A novel osteotropic biomaterial OG-PLG: Synthesis and in vitro release Kyumin Whang, 1 Jonathan McDonald, 2 Ambereen Khan, 3 Neera Satsangi 1 1 Department of Restorative Dentistry, Division of Biomaterials, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, MSC 7890, San Antonio, Texas 78229-3900 2 The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78229-3900 3 Department of Prosthodontics, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78229-3900 Received 30 June 2004; revised 9 December 2004; accepted 7 January 2005 Published online 24 June 2005 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jbm.a.30309 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, atten- uated total reflectance–Fourier transform infrared, and ul- traviolet–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 devel- oped. 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. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res 74A: 237–246, 2005 Key words: statin; controlled delivery; synthesis and char- acterization; poly[lactide-co-glycolide]; bone regeneration INTRODUCTION Therapies to aid healing of bone wounds and de- fects are major needs. In the last 10 years, there have been tremendous advances in the isolation of progen- itor cells and the development of recombinant growth factors such as the bone morphogenic proteins (BMPs). 1–5 The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) that have been safely administered orally for 15 years to reduce serum cholesterol and the subsequent risk of heart attack with few side effects were found to induce expression of the BMP-2 gene in osteoblasts and bone marrow cells, 6 –12 and reduce the risk of fractures clini- cally. 10 –12 Simvastatin, lovastatin, and mevastatin have shown to increase bone formation in vitro, and in vivo in mice when injected subcutaneously over the calvaria (50% increase after 5 days) comparable to maximal doses of BMP-2 and fibroblast growth fac- tor-1. Simvastatin caused a 35% increase in trabecular bone volume in intact and ovariectomized rats when administered orally, induced BMP-2 and alkaline phosphatase production in MC3T3-E1 cells, and in- creased matrix mineralization in both MC3T3-E1 and rat bone marrow cells. 7 Increased BMP-2 mRNA ex- pression was confirmed by Northern analysis in hu- man MG-63 osteoblasts and osteosarcoma cell lines. 8,9 Potential advantages are that statins are as potent as the most powerful bone growth factors that are cur- rently clinically Food and Drug Administration ap- proved only for one or two specific uses, are substan- tially (16,000-fold) cheaper to synthesize, and are not susceptible to proteolytic digestion at the tissue site. 8 Correspondence to: K. Whang; e-mail: whang@uthscsa.edu Contract grant sponsor: South Texas Health Research Center; contract grant number: 53 Contract grant sponsor: NIH/NIDCR; contract grant number: 1R03DE14653 Contract grant sponsor: CO*STAR NIH/NIDCR; contract grant number: DE14318 © 2005 Wiley Periodicals, Inc.