Abstract
Recently a submicron particle of biphasic calcium phosphate ceramic (BCP) with through-hole (donut-shaped BCP (d-BCP)) was developed for improving the osteoconductivity. This study was performed to examine the usefulness of d-BCP for the delivery of osteoinductive rhBMP2 and the effectiveness on cranial bone regeneration. The d-BCP was soaked in rhBMP2 solution and then freeze-dried. Scanning electron microscope (SEM), energy dispersive spectroscopy (EDS), and Raman spectroscopy analyses confirmed that rhBMP2 was well delivered onto the d-BCP surface and the through-hole. The bioactivity of the rhBMP2/d-BCP composite was validated in MC3T3-E1 cells as an in vitro model and in critical-sized cranial defects in C57BL/6 mice. When freeze-dried d-BCPs with rhBMP2 were placed in transwell inserts and suspended above MC3T3-E1, alkaline phosphatase activity and osteoblast-specific gene expression were increased compared to non-rhBMP2-containing d-BCPs. For evaluating in vivo effectiveness, freeze-dried d-BCPs with or without rhBMP2 were implanted into critical-sized cranial defects. Microcomputed tomography and histologic analysis showed that rhBMP2-containing d-BCPs significantly enhanced cranial bone regeneration compared to non-rhBMP2-containing control. These results suggest that a combination of d-BCP and rhBMP2 can accelerate bone regeneration, and this could be used to develop therapeutic strategies in hard tissue healing.
Highlights
Bone defects caused by accidents, trauma, or delayed recovery from diseases can result in major clinical skeletal problems that require reconstruction to restore bone function [1, 2]
The osteoconductive d-biphasic calcium phosphate ceramic (BCP) was soaked into the osteoinductive recombinant human BMP 2 (rhBMP2) solution and freezedried
The freeze-dried donut shape of BCP (d-BCP) with rhBMP2 solution had an irregular or closed spherical morphology with a relatively rough surface compared to d-BCP, indicating good packaging of rhBMP2 in the central through-hole of d-BCP (Figures 1(c) and 1(d))
Summary
Bone defects caused by accidents, trauma, or delayed recovery from diseases can result in major clinical skeletal problems that require reconstruction to restore bone function [1, 2]. Autologous bone grafting is a widely used approach, especially in the regeneration of craniofacial bone defects [3]. Autologous bone grafts have significant limitations, including often painful and limited access to the graft site, as well as morbidity to the donor site. Various synthetic biomaterials have been developed as bone substitutes to bone grafts, including bioactive ceramic, bioactive glasses, reinforced natural materials, and synthetic polymers [4]. Biphasic calcium phosphate ceramics (BCPs) are composed of two calcium phosphate phases: hydroxyapatite (HA) and beta-tricalcium phosphate (β-TCP) at a specific ratio, and they exhibit good biocompatibility and bone conduction performance [5]. Pure BCP mainly acts as an osteoconductive substance with limited bone formation and relatively long regeneration time. It is necessary to provide it with macro-/microporous structures for enhancing osteoconductivity or to combine the bioactive molecules such
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