A novel sheep vertebral bone defect model for injectable bioactive vertebral augmentation materials

Abstract

New injectable bone substitutes have been developed that are, unlike polymethylmethacrylate, biologically active and have an osteogenic effect leading to osteogenesis and bone remodeling for vertebroplasty or kyphoplasty. In this study, we developed a sheep vertebral bone defect model to evaluate the new bioactive materials and assessed the feasibility of the model in vivo. Bone voids were experimentally created on lumbar vertebrae L2-L5 with L1 and L6 left intact as a normal control in mature sheep. The defect vertebrae L2-L5 in each sheep were randomized to receive augmentation with calcium phosphate cement (CPC) or sham. Vertebrae (L1-L6) were collected after 2 and 24 weeks of the cement augmentation and their strength and stiffness, as well as osseointegration activity and biodegradability, were evaluated. Finally, CPC significantly improved the strength and stiffness of vertebrae but did not yet restore it to the normal level at 24 weeks. Osteogenesis occurred at a substantially high level after 24 weeks of CPC augmentation or sham. Therefore, the sheep vertebral model with one void, 6.0 mm in diameter and 15.0 mm in depth, is replicable and can be used for evaluating the new injectable bioactive materials in vertebral augmentation or reconstruction.

Effectiveness of a bone substitute (CERAMENT™) as an alternative to PMMA in percutaneous vertebroplasty: 1-year follow-up on clinical outcome

“…Radiology assessment post-procedure was carried out by X-ray, CT, and MRI at 1, 6 and 12 months post-op (Figs. 4,5,6,7,8,9). Intake of analgesic medications pre-and post-procedure was also registered (Fig.…”

“…Two different procedures have been developed to restore vertebral body stability and avoid further height compression: vertebroplasty (VP) where the fracture lines and cancellous bone are filled with injectable bone cement, and kyphoplasty (KP) where the created void and cancellous bone are filled with injectable bone cement [1,4,5]. Both procedures are today proven and accepted as standard of care for pain caused by compression fractures of the spine, such as traumatic non-osteoporotic vertebral fractures and traumatic compressive vertebral collapses, especially in younger patients [3,6,7].…”

“…The success of this material is based on immediate relief of pain and mechanical stabilization improving physical functions [3,8] as well as low cost [9]. However, clinical trial results have exposed a high complication rate in percutaneous vertebroplasty with PMMA range from 1 to 10 % [10,11], highlighting potential weaknesses such as thermal injury to surrounding tissues, potentially causing neurological damage, increasing fracture risk at adjacent levels due to the high inherent stiffness, and potential toxicity caused by the reactive material [2,4,9,12].…”

“…However, these materials have poor injectability, poor handling, lower viscosity and/or too fast absorption [9,12,14]. To bypass these drawbacks, a new kind of biphasic cement has been developed consisting of 60 % a-CaS hemihydrates and 40 % hydroxyapatite (HA) [2,4], marked as CERA-MENT Spine Support (CSS) (Bone Support, Sweden). This product allows delayed absorbable of the CaS and controlled bone in-growth by osteoconductivity of the HA.…”

Preclinical testing of drug delivery systems to bone

“…Sheep have smaller, longer and narrower vertebral bodies, longer transverse processes, shorter dorsal spinous processes and narrower, higher pedicles with more lateral angulations [255]. Most studies on the ovine spine concerning vertebral fractures dealt with injection or impaction of biomaterials or drug delivery systems in the vertebral body [256][257][258][259][260][261][262][263][264]. The observation times should be long and some studies even go up to three years [260].…”