Репозиторий Университета

Thanks to their biocompatibility, biodegradability, injectability and self-setting properties, calcium phosphate cements (CPCs) have been the most economical and effective biomaterials of choice for use as bone void fillers. They have also been extensively used as drug delivery carriers owing to their ability to provide for a steady release of various organic molecules aiding the regeneration of defective bone, including primarily antibiotics and growth factors. This review provides a systematic compilation of studies that reported on the controlled release of drugs from CPCs in the last 25 years. The chemical, compositional and microstructural characteristics of these systems through which the control of the release rates and mechanisms could be achieved have been discussed. In doing so, the effects of (i) the chemistry of the matrix, (ii) porosity, (iii) additives, (iv) drug types, (v) drug concentrations, (vi) drug loading methods and (vii) release media have been distinguished and discussed individually. Kinetic specificities of in vivo release of drugs from CPCs have been reviewed, too. Understanding the kinetic and mechanistic correlations between the CPC properties and the drug release is a prerequisite for the design of bone void fillers with drug release profiles precisely tailored to the application area and the clinical picture. The goal of this review has been to shed light on these fundamental correlations.

Thanks to their biocompatibility, biodegradability, injectability and self-setting properties, calcium phosphate cements (CPCs) have been the most economical and effective biomaterials of choice for use as bone void fillers. They have also been extensively used as drug delivery carriers owing to their ability to provide for a steady release of various organic molecules aiding the regeneration of defective bone, including primarily antibiotics and growth factors. This review provides a systematic compilation of studies that reported on the controlled release of drugs from CPCs in the last 25 years. The chemical, compositional and microstructural characteristics of these systems through which the control of the release rates and mechanisms could be achieved have been discussed. In doing so, the effects of (i) the chemistry of the matrix, (ii) porosity, (iii) additives, (iv) drug types, (v) drug concentrations, (vi) drug loading methods and (vii) release media have been distinguished and discussed individually. Kinetic specificities of in vivo release of drugs from CPCs have been reviewed, too. Understanding the kinetic and mechanistic correlations between the CPC properties and the drug release is a prerequisite for the design of bone void fillers with drug release profiles precisely tailored to the application area and the clinical picture. The goal of this review has been to shed light on these fundamental correlations.

© 2020 Elsevier B.V. A self-setting bone cement containing β-tricalcium phosphate (TCP) supplemented with boron nitride nanotubes (BNNTs, 1 wt%) was synthesized and analyzed in situ for its kinetics of hardening and selected physicochemical and biological properties. Moderately delayed due to the presence of BNNTs, the hardening reaction involved the transformation of the TCP precursor to the dicalcium phosphate (DCPD) product. In spite of the short-lived chemical transformations in the cement upon its hardening, the structural changes in it were extended. As a result, the compressive strength increased from day 1 to day 7 of the hardening reaction and the presence of BNNTs further increased it by ~25%. Fitting of the time-resolved energy-dispersive diffractometric data to the Johnson-Mehl-Avrami-Kolmogorov crystallization kinetics model conformed to the one-dimensional nucleation at a variable rate during the growth of elongated DCPD crystals from round TCP grains. For the first seven days of growth of human mesenchymal stem cells (hMSCs) on the cement, no difference in their proliferation was observed compared to the control. However, between the 7th and the 21st day, the cell proliferation decreased compared to the control because of the ongoing stem cell differentiation toward the osteoblast phenotype. This differentiation was accompanied by the higher expression of alkaline phosphatase, an early marker of hMSC differentiation into a pre-osteoblast phenotype. The TCP cement supplemented with BNNTs was able to thwart the production of reactive oxygen species (ROS) in hMSCs treated with H2O2/Fe2+ and bring the ROS levels down to the concentrations detected in the control cells, indicating the good capability of the material to protect the cells against the ROS-associated damage. Simultaneously, the cement increased the expression of mediators of inflammation in a co-culture of osteoblasts and macrophages, thus attesting to the direct reciprocity between the degrees of inflammation and stimulated new bone production.