Combination therapy with BMP-2 and BMSCs enhances bone healing efficacy of PCL scaffold fabricated using the 3D plotting system in a large segmental defect model

The three-dimensional (3D) plotting system is a rapidly-developing scaffold fabrication method for bone tissue engineering. It yields a highly porous and inter-connective structure without the use of cytotoxic solvents. However, the therapeutic effects of a scaffold fabricated using the 3D plotting system in a large segmental defect model have not yet been demonstrated. We have tested two hypotheses: whether the bone healing efficacy of scaffold fabricated using the 3D plotting system would be enhanced by bone marrow-derived mesenchymal stem cell (BMSC) transplantation; and whether the combination of bone morphogenetic protein-2 (BMP-2) administration and BMSC transplantation onto the scaffold would act synergistically to enhance bone regeneration in a large segmental defect model. The use of the combined therapy did increase bone regeneration further as compared to that with monotherapy in large segmental bone defects.

[1]  A. Meunier,et al.  Tissue-engineered bone regeneration , 2000, Nature Biotechnology.

[2]  Abraham J. Verbout,et al.  Three-dimensional fiber deposition of cell-laden, viable, patterned constructs for bone tissue printing. , 2008, Tissue engineering. Part A.

[3]  A I Caplan,et al.  Characterization of cells with osteogenic potential from human marrow. , 1992, Bone.

[4]  Yen Wah Tong,et al.  Characterization of porous poly(D,L‐lactic‐co‐glycolic acid) sponges fabricated by supercritical CO2 gas‐foaming method as a scaffold for three‐dimensional growth of Hep3B cells , 2008, Biotechnology and bioengineering.

[5]  R. M. Sharrard,et al.  A study of death by anoikis in cultured epithelial cells , 2001, Cell proliferation.

[6]  Byung‐Hyun Cha,et al.  Effect of a scaffold fabricated thermally from acetylated PLGA on the formation of engineered cartilage. , 2011, Macromolecular bioscience.

[7]  S M Perren,et al.  EVOLUTION OF THE INTERNAL FIXATION OF LONG BONE FRACTURES , 2002 .

[8]  M. S. Park,et al.  Enhancement of in vivo bone regeneration efficacy of human mesenchymal stem cells. , 2008, Journal of microbiology and biotechnology.

[9]  K. Leong,et al.  Fabrication of controlled release biodegradable foams by phase separation. , 1995, Tissue engineering.

[10]  J. Vacanti,et al.  Biodegradable sponges for hepatocyte transplantation. , 1995, Journal of biomedical materials research.

[11]  R Cancedda,et al.  Repair of large bone defects with the use of autologous bone marrow stromal cells. , 2001, The New England journal of medicine.

[12]  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.

[13]  M. Li,et al.  The use of silk fibroin/hydroxyapatite composite co-cultured with rabbit bone-marrow stromal cells in the healing of a segmental bone defect. , 2010, The Journal of bone and joint surgery. British volume.

[14]  Wan-Geun La,et al.  Bone morphogenetic protein-2 enhances bone regeneration mediated by transplantation of osteogenically undifferentiated bone marrow-derived mesenchymal stem cells , 2008, Biotechnology Letters.

[15]  Geunhyung Kim,et al.  3D polycaprolactone scaffolds with controlled pore structure using a rapid prototyping system , 2009, Journal of materials science. Materials in medicine.

[16]  Dong-Woo Cho,et al.  Effect of Thermal Degradation of SFF-Based PLGA Scaffolds Fabricated Using a Multi-head Deposition System Followed by Change of Cell Growth Rate , 2010, Journal of biomaterials science. Polymer edition.

[17]  S. Cook,et al.  Healing Course of Primate Ulna Segmental Defects Treated With Osteogenic Protein-1 , 2002, Journal of investigative surgery : the official journal of the Academy of Surgical Research.

[18]  Dong-Woo Cho,et al.  Surface modification with fibrin/hyaluronic acid hydrogel on solid-free form-based scaffolds followed by BMP-2 loading to enhance bone regeneration. , 2011, Bone.

[19]  S. Bidic,et al.  rhBMP-2 delivered in a calcium phosphate cement accelerates bridging of critical-sized defects in rabbit radii. , 2006, The Journal of bone and joint surgery. American volume.

[20]  Stephan M Perren,et al.  Evolution of the internal fixation of long bone fractures. The scientific basis of biological internal fixation: choosing a new balance between stability and biology. , 2002, The Journal of bone and joint surgery. British volume.

[21]  R Langer,et al.  Laminated three-dimensional biodegradable foams for use in tissue engineering. , 1993, Biomaterials.

[22]  V. Rosen,et al.  The non-osteogenic mouse pluripotent cell line, C3H10T1/2, is induced to differentiate into osteoblastic cells by recombinant human bone morphogenetic protein-2. , 1990, Biochemical and biophysical research communications.