Effect of a synthetic hydroxyapatite-based bone grafting material compared to established bone substitute materials on regeneration of critical-size bone defects in the ovine scapula.

Lately, the potential risk of disease transmission due to the use of bovine-derived bone substitutes has become obvious, demonstrating the urgent need for a synthetic grafting material with comparable bioactive behaviour and properties. Therefore, the effect of a synthetic hydroxyapatite (HA) (Osbone®) bone grafting material on bone regeneration was evaluated 2 weeks, 1 month, and 3, 6, 12 and 18 months after implantation in critical-size bone defects in the ovine scapula and compared to that of a bovine-derived HA (Bio-Oss®) and ß-tricalcium phosphate (TCP) (Cerasorb® M). New bone formation and the biodegradability of the bone substitutes were assessed histomorphometrically. Hard tissue histology and immunohistochemical analysis were employed to characterize collagen type I, alkaline phosphatase, osteocalcin, as well as bone sialoprotein expression in the various cell and matrix components of the bone tissue to evaluate the bioactive properties of the bone grafting materials. No inflammatory tissue response was detected with any of the bone substitute materials studied. After 3 and 6 months, ß-TCP (Cerasorb® M) showed superior bone formation when compared to both HA-based materials (3 months: ß-TCP 55.65 ± 2.03% vs. SHA 49.05 ± 3.84% and BHA 47.59 ± 1.97%; p ≤ 0.03; 6 months: ß-TCP 62.03 ± 1.58%; SHA: 55.83 ± 2.59%; BHA: 53.44 ± 0.78%; p ≤ 0.04). Further, after 12 and 18 months, a similar degree of bone formation and bone-particle contact was noted for all three bone substitute materials without any significant differences. The synthetic HA supported new bone formation, osteogenic marker expression, matrix mineralization and good bone-bonding behaviour to an equal and even slightly superior degree compared to the bovine-derived HA. As a result, synthetic HA can be regarded as a valuable alternative to the bovine-derived HA without the potential risk of disease transmission.

Effect of silicon-doped calcium phosphate bone grafting materials on bone regeneration and osteogenic marker expression after implantation in the ovine scapula.

Compared to the currently clinically available bone grafting materials for alveolar ridge augmentation, there is a great demand for bioactive bone substitutes with higher resorbability, which enhance osteogenesis at the same time. This has prompted the development of a silicon-doped rapidly resorbable calcium alkali orthophosphate (Si-CAOP) and silicon-doped ß-tricalcium phosphate (Si-TCP). This study evaluated the effect of these two particulate graft materials as compared to the currently clinically used ß-TCP on bone formation and osteogenic marker expression after 2 weeks, 1, 3, 6, 12, and 18 months of implantation in critical size defects in the sheep scapula. Immunohistochemical analysis of collagen type I, alkaline phosphatase, and osteocalcin expression was performed on resin embedded sections. The bone and particle area fraction and the bone-biomaterial contact were determined histomorphometrically. After 2 weeks and 1 month defects grafted with Si-CAOP displayed a significantly greater bone area fraction, bone-particle-contact, osteogenic marker expression and significantly lower particle area fraction than defects grafted with Si-TCP and TCP. By 3 and 6 months all materials studied mediated excellent defect regeneration with further bone remodeling at 12 and 18 months. Taken together, Si-CAOP induced the most expeditious bone regeneration of critical size defects in the sheep scapula. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 594-614, 2019.

A large animal model for standardized testing of bone regeneration strategies.

BACKGROUND: The need for bone graft substitutes including those being developed to be applied together with new strategies of bone regeneration such as tissue engineering and cell-based approaches is growing. No large animal model of bone regeneration has been accepted as a standard testing model. Standardization may be the key to moving systematically towards better bone regeneration. This study aimed to establish a model of bone regeneration in the sheep that lends itself to strict standardization and in which a number of substances can be tested within the same animal. To this end the caudal border of the ovine scapula was used as a consistent bed of mineralized tissue that provided sufficient room for a serial alignment of multiple experimental drill holes. RESULTS: The findings show that for the sake of standardization, surgery should be restricted to the middle part of the caudal margin, an area at least 80 mm proximal from the Glenoid cavity, but not more than 140 mm away from it, in the adult female Land Merino sheep. A distance of 5 mm from the caudal margin should also be observed. CONCLUSIONS: This standardized model with defined uniform defects and defect sites results in predictable and reproducible bone regeneration processes. Defects are placed unilaterally in only one limb of the animal, avoiding morbidity in multiple limbs. The fact that five defects per animal can be evaluated is conducive to intra-animal comparisons and reduces the number of animals that have to be subject to experimentation.