Development of Poly(ɛ-Caprolactone) Scaffold Loaded with Simvastatin and Beta-Cyclodextrin Modified Hydroxyapatite Inclusion Complex for Bone Tissue Engineering

In this study, we developed poly(ɛ-caprolactone) (PCL) 3D scaffolds using a solid free form fabrication (SFF) technique. β-cyclodextrin (βCD) was grafted to hydroxyapatite (HAp) and this βCD grafted HAp was coated onto the PCL scaffold surface, followed by drug loading through an inclusion complex interaction between the βCD and adamantane (AD) or between βCD and simvastatin (SIM). The scaffold structure was characterized by scanning electron microscopy (SEM). The release profile of simvastatin in the β-CD grafted HAp was also evaluated. Osteogenic differentiation of adipose-derived stromal cells (ADSCs) was examined using an alkaline phosphatase activity (ALP) assay. The results suggest that drug loaded PCL-HAp 3-D scaffolds enhances osteogenic differentiation of ADSCs.

[1]  Lijie Grace Zhang,et al.  Three-dimensional printing of nanomaterial scaffolds for complex tissue regeneration. , 2015, Tissue engineering. Part B, Reviews.

[2]  Su A Park,et al.  Fabrication of biomimetic PCL scaffold using rapid prototyping for bone tissue engineering , 2014, Macromolecular Research.

[3]  Min-Ah Koo,et al.  Biological advantages of porous hydroxyapatite scaffold made by solid freeform fabrication for bone tissue regeneration. , 2013, Artificial organs.

[4]  Cho-Pei Jiang,et al.  Solid freeform fabrication and in-vitro response of osteoblast cells of mPEG-PCL-mPEG bone scaffolds , 2013, Biomedical microdevices.

[5]  M. Soleimani,et al.  New approach to bone tissue engineering: simultaneous application of hydroxyapatite and bioactive glass coated on a poly(L-lactic acid) scaffold. , 2011, ACS applied materials & interfaces.

[6]  Su A. Park,et al.  Fabrication of porous polycaprolactone/hydroxyapatite (PCL/HA) blend scaffolds using a 3D plotting system for bone tissue engineering , 2011, Bioprocess and biosystems engineering.

[7]  Wei Sun,et al.  Microfluidic hydrogels for tissue engineering , 2011, Biofabrication.

[8]  J. Cha,et al.  Simvastatin induces osteogenic differentiation of murine embryonic stem cells , 2010, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[9]  F. Melchels,et al.  A review on stereolithography and its applications in biomedical engineering. , 2010, Biomaterials.

[10]  Jui-Sheng Sun,et al.  Simvastatin promotes osteoblast viability and differentiation via Ras/Smad/Erk/BMP-2 signaling pathway. , 2010, Nutrition research.

[11]  R. Tang,et al.  In vitro effects of nanophase hydroxyapatite particles on proliferation and osteogenic differentiation of bone marrow-derived mesenchymal stem cells. , 2009, Journal of biomedical materials research. Part A.

[12]  Chang Liu,et al.  The Effect of Simvastatin on mRNA Expression of Transforming Growth Factor-β1, Bone Morphogenetic Protein-2 and Vascular Endothelial Growth Factor in Tooth Extraction Socket , 2009, International Journal of Oral Science.

[13]  Wei Sun,et al.  Fabrication of three-dimensional polycaprolactone/hydroxyapatite tissue scaffolds and osteoblast-scaffold interactions in vitro. , 2007, Biomaterials.

[14]  Farshid Guilak,et al.  A biomimetic three-dimensional woven composite scaffold for functional tissue engineering of cartilage. , 2007, Nature materials.

[15]  A. Boccaccini,et al.  Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering. , 2006, Biomaterials.

[16]  Colleen L Flanagan,et al.  Bone tissue engineering using polycaprolactone scaffolds fabricated via selective laser sintering. , 2005, Biomaterials.

[17]  Yu Liu,et al.  A unique tetramer of 4 ∶ 5 β-cyclodextrin–ferrocene in the solid state , 2005 .

[18]  H. Anderson,et al.  Impaired calcification around matrix vesicles of growth plate and bone in alkaline phosphatase-deficient mice. , 2004, The American journal of pathology.

[19]  Peter X Ma,et al.  Biomimetic polymer/apatite composite scaffolds for mineralized tissue engineering. , 2004, Macromolecular bioscience.

[20]  E. Sachlos,et al.  Making tissue engineering scaffolds work. Review: the application of solid freeform fabrication technology to the production of tissue engineering scaffolds. , 2003, European cells & materials.

[21]  J. Aubin,et al.  Global amplification polymerase chain reaction reveals novel transitional stages during osteoprogenitor differentiation , 2003, Journal of Cell Science.

[22]  L. Griffith,et al.  Tissue Engineering--Current Challenges and Expanding Opportunities , 2002, Science.

[23]  S. Harris,et al.  Stimulation of bone formation in vitro and in rodents by statins. , 1999, Science.

[24]  F. Hirayama,et al.  Cyclodextrin-based controlled drug release system. , 1999, Advanced drug delivery reviews.

[25]  J. Szejtli.  Introduction and General Overview of Cyclodextrin Chemistry. , 1998, Chemical reviews.

[26]  Zhengwei You,et al.  Hybrid small-diameter vascular grafts: Anti-expansion effect of electrospun poly ε-caprolactone on heparin-coated decellularized matrices. , 2016, Biomaterials.

[27]  P. McHugh,et al.  Laser sintering for the fabrication of tissue engineering scaffolds. , 2012, Methods in molecular biology.

[28]  M. Sefton,et al.  Tissue engineering. , 1998, Journal of cutaneous medicine and surgery.