Clinical StudyEfficacy of silicated calcium phosphate graft in posterolateral lumbar fusion in sheep
Introduction
Autograft has been considered the “gold standard” for posterolateral intertransverse process fusion yet arthrodesis success is inconsistent. Effective alternatives to autograft would eliminate the need for a second surgical site and the associated donor site pain and morbidity [1], [2]. Synthetic materials, particularly calcium phosphate–based ceramics, have been investigated as both grafting materials and autograft expanders for spine fusion applications [3], [4], [5], [6]. In general, grafting options that incorporated autologous graft improved fusion over ceramic alone, because of improved cellularity and biological activity [3], [5], [7], [8]. Improving healing responses to synthetic graft materials in the hope of obviating the need for autograft supplementation has been a primary focus of biomaterials development. The influence of silicon in bone formation and repair has been established [9], [10]. The role of silicon in promoting bone bonding and induction in silicon-containing bioactive glasses and glass ceramics has been studied both in vivo [11], [12], [13] and in vitro [14], [15], [16], [17], [18]. Low levels of ionic silicate, particularly in the presence of calcium ions, have been shown to up-regulate osteoblast proliferation and differentiation [19], [20], [21], promote osteoinductive gene expression [14], [20], and increase Type I collagen synthesis [19].
Recently, a phase-pure silicated calcium-phosphate material (Si-CaP), Actifuse Synthetic Bone Graft (ApaTech Limited, London), has been developed to exploit the osteo-stimulatory effects of silicon. This material is similar to the structure of bone mineral but with site-specific substitution of phosphate (PO43-) ions with silicate (SiO44-) ions resulting in a biomaterial containing 0.8 wt% silicon [22], [23]. The interconnected porous structure provides a scaffold for osteoconduction, and the release of silicate ions from the matrix promotes rapid bone formation [22]. Other in vivo studies have shown this material to be effective in healing lapine and large ovine osseous defects [22], [23], [24]. The aforementioned in vitro and in vivo studies have established that Si-CaP enhances the bioactivity when compared with phase-pure calcium phosphates of equivalent structure. No study has ascertained whether this silicate enhancement of calcium phosphates can achieve the healing standards of autograft, particularly in the challenging healing environment of posterior spinal fusion. We hypothesized that Si-CaP would generate solid lumbar intertransverse process fusion, similar to that seen with autograft, in an ovine model. Fusion was quantitatively and qualitatively assessed using plain radiographs, computed tomography (CT), biomechanics, and histological evaluations to prove this hypothesis.
Section snippets
Materials and methods
All animal procedures were approved by the Animal Care and Use Committee at Colorado State University. Eighteen skeletally mature ewes were used for the study. Each surgery was performed under general anesthesia and strict sterile conditions. With the animal in the sternal recumbency, a 6–8 cm longitudinal incision was made overlying the palpable spinous processes from L2 to L5. The fascia was split bilaterally, approximately 2–3 cm from the midline, and an intermuscular plane developed to the
Results
All animals tolerated the procedure and were ambulatory within 12 hours. One animal in the Si-CaP group experienced hardware failure during the healing period and was eliminated from the data analysis. No wound complications or infections were noted during the study period.
All animals (Si-CaP and AG) received a qualitative radiographic fusion score of 0 at 60 days (0% fusion rate). By 120 days the Si-CaP group fusion score improved to an average score of 1.25±0.5 (mean±SD). The average
Discussion
This study provided a comprehensive analysis by assessing fusion from radiographic, functional, and biological approaches. Grafting with Si-CaP was equivalent to using autograft in an instrumented sheep lumbar intertransverse process fusion model. Although minor differences were detected in morphometric indices, the overall biomechanical function and radiographic fusion scores between treatment groups were equivalent.
Plain radiographs and CT are clinical tools often used to appraise fusion in
Acknowledgments
We thank Howard Seim III, DVM and Lisa S. Klopp, DVM, MS, for their surgical expertise; Diane Beranek and Mike Karr for preparation of histological specimens; Amy Lyons and Tatiana Motta for their assistance in histological evaluations; and Jon Kushner, staff and students of the Orthopaedic Bioengineering Research Lab for technical support.
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FDA device/drug status: not approved for this indication (Actifuse Synthetic Bone Graft).
Support was received from ApaTech Ltd, London, UK. No other funds were received from a commercial entity related to this manuscript.