Enhanced osteoinductive capacity of poly(lactic-co-glycolic) acid and biphasic ceramic scaffolds by embedding simvastatin.

Mariane B Sordi, Raissa B Curtarelli, Iara F Mantovani, Anderson C Moreira, Celso P Fernandes, Ariadne C C Cruz, Ricardo S Magini

Journal: Clinical oral investigations 2022;26(3):2693-2701

PMID: 34694495

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Abstract

OBJECTIVES

This study evaluated the effect of embedding simvastatin (SIM) on the osteoinductive capacity of PLGA + HA/βTCP scaffolds in stem cells from human exfoliated deciduous teeth (SHED).

MATERIALS AND METHODS

Scaffolds were produced by PLGA solvent dissolution, addition of HA/βTCP, solvent evaporation, and leaching of sucrose particles to impart porosity. Biphasic ceramic particles (70% HA/30% βTCP) were added to the PLGA in a 1:1 (w:w) ratio. Scaffolds with SIM received 1% (w:w) of this medication. Scaffolds were synthesized in a disc-shape and sterilized by ethylene oxide. The experimental groups were (G1) PLGA + HA/βTCP and (G2) PLGA + HA/βTCP + SIM in non-osteogenic culture medium, while (G3) SHED and (G4) MC3T3-E1 in osteogenic culture medium were the positive control groups. The release profile of SIM from scaffolds was evaluated. DNA quantification assay, alkaline phosphatase activity, osteocalcin and osteonectin proteins, extracellular calcium detection, von Kossa staining, and X-ray microtomography were performed to assess the capacity of scaffolds to induce the osteogenic differentiation of SHED.

RESULTS

The release profile of SIM followed a non-liner sustained-release rate, reaching about 40% of drug release at day 28. Additionally, G2 promoted the highest osteogenic differentiation of SHED, even when compared to the positive control groups.

CONCLUSIONS

In summary, the osteoinductive capacity of poly(lactic-co-glycolic) acid and biphasic ceramic scaffolds was expressively enhanced by embedding simvastatin.

CLINICAL RELEVANCE

Bone regeneration is still a limiting factor in the success of several approaches to oral and maxillofacial surgeries, though tissue engineering using mesenchymal stem cells, scaffolds, and osteoinductive mediators might collaborate to this topic.

Address: Department of Dentistry, Center for Research On Dental Implants (CEPID), Federal University of Santa Catarina, Florianopolis, Brazil.; Department of Microbiology, Immunology, and Parasitology, Laboratory of Applied Virology (LVA), Federal University of Santa Catarina, Florianopolis, Brazil.; Department of Mechanical Engineering, Laboratory of Porous Media and Thermophysical Properties (LMPT), Federal University of Santa Catarina, Florianopolis, Brazil.; Department of Dentistry, Center for Research On Dental Implants (CEPID), Federal University of Santa Catarina, Florianopolis, Brazil. [email protected].; Department of Microbiology, Immunology, and Parasitology, Laboratory of Applied Virology (LVA), Federal University of Santa Catarina, Florianopolis, Brazil. [email protected].

DOI: 10.1007/s00784-021-04240-9

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https://dx.doi.org/10.1007/s00784-021-04240-9

MeSH Terms: Cell Differentiation, Ceramics, Glycols, Humans, Osteogenesis, Polylactic Acid-Polyglycolic Acid Copolymer, Simvastatin, Tissue Engineering, Tissue Scaffolds