Porous Composite Granules with Potential Function of Bone Substitute and Simvastatin Releasing System: A Preliminary Study

Abstract

In this work, 3D porous granules based on Zn and Se-containing calcium phosphates (CaPs) were fabricated using a droplet-extrusion technique. The composite beads varied in composition and contained two different natural polymers: sodium alginate (SA) and gelatin (GEL). To analyse and compare their physicochemical properties, such as porosity and morphology, different techniques were applied, including scanning electron microscopy (SEM), sorption of N2 and mercury porosimetry. Prior to the fabrication of the granules, the properties of CaPs materials, (the bioceramic base of the beads), selenium (IV)-substituted hydroxyapatite (Se-HA) and zinc-substituted dicalcium phosphate dihydrate (Zn-DCPD), were also investigated. The results of cell viability assessment showed that Se-HA powder was non-toxic to human osteoblasts (hFOB 1.19) and simultaneously exhibited high toxicity to tumour cells (Saos-2). Once the cytotoxicity assay was completed, Se-HA and Zn-DCPD were used to prepare 3D materials. The prepared porous granules were used as matrices to deliver simvastatin to bones. Simvastatin was applied in either the lipophilic form or hydrophilic form. The release kinetics of simvastatin from granules of different composition was then assessed and compared.

Simvastatin-hydroxyapatite coatings prevent biofilm formation and improve bone formation in implant-associated infections

“…Sim-HA coatings decreased the contact angle of the control and HA groups. One of the reasons for this decrease is that the hydrophilic form of simvastatin [ 26 , 64 ] was used to generate Sim-HA coatings on the implants. In addition, the roughness results were consistent with the change in the contact angles.…”

“…S imvastatin (Yuanye Bio-Technology, China) solution was prepared as previously described [ 25 , 26 ]. Briefly, 42 mg simvastatin was dissolved in 1 ml 95% ethanol.…”

“…The drug release process of Sim-HA-Ti6Al4V was evaluated according to previous studies, with modifications [ 26 , [28] , [29] , [30] ]. Sim-Low and Sim-High plates were placed into 5 ml falcon cubes containing 2 ml PBS.…”

Statins—Their Role in Bone Tissue Metabolism and Local Applications with Different Carriers

“…Various release profiles have been observed depending on the chemical composition of the carrier, its form, and its preparation method. Generally, the constructed carriers are designed to release statins gradually over an extended period (from 50-90% within 7 days) [76][77][78]. In the study by [78], a typical microporous structure of calcium phosphate foam was employed, which proved to be a suitable carrier for pitavastatin: the "burst release" effect was relatively minimal, followed by the gradual release of the statin over 72 h. Various approaches have been applied to prolong the release time.…”