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Bone substitutes are biomaterials applied in surgical therapy to repair many cases of a damaged bone. More than two million bone surgeries using biomaterials are realised each year worldwide. In this line of research, the researchers of this project study developed a bioresorbable synthetic bone substitute designated by (β-TCP/DCPD)-PHBV which is a mixture of the two materials: β-TCP/DCPD and PHBV in a 60/40 weight fraction. This research study attempts to categorize the (β-TCP/DCPD)-PHBV and evaluate its ability on triggering bone regeneration by making bone implants on 12 New Zealand white male rabbits. The RESEARCHERS performed multi-scale studies namely; a uniaxial compression test, an examination by scanning electron microscopy, and analysis with infrared spectroscopy in order to get the characteristics. The neoformed bone is examined by SEM coupled with energy dispersive spectroscopy (EDS). In addition to the salient mechanical benefits; attenuation of the modulus of elasticity and limitation of brittleness, the biomaterial has also proven to be effective in giving rise to new bone tissues having a suitable mineral composition. [ABSTRACT FROM AUTHOR]

The standard grafts used for anterior cruciate ligament (ACL) reconstruction are tendon, either patellar tendon, hamstring, or quadriceps. However, the microstructure and composition of tendon differs from ligament. Ideally, the ACL would be replaced with the same tissue. To evaluate the incorporation of a bone‐ACL‐bone (B‐ACL‐B) graft for ACL reconstruction, we performed a controlled laboratory study in a rabbit model with microcomputed tomography (μCT). Forty‐six New Zealand white rabbits were used, with 17 donor rabbits to harvest bilateral B‐ACL‐B allografts and 29 rabbits undergoing unilateral ACL reconstruction with B‐ACL‐B allograft. Knee specimens were collected for biomechanical testing (n = 14) at 4 and 8 weeks and for μCT analysis (n = 15) at 2, 4, and 8 weeks after surgery. Gross inspection and μCT examination confirmed bone blocks in the appropriate anatomic position. Biomechanical tests revealed no difference in mean load‐to‐failure force for B‐ACL‐B allografts between 4 and 8 weeks. Progressive healing occurred between the bone block and the tunnel as demonstrated by a gradual increase on average bone‐volume fraction and total mineral density (TMD) in both femoral and tibial tunnels. Remodeling of the bone block was evidenced by a significant decrease in TMD of both tibial and femoral bone blocks. This is a report of a novel rabbit B‐ACL‐B allograft reconstruction model demonstrating early signs of graft remodeling and incorporation. Clinical Relevance: This study demonstrates ACL reconstruction using an anatomically matched ACL allograft, rather than a tendon graft, may be possible based on early findings in this lapine model. [ABSTRACT FROM AUTHOR]

Purpose: Advances in the design and manufacturing of novel synthetic bioactive scaffolds as bone substitute in bone reconstruction are at the forefront of orthopedic study due to their excellent biological performances. However, fabricating bioactive scaffolds with similar osteogenic and mechanical properties of a natural bone still remains a challenge. Our aim was to produce functional bioactive scaffolds with biologically interactive ions, microstructure for cell proliferation and a suitable biodegradation rate in critical-size bone defect. Methods: A homogenous strontium-doped calcium silicate (Sr-CaSi) bioactive granule with interconnected porous network was fabricated. Critical-size bone defect (Ø ~6.5 × 8.5 mm) was created at the distal femur of New Zealand rabbit and the animals were divided into two groups (blank group and implanted/Sr-CaSi group). The blank had no granules while the implanted group was grafted with Sr-CaSi granules at the defect. Bone repair was assed using investigations of micro-CT, 3D argumentation and histological evaluations. Results: The Sr-CaSi group had complete bone healing and reconstruction. The granule showed physiochemical tolerance and was able to biodegrade enhancing the formation of new bone matrix and remodeling. However, the blank group had limited proliferation and osteogenic differentiation of new bone tissue, hence there was retarded ingrowth of new bone tissues. Conclusion: The Sr-CaSi group saw excellent bone mineralization due to biostimulation effect of the bioceramic granules. The extensive stimulation and osteogenic factors in bone healing by the novel Sr-CaSi shows it is indispensable in bone tissue engineering and regenerative medicine. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the impact of the Tantalum Trabecular Metal dental implant design on implant stability and the process of osseointegration following its placement in the rabbit femoral condyle. The subjects for the experiment consisted of 10 New Zealand white rabbits. Twenty implants, comprising 10 Trabecular Metal (TM) and 10 Traditional Screw Vent (TSV) implants, were placed into the femoral condyles of these rabbits. The implant type was alternated based on a random sequence. Following a healing period of 8 weeks, the implants were retrieved for further analysis using micro-computed tomography (micro-CT), histological studies, and histomorphometry evaluations. The Bone-to-Implant Contact (BIC) ratio and the Bone Volume (BV) percentage in the region of interest were subsequently assessed. The BIC and BV values between TM and TSV implants were compared using the Student t-test. The TM implants exhibited significantly greater BIC and BV scores. In particular, the BIC percentage was recorded as 57.9 ± 6.5 for the TM implants, as opposed to 47.6 ± 8 for the TSV implants. Correspondingly, the BV percentage was 57 ± 7.3 for the TM implants and 46.4 ± 7.4 for the TSV implants. The bone volume percentage measured using micro-CT evaluation was 89.1 ± 8.7 for the TM implants and 79.1 ± 8.6 for the TSV implants. Given the observed results, it is plausible to suggest that the bone growth surrounding the tantalum mesh could have improved the integration of the bone and facilitated its ingrowth into the TM implant. [ABSTRACT FROM AUTHOR]

Background: While suggested to be effective in tissue regeneration, the effects of horizontal platelet‐rich fibrin (H‐PRF) bone block in sinus augmentation have not been verified in an animal model. Methods: A total of 12 male New Zealand white rabbits that underwent sinus augmentation were divided into two groups: deproteinized bovine bone mineral (DBBM) only and H‐PRF bone block. H‐PRF was prepared at 700 × g for 8 min using a horizontal centrifuge. The H‐PRF bone block was prepared by mixing 0.1 g DBBM with H‐PRF fragments and then adding liquid H‐PRF. Samples were collected after 4 and 8 weeks and analyzed using microcomputed tomography (micro‐CT) for vertical bone gain of the sinus, bone volume/total volume (BV/TV) percentage, trabecular number (Tb.N), trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp). Then, histological analyses were performed to investigate new blood vessels, material residue, bone formation and osteoclasts. Results: Higher vertical bone gain of the sinus floor, BV/TV percentage, Tb.Th, and Tb.N and lower Tb.Sp were found in the H‐PRF bone block group at both time points compared with the DBBM group. Higher amounts of new blood vessels and more osteoclasts were found in the H‐PRF bone block group than in the DBBM group at both time points, especially in the regions close to the bone plate. More new bone formation and less material residue were observed in the H‐PRF bone block group at 8 weeks. Conclusions: H‐PRF bone block showed greater potential for sinus augmentation by promoting angiogenesis, bone formation and bone remodeling in a rabbit model. [ABSTRACT FROM AUTHOR]

Bone healing is a tissue process after a surgical operation. Many formulated materials have been designed for improving these procedures. The purpose of this study was to evaluate the effectiveness of nanocomposite tricalcium phosphate scaffolds combined with Titanium dioxide scaffold (TCP/TiO2) for femoral defects regeneration in rabbits. We studied 80 mature male New Zealand white rabbits weighing between 3 and 3.5 kg. Rabbits were subdivided into four groups. Anesthesia was performed before surgical operation by 50 mg/kg Ketamine 10% and 5 mg/kg xylazine 5% intramuscularly. We inducted a 6 × 5 mm diameter cylinder defect on the femur. Animals were separated into four trial groups of 20 animals each. After defecting, the experimental groups include control, autograft, hydroxyapatite, and TCP/TiO2 (received pure nanocomposite TCP/TiO2 material). A pathologist evaluated the sections on days 15, 30, 45, and 60 after surgery. The improvement of new and lamellar bone formation was the best in the nanocomposite TCP/TiO2 group at various point times, especially 60 days after surgery. We found that TCP/TiO2 nanocomposite has a significant improving function in the remodeling of bone in the defect areas. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to confirm the in vivo effect of surface-modified titanium (Ti) implants with zinc (Zn) prepared by a plasma electrolytic oxidation (PEO) method on the process of osseointegration. Materials and Methods: Forty-five New Zealand white rabbits were used. Implants were divided into three groups due to different surface treatments (the PEO-Zn group, the PEO-calcium phosphorus [Ca/P] group, and the sandblasted [control] group) and were randomly inserted into rabbit's mandibles. The implant surface morphology and chemical state of the relevant elements were observed. The maximum push-out force, the bone-to-implant contact (BIC) and the mineral apposition ratio (MAR) were detected at 4, 8 and 12 weeks after implantation. Results: A two-layer structure, with a dense inner layer and a porous outer layer, was found in the PEO samples. In the PEO-Zn group, CaHPO4.2H2O (dicalcium phosphate dihydrate) was the main calcium compound and ZnO was identified as the predominant form of Zn. More bone deposition was found on the top of the PEO-Zn implant, which was also confirmed by scanning electron microscope (SEM) afterward and the shear strength reached a maximum value of 1.57 ± 0.26 MPa at 12 weeks compared with the sandblasted group and the PEO-Ca/P group. The BIC values and the MARs of the PEO-Zn group were significantly higher than the control group, especially at the early weeks (P < .05) and first reached maximum values of 73.91% ± 9.01% and 4.89 ± 0.60 μm/d at 12 weeks, respectively. Conclusion: Implants with Zn coating by the PEO method could accelerate bone formation and bone remodeling, shorten the osseointegration period and enhance bone-implant bonding force. [ABSTRACT FROM AUTHOR]

Bone grafts a commonly used therapeutic technique for the reconstruction and facilitation of bone regeneration due to fractures. BHA–GEL (bovine hydroxyapatite–gelatin) pellet implants have been shown to be able accelerate the process of bone repair by looking at the percentage of new bone, and the contact between the composite and bone. Based on these results, a study was conducted by placing BHA–GEL (9:1) pellet implants in rabbit femoral bone defects, accompanied by 500 mg oral supplement of BHA or calcium lactate to determine the effectiveness of addition supplements. The research model used was a burr hole defect model with a diameter of 4.2 mm in the cortical part of the rabbit femur. On the 7th, 14th and 28th days after treatment, a total of 48 New Zealand rabbits were divided into four groups, namely defect (control), implant, implant + oral BHA, and implant + oral calcium lactate. Animal tests were terminated and evaluated based on X-ray radiology results, Hematoxylin-Eosin staining, vascular endothelial growth Factor (VEGF), osteocalcin, and enzyme-linked immunosorbent assay (ELISA) for bone alkaline phosphatase (BALP) and calcium levels. From this research can be concluded that Oral BHA supplementation with BHA–GEL pellet implants showed faster healing of bone defects compared to oral calcium lactate with BHA–GEL pellet implants. [ABSTRACT FROM AUTHOR]

Background. Bone healing is a complex and dynamic process that represents a well-orchestrated series of biological events of cellular recruitment, proliferation, and differentiation. The use of medicinal plants in bone healing has attracted increasing interest because of their lower side effects. Punica granatum seed oil (PSO) contains high levels of phenolic compounds, promotes osteoblast function, and plays an important role in bone remodeling. A gelatin sponge (Spongostan) is a hemostatic agent that is extensively applied as scaffolds in engineering and as drug carriers in the medical field. This study aimed to evaluate the effectiveness of PSO for bone healing enhancement. Twenty adult male New Zealand rabbits, weighing an average of 1.5–2 kg, were used in this study. Three intrabony holes were created in the tibiae of each animal, which were filled with a gelatin sponge (GS group) and combined gelatin sponge and PSO (GS/PSO group). Holes without material application were designated as the control group (C group). The animals were sacrificed at the healing duration (2–4 weeks) to prepare bone specimens for histological and histomorphometric analyses. Results. Histological findings indicated that the bone defects in the GS/PSO group showed more bone formation, mineralization, and maturation compared with the C and GS groups. Multiple group differences for bone cells showed a highly significant difference among all groups in the 2- and 4-week healing periods except for the C/GS and GS/GS/PSO groups at 4-weeks duration. Furthermore, highly significant results were obtained between both durations regarding the trabecular area, trabecular number, and bone marrow area. Conclusion. The study revealed that the combined application of GS and PSO was more effective in enhancing bone regeneration and accelerating bone healing compared with the other groups. [ABSTRACT FROM AUTHOR]

Bone is dynamic, undergoing metabolic changes in response to behavioral and pathological stimuli. This information can be reconstructed in bioarchaeology using histological methods, providing another avenue to explore the experiences of past peoples. We report histological findings from midshaft femoral cortical bone of an identified individual from nineteenth-century New Zealand, who suffered from tuberculosis and had a historically documented period of invalidism. Materials: Burial 21 (B21) is a middle-aged male excavated from the nineteenth-century site of St. John's burial ground, Milton. B21's left proximal femur and acetabulum exhibited lytic lesions associated with tuberculosis-induced destruction of bone. Documentation, including a cause of death of "pneumonic phthisis haemorrhage," and various biographic details exist for this burial. These suggest that B21's left and right midshaft femur were under asymmetric biomechanical and pathological conditions and should show differences in the underlying bone remodeling. Methods: We collected data on Haversian bone microstructure geometric properties and densities from a total of 148 secondary osteons and 481 Haversian canals. Results: The left femur, from the tuberculosis-inflicted hip joint, had fewer, larger, and more irregularly shaped canals and osteons than the right femur. Discussion and Conclusion: These findings may indicate the left femur received less biomechanical stimulation than the right femur due to decreased weightbearing. It is also possible that the tuberculosis infection in this individual impacted his bone metabolic activity, leading to increased experiences of bone loss. The presented histological approach may enhance interpretations in bioarchaeology by identifying whether bone remodeling changes occur as a result of long-or short-term disuse. [ABSTRACT FROM AUTHOR]

Background and Objectives: The gold standard for a successful prosthetic approach is the osseointegration of an implant. However, this integration can be a problem in cases where the implant needs to be removed. Removing the implant with minimal damage to the surrounding tissues is important. Osteocytes cannot survive below −2 °C, but epithelial cells, fibroblasts, and other surrounding tissue cells can. Remodeling can be triggered by cryotherapy at temperatures that specifically affect osteocyte necrosis. In this study, we aimed to develop a method for reversing the osseointegration mechanism and for protecting the surrounding tissues by bone remodeling induced by CO2 cryotherapy. Materials and Methods: In this study, eight 2.8 mm diameter, one-piece mini implants were used in New Zealand rabbit tibias. Two control and six implants were tested in this study. After 2 months of osseointegration, a reverse torque force method was used to remove all osseointegrated implants at 5, 10, 20, and 30 Ncm. The osseointegration of the implants was proven by periotest measurements. Changes in bone tissue were examined in histological sections stained with toluidine blue after rabbit sacrifice. The number of lacunae with osteocyte, empty lacunae, and lacunae greater than 5 µm and the osteon number in a 10,000 µm2 area were calculated. Cryotherapy was applied to the test implants for 1 min, 2 min, and 5 min. Three implants were subjected to cryotherapy at −40 °C, and the other implants were subjected to cryotherapy at −80 °C. Results: Empty lacunae, filled osteocytes, lacunae >5 µm, and the osteon count around the implant applied at −40 °C were not significantly different from the control implants. The application of −40 °C for 1 min was found to cause minimal damage to the bone cells. The implants, which were applied for 1 min and 2 min, were successfully explanted on the 2nd day with the 5 Ncm reverse torque method. Test implants, which were applied cold for 5 min, were explanted on day 1. Tissue damage was detected in all test groups at −80 °C. Conclusions: The method of removing implants with cryotherapy was found to be successful in −40 °C freeze–thaw cycles applied three times for 1 min. To prove implant removal with cryotherapy, more implant trials should be conducted. [ABSTRACT FROM AUTHOR]

This study compared the osseointegration of acid-etched, ultrahydrophilic, micro- and nanostructured implant surfaces (ANU) with non-ultra-hydrophilic, microstructured (SA) and non-ultrahydrophilic, micro- and nanostructured implant surfaces (AN) in vivo. Fifty-four implants (n = 18 per group) were bilaterally inserted into the proximal tibia of New Zealand rabbits (n = 27). After 1, 2, and 4 weeks, bone-implant contact (BIC, %) in the cortical (cBIC) and spongious bone (sBIC), bone chamber ingrowth (BChI, %), and the supra-crestal, subperiosteal amount of newly formed bone, called percentage of linear bone fill (PLF, %), were analyzed. After one week, cBIC was significantly higher for AN and ANU when compared to SA (p = 0.01 and p = 0.005). PLF was significantly increased for ANU when compared to AN and SA (p = 0.022 and p = 0.025). After 2 weeks, cBIC was significantly higher in SA when compared to AN (p = 0.039) and after 4 weeks, no significant differences in any of the measured parameters were found anymore. Ultrahydrophilic implants initially improved osseointegration when compared to their non-ultrahydrophilic counterparts. In accordance, ultrahydrophilic implants might be appropriate in cases with a necessity for an accelerated and improved osseointegration, such as in critical size alveolar defects or an affected bone turnover. [ABSTRACT FROM AUTHOR]

BACKGROUND: Internal heat-type acupuncture needle therapy is an updated physical therapy method based on warm-needle moxibustion therapy with a dual effect of acupuncture and thermal therapy. It has significant clinical effect in the treatment of knee osteoarthritis, but there is no full understanding of its specific mechanism. OBJECTIVE: To explore the effect of internal heat-type acupuncture needle on the expression of type I collagen, matrix metalloproteinases-3, and osteopontin in the subchondral bone of a rabbit knee osteoarthritis model as well as the possible mechanism of action. METHODS: A total of 30 New Zealand rabbits (specific-pathogen-free level) were divided into a blank group, a model group and a treatment group by a random digital table, with 10 rabbits in each group. A model of knee osteoarthritis was made in the left hind leg of the rabbit by Hulth’s method. The treatment group was given internal heat-type acupuncture needle on the left hind limb knee joint, once a week, for 20 minutes once. The blank group and the model group received no intervention. Knee joint sampling was performed after behavioral evaluation using the modified Lequesne MG scale after 4 weeks of intervention. Toluidine blue staining was used to observe the morphological changes of subchondral bone tissue of rabbits in each group. Western blot and real-time quantitative PCR were used to detect the expressions of type I collagen, matrix metalloproteinases-3, and osteopontin protein and mRNA in the subchondral bone of the rabbits. The animal experiment protocol was approved by the Medical Research Ethics Review Committee of the General Hospital of Ningxia Medical University (approval No. 2018064). RESULTS AND CONCLUSION: Compared with the blank group, behavioral scores were significantly increased in the model group and treatment group (P < 0.05). Compared with the model group, behavioral scores were significantly decreased in the treatment group (P < 0.05), and the difference between the two groups was significantly enlarged after intervention (P < 0.05). Compared with the blank group, the percentage of subchondral bone trabecular area, trabecular thickness and trabecular number were significantly decreased in the model group (P < 0.05), while trabecular spacing was significantly increased (P < 0.05). Compared with the blank group, the protein and mRNA expression levels of type I collagen were significantly decreased in the model group (P < 0.001), while the protein and mRNA expression levels of matrix metalloproteinases-3 and osteopontin were significantly increased (P < 0.001). Compared with the model group, the percentage of trabecular area and trabecular number were significantly increased in the treatment group (P < 0.05), while trabecular spacing was significantly decreased (P < 0.05). Compared with the model group, the protein and mRNA expression levels of type I collagen were significantly increased in the treatment group (P < 0.05), while the protein and mRNA expression levels of matrix metalloproteinases-3 and osteopontin were significantly decreased (P < 0.05). Moreover, the change of type I collagen level was positively correlated with the percentage of trabecular area and the trabecular number, but negatively correlated with trabecular spacing. The changes of osteopontin, matrix metalloproteinases-3 and their ratio were negatively correlated with the percentage of trabecular area and trabecular number, and positively correlated with trabecular spacing. To conclude, internal heat-type acupuncture needle may restore subchondral bone microstructure through up-regulating type I collagen expression and down-regulating matrix metalloproteinases-3 and osteopontin expression. [ABSTRACT FROM AUTHOR]

BACKGROUND: The implantation of titanium alloy prosthesis would produce stress shielding to damage mechanical microenvironment of bone tissue. This might affect normal bone remodeling process. Interference fit was used to generate preload to reconstruct mechanical microenvironment in this area. It may have important theoretical significance and clinical application value to promote bone remodeling in the mid-long-term after surgery. OBJECTIVE: To analyze the promoting effect of preload on osseointegration of porous titanium alloy prosthesis. METHODS: Fourteen male New Zealand rabbits were divided into two groups. The three-dimensional (3D) printed titanium alloy prosthesis was implanted into the outside of right femoral condyle with interference fit in experimental group (n=7). Rabbits in the control group (n=7) were feed free. Femurs at the surgery side were extracted at 12 weeks after surgery. Micro-CT scanning and 3D reconstruction were performed to measure bone density and trabecular morphological parameters around the prosthesis. Animal experiment was approved by Animal Ethics Committee of Tianjin Institute of Medical Science (approval No. IMPS-EAEP-Z-2019108-01). RESULTS AND CONCLUSION: (1) Bone mineral density was reduced significantly in the experimental group compared with the control group (P < 0.05). (2) Bone volume fraction, trabecular thickness, trabecular number were reduced in the experimental group compared with the control group (P < 0.05). Bone surface area ratio and trabecular separation were larger in the experimental group than those in the control group (P < 0.05). There was no significant change in degree of anisotropy between the two groups (P > 0.05). (3) The results showed that preload could promote osseointegration of porous titanium alloy prosthesis. However, the structural characteristics of the in-growth bone were worse than healthy bone. This might lead to a high fracture risk in the mid-long-term after surgery. [ABSTRACT FROM AUTHOR]

There are over two million long bone defects treated in the United States annually, of which ~5% will not heal without significant surgical intervention. While autogenous grafting is the standard of care in simple defects, a customized scaffold for large defects in unlimited quantities is not available. Recently, a three‐dimensionally (3D)‐printed bioactive ceramic (3DPBC) scaffold has been successfully utilized in the of repair critical‐sized (CSD) long bone defects in vivo. In this study, 3DPBC scaffolds were augmented with dipyridamole (DIPY), an adenosine A2A receptor (A2AR) indirect agonist, because of its known effect to enhance bone formation. CSD full thickness segmental defects (~11 mm × full thickness) defects were created in the radial diaphysis in New Zealand white rabbits (n = 24). A customized 3DPBC scaffold composed of β‐tricalcium phosphate was placed into the defect site. Groups included scaffolds that were collagen‐coated (COLL), or immersed in 10, 100, or 1,000 μM DIPY solution. Animals were euthanized 8 weeks post‐operatively and the radii/ulna‐scaffold complex retrieved en bloc, for micro‐CT, histological, and mechanical analysis. Bone growth was assessed exclusively within scaffold pores and evaluated by microCT and advanced reconstruction software. Biomechanical properties were evaluated utilizing nanoindentation to assess the newly regenerated bone for elastic modulus (E) and hardness (H). MicroCT reconstructions illustrated bone in‐growth throughout the scaffold, with an increase in bone volume dependent on the DIPY dosage. The histological evaluation did not indicate any adverse immune response while revealing progressive remodeling of bone. These customized biologic 3DPBC scaffolds have the potential of repairing and regenerating bone. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2499–2507, 2019 [ABSTRACT FROM AUTHOR]

The activity of basic multicellular units (BMU) in cortical bone is classically described as a sequential order of events— resorption, reversal and formation. This simplified portrayal of the remodeling process is pervasive despite the reported variability in remodeling space morphology. These variations may reflect meaningful nuances in BMU activity but methods to quantify 3D remodeling space morphology within the context of the cellular activity are currently lacking. This study developed new techniques to define zones of BMU activity based on the 3D morphology of remodeling spaces in rabbit cortical bone and integrated morphological data with the BMU longitudinal erosion rate (LER) to elucidate the spatial-temporal coordination of BMUs and estimate mineral apposition rate (MAR). The tibiae of New Zealand white rabbits (n = 5) were imaged in vivo using synchrotron radiation and two weeks later ex vivo with desktop microCT. The in vivo and ex vivo datasets were co-registered, and 27 remodeling spaces were identified at both timepoints. A radial profile representing the 3D morphology was the platform for partitioning the remodeling spaces into resorption, reversal and formation zones. Manual, automated and semi-automated partitioning approaches were compared, and the zone-segmentations were used to calculate the length, change in radius and slope of each zone. The manual approach most accurately defined the zones of idealized remodeling spaces with known dimensions (relative error = 0.9–9.2 %) while the semi-automated method reliably defined the zones in rabbit remodeling spaces (ICC = 0.85–1.00). Combining LER and the manually derived zone dimensions indicated that a BMU passes through a cross-section in approximately 18.8 days with resorption, reversal and formation taking 4.1, 2.2, and 12.5 days, respectively. MAR estimated by the 3D analysis was not significantly different than that determined with classic histomorphometry (p = 0.48). These techniques have the potential to assess dynamic parameters of bone resorption and formation, eliminate the need for fluorochrome labeling and provide a more comprehensive perspective of the remodeling process. • New methods defining zones of BMU activity based on the remodeling space 3D morphology were developed. • Manual segmentation of remodeling zones was highly sensitive but semi-automated segmentation was most reliable. • Rabbit cortical BMUs pass through a cross section in ~18 days. • Mineral apposition rate can be derived from remodeling space morphology without fluorochrome labels. [ABSTRACT FROM AUTHOR]

Basic Multicellular Units (BMUs) conduct bone remodeling, a critical process of tissue turnover which, if imbalanced, can lead to disease, including osteoporosis. Parathyroid hormone (PTH 1–34; Teriparatide) is an osteoanabolic treatment for osteoporosis; however, it elevates the rate of intra-cortical remodeling (activation frequency) leading, at least transiently, to increased porosity. The purpose of this study was to test the hypothesis that PTH not only increases the rate at which cortical BMUs are initiated but also increases their progression (Longitudinal Erosion Rate; LER). Two groups (n = 7 each) of six-month old female New Zealand white rabbits were both administered 30 μg/kg of PTH once daily for a period of two weeks to induce remodeling. Their distal right tibiae were then imaged in vivo by in-line phase contrast micro-CT at the Canadian Light Source synchrotron. Over the following two weeks the first group (PTH) received continued daily PTH while the second withdrawal group (PTHW) was administrated 0.9 % saline. At four weeks all animals were euthanized, their distal tibiae were imaged by conventional micro-CT ex vivo and histomorphometry was performed. Matching micro-CT datasets (in vivo and ex vivo) were co-registered in 3D and LER was measured from 612 BMUs. Counter to our hypothesis, mean LER was lower (p < 0.001) in the PTH group (30.19 ± 3.01 μm/day) versus the PTHW group (37.20 ± 2.77 μm/day). Despite the difference in LER, osteonal mineral apposition rate (On.MAR) did not differ between groups indicating the anabolic effect of PTH was sustained after withdrawal. The slowing of BMU progression by PTH warrants further investigation; slowed resorption combined with elevated bone formation rate, may play an important role in how PTH enhances coupling between resorption and formation within the BMU. Finally, the prolonged anabolic response following withdrawal may have utility in terms of optimizing clinical dosing regimens. • In-line phase contrast Micro-CT tracks rabbit cortical bone remodeling events in 4D. • PTH 1–34 slows Basic Multicellular Units (BMU) advancement in rabbit cortical bone. • Osteonal mineral apposition remains elevated 2 weeks after PTH withdrawal in rabbits. [ABSTRACT FROM AUTHOR]

Abstract: Clinical data suggest that reductions in fractures associated with osteoporosis may occur sooner in patients treated with risedronate (RIS) compared to those treated with alendronate (ALN). This could be explained by differences in the time course of turnover suppression between these two bisphosphonates. To determine if differences in the onset of turnover suppression exist between RIS and ALN, female New Zealand white rabbits (total n=32) were treated with clinically relevant doses of RIS or ALN and then administered different fluorochrome labels weekly for four weeks in order to allow histological assessment of the time-course of turnover suppression. By the third week of treatment vertebral trabecular bone formation rate (BFR/BS) was significantly suppressed with RIS-treatment compared to both VEH and ALN. By the 4th week of treatment, turnover rates in RIS-treated animals remained significantly lower than in VEH-treated animals and were also lower than ALN; at this time-point ALN was significantly lower than VEH. There was no significant reduction in intra-cortical remodeling in the tibial mid-diaphysis at any time point for either RIS or ALN. This greater effect on turnover suppression with RIS early in treatment compared to ALN is likely the result of both risedronate''s greater potency on osteoclast inhibition and its lower binding affinity. Together with studies showing more rapid return toward baseline turnover following withdrawal of RIS compared to ALN, this pre-clinical study provides evidence of the differences between bisphosphonates with respect to onset and recovery of bone turnover suppression. This article is part of a Special Issue entitled Bisphosphonates. [Copyright &y& Elsevier]

Hydroxyapatite cement (BoneSource®) and brushite calcium phosphate cement (chronOS™ Inject) were tested for fixation of glass ceramic implants (Bioverit®) in experimentally created cranial defects in 24 adult New Zealand White rabbits. Aim of the in vivo study was to assess and compare the biocompatibility and osseointegration of the implanted materials. Macroscopic and histological evaluations were performed 1 month, 3 months, and 6 months postoperatively. All implanted materials were well tolerated by the surrounding tissue. Both bone cements exhibited osteoconductive properties. Differences could be detected regarding to the rates of cement resorption and new bone formation. The brushite cement was resorbed faster than the hydroxyapatite cement. The chronOS™ Inject samples exhibited a higher rate of connective tissue formation and an insufficient osseointegration. BoneSource® was replaced by bone with minimal invasion of connective tissue. New bone formation occurred faster compared to the chronOS™ Inject group. Bioverit® implants fixed with BoneSource® were successfully osseointegrated. [ABSTRACT FROM AUTHOR]

The Tuatara, Sphenodon, is a small reptile currently restricted to islands off the coast of New Zealand where it feeds mainly on arthropods. A widely held misconception is that 'Sphenodon does not have real teeth' and instead possesses 'serrations on the jaw bone'. One hatchling and one adult dentary were examined under SEM. Two longitudinal ground sections 100-µm thick were prepared through a lower canine tooth and its supporting tissues. There was clear evidence of aprismatic enamel (primless enamel) containing dentine tubules crossing the EDJ, dentine, cementum and a basal-bone attachment. Enamel increments averaged ∼3 µm/day and extension rates were ∼30 µm/day. The base of the tooth consisted of basal attachment bone that graded from few cell inclusions to lamella or even Haversian-like bone with evidence of remodeling. A string of sclerosed pulp-stone like structures filled the pulp chamber and were continuous with the bone of attachment. Bone beneath the large central nutrient mandibular (Meckel's) canal was quite unlike lamella bone and appeared to be fast growing and to contain wide alternating cell-rich and cell-free zones. Bone cells were rounded (never fusiform) and had few, if any, canaliculi. The dentine close to the EDJ formed at about the same rate as enamel but also contained longer period increments ∼100 µm apart. These were spaced appropriately for monthly lunar growth bands, which would explain the basis of the banding pattern observed in the fast growing basal bone beneath the Meckel's canal. [ABSTRACT FROM AUTHOR]

Due to autogenous bone limitations, some substitute bone grafts were developed. Collagenated porcine graft (CPG) is able to regenerate new bone, although the number of studies is insufficient, highlighting the need for future studies to better understand the biomaterial. In order to understand better CPG′s possible dental guided bone regeneration indications, the aim of this work was to determine CPG′s biological capacity to induce osteoblast differentiation in vitro and guided bone regeneration in vivo, whilst being compared with commercial hydroxyapatite and beta tricalcium phosphate (HA/β-TCP) and porcine graft alone. Cell cytotoxicity (WST-1), alkaline phosphatase activity (ALP), and real-time polymerase chain reaction (qPCR) were assessed in vitro. Critical size defects of New Zealand white rabbits were used for the in vivo part, with critical size defect closures and histological analyses. WST-1 and ALP indicated that CPG directly stimulated a greater proliferation and confluency of cells with osteoblastic differentiation in vitro. Gene sequencing indicated stable bone formation markers, decreased resorption makers, and bone remodeling coupling factors, making the transition from osteoclast to osteoblast expression at the end of seven days. CPG resulted in the highest new bone regeneration by osteoconduction in critical size defects of rabbit calvaria at eight weeks. Nonetheless, all biomaterials achieved nearly complete calvaria defect closure. CPG was found to be osteoconductive, like porcine graft and HA/β-TCP, but with higher new bone formation in critical size defects of rabbit calvaria at eight weeks. CPG can be used for different dental guided bone regeneration procedures; however, further studies are necessary. [ABSTRACT FROM AUTHOR]

Purpose: Treatment of chronic osteomyelitis (bone infection) remains a clinical challenge. Our previous study had demonstrated that NEMO-binding domain (NBD) peptide effectively ameliorates the inhibition of osteoblast differentiation by TNF-α in vitro. In this work, NBD peptide was evaluated in vivo for treating chronic osteomyelitis induced by methicillin-resistant Staphylococcus aureus (MRSA) in a rabbit model. Methods: Tibial osteomyelitis was induced in 50 New Zealand white rabbits by tibial canal inoculation of MRSA strain. After 3 weeks, 45 rabbits with osteomyelitis were randomly divided into four groups that correspondingly received the following interventions: 1) Control group (9 rabbits, no treatment); 2) Van group (12 rabbits, debridement and parenteral treatment with vancomycin); 3) NBD + Van group (12 rabbits, debridement and local NBD peptide injection, plus parenteral treatment with vancomycin); 4) NBD group (12 rabbits, debridement and local NBD peptide injection). Blood samples were collected weekly for the measurement of leucocyte count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels. The rabbits in all four groups were sacrificed 6 weeks after debridement; the anti-infective efficacy was evaluated by radiological, histological, and microbiological examination, and promotion of bone remodeling was quantified by micro-CT using the newly formed bone. Results: Except two rabbits in the Control group and one in the NBD group that died from severe infection before the end point, the remaining 42 animals (7, 12, 12, 11 in the Control, Van, NBD + Van, and NBD group respectively) were sacrificed 6 weeks after debridement. In general, there was no significant difference in the leucocyte count, and ESR and CRP levels, although there were fluctuations throughout the follow-up period after debridement. MRSA was still detectable in bone tissue samples of all animals. Interestingly, treatment with NBD peptide plus vancomycin significantly reduced radiological and histological severity scores compared to that in other groups. The best therapeutic efficacy in bone defect repair was observed in the NBD peptide + Van group. Conclusions: In a model of osteomyelitis induced by MRSA, despite the failure in demonstrating antibacterial effectiveness of NBD peptide in vivo, the results suggest antibiotics in conjunction with NBD peptide to possibly have promising therapeutic potential in osteomyelitis. [ABSTRACT FROM AUTHOR]

Backpack harnesses are commonly used to attach radio and satellite transmitters to a wide range of bird species for research and conservation management. They are an integral part of the conservation management of the New Zealand Takahē (Porphyrio hochstetteri), an endangered flightless rail. Radio transmitters mounted on backpack harnesses enable the birds to be tracked in their remaining native range of remote, mountainous Fiordland, New Zealand. We evaluated 26 Takahē retrospectively at necropsy by gross examination, radiography, and computed tomography to assess damage from the backpack harness. Ten birds that had never worn a harness had no evidence of wing injury. Of the 16 birds that had worn a harness, 10 (63%) had superficial soft tissue injury to skin or patagium or more severe injury, such as remodeling of the distal humerus at the harness cord-wing interface, or pathologic fractures. Such injuries are hypothesized to be associated with discomfort, increased risk of infection or fracture, and therefore reduced fitness. These findings have implications for all avian species deployed with backpack harnesses.