Sustained Release of Vitamin D3 Enhanced Osseointegration Capacity: An Experimental Sheep Study

This study aimed to investigate the effect of sustained-release vitamin D loaded in poly-lactic acid (PLA) nanoparticles and applied to grafting materials around titanium (ti) dental implants. A total of 48 implants were inserted into the standardized bone defects created in the iliac crest of 6 sheep, divided into 4 different experimental sites (empty control, autografted, xenografted, and autograft + xenografted). Vitamin D3, which was encapsulated by PLA nanoparticles, was prepared and applied in half of the defects and left to heal for 3 and 6 weeks. New bone formation (NBF%) and bone-implant contact (BIC%) values were evaluated by histologic and histomorphometric analyses (P < 0.05). Nanoparticles with a yield of 80.30% ± 2.14% and high encapsulation efficiency of 72.99% ± 2.20% were achieved. In all sections, osseointegration was observed, with no signs of inflammation, necrosis, or foreign body reaction. NBF% and BIC% were significantly higher in vitamin D3–loaded groups (P < 0.001). In both healing periods, the highest NBF% and BIC% have been recorded in the autograft + xenograft groups. (For the respective third and sixth weeks: the NBF% was 49.63 ± 1.53 and 74.25 ± 0.96, and BIC% was 54.26 ± 0.66 and 82.59 ± 2.09, respectively; P < 0.001). Sustained-release of vitamin D loaded into the PLA system demonstrated high biocompatibility, favorable sustained release of vitamin D3, and improved NBF% and BIC% around ti implants placed in box-shaped sheep iliac crest defects. Further investigations are required for their clinical applicability.