Pre-clinical in vivo evaluation of Malaysian-made "osteopaste" self hardened synthetic bone cement in critical size bone defects

Abstract

Calcium phosphate is an ideal bone substitute material that is widely used for bone repair due to its excellent biological properties including biocompatibility and osteoconductivity. In order to improve the properties of calcium phosphate materials for clinical use, a new injectable self-hardened synthetic bone cement (Osteopaste) was developed. Osteopaste consists of tetra-calcium phosphate (TTCP) and tricalcium phosphate (TCP) powder. It was intended for the treatment of bone fracture or reconstruction of bone defects. The objective of this study was to compare bone formation between Osteopaste and commercialized synthetic bone grafts; JectOS (calcium phosphate) and MIIG-X3 (calcium sulphate) at three different assessment periods. The first phase of the study was to establish the critical size defect in New Zealand White rabbit model. The second phase involved the implantation of Osteopaste, JectOs and MIIG-X3 in critical size defects. Thirty-nine New Zealand White rabbits were divided into four groups (Osteopaste, JectOs, MIIG-X3 and sham). Each group was further divided into three subgroups according to the assessment period either at 6, 12 or 24 weeks. Each subgroup consisted of four rabbits except the sham group which consisted of only one rabbit. A critical size defect of approximately 4.5 mm (width) X 9.0 mm (length) was created at the proximal tibial metaphysis of rabbit's right leg and then implanted with either Osteopaste, JectOs or MIIG-X3. At each assessment period, plain radiograph and computed tomography (CT) scan were performed before the animals were sacrificed for undecalcified histology, histomorphometry and scanning electron microscopy assessments. Using the histomorphometric data, the mean percentage of new bone areas and the length of unbridged defects were compared between groups. In this study, a simple and safe method for performing critical size defect at proximal tibial metaphysis was established. The Osteopaste group exhibited radiographic density in between JectOS and MIIG-X3. The critical size defect in Osteopaste group was bridged by new bone at 12 weeks. In MIIG-X3 group, the defect was bridged at 24 weeks whereas in JectOS group, the defect was not bridged at all assessment periods. New bone area was the largest in MIIG-X3 group followed by Osteopaste and JectOS groups. Osteopaste had formed direct bonding with host bone without intervening soft tissue compared to JectOS and MilG-X3. There were significant differences in new bone area percentages between Osteopaste, JectOs and MIIG-X3 at 6, 12 and 24 weeks post-surgery (P<0.0001 ). In conclusion, the performance of Osteopaste to promote new bone formation is in between JectOS and MIIG-X3.