In vitro and in vivo evaluation of bone formation using solid freeform fabrication-based bone morphogenic protein-2 releasing PCL/PLGA scaffolds

被引:33
作者
Kim, Tae-Hoon [1 ]
Yun, Young-Pil [2 ,3 ]
Park, Young-Eun [2 ,3 ]
Lee, Suk-Ha [1 ]
Yong, Woonjae [4 ]
Kundu, Joydip [4 ]
Jung, Jin Woo [4 ]
Shim, Jin-Hyung [4 ]
Cho, Dong-Woo [4 ,5 ]
Kim, Sung Eun [2 ,3 ]
Song, Hae-Ryong [2 ,3 ]
机构
[1] Konkuk Univ, Sch Med, Dept Orthoped Surg, Seoul 143729, South Korea
[2] Korea Univ, Coll Med, Guro Hosp, Dept Orthoped Surg, Seoul 152703, South Korea
[3] Korea Univ, Coll Med, Guro Hosp, Rare Dis Inst, Seoul 152703, South Korea
[4] Pohang Univ Sci & Technol POSTECH, Dept Mech Engn, Pohang 790784, Kyungbuk, South Korea
[5] Pohang Univ Sci & Technol POSTECH, Div Integrat Biosci & Biotechnol, Pohang 790784, South Korea
基金
新加坡国家研究基金会;
关键词
bone morphogenic protein-2 (BMP-2); solid; freeform fabrication (SFF); osteoblast activity; bone formation; polycaprolactone (PCL); poly(lactic-co-glycolic acid) (PLGA); ANGIOGENIC GROWTH-FACTOR; LUMBAR INTERBODY FUSION; MESENCHYMAL STEM-CELLS; MARROW STROMAL CELLS; POROUS SCAFFOLDS; OSTEOBLAST FUNCTIONS; CALCIUM PHOSPHATES; BACTERIAL ADHESION; PLGA MICROSPHERES; FACTOR DELIVERY;
D O I
10.1088/1748-6041/9/2/025008
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
The aim of this study was to develop novel polycaprolactone/poly(lactic-co-glycolic acid) (PCL/PLGA) scaffolds with a heparin-dopamine (Hep-DOPA) conjugate for controlled release of bone morphogenic protein-2 (BMP-2) to enhance osteoblast activity in vitro and also bone formation in vivo. PCL/PLGA scaffolds were prepared by a solid freeform fabrication method. The PCL/PLGA scaffolds were functionalized with Hep-DOPA and then BMP-2 was sequentially coated onto the Hep-DOPA/PCL/PLGA scaffolds. The characterization and surface elemental composition of all scaffolds were evaluated by scanning electron microscope and x-ray photoelectron spectroscopy. The osteoblast activities on all scaffolds were assessed by cell proliferation, alkaline phosphatase (ALP) activity and calcium deposition in vitro. To demonstrate bone formation in vivo, plain radiograph, micro-computed tomography (micro-CT) evaluation and histological studies were performed after the implantation of all scaffolds on a rat femur defect. Hep-DOPA/PCL/PLGA had more controlled release of BMP-2, which was quantified by enzyme-linked immunosorbent assay, compared with Hep/PCL/PLGA. The in vitro results showed that osteoblast-like cells (MG-63 cells) grown on BMP-2/Hep-DOPA/PCL/PLGA had significantly enhanced ALP activity and calcium deposition compared with those on BMP-2/Hep/PCL/PLGA and PCL/PLGA. In addition, the plain radiograph, micro-CT evaluation and histological studies demonstrated that the implanted BMP-2/Hep-DOPA/PCL/PLGA on rat femur had more bone formation than BMP-2/Hep/PCL/PLGA and PCL/PLGA in vivo.
引用
收藏
页数:11
相关论文
共 49 条
[1]   Osteogenic differentiation of dura mater stem cells cultured in vitro on three-dimensional porous scaffolds of poly(ε-caprolactone) fabricated via co-extrusion and gas foaming [J].
Aronin, C. E. Petrie ;
Cooper, J. A., Jr. ;
Sefcik, L. S. ;
Tholpady, S. S. ;
Ogle, R. C. ;
Botchwey, E. A. .
ACTA BIOMATERIALIA, 2008, 4 (05) :1187-1197
[2]   Use of recombinant human bone morphogenetic protein-2 to achieve posterolateral lumbar spine fusion in humans - A prospective, randomized clinical pilot trial - 2002 Volvo Award in clinical studies [J].
Boden, SD ;
Kang, J ;
Sandhu, H ;
Heller, JG .
SPINE, 2002, 27 (23) :2662-2673
[3]   Physical and chemical aspects of calcium phosphates used in spinal surgery [J].
Bohner, M .
EUROPEAN SPINE JOURNAL, 2001, 10 (Suppl 2) :S114-S121
[4]   A composite fibrin-based scaffold for controlled delivery of bioactive pro-angiogenetic growth factors [J].
Briganti, Enrica ;
Spiller, Dario ;
Mirtelli, Chiara ;
Kull, Silvia ;
Counoupas, Claudio ;
Losi, Paola ;
Senesi, Sonia ;
Di Stefano, Rossella ;
Soldani, Giorgio .
JOURNAL OF CONTROLLED RELEASE, 2010, 142 (01) :14-21
[5]   Differential temporal expression of members of the transforming growth factor β superfamily during murine fracture healing [J].
Cho, TJ ;
Gerstenfeld, LC ;
Einhorn, TA .
JOURNAL OF BONE AND MINERAL RESEARCH, 2002, 17 (03) :513-520
[6]   Segmental bone regeneration using a load-bearing biodegradable carrier of bone morphogenetic protein-2 [J].
Chu, Tien-Min G. ;
Warden, Stuart J. ;
Turner, Charles H. ;
Stewart, Rena L. .
BIOMATERIALS, 2007, 28 (03) :459-467
[7]   Surface functionalization of titanium with hyaluronic acid/chitosan polyelectrolyte multilayers and RGD for promoting osteoblast functions and inhibiting bacterial adhesion [J].
Chua, Poh-Hui ;
Neoh, Koon-Gee ;
Kang, En-Tang ;
Wang, Wilson .
BIOMATERIALS, 2008, 29 (10) :1412-1421
[8]   Heparin immobilized porous PLGA microspheres for angiogenic growth factor delivery [J].
Chung, Hyun Jung ;
Kim, Hong Kee ;
Yoon, Jun Jin ;
Park, Tae Gwan .
PHARMACEUTICAL RESEARCH, 2006, 23 (08) :1835-1841
[9]   EFFECT OF RECOMBINANT HUMAN OSTEOGENIC PROTEIN-1 ON HEALING OF SEGMENTAL DEFECTS IN NONHUMAN-PRIMATES [J].
COOK, SD ;
WOLFE, MW ;
SALKELD, SL ;
RUEGER, DC .
JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME, 1995, 77A (05) :734-750
[10]   Mineralization dynamics of regenerate bone during mandibular osteodistraction [J].
Cope, JB ;
Samchukov, ML .
INTERNATIONAL JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY, 2001, 30 (03) :234-242