The aim of this study was to synthesize and characterize a nano-hydroxyapatite (nHAP) and calcium sulfate bone substitute (NC) for cranioplasty. The NC was functionalized with low concentrations of bone morphogenetic protein-2 (BMP-2) and zoledronic acid (ZA) and characterized both in vitro and in vivo. In vitro studies included MTT, ALP assays, and fluorescent staining of Saos-2 (human osteoblasts) and MC3T3-E1 (murine preosteoblasts) cells cultured on NC. An in vivo study divided 20 male Wistar rats into four groups: control (defect only), NC, NC + ZA, and NC + ZA + rhBMP-2. The materials were implanted in an 8.5 mm critical size defect in the calvarium for 12 weeks. Micro-CT quantitative analysis was carried out in vivo at 8 weeks and ex vivo after 12 weeks. Mineralization was highest in the NC + ZA + rhBMP-2 group (13.0 ± 2.8 mm) compared to the NC + ZA group (9.0 ± 3.2 mm), NC group (6.4 ± 1.9 mm), and control group (3.4 ± 1.0 mm) after 12 weeks. Histological and spectroscopic analysis of the defect site provided a qualitative confirmation of neo-bone, which was in agreement with the micro-CT results. In conclusion, NC can be used as a carrier for bioactive molecules, and functionalization with rhBMP-2 and ZA in low doses enhances bone regeneration.

No abstract

Long bone defects can be managed by the induced membrane technique together with autologous bone graft. However, graft harvest is associated with donor site morbidity. This study investigates if a tricalcium phosphate hydroxyapatite scaffold can be used alone or in combination with bone active drugs to improve healing. Sprague Dawley rats (n ¼ 40) were randomized into four groups. (A) scaffold, (B) BMP-7, (C) BMP-7 þ scaffold, and (D) BMP-7 þ scaffold þ systemic bisphosphonate at 2 weeks. Locked femoral nailing was followed by 6 mm segment removal and implantation of an epoxy spacer. At 4 weeks, the spacers were removed and the defects grafted. Eleven weeks later, the bones were explanted for evaluation with radiography, manual assessment, micro-CT, histology, and Fourier Transform Infrared spectroscopy (FTIR). Isolated scaffolds (A) did not heal any defects, whereas the other treatments led to healing in 7/10 (B), 10/10 (C), and 9/10 (D) rats. Group D had greater volume of highly mineralized bone (p < 0.01) and higher bone volume fraction (p < 0.01) compared to all other groups. A synthetic scaffold þ BMP-7 combined with a bisphosphonate improved the callus properties in a rat femoral critical size defect, compared to both BMP-7 and scaffold alone or the two combined.

No abstract

It is well established that the mechanical environment modulates tissue differentiation, and a number of mechanoregulatory theories for describing the process have been proposed. In this study, simulations of an in vivo bone chamber experiment were performed that allowed direct comparison with experimental data. A mechanoregulation theory for mesenchymal stem cell differentiation based on a combination of fluid flow and shear strain (computed using finite element analysis) was implemented to predict tissue differentiation inside mechanically controlled bone chambers inserted into rat tibae. To simulate cell activity, a lattice approach with stochastic cell migration, proliferation, and selected differentiation was adopted; because of its stochastic nature, each run of the simulation gave a somewhat different result. Simulations predicted the load-dependency of the tissue differentiation inside the chamber and a qualitative agreement with histological data; however, the full variability found between specimens in the experiment could not be predicted by the mechanoregulation algorithm. This result raises the question whether tissue differentiation predictions can be linked to genetic variability in animal populations. ß