A novel osteotropic biomaterial OG‐PLG: Synthesis and in vitro release

Abstract

Statins (e.g., simvastatin) have shown to induce expression of the bone morphogenic protein-2 gene in bone cells, but they are not used clinically because of a lack of a suitable delivery device. The overall objective is to develop optimized statin delivery devices for bone regeneration. The specific objective was to determine the effect of grafting statins to biodegradable poly[lactide-co-glycolide] (PLG) on release kinetics. Simvastatin was grafted to PLG (OG-PLG) and characterized using contact-angle measurements, attenuated total reflectance-Fourier transform infrared, and ultraviolet-visible spectroscopy to determine success of the synthesis. An ultraviolet-visible assay for measuring release of statins and degraded OG-PLG in media was also developed. In vitro release studies using films and scaffolds made with PLG, PLG blended with simvastatin (PLG + Sim), and OG-PLG (simvastatin grafted to PLG) blended into PLG at different concentrations showed that release rate of OG-PLG from films was significantly greater than that of PLG + Sim. However, release rate from scaffolds showed PLG + Sim to be significantly higher than that of OG-PLG. The diffusion-controlled release kinetics of simvastatin from PLG + Sim seems to be more heavily affected by device morphology, whereas the degradation-controlled release kinetics seem to be less affected. In short, release kinetics can be modulated by grafting statins to PLG.

Efficacy of Simvastatin in Bone Regeneration After Surgical Removal of Mandibular Third Molars: A Clinical Pilot Study

“…In recent years, many researchers have investigated the utilization of statin, a drug that turns on the genes for bone formation, in bone grafting and found that this drug has tremendous osteoinductive effect and great promise in routine use in ridge augmentation and bone grafting in the craniofacial region [10][11][12][13][14]. Alternate materials and methods have been sought as effective bone graft substitutes because of various disadvantages of using autografts (the current gold standard) and allografts.…”

Review:Ex VivoEngineering of Living Tissues with Adult Stem Cells

“…99 The slow release of the cholesterol-lowering drug simvastatin from degrading poly(lactide-co-glycolide) promotes bone mineralization of rat BMSCs more effectively than when the drug is dissolved in culture medium or even released by passive diffusion from scaffolds. 100 Advanced manufacturing techniques can be used to control the spatial architecture in engineered tissues, manipulating the scaffold topography on the length scale of the stem cell niche and smaller. Fused deposition modeling allows for the creation of computer-designed poly (caprolactone)/calcium phosphate scaffolds with honeycomblike 300-to 500-mm pores.…”

Osteogenic effect of fluvastatin combined with biodegradable gelatin-hydrogel

“…When administered by injection their effect has been reported to be lost within 5 days 7) , making this modality impractical for clinical application in bone healing. Therefore, various methods of local administration, or drug delivery system (DDS), have been explored, and include the use of collagen gel, polyethylene glycol, and polylactide-co-glycolide [8][9][10] . One such carrier, gelatin-hydrogel, is biodegradable and already in use in various types of food and drug.…”