Platelet-derived extracellular vesicles formulated with hyaluronic acid gels for application at the bone-implant interface: An animal study.

Background/Objective: Platelet derived extracellular vesicles (pEV) are promising therapeutical tools for bone healing applications. In fact, several in vitro studies have already demonstrated the efficacy of Extracellular Vesicles (EV) in promoting bone regeneration and repair in various orthopedic models. Therefore, to evaluate the translational potential in this field, an in vivo study was performed. Methods: Here, we used hyaluronic acid (HA) gels formulated with pEVs, as a way to directly apply pEVs and retain them at the bone defect. In this study, pEVs were isolated from Platelet Lysate (PL) through size exclusion chromatography and used to formulate 2% HA gels. Then, the gels were locally applied on the tibia cortical bone defect of New Zeland White rabbits before the surgical implantation of coin-shaped titanium implants. After eight weeks, the bone healing process was analyzed through biomechanical, micro-CT, histological and biochemical analysis. Results: Although no biomechanical differences were observed between pEV formulated gels and non-formulated gels, biochemical markers of the wound fluid at the interface presented a decrease in Lactate dehydrogenase (LDH) activity and alkaline phosphatase (ALP) activity for pEV HA treated implants. Moreover, histological analyses showed that none of the treatments induced an irritative effect and, a decrease in the fibrotic response surrounding the implant for pEV HA treated implants was described. Conclusion: In conclusion, pEVs improve titanium implants biocompatibility at the bone-implant interface, decreasing the necrotic effects of the surgery and diminishing the fibrotic layer associated to the implant encapsulation that can lead to implant failure.

Use of 3D-printed polylactic acid/bioceramic composite scaffolds for bone tissue engineering in preclinical in vivo studies: A systematic review.

3D-printed composite scaffolds have emerged as an alternative to deal with existing limitations when facing bone reconstruction. The aim of the study was to systematically review the feasibility of using PLA/bioceramic composite scaffolds manufactured by 3D-printing technologies as bone grafting materials in preclinical in vivo studies. Electronic databases were searched using specific search terms, and thirteen manuscripts were selected after screening. The synthesis of the scaffolds was carried out using mainly extrusion-based techniques. Likewise, hydroxyapatite was the most used bioceramic for synthesizing composites with a PLA matrix. Among the selected studies, seven were conducted in rats and six in rabbits, but the high variability that exists regarding the experimental process made it difficult to compare them. Regarding the results, PLA/Bioceramic composite scaffolds have shown to be biocompatible and mechanically resistant. Preclinical studies elucidated the ability of the scaffolds to be used as bone grafts, allowing bone growing without adverse reactions. In conclusion, PLA/Bioceramics scaffolds have been demonstrated to be a promising alternative for treating bone defects. Nevertheless, more care should be taken when designing and performing in vivo trials, since the lack of standardization of the processes, which prevents the comparison of the results and reduces the quality of the information. STATEMENT OF SIGNIFICANCE: 3D-printed polylactic acid/bioceramic composite scaffolds have emerged as an alternative to deal with existing limitations when facing bone reconstruction. Since preclinical in vivo studies with animal models represent a mandatory step for clinical translation, the present manuscript analyzed and discussed not only those aspects related to the selection of the bioceramic material, the synthesis of the implants and their characterization. But provides a new approach to understand how the design and perform of clinical trials, as well as the selection of the analysis methods, may affect the obtained results, by covering authors' knowledgebase from veterinary medicine to biomaterial science. Thus, this study aims to systematically review the feasibility of using polylactic acid/bioceramic scaffolds as grafting materials in preclinical trials.

Development of a new preclinical model to study early implant loss: a validation study in the beagle dog.

OBJECTIVES: To develop a new preclinical model to study early implant loss, where local infection conditions would impair the implant osseointegration. MATERIALS AND METHODS: Forty-eight smooth, 2.9-mm diameter experimental implants were placed in the mandible of 8 beagle dogs (3 in each side). In half of the animals (test group, n = 24 implants), the implants received ligatures around the implant-abutment connection. In the other half, no ligatures were placed (control group, n = 24 implants). Four weeks later, implants were extracted in a flapless approach and standard 3.3-mm diameter SLActive implants were placed into the same osteotomy site without any further drilling. Eight weeks after the second implantation, animals were sacrificed and analyzed in terms of implant survival. RESULTS: After 8 weeks of healing, 4 implants were lost in the control group and 14 in the test group. This corresponded to a 17.4% of early implant loss in the control group and 58.3% in the test. Most of the early failures occurred within the first 5 weeks of healing. CONCLUSIONS: Implants placed in a pre-contaminated site present higher early loss than those placed in a non-contaminated site. This study represents a valid and robust preclinical model to study mechanisms and reduction of early implant loss as new technologies become available. CLINICAL RELEVANCE: Scientific rationale for the study: There is lack of animal models to study early implant loss. Thus, a proposal of a new model is presented. With the validation of this model, new technologies can be implemented to prevent early implant loss.

Antimicrobial Consumption in Latin American Countries: First Steps of a Long Road Ahead.

BACKGROUND: Irrational antimicrobial consumption (AMC) became one of the main global health problems in recent decades. OBJECTIVE: In order to understand AMC in Latin-American Region, we performed the present research in 6 countries. METHODS: Antimicrobial consumption (J01, A07A, P01AB groups) was registered in Argentina, Chile, Colombia, Costa Rica, Paraguay, and Peru. Source of information, AMC type, DDD (Defined Daily Doses), DID (DDD/1000 inhabitants/day), population were variables explored. Data was analyzed using the Global Antimicrobial Resistance and Use Surveillance System (GLASS) tool. RESULTS: Source of information included data from global, public, and private sectors. Total AMC was highly variable (range 1.91-36.26 DID). Penicillin was the most consumed group in all countries except in Paraguay, while macrolides and lincosamides were ranked second. In terms of type of AMC according to the WHO-AWaRe classification, it was found that for certain groups like "Reserve," there are similarities among all countries. CONCLUSION AND RELEVANCE: This paper shows the progress that 6 Latin-American countries made toward AMC surveillance. The study provides a standardized approach for building a national surveillance system for AMC data analysis. These steps will contribute to the inclusion of Latin-America among the regions of the world that have periodic, regular, and quality data of AMC.

3D-printed titanium cages without bone graft outperform PEEK cages with autograft in an animal model.

BACKGROUND CONTEXT: Modernization of 3D printing has allowed for the production of porous titanium interbody cages (3D-pTi) which purportedly optimize implant characteristics and increase osseointegration; however, this remains largely unstudied in vivo. PURPOSE: To compare osseointegration of three-dimensional (3D) titanium cages without bone graft and Polyether-ether-ketone (PEEK) interbody cages with autologous iliac crest bone graft (AICBG). STUDY DESIGN: Animal study utilizing an ovine in vivo model of lumbar fusion. METHODS: Interbody cages of PEEK or 3D-pTi supplied by Spineart SA (Geneva, Switzerland) were implanted in seven living sheep at L2-L3 and L4-L5, leaving the intervening disc space untreated. Both implant materials were used in each sheep and randomized to the aforementioned disc spaces. Computed tomography (CT) was obtained at 4 weeks and 8 weeks. MicroCT and histological sections were obtained to evaluate osseointegration. RESULTS: MicroCT demonstrated osseous in-growth of native cancellous bone in the trabecular architecture of the 3D-pTi interbody cages and no interaction between the PEEK cages with the surrounding native bone. Qualitative histology revealed robust osseointegration in 3D-pTi implants and negligible osseointegration with localized fibrosis in PEEK implants. Evidence of intramembranous and endochondral ossification was apparent with the 3D-pTi cages. Quantitative histometric bone implant contact demonstrated significantly more contact in the 3D-pTi implants versus PEEK (p<.001); region of interest calculations also demonstrated significantly greater osseous and cartilaginous interdigitation at the implant-native bone interface with the 3D-pTi cages (p=.008 and p=.015, respectively). CONCLUSIONS: 3D-pTi interbody cages without bone graft outperform PEEK interbody cages with AICBG in terms of osseointegration at 4 and 8 weeks postoperatively in an ovine lumbar fusion model. CLINICAL SIGNIFICANCE: 3D-pTi interbody cages demonstrated early and robust osseointegration without any bone graft or additive osteoinductive agents. This may yield early stability in anterior lumbar arthrodesis and potentially bolster the rate of successful fusion. This could be of particular advantage in patients with spinal neoplasms needing post-ablative arthrodesis, where local autograft use would be ill advised.

A randomized controlled preclinical trial on 3 interposal temporomandibular joint disc implants: TEMPOJIMS-Phase 2.

The effort to develop an effective and safe temporomandibular joint (TMJ) disc substitute has been one of the mainstreams of tissue engineering. Biodegradable customized scaffolds could approach safety and effectiveness to regenerate a new autologous disc, rather than using non-biodegradable materials. However, it is still technically challenging to mimic the biomechanical properties of the native disc with biodegradable polymers. In this study, new 3D tailored TMJ disc implants were developed: (1) Poly(glycerol sebacate) (PGS) scaffold reinforced with electrospun Poly(εcaprolactone) (PCL) fibers on the outer surface (PGS+PCL); (2) PCL and polyethylene glycol diacrylate (PEGDA) (PCL+PEGDA); and (3) PCL. The TMJ implants were tested in a randomized preclinical trial, conducted in 24 black Merino sheep TMJ, perfoming bilateral interventions. Histologic, imaging, and kinematics analysis was performed. No statistical changes were observed between the PGS+PCL disc and the control group. The PCL+PEGDA and PCL groups were associated with statistical changes in histology (p = 0.004 for articular cartilage mid-layer; p = 0.019 for structure changes and p = 0.017 for cell shape changes), imaging (p = 0.027 for global appreciation) and dangerous material fragmentation was observed. No biomaterial particles were observed in the multi-organ analysis in the different groups. The sheep confirmed to be a relevant animal model for TMJ disc surgery and regenerative approaches. The PCL and PCL+PEGDA discs presented a higher risk to increase degenerative changes, due to material fragmentation. None of the tested discs regenerate a new autologous disc, however, PGS+PCL was safe, demonstrated rapid resorption, and was capable to prevent condyle degenerative changes.

Glucosamine and Chondroitin Sulfate: Is There Any Scientific Evidence for Their Effectiveness as Disease-Modifying Drugs in Knee Osteoarthritis Preclinical Studies?-A Systematic Review from 2000 to 2021.

Glucosamine and chondroitin sulfate have been proposed due to their physiological and functional benefits in the management of osteoarthritis in companion animals. However, the scientific evidence for their use is still controversial. The purpose of this review was to critically elucidate the efficacy of these nutraceutical therapies in delaying the progression of osteoarthritis, evaluating their impact on the synovial knee joint tissues and biochemical markers in preclinical studies by systematically reviewing the last two decades of peer-reviewed publications on experimental osteoarthritis. Three databases (PubMed, Scopus and, Web of Science) were screened for eligible studies. Twenty-two articles were included in the review. Preclinical studies showed a great heterogeneity among the experimental designs and their outcomes. Generally, the evaluated nutraceuticals, alone or in combination, did not seem to prevent the subchondral bone changes, the synovial inflammation or the osteophyte formation. However, further experimental studies may be needed to evaluate their effect at those levels. Regarding the cartilage status and biomarkers, positive responses were identified in approximately half of the evaluated articles. Furthermore, beneficial effects were associated with the pre-emptive administrations, higher doses and, multimodality approaches with some combined therapies. However, additional studies in the long term and with good quality and systematic design are required.

Histomorphometric Quantitative Evaluation of Long-Term Risedronate Use in a Knee Osteoarthritis Rabbit Model.

Osteoarthritis (OA) treatment is a major orthopedic challenge given that there is no ideal drug capable to reverse or stop the progression of the OA. In that regard, bisphosphonates have been proposed as potential disease-modifying drugs due to their possible chondroprotective effect related to obtaining a greater subchondral bone quality. However, their effectiveness in OA is still controversial and additionally, there is little evidence focused on their long-term effect in preclinical studies. The aim of this study was to evaluate the risedronate quantitative effect on articular and subchondral periarticular bone by histomorphometry, in an experimental rabbit model in an advanced stage of OA. Twenty-four adult New Zealand rabbits were included in the study. OA was surgically induced in one randomly chosen knee, using the contralateral as healthy control. Animals were divided into three groups (n = 8): placebo control group, sham surgery group and risedronate-treated group. After 24 weeks of treatment, cartilage and subchondral femorotibial pathology was evaluated by micro-computed tomography (micro-CT) and undecalcified histology. The research results demonstrated that the experimental animal model induced osteoarthritic changes in the operated joints, showing an increased cartilage thickness and fibrillation associated with underlying subchondral bone thinning and decreased trabecular bone quality. These changes were especially highlighted in the medial tibial compartments as a possible response to surgical instability. Regarding the trabecular analysis, significant correlations were found between 2D histomorphometry and 3D imaging micro-CT for the trabecular bone volume, trabecular separation, and the trabecular number. However, these associations were not strongly correlated, obtaining more precise measurements in the micro-CT analysis. Concerning the long-term risedronate treatment, it did not seem to have the capacity to reduce the osteoarthritic hypertrophic cartilage response and failed to diminish the superficial cartilage damage or prevent the trabecular bone loss. This study provides novel information about the quantitative effect of long-term risedronate use on synovial joint tissues.

Periodontal response to a tricalcium silicate material or resin composite placed in close contact to the supracrestal tissue attachment: a histomorphometric comparative study.

OBJECTIVE: Subgingival dental restorations and periodontal health have been studied for many years; however, there is a low histological evidence on the behavior of new materials in the supracrestal tissue attachment. The aim of this study is to analyze the periodontal response when a tricalcium silicate material (TSM) or composite margin restorations is placed to 0.5 mm and 1.5 mm from the bone crest with a histomorphometric analysis in dogs. METHODS: Nine mongrel dogs were used in this study: four dogs (8 canine teeth) for TSM group, 4 dogs (8 canine teeth) for composite group, and 1 dog (2 canine teeth) with cavities without restorations. Cavity preparation of 2×2×1 mm was created on the buccal aspect of the canines at 0.5 and 1.5 mm of the crestal bone. Cavities were restored with composite and TSM or were left unrestored as control. After 12 weeks of healing, the dogs were euthanized and blocks containing the tooth and soft tissues were processed. RESULTS: In all the specimens, the junction epithelium was stablished apical to the tooth preparations. A shorter distance to the bone (0.5 cavity) implies greater apical periodontal migration regardless of the material used. In the TSM groups, the connective tissue height and the distance between bone level and apical margin preparation were greater than those in the composite groups, while the epithelium height was less. However, there were no statistically significant differences comparing TSM and composite groups at either 0.5 mm or 1.5 mm (p > 0.05). CONCLUSION: Histologic analysis did not show periodontal reattachment to TSM or composite. In both cases, bone crest migrates apically. For that reason, it is recommended to perform composite restorations at the subgingival level whenever the distance to the bone crest is at least 2 mm. CLINICAL RELEVANCE: Both composite and TSM do not achieve reinsertion of the connective tissue in the biological width.

Systematic Review and Quality Evaluation Using ARRIVE 2.0 Guidelines on Animal Models Used for Periosteal Distraction Osteogenesis.

The objective of this systematic review was to synthesize all the preclinical studies carried out in periosteal distraction osteogenesis (PDO) in order to evaluate the quality using the ARRIVE guidelines. The animal models used, and the influence of the complications, were analysed in order to establish the most appropriate models for this technique. The PRISMA statements have been followed. Bibliographic sources have been consulted manually by two reviewers. Risk of bias was evaluated using the SYRCLE tool for animal studies, and the quality of the studies with the ARRIVE 2.0 guidelines. The selection criteria established by expert researchers were applied to decide which studies should be included in the review, that resulted in twenty-four studies. Only one achieved the maximum score according to the ARRIVE 2.0 guidelines. The rabbit as an animal model has presented good results in PDO, both for calvaria and jaw. Rats have shown good results for PDO in calvaria. The minipig should not be recommended as an animal model in PDO. Despite the increase in the quality of the studies since the implementation of the ARRIVE 2.0 guidelines, it would be necessary to improve the quality of the studies to facilitate the transparency, comparison, and reproducibility of future works.

Case Report: First Evidence of a Benign Bone Cyst in an Adult Teckel Dog Treated With Shark Teeth-Derived Bioapatites.

Bone cysts are a very rare orthopedic pathology in veterinary medicine, the general prevalence of which is unknown. A unicameral bone cyst was diagnosed in an adult female Teckel dog with a limp that was treated surgically by filling the defect with marine bioapatites. The treatment was effective and at 8 weeks the defect had remodeled 50.24%. Eighteen months after surgery, the defect had remodeled 94.23%. The limp disappeared after surgery, and functional recovery was good in all stages after surgery. No adverse reactions were observed at the local or systemic level. This is the first report of a benign bone cyst in an lame adult female Teckel successfully treated with a novel marine bioapatite.

Bisphosphonates as disease-modifying drugs in osteoarthritis preclinical studies: a systematic review from 2000 to 2020.

Bisphosphonates have been proposed as possible disease-modifying drugs in osteoarthritis. However, the evidence of their efficacy is poor and their outcomes presented a great heterogeneity. Therefore, the aim of this study is to systematically review the main effects of bisphosphonate use on synovial joint tissues and biochemical markers in preclinical studies over the past two decades (2000-2020). Three databases (Pubmed, Scopus, and Web of Science) were searched, and after screening, twenty-six studies with five different types of bisphosphonates were included in the review. The animal model selected, the type of bisphosphonate used, the therapy duration, and the main effects of individual drugs on synovial tissues were evaluated. Additionally, the quality and risk of bias assessments were performed using the Animals in Research Reporting In Vivo Experiments guidelines and the Systematic Review Centre for Laboratory animal Experimentation tool. Studies showed high variability in experimental designs. Consequently, the comparison of the findings in order to draw specific conclusions about the effectiveness of the drugs is complicated. However, the results of this systematic review suggested that bisphosphonates seemed to reduce the osteoarthritic changes in a dose-dependent manner showing better chondroprotective effects at high doses. Besides, a time-dependent efficacy was also detected in terms of cartilage status. One can conclude that the disease stage of the time-point of treatment initiation may constitute a key factor in the antiresorptive drug efficacy. Generally, we noted that bisphosphonate administration seemed to show positive subchondral bone conservation and fewer biomarker alterations. However, they did not appear to suppress the osteophyte development and their chondroprotective effect is highly variable among the studies. Bisphosphonates appeared to show a positive anti-inflammatory effect on the synovial membrane. However, only a few included publications were focused on their investigation. Regarding the therapy duration, there is a significant lack of evidence on evaluating their effectiveness in preclinical long-term studies and further experimental studies may be needed to examine the pharmacological response in these circumstances. This systematic review might help to clarify the efficacy of bisphosphonates and their function as disease-modifying treatments in osteoarthritis.

Does the Animal Model Influence in Vertical Alveolar Distraction? A Systematic Review of the Literature.

This study is aimed at synthesizing all available evidence on vertical alveolar osteogenesis distraction (VAOD) in animal trials to determine whether the animal model used and its handling influence or not, and find which is the most appropriate animal model for this specific technique. This systematic review has been carried out following the PRISMA statements. Bibliographic sources have been consulted manually by two reviewers. Risk of bias was assessed using a version of the Newcastle-Ottawa-Scale (NOS). The selection criteria established by expert researchers were applied in order to decide which studies should be included in the review. Twenty-six studies met the inclusion criteria and were included in the review. Twenty-four of them had a high quality (score between 7 and 9), two medium quality (score between 4 and 6), and none low quality (score between 1 and 3). The highest possible score was 9 (using the NOS). Six studies complied with all NOS criteria. The animal model has been seen to influence the results, leading to failure in some cases. The most used animal model on VAOD, with fewer complications, was the Mongrel dog. The use of the pig and minipig is not recommended, due to the difficulties in handling and complications encountered.

No Effect of Long-Term Risedronate Use on Cartilage and Subchondral Bone in an Experimental Rabbit Model of Osteoarthritis.

Osteoarthritis (OA) is the most prevalent degenerative joint disease in animals and humans. It is characterized by pain, articular cartilage damage and joint stiffness. It has been suggested that the status of the subchondral bone compartment plays an important role in the initiation and progression of OA. Bisphosphonates have been proposed as a potential disease-modifying treatment for OA, however their effectiveness is not yet clear. Twenty-four male adult New Zealand rabbits were used to evaluate the effects of risedronate on the subchondral bone quality and cartilage degradation in a long-term model of experimentally induced OA. Animals underwent an anterior cruciate ligament transection and partial medial meniscectomy or sham operation in only one knee, which was randomly chosen, using the contralateral as healthy control. Animals were divided into three groups (n = 8): untreated control group and sham surgery control group; both groups received only vehicle; and risedronate group, treated with 2.5 mg orally weekly for 24 weeks. Stifle joints were harvested and scanned using a high-resolution micro-CT to evaluate the subchondral plate and trabecular bone changes. The macroscopic evaluation and histological analysis were determined using an adapted Osteoarthritis Research Society International scoring scheme to assess the cartilage degeneration. The lateral and medial femoral condyle and tibial plateau were evaluated. Additionally, the histological synovial membrane assessment was carried out. Sample analysis showed that the experimental model induced osteoarthritic changes in the operated joints, whereas in sham-operated rabbits, almost no histological changes were observed on articular cartilage surfaces. In terms of macroscopic and histological analyses, risedronate-treated animals did not show improved cartilage health compared with untreated operated rabbits, but a slightly anti-inflammatory activity was observed in the synovial membrane. Risedronate administration showed a slight tendency to increase subchondral bone plate thickness in lateral compartments but, it did not show conservation of periarticular bone and was not be able to suppress the osteophyte formation. In conclusion, long-term risedronate use did not demonstrate a positive effect on reducing the cartilage damage, and failed to prevent the subchondral bone changes and osteophytogenesis in an experimental rabbit model of OA.

Coating doxycycline on titanium-based implants: Two in vivo studies.

Regardless of the substantial progress in designing titanium-based dental implants and aseptic techniques, infection remains as the most common complication after implantation surgeries. Although, having a weakened immune system or systematic diseases is not seen as contraindicated for dental implants anymore, controlling the immune system is required to avoid surgical site infections after implantation. These patients have to control the surgical site infections by taking a high daily dose of oral antibiotics after dental implantation. The antibiotics oral administration has many side effects such as gastrointestinal symptoms, skin rashes and thrush. Coating antibiotics on the biomaterials surface could be a promising solution to reduce these disadvantages through locally releasing antibiotics in a controlled manner. The aim of this study was to investigate the effects of doxycycline coating layer on titanium-zirconium alloy surfaces in vitro and in vivo. In our previous studies, we demonstrated the chemical presence of doxycycline layer in vitro. In this study, we examined its physical presence using field emission scanning electron microscope and confocal microscope. We also analyzed its controlled released manner using Nano-Drop UV Vis spectrometer. After in vitro characterization of the coating layer, we evaluated its effects on the implant osseointegration in dogs and rabbits. The histological and histomorphometrical results exhibited no significant difference between doxycycline coated and uncoated groups regarding the implants osseointegration and biocompatibility for dental applications. Therefore, coating a doxycycline layer on TiZr implants could be favorable for reducing or removing the antibiotics oral administration after the implantation surgery.

An elastin-like recombinamer-based bioactive hydrogel embedded with mesenchymal stromal cells as an injectable scaffold for osteochondral repair.

The aim of this study was to evaluate injectable, in situ cross-linkable elastin-like recombinamers (ELRs) for osteochondral repair. Both the ELR-based hydrogel alone and the ELR-based hydrogel embedded with rabbit mesenchymal stromal cells (rMSCs) were tested for the regeneration of critical subchondral defects in 10 New Zealand rabbits. Thus, cylindrical osteochondral defects were filled with an aqueous solution of ELRs and the animals sacrificed at 4 months for histological and gross evaluation of features of biomaterial performance, including integration, cellular infiltration, surrounding matrix quality and the new matrix in the defects. Although both approaches helped cartilage regeneration, the results suggest that the specific composition of the rMSC-containing hydrogel permitted adequate bone regeneration, whereas the ELR-based hydrogel alone led to an excellent regeneration of hyaline cartilage. In conclusion, the ELR cross-linker solution can be easily delivered and forms a stable well-integrated hydrogel that supports infiltration and de novo matrix synthesis.

Rabbit as model for osteoporosis research.

Osteoporosis is a major public health problem affecting more than 200 million people worldwide. The use of different animal models, for the study of its pathophysiology and treatments, is important being actually the ovariectomized rat the most widely used; although this model has several problems due its small size, lack of true closure of epiphyseal plate and bone differences with humans. This review is aimed at summarizing the most common methods published for osteoporosis induction in rabbits as model for human disease with their advantages and disadvantages. The paper shows the advantages of the use of this specie compared with the rat. All the techniques seemed to achieve the osteoporotic condition, but the one which obtained the most consistent bone mineral reduction in less time was the combination of surgery and corticoid treatment. The conclusion of the review was that rabbits are promising as a model of osteoporosis research because of their size, haversian remodelling and closure of epiphyseal plate, which solve some of the problems of the rat model. There are different techniques in the literature used to achieve the osteoporotic condition with diverse results, but there is a lack of consensus as to the best one.

Evaluation of a new tricalcium phosphate for guided bone regeneration: an experimental study in the beagle dog.

This study compared the in vivo behavior of two biomaterials, xenograft (Bio-Oss®) and alloplastic tricalcium phosphate (Sil-Oss®), vs a control (no biomaterial) in beagle dogs treated with guided bone regeneration (GBR). Six male adult beagle dogs were included. The third and fourth mandibular premolars and first mandibular molars (3P3, 4P4 and 1M1) on both sides were extracted. After 12 weeks of healing, Straumann implants (3.3 × 8 mm) were placed, performing standardized defects (3.3 × 6 mm) in the vestibular aspect of the alveolar bone. The defects were surgically treated by randomized placement of xenograft (Bio-Oss®), alloplastic tricalcium phosphate (Sil-Oss®) or no biomaterial and covered with a resorbable collagen membrane (BioGide®). After an additional 12-week healing period, the lower jaws were dissected. Total area regenerated in the region of interest, total volume, bone to implant contact in the regenerated area, and volumetric changes were measured through histological, histomorphometrical and microcomputed tomography (microCT) techniques. The negative control group showed bone ingrowth inside the defect, with a partial collapse of the buccal bone. This was not observed in the biomaterial-treated groups. Defects treated with the xenograft showed 51.40% (SD 19.83) newly mineralized tissue, while those treated with alloplastic tricalcium showed 62.54% (SD 11.54) newly mineralized tissue; the control showed 71.52% (SD 6.46). Alloplastic tricalcium phosphate modified with monetite and zinc showed similar features in alveolar regeneration of defects to those treated with the xenograft or conventional GBR, but it showed an ideally higher rate of new mineralized tissue formation and accelerated resorption.

Evaluation of bone turnover markers and serum minerals variations for predicting fracture healing versus non-union processes in adult sheep as a model for orthopedic research.

Bone turnover markers (BTMs) have been considered as an auxiliary method of following the fracture healing process and for early prediction of impaired bone healing. A better understanding of the potential of BTMs in this application could allow for earlier interventions and improved patient care. The aim of this study with a large animal experimental model was to assess the variation of bone formation markers - namely the total alkaline phosphatase (ALP) and its bone-specific isoform (BALP), serum concentration of intact osteocalcin (OC), N-terminal propeptide type III procollagen (PIIINP) and of bone resorption markers - namely tartrate resistant acid phosphatase (TRAP) and deoxypyridinoline crosslink (DPD) during the first stages of a normal fracture healing process and of a segmental critical size defect (CSD), which progresses to a non-union process. Thirty healthy female sheep (Portuguese Churra-da-Terra-Quente breed), approximately 4-years-old, were enrolled in this study. Jugular venous blood samples were collected pre-operatively and at 1, 2, 3, 4, 6, 8, 10 and 12 post-operative weeks. The animals of the CSD group showed significant lower serum levels of BALP, OC and significant higher serum PIIINP levels at early stages of the fracture healing process, compared with animals that progressed in a normal fracture healing process. Serum BALP, OC and PIIINP levels could be useful as non-invasive auxiliary tools with other complementary methods for predicting the outcome of traumatic bone fractures.