A case of polyostotic osteosarcoma with kidney metastases in a dog: histopathology and microcomputed tomographic analysis.

A 7-year- old sexually intact female Leonberg dog was evaluated for chronic lameness of the right forelimb. The bitch showed mild hyperthermia (39.3°C), a decrease in its activity, a capricious appetite, a high weight loss (4 kg in 15 days) and a right foreleg lameness. A careful clinical examination revealed a deformation of the right proximal humerus and right tibia. Radiographic examination of the right tibia, right humerus showed osteolysis of both cortical and trabecular bone with a periosteal bone proliferation in the vicinal soft tissues. The owner having refused a bone biopsy, a treatment with NSAIDs and antibiotics was prescribed. After a marked improvement during the first two weeks, an increase in lameness and activity was observed. At that time, the owner accepted the bone biopsy. Histopathologic examination evidenced an osteosarcoma but the amount of available tissue was limited. Due to the poor prognosis, he declined treatment and decided to euthanize the dog. An osteosarcoma with a large chondroid component was observed at autopsy together with ossifying kidney metastases. Histological findings revealed a grade III osteosarcoma. Conventional and undecalcified histology and X-ray microcomputed tomography findings evidenced a large and partially mineralized osteoid part with a sunburst extension in the soft tissues. This is the first time that microCT and undecalcified analyses of an osteosarcoma are presented. The osteolytic and metaplastic bone foci were easily demonstrated by this method.

Biofunctionality of MBCP ceramic granules (TricOs) plus fibrin sealant (Tisseel) versus MBCP ceramic granules as a filler of large periprosthetic bone defects: an investigative ovine study.

We aimed to quantify bone colonization toward an untreated titanium implant with primary stability following filling of the defect with micromacroporous biphasic calcium phosphate (MBCP) granules (TricOs) or MBCP granules mixed with fibrin sealant (Tisseel). Medial arthrotomy was performed on the knees of 20 sheep to create a bone defect (16 mm deep; 10 mm diameter), followed by anchorage of a titanium screw. Defects were filled with TricOs or TricOs-Tisseel granules, a perforated MBCP washer, a titanium washer and titanium screw. Sheep were euthanized at 3, 6, 12 and 26 weeks. From Week 12 onwards, the percentage of bone in contact with the 8 mm anchorage part of the screw increased in both groups, confirming its primary stability. At 26 weeks, whereas bone colonization was similar in both groups, biodegradation of ceramic was more rapid in the TricOs-Tisseel group (P = 0.0422). The centripetal nature of bone colonization was evident. Bone contact with the titanium implant surface was negligible. In conclusion, the use of a model that reproduces a large metaphyseal bone defect around a titanium implant with primary stability, filled with a mixture of either TricOs ceramic granules or TricOs granules mixed with Tisseel fibrin sealant, suggests that the addition of fibrin to TricOs enhances bone filling surgical technology.

Radiation effects on bone healing and reconstruction: interpretation of the literature.

OBJECTIVE: Reconstructing irradiated mandibles with biomaterials is still a challenge but little investigated. We collected data that could help us understand studies in the field of regeneration with biomaterials and irradiated bone. STUDY DESIGN: Systematic review of the literature. RESULTS: Delay and duration of radiation delivery and total equivalent dose are the most variable parameters in the various studies, resulting in confusion when interpreting the literature. Most reproducible experiments show that radiation reduces osteogenic cell numbers, alters cytokine capacity, and delays and damages bone remodeling. Interindividual variations and how such changes become irreversible lesions are still uncertain. In the case of regeneration using biomaterials, most studies have addressed the question of reconstruction in previously irradiated bone. The results show that osseointegration is often possible, although the failure rate is higher. The sooner the implantation takes place after the end of the radiation, the higher the likelihood of failure. Few studies have focused on primary reconstruction followed by early irradiation, and most of the currently available engineering models would be altered by radiation. Good outcomes have been obtained with bone morphogenetic protein and with total bone marrow transplanation. CONCLUSION: This review points out the difficulties in achieving reproducible experiments and interpreting literature in this underinvestigated field.

Developments in injectable multiphasic biomaterials. The performance of microporous biphasic calcium phosphate granules and hydrogels.

Calcium phosphate bioceramic granules associated with hydrosoluble polymers were developed as bone substitutes for various maxillofacial and orthopaedic applications. These injectable bone substitutes, support and regenerate bone tissue and resorb after implantation. The efficiency of these multiphasic materials is due to the osteogenic and osteoconductive properties of the microporous biphasic calcium phosphate. The associated hydrosoluble polymers are considered as carriers in order to achieve the rheological properties of injectable bone substitutes (IBS). In this study, we used 2 semi synthetic hydrosoluble polymers of polysaccharidic origin. The hydroxy propyl methyl cellulose (HPMC), with and without silane, was combined with microporous BCP granules. The presence of silane induced considerable gelation of the suspension. The 2 IBS used (without gelation, IBS1, with gelation, IBS2) were implanted in critical size femoral epiphysis defects in rabbits. No foreign body reactions were observed in either sample. However, because of the higher density from gelation, cell colonisation followed by bone tissue ingrowth was delayed over time with IBS2 compared to the IBS1 without gelation. The results showed resorption of the BCP granule and bone ingrowth at the expense of both IBS with different kinetics. This study demonstrates that the hydrogel cannot be considered merely as a carrier. The gelation process delayed cell and tissue colonisation by slow degradation of the HPMC Si, compared to the faster release of HPMC with IBS1, in turn inducing faster permeability and spaces for tissue ingrowth between the BCP granules.

Bone growth in rapid prototyped porous titanium implants.

Two porous titanium implants with a pore size diameter of 800 and 1200 microm (Ti800 and Ti1200) and an interconnected network were manufactured using rapid prototyping. Their dimensions and structure matched those of the computer assisted design. The porosity of the implants was around 60%. Their compressive strength and Young's modulus were around 80 MPa and 2.7 GPa, respectively. These values are comparable to those of cortical bone. The implants were implanted bilaterally in the femoral epiphysis of 15 New Zealand White rabbits. After 3 and 8 weeks, abundant bone formation was found inside the rapid prototyped porous titanium implants. For the Ti1200 implants, bone ingrowth was (23.9 +/- 3.5)% and (10.3 +/- 2.8)%, respectively. A significant statistical difference (p < 0.05) was found for bone ingrowth in the Ti1200 between the two delays. The percentage of bone directly apposited on titanium was (35.8 +/- 5.4)% and (30.5 +/- 5.0)%. No significant difference was found for bone-implant contact between the different time periods and pore sizes. This work demonstrates that manufacturing macroporous titanium implants with controlled shape and porosity using a rapid prototyping method is possible and that this technique is a good candidate for orthopedic and maxillofacial applications.

Small-animal models for testing macroporous ceramic bone substitutes.

The aim of this study was to compare the bone colonization of a macroporous biphasic calcium phosphate (MBCP) ceramic in different sites (femur, tibia, and calvaria) in two animal species (rats and rabbits). A critical size defect model was used in all cases with implantation for 21 days. Bone colonization in the empty and MBCP-filled defects was measured with the use of backscattered electron microscopy (BSEM). In the empty cavities, bone healing remained on the edges, and did not bridge the critical size defects. Bone growth was observed in all the implantation sites in rats (approximately 13.6-36.6% of the total defect area, with ceramic ranging from 46.1 to 51.9%). The bone colonization appeared statistically higher in the femur of rabbits (48.5%) than in the tibia (12.6%) and calvaria (22.9%) sites. This slightly higher degree of bone healing was related to differences in the bone architecture of the implantation sites. Concerning the comparison between animal species, bone colonization appeared greater in rabbits than in rats for the femoral site (48.5% vs. 29.6%). For the other two sites (the tibia and calvaria), there was no statistically significant difference. The increased bone ingrowth observed in rabbit femurs might be due to the large bone surface area in contact with the MBCP ceramics. The femoral epiphysis of rabbits is therefore a favorable model for testing the bone-bonding capacity of materials, but a comparison with other implantation sites is subject to bias. This study shows that well-conducted and fully validated models with the use of small animals are essential in the development of new bone substitutes.

Bilayered calcium phosphate coating to promote osseointegration of a femoral stem prosthesis.

A bilayered bioactive-gradient coating, consisting of a superficial layer of biphasic calcium phosphate (BCP) and a deep layer of hydroxyapatite (HA), promotes faster osseointegration and higher shear strength in non-loading conditions than do monolayer BCP or HA coatings. This study evaluated the biofunctionality of this coating in weight-bearing conditions at 6 and 12 months. The coating was plasma-sprayed on the metaphyseal portion of a sandblasted Ti6Al4V canine femoral prosthesis implanted using the surgical press-fit technique. An identical uncoated stem served as the control. Metaphyseal bone-to-implant apposition was increased for coated ( approximately 90% and 80% respectively at 6 and 12 months) as compared to uncoated implant ( approximately 7% at 6 and 12 months). Limited bone apposition was observed at the diaphyseal level. After 12 months, the uncoated implant interface consisted of well-organized, active fibrous tissue, whereas only inactive fibrous tissue interposition was observed at diaphyseal levels of the coated implant. At 6 months, the mineralization apposition rate (MAR) was similar, regardless of implant or bone structures. At 12 months, a significant decrease of MAR was observed around the uncoated implant. Transmission electron microscopy studies of the interface showed precipitation of biological apatite crystals in close association with mineralized collagenous bone matrix. Our results suggest a direct relationship between bioactivity and enhanced bone formation. The sandwich coating used is effective in promoting massive metaphyseal osseointegration, which ensures mechanical stability for early weight-bearing and should prevent long-term complications.

Macroporous biphasic calcium phosphate ceramics versus injectable bone substitute: a comparative study 3 and 8 weeks after implantation in rabbit bone.

Macroporous biphasic calcium phosphate ceramics (MBCP) and a calcium phosphate injectable bone substitute (IBS), obtained by the association of biphasic calcium phosphate (BCP) ceramic granules and an aqueous solution of a cellulosic polymer, were compared in the same animal model. The two tested biomaterials were implanted in distal femoral osseous defects in rabbits. Qualitative and quantitative histological evaluation was performed three and eight weeks after implantation to investigate bone colonization and ceramic biodegradation associated with the two bone substitutes. Both biomaterials expressed osteoconduction properties and supported the apposition of a well-mineralized lamellar newly-formed bone. Bone colonization occurred much earlier and faster for IBS than for MBCP implants, although the respective rates of newly-formed bone after eight weeks of implantation did not differ significantly. For both biomaterials, ceramic resorption occurred regularly throughout the implantation period, though to a greater extent with IBS than with MBCP implants. The associated polymer in IBS produced intergranular spaces allowing body fluids to reach each BCP ceramic granule immediately after implantation, which may have favored osteoblastic activity, new bone formation and ceramic resorption. This completely interconnected open macroporosity could account for the earlier and more satisfactory bone substitution achieved with IBS.