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Effect Of Local Modulation In Enzymatic Homeostasis On Bone Turnover Marker Dynamics In Blood At Substituting Femur Defects With Vaterite Scaffolds

The goal of this research was the investigation of concentration changes in the blood bone turnover markers during local modulation of enzymatic homeostasis by means of targeted delivery of alkaline phosphatase (ALP) with polycaprolactone (PCL) and vaterite (VT) scaffolds implanted into the femur defects in white rats. Material and Methods ― The tests of PCL/VT/ALP scaffold implantations into the bone defects were performed on 30 white rats, and the serum of intact animals was used as the control. ELISA and multiplex assay were used to find inflammatory and bone turnover markers including monocyte chemoattractant-1, sclerostin, fibroblast growth factor-23, connective tissue growth factor (CTGF), osteoprotegerin, osteocalcin, β-сross laps and the activity of tartrate-resistant acid phosphatase-5b in the blood of experimental animals. The activity of serum ALP was tested with the conventional kinetic method. The morphology of the reparative processes was verified by microscopy of specimens taken from the implantation areas and stained with hematoxylin or eosin. Results ― The PCL/VT/ALP scaffold implantations into the bone defects of white rats caused active osteogenesis along with the steady rise in osteocalcin concentration in blood. ALP activity in the blood did not depend on the exogenous enzyme in the scaffold and rose by the 28th day after the implantations. The targeted ALP delivery into the defect area caused the rise in CTGF concentration as well as the decrease in blood sclerostin within a short time after the implantations. Conclusion ― The modulation of the local enzyme homeostasis by means of the targeted ALP delivery with PCL/VT scaffolds stimulated reparative osteogenesis within a short time after the implantations with no changes to the bloodstream or local inflammatory changes suggesting their biocompatibility and the safety in use.