Assessment of the regenerative potential of macro-porous chitosan-calcium simvastatin scaffolds on bone cells

Abstract

This study evaluated the bioactive potential of a macro-porous chitosan scaffold incorporated with calcium hydroxide (CH-Ca) and functionalized with bioactive doses of simvastatin (SV) for bone tissue regeneration. Initially, the bioactive dose of SV in osteoblastic cells (SAOS-2) was determined. For the direct contact experiment, SAOS-2 cells were plated on scaffolds to assess cell viability and osteogenic differentiation. The second assay was performed at a distance using extracts from scaffolds incubated in culture medium to assess the effect of conditioned medium on viability and osteogenic differentiation. The initial screening showed that 1 μM SV presented the best biostimulating effects, and this dose was selected for incorporation into the CH-Ca and pure chitosan (CH) scaffolds. The cells remained viable throughout the direct contact experiment, with the greatest cell density in the CH-Ca and CH-Ca-SV scaffolds because of their higher porosity. The CH-Ca-SV scaffold showed the most intense bio-stimulating effect in assays in the presence and absence of osteogenic medium, leading to an increased deposition of mineralized matrix. There was an increase in the viability of cells exposed to the extracts for CH-Ca, CH-SV, and CH-Ca-SV during the one-day period. There was an increase in ALP activity in the CH-Ca and CH-Ca-SV; however, the CH-Ca-SV scaffold resulted in an intense increase in the deposition of mineralized nodules, approximately 56.4% at 7 days and 117% at 14 days, compared with CH (control). In conclusion, functionalization of the CH-Ca scaffold with SV promoted an increase in bioactivity, presenting a promising option for bone tissue regeneration.

Chitosan Nanoparticle/Simvastatin for Experimental Maxillary Bony Defect Healing: A Histological and Histomorphometrical Study

“…This notion is further supported by the anti-osteoclastogenesis effect of Sim, which could be responsible for reducing OCL populations. These findings disagree with those of Gallinari et al [ 48 ], which could be explained by the differences in the delivery system, inclusion of calcium hydroxide and utilizing an OB cell line derived from osteosarcoma. The results of this study also indicate the better bone formation capacity of ChN compared to ChSimN.…”

“…Interestingly, the number of OBs and OCLs was significantly higher in the ChN group compared to ChSimN. This indicated the reducing OB differentiation capacity of ChSimN [ 48 ], suggesting an antagonist effect of Sim when combined with ChN. This was further demonstrated by the significantly higher number of OCs that were derived from OBs in association with ChN than ChSimN, which is consistent with results obtained by Ghadri et al [ 49 ].…”

Application of Mineralized Chitosan Scaffolds in Bone Tissue Engineering

“…With the adding alginate of BCA, the mechanical strength of BCA and the mineralization ability of Bioglass were effectively enhanced [108]. Chitosan scaffolds incorporated with calcium hydroxide (CH-Ca) and simvastatin (SV) promoted an increase in bioactivity [109]. The in vivo results demonstrated that in the animals implanted with PVA-chitosan-HA, the defect was repaired to a good extent, but in those animals that received MSCs-seeded PVA-chitosan-HA, the defects were almost filled.…”