Vancomycin was superior to the no-drug control (P=0.002), and fosfomycin was superior to the no-drug control and vancomycin (P<0.001). The cultures from the wires were positive in all untreated animals (median, 2.5×10(3) CFU/implant), in 10 animals in the vancomycin group (median, 1.15×10(3) CFU/implant), and negative in all animals in the fosfomycin group. Based on the bacterial counts from the implants, vancomycin was not superior to the no-drug control (P=0.324), and fosfomycin was superior to the no-drug control and vancomycin (P<0.001). No emergence of resistance was observed. In conclusion, it was demonstrated that fosfomycin monotherapy is highly effective for the treatment of experimental implant-associated MRSA osteomyelitis.

Early bone apposition to hydrophilic and hydrophobic titanium implant surfaces: a histologic and histomorphometric study in minipigs.

OBJECTIVE: The first objective of this pilot study was to evaluate the impact of the hydrophilicity on the early phases of osseointegration. The second objective was to compare two hydrophilic implant surfaces with different geometries, surface roughness, and technologies achieving hydrophilicity. MATERIAL AND METHODS: Twelve weeks after extraction, all four quadrants of nine minipigs received three dental implants, alternating between hydrophilic microrough surfaces (INICELL and SLActive) and a conventional hydrophobic microrough surface. After 5, 10, and 15 days of submerged healing, ground sections were prepared and subjected to histologic and histomorphometric analysis. RESULTS: The histologic analysis revealed a similar healing pattern among the hydrophilic and hydrophobic implant surfaces, with extensive bone formation occurring between day 5 and day 10. With BIC values of greater than 50% after 10 days, all examined surfaces indicated favorable osseointegration at this very early point in healing. At day 15, the mean new bone-to-implant contact (newBIC) of one hydrophilic surface (INICELL; 55.8 ± 14.4%) was slightly greater than that of the hydrophobic microrough surface (40.6 ± 20.2%). At day 10 and day 15, an overall of 21% of the implants had to be excluded from analysis due to inflammations primarily caused by surgical complications. CONCLUSION: Substantial bone apposition occurs between day 5 and day 10. The data suggest that the hydrophilic surface can provoke a slight tendency toward increased bone apposition in minipigs after 15 days. A direct comparison of two hydrophilic surfaces with varying geometries is of limited relevance.

A histomorphometric analysis of the nature of the mandibular canal in the anterior molar region.

OBJECTIVES: Knowledge of the position and configuration of the mandibular canal is a basic requirement before implant placement in the mandible. Radiological studies suggest a positive correlation between alveolar trabecular bone quality and mandibular canal corticalization. The aim of this study was to test this assumption histomorphometrically in the anterior molar region, which is one of the most frequent places for implantation. MATERIALS AND METHODS: Fifty thin ground sections (from 28 male and 22 female cadavers) of the first molar region were investigated for trabecular bone volume and thickness and the presence of a mandibular canal wall. RESULTS: Trabecular bone volume was significantly higher in males (p = 0.009). Further, it correlated significantly with the presence of a canal wall (rho = 0.585, p < 0.001), indicating that a reduced trabecular bone volume is associated with a reduced amount of bone surrounding the alveolar nerve. The cranial aspects of the canal wall were present at a significantly lower frequency (64.64 %) than the buccal, lingual, or caudal sides (p < 0.006). CONCLUSION: The present study demonstrated that low trabecular bone volume correlates with only a fragmentarily present mandibular canal wall. This suggests that bone surrounding the alveolar nerve is of trabecular, not cortical, origin and possibly affected by reduction of the trabecular bone. CLINICAL RELEVANCE: These results imply that oral surgeons should pay particular attention to implant placement in patients with low alveolar bone quality. The cranial aspects of the mandibular canal might be only fragmentarily or even completely missing. Consequently, they hardly present resistance during implant site preparation, and the risk for nerve injury, e.g., due to post-surgery hematoma, could be increased.

Maxillary Sinus Augmentation with Anorganic Bovine Bone Mineral of Different Particle Sizes: A Split-Mouth Study with Histomorphometric, Radiographic, and Clinical Analyses.

PURPOSE: The aim of the present study was to compare the histomorphometrically evaluated new bone formation (NB), the radiographically measured graft stability, and the clinical implant outcome for maxillary sinus augmentation grafted with deproteinized bovine bone mineral (DBBM) with either small (Bio-Oss-S, Geistlich) or large (Bio-Oss-L, Geistlich) particles. MATERIALS AND METHODS: Using a split-mouth study design, bilateral maxillary sinus augmentation was performed in 13 patients either with Bio-Oss-S particles (0.25 to 1 mm) or Bio-Oss-L particles (1 to 2 mm). After a healing period of 6 months, bone biopsies were axially retrieved in the molar region for histologic/histomorphometric analysis of NB, including subsequent staged implant placement. To determine graft stability, the maxillary sinus augmentation vertical graft heights were radiographically measured immediately after sinus augmentation, at implant placement, and at the 2- and 4-year post-augmentation follow-ups. In addition, the clinical implant-prosthodontic outcome (survival/ success/marginal bone loss) was assessed at 1 and 3 years post-loading. RESULTS: A total of 22 sinuses from 11 patients with split-mouth evaluation were ultimately available for data and statistical analysis. Histomorphometric analysis of the axially retrieved bone biopsies revealed the presence of NB (S: 25.5% ± 7.0% vs L: 23.6% ± 11.9%; P = .640), residual graft particles (S: 19.6% ± 9.2% vs L: 17.5% ± 6.3%; P = .365) as well as connective tissue (S: 54.9% ± 9.2% vs L: 58.9% ± 12.5%; P = .283), without significant differences between the use of small (Bio-Oss-S) and large (Bio-Oss-L) particles. However, there was significantly (P = .021) higher bone-to-graft contact (BGC) for the small-particle graft sites (27.9% ± 14.8%) compared to the large-particle graft sites (19.9% ± 12.9%), representing a significantly higher osteoconductivity. Both particle sizes showed significant (P < .01) vertical graft height reduction over time (4 years) of about 10%, with predominant graft reduction in the time period between sinus augmentation and implant placement compared to any follow-up periods after implant placement. At the 3-year post-loading implant evaluation, all implants and prostheses survived (100%), and the peri-implant marginal bone loss (S: 0.52 ± 0.19 mm; L: 0.48 ± 0.15 mm) as well as the peri-implant health conditions (S: 87.5%, L:81.2%) did not differ between implants inserted with the two different xenograft particles used. CONCLUSIONS: The use of small and large bovine xenograft particles for maxillary sinus augmentation provides for comparable bone formation, ensuring stable graft dimensions combined with high implant success and healthy peri-implant conditions. However, small particle size resulted in a higher BGC, providing for higher osteoconductivity than with the larger particle size.

Sheep Bone Ultrastructure Analyses Reveal Differences in Bone Maturation around Mg-Based and Ti Implants.

Magnesium alloys are some of the most convenient biodegradable materials for bone fracture treatment due to their tailorable degradation rate, biocompatibility, and mechanical properties resembling those of bone. Despite the fact that magnesium-based implants and ZX00 (Mg-0.45Zn-0.45Ca in wt.%), in particular, have been shown to have suitable degradation rates and good osseointegration, knowledge gaps remain in our understanding of the impact of their degradation properties on the bone's ultrastructure. Bone is a hierarchically structured material, where not only the microstructure but also the ultrastructure are important as properties like the local mechanical response are determined by it. This study presents the first comparative analysis of bone ultrastructure parameters with high spatial resolution around ZX00 and Ti implants after 6, 12, and 24 weeks of healing. The mineralization was investigated, revealing a significant decrease in the lattice spacing of the (002) Bragg's peak closer to the ZX00 implant in comparison to Ti, while no significant difference in the crystallite size was observed. The hydroxyapatite platelet thickness and osteon density demonstrated a decrease closer to the ZX00 implant interface. Correlative indentation and strain maps obtained by scanning X-ray diffraction measurements revealed a higher stiffness and faster mechanical adaptation of the bone surrounding Ti implants as compared to the ZX00 ones. Thus, the results suggest the incorporation of Mg2+ ions into the bone ultrastructure, as well as a lower degree of remodeling and stiffness of the bone in the presence of ZX00 implants than Ti.

Pulp Revascularization in an Autotransplanted Mature Tooth: Visualization with Magnetic Resonance Imaging and Histopathologic Correlation.

Autotransplantation of a mature tooth usually leads to pulpal necrosis. Root canal treatment is recommended to prevent related inflammatory complications a few weeks after surgery. Extraoral root-end resection may facilitate reperfusion and obviate root canal treatment, but cannot be pictured with conventional dental radiography at this point in time. In the case of a lower mature transplanted molar, contrast-enhanced magnetic resonance imaging proved to be a feasible method for visualizing pulp revascularization just 4 weeks after autotransplantation. Consequently, root canal treatment was obviated. Nevertheless, the tooth had to be extracted 18 months postoperatively due to external cervical root resorption, probably caused by the extraction trauma. This allowed the histological processing and examination of the newly generated intracanal tissue. Uninflamed fibrovascular connective tissue was found, while odontoblasts or cementoblast-like cells were absent. These findings indicated that it was most likely stem cells from the bone marrow and the periodontal ligament that drove the regeneration.

Does early post-operative exercise influence bone healing kinetics? Preclinical evaluation of non-critical sized femur defect healing.

Physical exercise is a well-known modality for maintaining healthy locomotor mechanism. A detailed preclinical research on physical exercise effect on bone healing kinetics could help to improve the rehabilitation process after fracture treatment and bone remodeling. Our aim was to evaluate the effect of early post-operative exercise effect on bone microstructural changes in a rat model. Twenty Sprague Dawley male rats underwent bi-cortical 1.6 mm hole drilling in both femur diaphysis, after which (n = 10) underwent continuous treadmill training (TR) over two weeks, while the other group of rats (n = 10) was assigned to non-training (NT) control group. New bone formation labeling was performed by subcutaneous fluorochrome injections at day 5, 14 and 31. In vivo micro-computed tomography (µCT) scans were performed once a week during the 6-week post-operative period. Ten animals (five from each group) were euthanized at 3rd week while remaining animals were euthanized at 6th week. Femur samples were extracted and underwent ex vivo µCT and histological evaluation, while serum was used for evaluating alkaline phosphatase (ALP). µCT data demonstrated increased volume and surface of newly formed bone in defect area of TR group. Bone volume/Tissue volume (BV/TV) ratio and number of osteocytes showed an increase in TR group after 3-week period. Fluorochrome distances were increased between day 5 and 14 within the training group. Serum ALP level increased in both groups over 3- and 6-weeks. Post-operative exercise increases the bone healing kinetics and stimulates the new bone formation during and after the training protocol has ended.

The combined effect of zinc and calcium on the biodegradation of ultrahigh-purity magnesium implants.

Magnesium (Mg)-based implants are promising candidates for orthopedic interventions, because of their biocompatibility, good mechanical features, and ability to degrade completely in the body, eliminating the need for an additional removal surgery. In the present study, we synthesized and investigated two Mg-based materials, ultrahigh-purity ZX00 (Mg-Zn-Ca; <0.5 wt% Zn and <0.5 wt% Ca, in wt%; Fe-content <1 ppm) and ultrahigh-purity Mg (XHP-Mg, >99.999 wt% Mg; Fe-content <1 ppm), in vitro and in vivo in juvenile healthy rats to clarify the effect of the alloying elements Zn and Ca on mechanical properties, microstructure, cytocompatibility and degradation rate. Potential differences in bone formation and bone in-growth were also assessed and compared with state-of-the-art non-degradable titanium (Ti)-implanted, sham-operated, and control (non-intervention) groups, using micro-computed tomography, histology and scanning electron microscopy. At 6 and 24 weeks after implantation, serum alkaline phosphatase (ALP), calcium (Ca), and Mg level were measured and bone marrow stromal cells (BMSCs) were isolated for real-time PCR analysis. Results show that ZX00 implants have smaller grain size and superior mechanical properties than XHP-Mg, and that both reveal good biocompatibility in cytocompatibilty tests. ZX00 homogenously degraded with an increased gas accumulation 12 and 24 weeks after implantation, whereas XHP-Mg exhibited higher gas accumulation already at 2 weeks. Serum ALP, Ca, and Mg levels were comparable among all groups and both Mg-based implants led to similar relative expression levels of Alp, Runx2, and Bmp-2 genes at weeks 6 and 24. Histologically, Mg-based implants are superior for new bone tissue formation and bone in-growth compared to Ti implants. Furthermore, by tracking the sequence of multicolor fluorochrome labels, we observed higher mineral apposition rate at week 2 in both Mg-based implants compared to the control groups. Our findings suggest that (i) ZX00 and XHP-Mg support bone formation and remodeling, (ii) both Mg-based implants are superior to Ti implants in terms of new bone tissue formation and osseointegration, and (iii) ZX00 is more favorable due to its lower degradation rate and moderate gas accumulation.

Degradation behavior and osseointegration of Mg-Zn-Ca screws in different bone regions of growing sheep: a pilot study.

Magnesium (Mg)-based implants are highly attractive for the orthopedic field and may replace titanium (Ti) as support for fracture healing. To determine the implant-bone interaction in different bony regions, we implanted Mg-based alloy ZX00 (Mg < 0.5 Zn < 0.5 Ca, in wt%) and Ti-screws into the distal epiphysis and distal metaphysis of sheep tibiae. The implant degradation and osseointegration were assessed in vivo and ex vivo after 4, 6 and 12 weeks, using a combination of clinical computed tomography, medium-resolution micro computed tomography (µCT) and high-resolution synchrotron radiation µCT (SRµCT). Implant volume loss, gas formation and bone growth were evaluated for both implantation sites and each bone region independently. Additionally, histological analysis of bone growth was performed on embedded hard-tissue samples. We demonstrate that in all cases, the degradation rate of ZX00-implants ranges between 0.23 and 0.75 mm/year. The highest degradation rates were found in the epiphysis. Bone-to-implant contact varied between the time points and bone types for both materials. Mostly, bone-volume-to-total-volume was higher around Ti-implants. However, we found an increased cortical thickness around the ZX00-screws when compared with the Ti-screws. Our results showed the suitability of ZX00-screws for implantation into the distal meta- and epiphysis.

Osteotomy after medial malleolus fracture fixed with magnesium screws ZX00 - A case report.

Magnesium alloys have recently become the focus of research, as these implants exhibit suitable biocompatibility and appropriate mechanical properties (Grün et al., 2018 [1]). Through intensive preclinical and clinical investigation, many questions regarding stability, biocompatibility and degradation behavior have been answered (Holweg et al., 2020 [2]). This case report aims to describe handling of these implants in a revision situation, especially when located in situ. To describe available options and relevant considerations, including planning and implementation, a revision surgery of a healed medial malleolus fracture is presented. A medial malleolus fracture was primarily treated by a trauma surgeon with two magnesium screws. Due to an osteochondral lesion of the talus, a revision surgery with osteotomy of the medial malleolus was necessary after 17 months. In this revision, conventional screw removal was not possible due to the degradation of the implant. Taking the degradation and the yield strength of the implant into account, we have chosen on the one hand to over-drill and on the other to leave and perforate the screw. To the best of our knowledge, this is the first case study focusing on the clinical intraoperative site of human bone stabilized with magnesium screws. Despite the hydrogen gas production that occurs during degradation, a solid bone-to-implant interface was evident. With this report, we want to encourage the surgical user to get more involved with resorbable magnesium implants.

Implant degradation of low-alloyed Mg-Zn-Ca in osteoporotic, old and juvenile rats.

Implant removal is unnecessary for biodegradable magnesium (Mg)-based implants and, therefore, the related risk for implant-induced fractures is limited. Aging, on the other hand, is associated with low bone-turnover and decreased bone mass and density, and thus increased fracture risk. Osteoporosis is accompanied by Mg deficiency, therefore, we hypothesized that Mg-based implants may support bone formation by Mg2+ ion release in an ovariectomy-induced osteoporotic rat model. Hence, we investigated osseointegration and implant degradation of a low-alloyed, degrading Mg-Zn-Ca implant (ZX00) in ovariectomy-induced osteoporotic (Osteo), old healthy (OH), and juvenile healthy (JH) groups of female Sprague Dawley rats via in vivo micro-computed tomography (µCT). For the Osteo rats, we demonstrate diminished trabecular bone already after 8 weeks upon ovariectomy and significantly enhanced implant volume loss, with correspondingly pronounced gas formation, compared to the OH and JH groups. Sclerotic rim development was observed in about half of the osteoporotic rats, suggesting a prevention from foreign-body and osteonecrosis development. Synchrotron radiation-based µCT confirmed lower bone volume fractions in the Osteo group compared to the OH and JH groups. Qualitative histological analysis additionally visualized the enhanced implant degradation in the Osteo group. To date, ZX00 provides an interesting implant material for young and older healthy patients, but it may not be of advantage in pharmacologically untreated osteoporotic conditions. STATEMENT OF SIGNIFICANCE: Magnesium-based implants are promising candidates for treatment of osteoporotic fractures because of their biodegradable, biomechanical, anti-bacterial and bone regenerative properties. Here we investigate magnesium‒zinc‒calcium implant materials in a rat model with ovariectomy-induced osteoporosis (Osteo group) and compare the related osseointegration and implant degradation with the results obtained for old healthy (OH) and juvenile healthy (JH) rats. The work applied an appropriate disease model for osteoporosis and focused in particular on long-term implant degradation for different bone conditions. Enhanced implant degradation and sclerotic rim formation was observed in osteoporotic rats, which illustrates that the setting of different bone models generates significantly modified clinical outcome. It further illustrated that these differences must be taken into account in future biodegradable implant development.

Size changes in miR­21 knockout mice: Geometric morphometrics on teeth, alveolar bone and mandible.

MicroRNA­21 (miR­21) is a small non­coding RNA that is differentially expressed during tooth development, particularly during amelogenesis. Although orthodontic tooth movement and the innate immune response are impaired, miR­21 knockout mice demonstrate no obvious skeletal phenotype. However, the consequence of miR­21 knockout on tooth phenotype and corresponding alveolar bone is unknown. The current study utilized landmark­based geometric morphometrics to identify anatomical dissimilarities of the three lower and upper molars, and the corresponding alveolar bone, in miR­21 knockout and wild­type control mice. The anatomical structures were visualized by microcomputer tomography. A total of 36 and 38 landmarks were placed on mandibular and maxillary molars, respectively. For the alveolar bone, 16 landmarks were selected on both anatomical sites. General Procrustes analysis revealed significantly smaller molars and dimensions of the alveolar bone in the mandible of the miR­21 knockout mice when compared with wild­type controls (P=0.03 and P=0.04, respectively). The overall dimension of the mandible was reduced by the lack of miR­21 (P=0.02). In the maxilla, the dimension of the alveolar bone was significant (P=0.02); however, this was not observed in the molars (P=0.36). Based on principal component analysis, no changes in shape for any of the anatomical sites were observed. Dental and skeletal jaw length were calculated and no prognathism was identified. However, the fluctuating asymmetry of the molars in the mandible and the maxilla was reduced in the miR­21 knockout mice by 38 and 27%, respectively. Taken together, the results of the present study revealed that the molars in the mandible and the dimension of the respective alveolar bone were smaller in miR­21 mice compared with wild­type littermates, suggesting that miR­21 influences tooth development.