Alendronate-loaded gelatin microparticles as templating agents for macroporous magnesium phosphate-based bone cements

Abstract

Magnesium phosphate-based cements (MPCs) have recently attracted great attention as materials for bone repair. However, the lack of macroporosity, fundamental for cells permeation and bone ingrowth, is one of the main limitations hampering MPCs full exploitation. In this work gelatin microparticles are exploited as templating agents for the creation of macroporosities in MPCs. In addition, gelatin particles were loaded with a well-recognized drug for the treatment of osteoporosis, alendronate, to locally release the therapeutic agent. Gelatin microparticles of different size were prepared with a simple water-in-oil emulsion method and included in MPCs at various concentrations. The properties of both the MPCs and the final material were characterized by assessing the composite in terms of injectability, setting time, infrared spectroscopy, scanning electron microscopy and confocal Raman microscopy. The MPC-gelatin composites were then incubated in water at physiological temperature, to promote the dissolution of the gelatin, obtain a macroporous cement, and release gelatin and alendronate. The obtained results show that gelatin microparticles have a twofold action as they allow for the formation of MPC with an interconnected and hundreds of µm-sized porosity and the local release of alendronate, resulting in a material with ideal features for bone repair. Graphical abstract

Effect of Atmospheric Pressure Plasma Jet Treatments on Magnesium Phosphate Cements: Performance, Characterization, and Applications

“…These studies also proved that CAPP treatments increase the biological activity of MPC scaffolds in terms of the osteogenic stimulus. Overall, we demonstrated that MPCs, already proven as injectable and moldable materials, 15,40 preserve a good biocompatibility upon CAPP treatment despite modifying their phase composition. As a future perspective, the comparison of the effect of CAPP toward MPCs vs CPCs would also be of great interest to further demonstrate the potential of such materials and the use of CAPP treatments on them.…”

“…6 The interest in MPCs toward biomedical applications is rapidly growing, 12−18 and various strategies have been recently developed to further improve MPCs' features, such as the inclusion of polymeric additives to enhance the injectability and printability 19,20 or the addition of porogens and templating agents to the formulation to induce the presence of macroporosity in the cement matrix. 15,21,22 Along with the modifications of the bulk material, the cement surface is of great importance, as it represents the first region that cells encounter when they get in contact with the material, being crucial for their adhesion, spreading, and ultimately for the material biocompatibility. 23 Surface modifications aim at creating a specific chemical and physical environment that offers a favorable cellular response in tissues and include changes in topography and morphology, functionalization, and coatings.…”

“…In this context, it was demonstrated that MPC-based implants are entirely resorbed over time maintaining the structural stiffness , and, in comparison to CPCs, a higher resorption rate and the enhanced bone regeneration were often reported. − Moreover, MPCs also play a vital role in the bone metabolism for healing as their degradation products stimulate the osteogenesis and bone defect repair . The interest in MPCs toward biomedical applications is rapidly growing, − and various strategies have been recently developed to further improve MPCs’ features, such as the inclusion of polymeric additives to enhance the injectability and printability , or the addition of porogens and templating agents to the formulation to induce the presence of macroporosity in the cement matrix. ,, …”

“… 6 The interest in MPCs toward biomedical applications is rapidly growing, 12 − 18 and various strategies have been recently developed to further improve MPCs’ features, such as the inclusion of polymeric additives to enhance the injectability and printability 19 , 20 or the addition of porogens and templating agents to the formulation to induce the presence of macroporosity in the cement matrix. 15 , 21 , 22 …”

An Overview of Magnesium-Phosphate-Based Cements as Bone Repair Materials

“…Typically, the % of extruded paste with respect to the amount initially loaded in the syringe is calculated, and the injectability % is obtained. The injection can be performed manually [ 109 , 158 ] or in controlled conditions, using specific loads and testing machines [ 58 , 160 , 162 ]. Mestres et al compared Na-MPCs, NH 4 -MPCs, and a mixed system, observing that Na-based MPCs had a higher injectability % [ 58 ].…”