A Novel Resorbable Composite of Calcium Sulfate and Amorphous Calcium Phosphate Bone Substitute for Dental Implants

Abstract

Objectives: The purpose of this study was to develop a novel resorbable α-calcium sulfate hemihydrate/amorphous calcium phosphate (α-CSH/ACP) bone graft substitute specifically for alveolar ridge augmentation that could mimic the natural regeneration rate of human jaw bone by resorbing and substituted by bone within three to six months. A canine model was used to investigate the in vivo biocompatibility, biodegradation and osteoconductivity of the novel bone substitute. Materials and Methods: An innovative single process was used to produce synthetic bone graft substitute (SBGS) of α-CSH/ACP. Setting test for various hydrated α-CSH/ACP compositions was conducted by the Vicat needle to determine formulation good for granular particles preparation. In vitro dissolution was conducted by immersing of specimens (granules of, α-CSH/ACP 60/40, 70/30, 80/20 and CS/β-TCP 60/40, 70/30, 80/20, pellets of TMU CS and Osteoset®) in phosphate buffered solution (PBS) and incubated in a shaking bath operated at 30 rpm and 37oC. Bone defects of φ 5mm x 8 mm depth were created bilaterally in mandibles of beagle dogs and implanted with α-CSH/ACP (60/40), CS/β-TCP (60/40) as well as (40/60), CS, Osteoset®(CS) and one defect was left empty as a control. After three weeks and six weeks, specimens were harvested with trephine burs and prepared with H.E staining for histological and histomorphometrical analysis under microscope and Image J computer software. Unpaired and one tailed student t test, ANOVA and pos hoc tukey’s test were used for statistical interpretation of data. P value < 0.05 was stated as significance. Results: The results displayed high purity manufactured α-CSH and ACP. Setting time of α-CSH/ACP composites was shortened as the ACP content increasing. All materials displayed early rapid dissolution in PBS due to calcium sulfate followed by remarkable slow dissolution as a result of poor crystalline hydroxyapatite formation. Composites of α-CSH/ACP and CS/β-TCP resorbed slower than TMU CS alone. Resorption rate of composites α-CSH/ACP and CS/β-TCP reduced as the amount of ACP or β-TCP increasing. TMU CS and Osteoset pellets demonstrated similar resorption rates, while composites of α-CSH/ACP dissolute faster than CS/β-TCP composites. Histological examination after three weeks revealed no obvious presence of inflammation or immune rejection for all implanted SBGS. After six weeks, woven bone were replaced by lamellae bone and empty defects showed presence of big empty spaces. After three weeks, bone regeneration were α-CSH/ACP 21.1 ±9.5%, CS/β-TCP (60/40) 23.0 ±9.9, Osteoset (CS) 29.0 ±16.0, CS/β-TCP (40/60) 33.1 ±12.0% and empty control 13.6 ±9.5%. At six weeks, ratio of new bone formation for α-CSH/ACP, CS/β-TCP (60/40), CS/β-TCP (40/60), Osteoset®(100%CS),CS, and empty control were 62.2 ±6.8%, 48.9 ±8.1%, 52.7 ±6.7%, 53.3 ±4.6%, 42.4 ±8.8%, and 40.1 ±7.2%, respectively. All SBGS except CS exhibited more new bone formation than the control. Osteoset®(CS) and CS/β-TCP 40/60 regenerated more bone than TMU CS, while α-CSH/ACP yielded more new bone than all the other SBGS, p value < 0.05. Extrapolation graph approximated this novel composite of α-CSH/ACP to be resorbed and substituted by new bone within three to four months in human jaw bone. Conclusion: All experimented SBGS were resorbable, biocompatible and osteoconductive. Based on the extrapolation of ratio of new bone formation with time, the α-CSH/ACP (60/40) composite could be resorbed and substituted by bone within three to six months implying the resorption rate closely mimics the natural bone regeneration rate. Novel composite of α-CSH/ACP could shorten the healing and implant treatment period, therefore it could be an ideal SBGS for dental implants in the future.