EAO-SEPES Joint Meeting, Madrid, Spain, 5 - 07 October 2017, pp.198313
Calcium phosphate (CaP)-based materials have been studied broadly as bone substitute because of its biocompatibility and similarity to bone matrix. However, CaPs have some limitations such as lack of osteoinductive capability and insufficient resorbtion ability, therefore, current studies have been designed for improving the limitations. Since oxytocin has been approved of having both systemic and local osteoinductive effect on bone formation, it could be considered to utilize oxytocin for improving bone regeneration.
The aim of the study was to prepare oxytocin-loaded controlled-release system containing calcium phosphate hyrogel graft, and to assess whether the material promotes bone regeneration in rat calvarial bone defect compared to empty control and oxytocin-deficient groups.
250 µg oxytocin for each subject (for each bone defect) was used to encapsulate in PLGA-microparticles with single-emulsion method. In vitro release test of oxytocin-loaded PLGA-microparticles was performed by dissolving 10 mg of mikroparticles in 1.5 ml phosphate buffer, and the samples were left orbital shaker which adjusted 150 rpm. Samples were collected after 2, 4, 8, 24 hours and at certain time intervals until the release was completed. For animal experiment, 8 mm critical-size full-thickness defects in calvarias of 16-month-old 80 Wistar male rats were randomized to receive one of four interventions: oxytocin-loaded microparticles containing calcium phosphate hyrogel graft (OMCPH), empty microparticles containing calcium phosphate hyrogel graft (MCPH), calcium phosphate hyrogel graft (CPH) and empty defects (as control). Animals were assigned for the examinations after 4 weeks and 8 weeks separetely (10 rats for each group). Micro-computed tomography analysis was performed for bone mineral density (BMD, g/cm3) and bone volume (BV, mm3) analyses in each group.
Encapsulation capacity of the oxytocin-loaded PLGA-microparticles was detected 89.5%. Cumulative release was reached 50% after 7 days, and was completed after 24 days. In micro-computed tomography analysis, BV of OMCPH group was higher than MCPH group (p=.0044) and control group (p<0.0001) after 4 weeks of healing. While BV did not reveal statistical significant difference from 4 weeks to 8 weeks, BMD of OMCPH group was higher at both 4 weeks (42.21 ± 5.14 g/cm3) and 8 weeks of healing (46.94 ± 3.30 g/cm3) than the other groups (with statistically significant differences for 8 weeks’ analysis).
This study reveals that oxytocin-loaded controlled-release system containing calcium phosphate hyrogel graft provides an improvement for new bone volume more prominent in early phase of healing. Rather than BV, BMD of new bone could also be continued to increase in both early and mature healing period.