형상이 제어된 골 조직 재생용 3차원 지지체를 적용한 새로운 형태의 Perfusion Culture = Novel Perfusion Culture with 3-Dimensional Shape-Controlled Scaffolds for Bone Tissue Engineering

다국어 초록 (Multilingual Abstract)

The objective of this study was to investigate the efficacy of a newly designed perfusion bioreactor which provides flow-induced mechanical stimulation on the cells residing in the intra-morphology controllable scaffolds. For this, we fabricated scaffolds composed of poly e-caprolactone (PCL) and micro-sized hydroxyapatite (HA) particles using rapid-prototyping process. Also a new bioreactor system for perfusion culture was designed and developed. For the analyses of cellular responses of bone-tissue related cells cultured in the perfusion bioreactor system, various biological assays were performed such as MTT test, DNA content measurement, FE-SEM and live/dead staining. The cells used in this study were MG-63 (human osteoblast-like cell line) and mesenchymal stem cells from New Zealand white rabbits. Our results showed that the cells cultured by the perfusion bioreactor resulted in higher proliferation rate and mineralization of extracellular matrices than those cultured in static culture. From this study, we could confirm the potentials of 1) a newly developed perfusion bioreactor, 2) intra-morphology controllable scaffolds composed of PCL and HA particle and 3) the combination of the suggested scaffolds and perfusion culturing system in relation to bone tissue engineering.

참고문헌 (Reference)

1 S Xu, "The growth of stem cells within $\beta$- TCP scaffolds in a fluid-dynamic environment" 28 : 164-164, 2008

2 TD Brown, "Techniques for mechanical stimulation of cells in vitro" 33 : 3-3, 2000

3 DW Hutmacher, "Scaffolds in tissue engineering bone and cartilage" 21 : 2529-2529, 2000

4 WY Yeong, "Rapid prototyping in tissue engineering: challenges and potential" 22 : 643-643, 2004

5 H Hosseinkhani, "Perfusion Culture Enhances Osteogenic Differentiation of Rat Mesenchymal Stem Cells in Collagen Sponge Reinforced with Poly(Glycolic Acid) Fiber" 11 : 1476-1476, 2005

6 RL Duncan, "Mechanotransduction and the functional response of bone to mechanical strain" 57 : 344-344, 1995

7 DW Hutmacher, "Mechanical properties and cell cultural response of polycaprolactone scaffolds designed and fabricated via fused deposition modeling" 55 : 203-203, 2001

8 JR Mauney, "Mechanical Stimulation Promotes Osteogenic Differentiation of Human Bone Marrow Stromal Cells on 3-D Partially Demineralized Bone Scaffolds In Vitro" 74 : 458-458, 2004

9 EH Burger, "J Klein-Nulend. Mechanotransduction in bonerole of the lacuno-canalicular network" 13 : 101-101, 1999

10 SJ Heo, "In Vitro and Animal Study of Novel Nano-HA=PCL Composite Scaffolds Fabricated by Layer Manufacturing Process" 15 : 977-977, 2009

11 S Liao, "Human neutrophils reaction to the biodegraded nano-hydroxyapatite/collagen and nanohydroxyapatite/ collagen/poly(L-lactic acid) composites" 76 : 820-820, 2006

12 VI Sikavitsas, "Formation of threedimensional cell/polymer constructs for bone tissue engineering in a spinner flask and a rotating wall vessel bioreactor" 62 : 136-136, 2001

13 L Bjerre, "Flow perfusion culture of human mesenchymal stem cells on silicatesubstituted tricalcium phosphate scaffolds" 29 : 2616-2616, 2008

14 SH Cartmell, "Effects of Medium Perfusion Rate on Cell-Seeded Three-Dimensional Bone Constructs in Vitro" 9 : 1197-1197, 2004

15 D Li, "Effects of Flow Shear Stress 2and Mass Transporton the Construction of a Large-Scale Tissue- Engineered Bone in a Perfusion Bioreactor" 15 : 2773-2773, 2009

16 CR Jacobs, "Differential effect of steady versus oscillating flow on bone cells" 31 : 969-969, 1998

17 RM. Schulz, "Development and Validation of a Novel Bioreactor System for Load- and Perfusion-Controlled Tissue Engineering of Chondrocyte- Constructs" 101 : 714-714, 2008

18 GN Bancroft, "Design of a Flow Perfusion Bioreactor System for Bone Tissue-Engineering Applications" 9 : 549-549, 2003

19 MJ Jaasma, "Design and validation of a dynamic flow perfusion bioreactor for use with compliant tissue engineering scaffolds" 133 : 490-490, 2008

20 L Meinel, "Bone Tissue Engineering Using Human Mesenchymal Stem Cells: Effects of Scaffold Material and Medium Flow" 32 : 112-112, 2004

21 N Degirmenbasi, "Biocomposites of nanohydroxyapatite with collagen and poly(vinyl alcohol)" 48 : 42-42, 2006

22 L Kong, "A study on the bioactivity of chitosan/nano-hydroxyapatite composite scaffolds for bone tissue engineering" 42 : 3171-3171, 2006

23 C Jungreuthmayer, "A Comparative Study of Shear Stresses in Collagen- Glycosaminoglycan and Calcium Phosphate Scaffolds in Bone Tissue-Engineering Bioreactors" 15 : 1141-1141, 2009

24 SA Park, "3D polycaprolactone scaffolds with controlled pore structure using a rapid prototyping system" 20 : 229-229, 2009

25 B Porter, "3-D computational modeling of media flow through scaffolds in a perfusion bioreactor" 38 : 543-543, 2005