Imobilização de fraturas femorais em gatos usando pino intramedular conectado ou não ao fixador esquelético externo

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Treatment of radius, ulna and humerus fractures with the aid of a bone morphogenetic protein in a giant anteater (Myrmecophaga tridactyla)

A giant anteater (Myrmecophaga tridactyla) was found with closed comminuted fractures on the fight radius and ulna and left humerus he duration of which was unknown. The animal was unable to use either of he thoracic limbs. The fractures were stabilized with 3.5-mm titanium plates and a commercially available mixture of micro lyophilized bovine cortical osseous and bovine BMP (Gen-tech(R), Baumer, Brazil) was implanted into the fractures sites. Postoperative radiographic evaluations were performed every 30 days and after four months. Bone healing was observed in all of he fractures. The animal was able to be reintroduced into its natural habitat. From his case we conclude that despite he low metabolic fate of the giant anteater, which is an inherent characteristic of this species, he treatment of radius, ulna and humerus fractures by means of plates and screws, associated with BMP on the Myrmecophaga tridactyla, was a success.

Rigid internal fixation with titanium versus bioresorbable miniplates in the repair of mandibular fractures in rabbits

The purpose of this study was to compare by qualitative histology the efficacy of rigid internal fixation with titanium system and the Lacto Sorb® system in mandibular fractures in rabbits. Thirty male adult rabbits Oryctolagus cuniculus were used. Unilateral mandibular osteotomies were performed between the canine and first premolar. The animals were divided into two groups: for Group I - rigid internal fixation was performed with titanium system 1.5 mm (Synthes, Oberdorf, Switzerland), with two screws of 6 mm (bicortical) on each side of the osteotomy. For Group II-rigid internal fixation was performed with PLLA/PGA system 1.5 mm (Lacto Sorb®, WLorenz, Jacksonville, FL, USA). The histological analysis evaluated the presence of inflammatory reaction, degree of bone healing and degree of resorption of the Lacto Sorb® screws. The results of both fixation systems were similar, only with a small difference after 15 and 30 days. In Group I a faster bony healing was noted. But after 60 days, bony healing was similar in both groups. It is concluded that both PLLA/PGA and titanium plates and screws provide sufficient strength to permit mandibular bone healing. The resorption process of PLLA/PGA osteosynthesis material did not cause acute or chronic inflammatory reaction or foreign body reaction during the studied period. © 2004 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Comparison between polyurethanes containing castor oil (Soft Segment) and cancellous bone autograft in the treatment of segmental bone defect induced in rabbits

The aim of this study is to compare polyurethanes containing castor oil (soft segment) in granular form compared to cancellous bone autograft applied to a segmental bone defect. Norfolk adult female rabbits - approximately 13 months of age with a mean body weight of 4.5 kg - are used. In both radial diaphyses, 1 cm osteoperiosteal segmental defects are created. The defect in the left radius is filled with the castor-oil-based polyurethane, and the right one, filled with cancellous bone autograft, collected from the left proximal humerus. The rabbits are euthanazed at 15, 30, 60, and 120 days postsurgery (5 animals/ period), for histological analyses. By radiographic analyses, at these time points, the bone regeneration is more evident and accelerated in the bone defects treated with the cancellous bone autograft. At 120 days postsurgery, the segmental bone defects treated with the cancellous bone autograft are totally reconstituted and remodeled, while the bone defects treated with polyurethane polymer have bone formation of 79%. Histological study shows that the polyurethane acts as a space filler, minimizing the local production of fibrous tissue. No granule degradation, resorption or any inflammatory reaction is detected. Thus, it is possible to conclude that the castor-oil-plant-based polyurethane - in the granule presentation - is biocompatible and osteointegrated, but does not show the same bone regeneration capacity as the cancellous bone autograft. © 2007 SAGE Publications.

Bone mineralization in Brazilian adolescents: The years of maximum bone mass incorporation

Puberty is the fundamental period for bone mass (BM) acquisition. In this period mineralization is found to increase with levels of high bone formation. The critical years of intense bone anabolism deserve special attention, as adequate gain could minimize fracture risk in later years. The objective of this work was to study bone mineral content (BMC) and bone mineral density (BMD) in male adolescents with age bracket and maturation level. Sixty-one healthy male 10 to 19 year-olds were evaluated for calcium intake, weight, stature, BMI, puberty stage and BMC and BMD in the lumbar spine and femur. BM was measured by bone densitometry (DXA). Calcium intake was calculated by recording 3 days diet. Puberty stage was defined as per Tanner. Descriptive statistics was used with means and standard deviations, linear correlation, and analysis of variance for comparison between age groups, and the Tukey test (p<0.05). Linear correlation was positive and indicated body weight as the main correlation variable with BMD in both studied locations (p<0.01). BMC and BMD increased with age, differences were significant from 14 to 15 years, and when adolescents reached Tanner stage G4. These results showed a pronounced increase in bone mineralization, with the years after 14 to 15 being critical for BM acquisition in Brazilian adolescents.

Healing outcomes at implants installed in sites augmented with particulate autologous bone and xenografts. An experimental study in dogs

Aim: To evaluate the integration of implants installed at the interface of pristine and grafted tissue augmented with particulate autologous bone or deproteinized bovine bone mineral (DBBM), concomitantly with a collagen membrane. Material and methods: In 6 Labrador dogs, the distal root of 3P3 and 4P4 was endodontically treated and hemi-sected, and the mesial roots extracted concomitantly with the extraction of 2P2. The buccal bony walls were removed, and two box-shaped defects, one larger and one smaller, were created. After 3 months, flaps were elevated, and the defects were filled with particulate autologous bone or DBBM in the right and left side of the mandible, respectively. Collagen membranes were used to cover the grafted areas. Three months later, flaps were elevated, and a customized device was used as surgical guide to prepare the recipient sites at the interface between grafts and pristine bone. One implant was installed in each of the four defects. After 3 months, biopsies were harvested and ground sections prepared for histological evaluation. Results: The augmentation technique was effective at all sites and all the foreseen implants were installed. In the histological analysis, all implants were integrated in mature bone, at both the buccal and lingual aspects. The most coronal bone-to-implant contact and the top of the buccal bony crest were located at a similar distance between test and control implants. However, these distances were higher at the larger compared with the smaller defects. Especially in the large defect, residual particles of DBBM were found embedded into connective tissue and located outside the bony crest. Conclusions: Particulate autologous bone as well as DBBM particles used to augment horizontally the alveolar bony process allowed for the osseointegration of implants installed after 3 months of healing. © 2012 John Wiley & Sons A/S.

Repercussões minerais ósseas no alcoolismo crônico associado à deficiência hormonal em ratos

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Osteossíntese minimamente invasiva com placa bloqueada nas fraturas de tíbia em cães

Pós-graduação em Cirurgia Veterinária - FCAV

Healing Process of Autogenous Bone Graft in Spontaneously Hypertensive Rats Treated With Losartan: An Immunohistochemical and Histomorphometric Study

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Plasma rico em plaquetas, medula óssea ou quitosana nas osteossínteses minimamente invasivas na tíbia de cães

Pós-graduação em Cirurgia Veterinária - FCAV

Rank protein immunolabeling during bone-implant interface healing process

The purpose of this paper was to evaluate the expression of RANK protein during bone-healing process around machined surface implants. Twenty male Wistar rats, 90 days old, after having had a 2 mm diameter and 6 mm long implant inserted in their right tibias, were evaluated at 7, 14, 21, and 42 days after healing. After obtaining the histological samples, slides were subjected to RANK immunostaining reaction. Results were quantitatively evaluated. Results. Immunolabeling analysis showed expressions of RANK in osteoclast and osteoblast lineage cells. The statistical analysis showed an increase in the expression of RANK in osteoblasts at 7 postoperative days and a gradual decrease during the chronology of the healing process demonstrated by mild cellular activity in the final stage (P < .05). Conclusion. RANK immunolabeling was observed especially in osteoclast and osteoblast cells in primary bone during the initial periods of bone-healing/implant interface.

Influence of nonlinear stiffness on the dynamics of a slender elastic beam under torsional oscillations

This study focuses on analysing the effects of nonlinear torsional stiffness on the dynam-ics of a slender elastic beam under torsional oscillations, which can be subject to helical buckling.The helical buckling of an elastic beam confined in a cylinder is relevant to many applications. Someexamples include oil drilling, medical cateters and even the conformation and functioning of DNAmolecules. A recent study showed that the formation of the helical configuration is a result of onlythe torsional load, confirming that there is a different path to helical buckling which is not related tothe sinusoidal buckling, stressing the importance of the geometrical behaviour of the beam. A lowdimensional model of an elastic beam under torsional oscillations is used to analyse its dynamical be-haviour with different stiffness characteristics, which are present before and after the helical buckling.Hardening and softening characteristics are present, as the effects of torsion and bending are coupled.With the use of numerical algorithms applied to nonlinear dynamics, such as bifurcation diagramsand basins of attraction, it is shown that the nonlinear stiffness can shift the bifurcations and inducechanges in the stability of the desirable and undesirable solutions. Therefore, the proper modellingof these stiffness nonlinearities seems to be important for a better understanding of the dynamicalbehaviour of such beams.

Primary stability in cementless total hip replacement: measurement techniques and aided-surgery

Primary stability of stems in cementless total hip replacements is recognized to play a critical role for long-term survival and thus for the success of the overall surgical procedure. In Literature, several studies addressed this important issue. Different approaches have been explored aiming to evaluate the extent of stability achieved during surgery. Some of these are in-vitro protocols while other tools are coinceived for the post-operative assessment of prosthesis migration relative to the host bone. In vitro protocols reported in the literature are not exportable to the operating room. Anyway most of them show a good overall accuracy. The RSA, EBRA and the radiographic analysis are currently used to check the healing process of the implanted femur at different follow-ups, evaluating implant migration, occurance of bone resorption or osteolysis at the interface. These methods are important for follow up and clinical study but do not assist the surgeon during implantation. At the time I started my Ph.D Study in Bioengineering, only one study had been undertaken to measure stability intra-operatively. No follow-up was presented to describe further results obtained with that device. In this scenario, it was believed that an instrument that could measure intra-operatively the stability achieved by an implanted stem would consistently improve the rate of success. This instrument should be accurate and should give to the surgeon during implantation a quick answer concerning the stability of the implanted stem. With this aim, an intra-operative device was designed, developed and validated. The device is meant to help the surgeon to decide how much to press-fit the implant. It is essentially made of a torsional load cell, able to measure the extent of torque applied by the surgeon to test primary stability, an angular sensor that measure the relative angular displacement between stem and femur, a rigid connector that enable connecting the device to the stem, and all the electronics for signals conditioning. The device was successfully validated in-vitro, showing a good overall accuracy in discriminating stable from unstable implants. Repeatability tests showed that the device was reliable. A calibration procedure was then performed in order to convert the angular readout into a linear displacement measurement, which is an information clinically relevant and simple to read in real-time by the surgeon. The second study reported in my thesis, concerns the evaluation of the possibility to have predictive information regarding the primary stability of a cementless stem, by measuring the micromotion of the last rasp used by the surgeon to prepare the femoral canal. This information would be really useful to the surgeon, who could check prior to the implantation process if the planned stem size can achieve a sufficient degree of primary stability, under optimal press fitting conditions. An intra-operative tool was developed to this aim. It was derived from a previously validated device, which was adapted for the specific purpose. The device is able to measure the relative micromotion between the femur and the rasp, when a torsional load is applied. An in-vitro protocol was developed and validated on both composite and cadaveric specimens. High correlation was observed between one of the parameters extracted form the acquisitions made on the rasp and the stability of the corresponding stem, when optimally press-fitted by the surgeon. After tuning in-vitro the protocol as in a closed loop, verification was made on two hip patients, confirming the results obtained in-vitro and highlighting the independence of the rasp indicator from the bone quality, anatomy and preserving conditions of the tested specimens, and from the sharpening of the rasp blades. The third study is related to an approach that have been recently explored in the orthopaedic community, but that was already in use in other scientific fields. It is based on the vibration analysis technique. This method has been successfully used to investigate the mechanical properties of the bone and its application to evaluate the extent of fixation of dental implants has been explored, even if its validity in this field is still under discussion. Several studies have been published recently on the stability assessment of hip implants by vibration analysis. The aim of the reported study was to develop and validate a prototype device based on the vibration analysis technique to measure intra-operatively the extent of implant stability. The expected advantages of a vibration-based device are easier clinical use, smaller dimensions and minor overall cost with respect to other devices based on direct micromotion measurement. The prototype developed consists of a piezoelectric exciter connected to the stem and an accelerometer attached to the femur. Preliminary tests were performed on four composite femurs implanted with a conventional stem. The results showed that the input signal was repeatable and the output could be recorded accurately. The fourth study concerns the application of the device based on the vibration analysis technique to several cases, considering both composite and cadaveric specimens. Different degrees of bone quality were tested, as well as different femur anatomies and several levels of press-fitting were considered. The aim of the study was to verify if it is possible to discriminate between stable and quasi-stable implants, because this is the most challenging detection for the surgeon in the operation room. Moreover, it was possible to validate the measurement protocol by comparing the results of the acquisitions made with the vibration-based tool to two reference measurements made by means of a validated technique, and a validated device. The results highlighted that the most sensitive parameter to stability is the shift in resonance frequency of the stem-bone system, showing high correlation with residual micromotion on all the tested specimens. Thus, it seems possible to discriminate between many levels of stability, from the grossly loosened implant, through the quasi-stable implants, to the definitely stable one. Finally, an additional study was performed on a different type of hip prosthesis, which has recently gained great interest thus becoming fairly popular in some countries in the last few years: the hip resurfacing prosthesis. The study was motivated by the following rationale: although bone-prosthesis micromotion is known to influence the stability of total hip replacement, its effect on the outcome of resurfacing implants has not been investigated in-vitro yet, but only clinically. Thus the work was aimed at verifying if it was possible to apply to the resurfacing prosthesis one of the intraoperative devices just validated for the measurement of the micromotion in the resurfacing implants. To do that, a preliminary study was performed in order to evaluate the extent of migration and the typical elastic movement for an epiphyseal prosthesis. An in-vitro procedure was developed to measure micromotions of resurfacing implants. This included a set of in-vitro loading scenarios that covers the range of directions covered by hip resultant forces in the most typical motor-tasks. The applicability of the protocol was assessed on two different commercial designs and on different head sizes. The repeatability and reproducibility were excellent (comparable to the best previously published protocols for standard cemented hip stems). Results showed that the procedure is accurate enough to detect micromotions of the order of few microns. The protocol proposed was thus completely validated. The results of the study demonstrated that the application of an intra-operative device to the resurfacing implants is not necessary, as the typical micromovement associated to this type of prosthesis could be considered negligible and thus not critical for the stabilization process. Concluding, four intra-operative tools have been developed and fully validated during these three years of research activity. The use in the clinical setting was tested for one of the devices, which could be used right now by the surgeon to evaluate the degree of stability achieved through the press-fitting procedure. The tool adapted to be used on the rasp was a good predictor of the stability of the stem. Thus it could be useful for the surgeon while checking if the pre-operative planning was correct. The device based on the vibration technique showed great accuracy, small dimensions, and thus has a great potential to become an instrument appreciated by the surgeon. It still need a clinical evaluation, and must be industrialized as well. The in-vitro tool worked very well, and can be applied for assessing resurfacing implants pre-clinically.

Inhibition of endogenous antagonists with an engineered BMP-2 variant increases BMP-2 efficacy in rat femoral defect healing

Bone morphogenetic proteins (BMP) have been used successfully by orthopedic clinicians to augment bone healing. However, these osteoinductive proteins must be applied at high concentrations to induce bone formation. The limited therapeutic efficacy may be due to the local expression of BMP antagonists such as Noggin that neutralize exogenous and endogenous BMPs. If so, inhibiting BMP antagonists may provide an attractive option to augment BMP induced bone formation. The engineered BMP-2 variant L51P is deficient in BMP receptor type I binding, but maintains its affinity for BMP receptor type II and BMP antagonists including Noggin, Chordin and Gremlin. This modification makes L51P a BMP receptor-inactive inhibitor of BMP antagonists. We implanted β-tricalcium phosphate ceramics loaded with BMP-2 and/or L51P into a critical size defect model in the rat femur to investigate whether the inhibition of BMP antagonist with L51P enhances the therapeutic efficacy of exogenous BMP-2. Our study reveals that L51P reduces the demand of exogenous BMP-2 to induce bone healing markedly, without promoting bone formation directly when applied alone.

Role of the different isoforms of cyclooxygenase and nitric oxide synthase during gastric ulcer healing in cyclooxygenase-1 and -2 knockout mice

Traditional NSAIDs, selective cyclooxygenase (COX)-2 inhibitors, and inhibitors of nitric oxide synthase (NOS) impair the healing of preexisting gastric ulcers. However, the role of COX-1 (with or without impairment of COX-2) and the interaction between COX and NOS isoforms during healing are less clear. Thus we investigated healing and regulation of COX and NOS isoforms during ulcer healing in COX-1 and COX-2 deficiency and inhibition mouse models. In this study, female wild-type COX-1(-/-) and COX-2(-/-) mice with gastric ulcers induced by cryoprobe were treated intragastrically with vehicle, selective COX-1 (SC-560), COX-2 (celecoxib, rofecoxib, and valdedoxib), and unselective COX (piroxicam) inhibitors. Ulcer healing parameters, mRNA expression, and activity of COX and NOS were quantified. Gene disruption or inhibition of COX-1 did not impair ulcer healing. In contrast, COX-2 gene disruption and COX-2 inhibitors moderately impaired wound healing. More severe healing impairment was found in dual (SC-560 + rofecoxib) and unselective (piroxicam) COX inhibition and combined COX impairment (in COX-1(-/-) mice with COX-2 inhibition and COX-2(-/-) mice with COX-1 inhibition). In the ulcerated repair tissue, COX-2 mRNA in COX-1(-/-) mice, COX-1 mRNA in COX-2(-/-) mice, and, remarkably, NOS-2 and NOS-3 mRNA in COX-impaired mice were more upregulated than in wild-type mice. This study demonstrates that COX-2 is a key mediator in gastric wound healing. In contrast, COX-1 has no significant role in healing when COX-2 is unimpaired but becomes important when COX-2 is impaired. As counterregulatory mechanisms, mRNA of COX and NOS isoforms were increased during healing in COX-impaired mice.