70. In Vivo Effects of a Novel Anular Repair Device in Sheep

Phillips, Frank M.; Pimenta, L.H.M; Ferree, Bret; Turner, Simon; Seim, Howard B.; Sickle, David Van

doi:10.1016/j.spinee.2007.07.085

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“…Compared to young ewes (2-4 years), the lumbar vertebral bodies of the animals show significantly decreased histological parameters of bone structure and bone formation, and increased bone resorption, resulting in numerically decreased biomechanical properties [40]. This sheep model represents an innovative approach, since most studies have thus far used young ovariectomized or hormonally pretreated ewes [53,70,71]. In the present study, in contrast, the ewes showed functional cycling ovaries as reported previously [61]; therefore, a post-menopausal influence on bone can be excluded.…”

Section: Animal Modelmentioning

confidence: 99%

Single Application of Low-Dose, Hydroxyapatite-Bound BMP-2 or GDF-5 Induces Long-Term Bone Formation and Biomechanical Stabilization of a Bone Defect in a Senile Sheep Lumbar Osteopenia Model

et al. 2022

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Effects of hydroxyapatite (HA) particles with bone morphogenetic BMP-2 or GDF-5 were compared in sheep lumbar osteopenia; in vitro release in phosphate-buffered saline (PBS) or sheep serum was assessed by ELISA. Lumbar (L) vertebral bone defects (Ø 3.5 mm) were generated in aged, osteopenic female sheep (n = 72; 9.00 ± 0.11 years; mean ± SEM). Treatment was: (a) HA particles (2.5 mg; L5); or (b) particles coated with BMP-2 (1 µg; 10 µg) or GDF-5 (5 µg; 50 µg; L4; all groups n = 6). Untouched vertebrae (L3) served as controls. Three and nine months post-therapy, bone formation was assessed by osteodensitometry, histomorphometry, and biomechanical testing. Cumulative 14-day BMP release was high in serum (76–100%), but max. 1.4% in PBS. In vivo induction of bone formation by HA particles with either growth factor was shown by: (i) significantly increased bone volume, trabecular and cortical thickness (overall increase HA + BMP vs. control close to the injection channel 71%, 110%, and 37%, respectively); (ii) partial significant effects for bone mineral density, bone formation, and compressive strength (increase 17%; 9 months; GDF‑5). Treatment effects were not dose-dependent. Combined HA and BMPs (single low-dose) highly augment long-term bone formation and biomechanical stabilization in sheep lumbar osteopenia. Thus, carrier-bound BMP doses 20,000-fold to 1000-fold lower than previously applied appear suitable for spinal fusion/bone regeneration and improved treatment safety.

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