Lack of repair of rat skull critical size defect treated with bovine morphometric protein bound to microgranular bioabsorbable hydroxyapatite

Abstract

The ability of a pool of bovine bone morphogenetic proteins bound to synthetic microgranular hydroxyapatite (BMPb-HA) to stimulate bone repair was determined in rat critical size defects. An 8-mm diameter defect was created in the calvaria of 25 rats. In 15 rats, the defects were filled with BMPb-HA homogenized with blood (experimental group), and in 10 rats the defects were filled only with blood clots (control). The calvariae of experimental rats were collected 1, 3 and 6 months after surgery and of the control rats at the end of surgery and 6 months thereafter. The morphometric results obtained in the radiographs showed an absence of new bone formation at 1 and 3 months post-surgery and, histologically, the defects were filled with fibrous connective tissue and numerous foci of a foreign body-type granulomatous reaction around hydroxyapatite agglomerates. At the end of 6 months, the number and size of the granulomatous foci decreased and the area of the defects was reduced by 22% compared to the 0-hour control due to the formation of new bone at their borders, although the mean area was similar to the 6-month control. We conclude that the use of BMPb-HA in the treatment of critical size bone defects of the rat skull leads to the formation of a foreign body-type granulomatous reaction that markedly inhibits new bone formation, suggesting that synthetic microgranular hydroxyapatite does not represent a good carrier for BMPinduced bone formation.

Assessment of bovine biomaterials containing bone morphogenetic proteins bound to absorbable hydroxyapatite in rabbit segmental bone defects

“…A prominent foreign body reaction was observed around HA agglomerates, more so in Group B. Brandão et al 22 evaluating the same hydroxyapatite, mixed or not with pBMPs implanted in rat alveolar wounds, achieved delay in wound healing in both groups, suggesting an absence of osteogenic properties in these materials. A similar finding was observed by Ferreira et al 23 while using the same hydroxyapatite bound to pBMPs for treatment of critical size calvarial defects in rats. The authors showed occurrence of intense foreign body reaction around agglomerates of BMP-HA particles with high number of macrophages and multinucleate giant cells.…”

Hydroxyapatite-alginate biocomposite promotes bone mineralization in different length scales in vivo

“…Critical defects do not regenerate during the life span of the animal [12,26,[34][35][36]; thus they are a good model for the evaluation of the osteogenic potential of biomaterials designed to be used in bone regeneration. In our work we used 8 mm for the diameter of the defect in the calvaria of rat.…”

The rabbit as an animal model for experimental surgery

“…It was the Nuremberg Code (1947) that determined that research on humans must be based on the results of animal experimentation -a position reinforced by the Helsinki Declaration in 1975 14 . As equipment, procedures and drugs were developed, scientific investigation was performed in vitro, preferably in a standardized manner (International Organization for Standardization -ISO 10993-6, 1992) 15 , and in animals of small (rats, mice and guinea pigs) 1,3,6 , medium (rabbits, mini pigs, cats and dogs) 4,2,7,9 and large size (sheep and pigs) 5,8,16 . The choice of the model for an experiment is determined by factors such as cost, technical viability of the procedure, scientific principles, available data base and appropriateness of the model vis-à-vis the project 12 .…”

“…The use of animals in biomedical research has been recommended for perfecting and validating existing procedures 1,2,3 , developing new materials 4,5,6 and understanding the various physiological and pathological processes 7,8,9 because there are no in vitro models capable of fully mimicking the complexity of the human organism.…”