Bone augmentation for cancellous bone-development of a new animal model

Abstract

BackgroundReproducible and suitable animal models are required for in vivo experiments to investigate new biodegradable and osteoinductive biomaterials for augmentation of bones at risk for osteoporotic fractures. Sheep have especially been used as a model for the human spine due to their size and similar bone metabolism. However, although sheep and human vertebral bodies have similar biomechanical characteristics, the shape of the vertebral bodies, the size of the transverse processes, and the different orientation of the facet joints of sheep are quite different from those of humans making the surgical approach complicated and unpredictable. Therefore, an adequate and safe animal model for bone augmentation was developed using a standardized femoral and tibia augmentation site in sheep.MethodsThe cancellous bone of the distal femur and proximal tibia were chosen as injection sites with the surgical approach via the medial aspects of the femoral condyle and proximal tibia metaphysis (n = 4 injection sites). For reproducible drilling and injection in a given direction and length, a custom-made c-shaped aiming device was designed. Exact positioning of the aiming device and needle positioning within the intertrabecular space of the intact bone could be validated in a predictable and standardized fashion using fluoroscopy. After sacrifice, bone cylinders (∅ 32 mm) were harvested throughout the tibia and femur by means of a diamond-coated core drill, which was especially developed to harvest the injected bone area exactly. Thereafter, the extracted bone cylinders were processed as non-decalcified specimens for μCT analysis, histomorphometry, histology, and fluorescence evaluation.ResultsThe aiming device could be easily placed in 63 sheep and assured a reproducible, standardized injection area. In four sheep, cardiovascular complications occurred during surgery and pulmonary embolism was detected by computed tomography post surgery in all of these animals. The harvesting and evaluative methods assured a standardized analysis of all samples.ConclusionsThis experimental animal model provides an excellent basis for testing new biomaterials for their suitability as bone augmentation materials. Concomitantly, similar cardiovascular changes occur during vertebroplasties as in humans, thus making it a suitable animal model for studies related to vertebroplasty.

Feasibility Study of a Standardized Novel Animal Model for Cervical Vertebral Augmentation in Sheep Using a PTH Derivate Bioactive Material

“…Consequently, we were able to inject test materials in 43/45 augmentation sites into the intertrabecular spacing of cervical vertebral bodies again with accuracy and reproducibility. However, as already discussed in a previous study concerning the tibia and femur augmentation in sheep [20], the trabecular bone density, as well as the trabecular thickness is much higher in sheep than in humans, such that the needle placement and material injection is more difficult to achieve in comparison to humans. In osteoporotic, brittle human bone, the injection needle can be placed in position using manual pressure only, whereas in sheep, a hole had to be drilled with a burr first in order to be able to push the needle forward into the healthy and dense trabecular bone.…”

“…ȝ-CT analysis of the specimen was performed in 70% ethanol fixation (b-cube AG, Bio-Technopark, Schlieren-Zurich, Switzerland). After complete dehydration, the samples were degreased in xylene and subsequently infiltrated in liquid methymethacrylate (MMA) until polymerization occurred [20]. Using a special band saw (EXAKT ® Band System 300/301, EXAKT ® Apparatebau…”

“…For thin section preparation, the remaining bone blocks were cut in smaller segments comprising only the tip of the needle and surrounding tissue. Polymerization was achieved in special customized Teflon forms (D. Nadler, JOSSI AG, Islikon, Switzerland) [20]. Afterwards, the small blocks were mounted on plastic frames and cut using a microtome (Leica ® RM 2155, Leica Instruments GmbH).…”

“…Via cell migration and infiltration, the peptide is activated and released only into the surrounding tissue for the local increase of bone formation. In previous in vivo studies using a tibia and femur augmentation model in sheep, various concentrations of this engineered parathyroid hormone (TGplPTH ), incorporated in different formulations of fibrin matrices, has already shown good results [20]. However, it was unknown whether these results could actually be reproduced in the vertebral bodies, this due to its different anatomical structure, including high vascularity and sinus formations.…”

Osteoporotic sheep mandibular model for comparative alveolar bone healing research

“…Any animal model used for dental implant research should be consist of both cortical and cancellous bone, and resemble human mandible with respect to physical dimensions, embryological development and physiology [11].…”