Table 2.
Summary of studies (2010–2022) on 3D dynamic cell culture using perfusion bioreactors for bone tissue engineering compared to the static culture.
| Species | MSC source | Material | Scaffold | Medium | Flow type | Flow condition | Shear stress range | Time point | Growth | Upregulated osteogenic genes/PROTEIN | Downregulated osteogenic genes/PROTEIN |
ALP activity | Calcium deposition | Other | Ref |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Human | Bone marrow | Geratin-Alginate | 3D printed | OM | Steady | Contiuous, 7 ml/min | 10–100 mPa | Day 21 | NA | NA | NA | NA | ↑ | [128] | |
| Human | Adipose | Bio-Oss® | Blocks | GM | Oscillatory | 0.00167 Hz, 0.5 ml/min | NA | Hour 1 | NA | NA | NA | NA | NA | Cell distribution↑ | [132] |
| Rat | Bone marrow | LTMC | Salt-leached | GM | Steady | 8 hr/day, 1.6 ml/min | < 13.35 mPa (mean: 0.40 mPa) | Day 21 | ↓ | runx2, sp7, bsp, alp, spp1, ocn, RUNX2, COL1 | - | NC | ↑ | [92] | |
| Human | Bone marrow | Col | Sponge | CM | Steady | 3 ml/min overnight followed by 0.3 ml/min |
NA | Week 5 | NA | NA | NA | NA | ↑ | Cell distribution↑ Thicker mineralised layer |
[117] |
| Human | Adipose | gelatin-βTCP | Form-casting | OM | Steady | Continuous, 1 ml/min | NA | Day 16 | NA |
runx2, ocn, COL1, ALP |
- | ↑ | NA | [133] | |
| Human | Bone marrow | Chitosan-graphene | Freeze-dried | OM | Steady | 1 hr/day, 1 ml/min + 1% axial deformation (1 Hz) |
Mean: 0.001 mPa | Day 7 | ↑ | NA | NA | NA | ↑ | [134] | |
| Human | PT-2501 | PLA-nHA | Freeze-dried | GM | Steady | 1.21 ml/min for 20 hr followed by 0.3 ml/min |
NA | Day 21 | ↑ | runx2, sp7, alp, col1, spp1, ocn, | - | NA | ↑ | [135] | |
| Rabbit | Bone marrow | Col-HA | Freeze-dried | GM/OM | Steady | 4 hr/day, 10 ml/min + Mmagnetic field 15 Hz, 1 mT |
NA | Day 14 | NA | runx2, col1, ocn | - | ↑ | NA | in vivo bone formation↑ wnt1, lrp6, βcatenin↑ |
[136] |
| Porcine | Bone marrow | Col-PLA-CaP | Freeze-dried | GM | Steady | Continuous, 0.03 ml/min for 6 hr followed by static culture 1–2 ml/min |
NA | Day 7 | ↑ | NA | NA | NA | NA | Cell distribution↑ | [137] |
| Human | Adipose | PCL-nHA | Electrospun | OM | Steady | Continuous, 2, 4,5 ml/min | NA | Day 14 | ↓ | runx2 | - | ↑ | ↑ | [141] | |
| Rat | Bone marrow | Fibrin | Beads | OM | Steadt | Continuous, 10 ml/min | NA | Day 14 | NA | NA | NA | NA | ↑ | in vivo bone formation↑ | [107] |
| Human | Umbilical cord | PLA-PEG | Salt-leached | OM | Steady | Continuous, 3.47 ml/min | NA | Day 21 | ↑ | RUNX2, COL1, OCN | - | ↑ | ↑ | [108] | |
| Human | hES | Gelatin-coated PU | Not specified | OM | Steady | Continuous, 3.47 ml/min | NA | Day 10 | ↑ | NA | NA | ↑ | NA | [109] | |
| Human | Bone marrow | PLG-HA | Salt-leached | OM | Steady | Continuous, 3 ml/min | NA | Day 21 | ↓ | OCN | ibsp | NA | ↑ | *Compared to culture on orbital shaker | [110] |
| Human | Bone marrow | PLCL | Salt-leached | OM | Steady | Continuous, 1.6 ml/min + 1–2% axial deformation (1–2 Hz) |
0.125–0.175 mPa | Day 2 | NA | spp1, sparc, col1, alp, bmp2 | - | NA | NA | [111] | |
| Rat | Bone marrow | PLCL | Salt-leached | Not specified | Oscillatory | 0.5 Hz, 10 ml/min + 60 mmHg hydraulic pressure (0.5 Hz) |
NA | Day 14 | ↑ | ALP, OCN | - | NC | ↑ | [112] | |
| Human | Bone marrow | Silk fibroin | Salt-leached | OM | Steady | Continuous, 0.2 ml/min | < 0.39 mPa | Day 40 | ↑ | NA | NA | ↓ | ↓ | [113] | |
| Continuous, 12 ml/min | < 24 mPa | Day 40 | ↑ | NA | NA | ↑ | ↓ | ||||||||
| Human | Adipose | Decellularized bone | Granules | OM/GM | Steady | Continuous, 0.6 ml/min | < 4 mPa | Day 21 | NC | NA | NA | ↑ | NA | Viability decreased in flow rate-dependent manner | [114] |
| Human | Bone marrow | Col-Alginate | Casted | OM | Steady | Continuous, 3 ml/min | NA | Day 7/14 | NA | bmp2, BMP2 | - | NA | NA | *Co-culture with HUVEC | [115] |
| Rat | Bone marrow | Col-HA coated decellularized bone | Block | GM | Oscillatory | 0.0167 Hz, 1 ml/min 30 min/day |
NA | Day 21 | NA | OPN, OCN | - | NA | ↑ (Day 7) | [102] | |
| Human | hMPC 32 F | Gelatin-coated PU | Foam | OM | Steady | 2.5 ml/min, 2 hr on Day 3, 5, and 7 | NA | Day 8 | ↓ | NA | - | ↓ | NA | PGE2↑ *mRNA measured at 1 hr post-perfusion | [118] |
| 2.5 ml/min, 2 hr on Day 5 only | NA | Day 8 | ↓ | bmp2, runx2 | - | ↓ | NA | ||||||||
| 2.5 ml/min, 2 hr on Day 7 only | NA | Day 8 | NC | bmp2, runx2 | - | NC | NA | ||||||||
| 2.5 ml/min, 2 hr on Day 15 only | NA | Day 21 | NA | bmp2, runx2, ocn | - | NA | ↑ | ||||||||
| Human | Bone marrow | PLCL | Salt-leached | OM/GM | Steady | 1.6 ml/min for 1 hr followed by 0/8 ml/min for 4 × 5 min/hr |
Mean: 0.076 mPa | Day 7 | NA |
alp, col1, runx2, spp1 (Day 1), col1, spp1 (Day 7) |
- | NA | ↑ | Cell distribution↑ | [119] |
| Sheep | Bone marrow | CaP-coated TiAl6V4 | Mesh | OM | Steady | Continuous, 0.75 ml/min | NA | Day 14 | ↑ | NA | NA | ↑ (Day7, 14) | NA | [120] | |
| HA | Granules | OM | Steady | Continuous, 0.75 ml/min | NA | Day 14 | ↑ | NA | NA | ↑ (Day4, 7) | NA | ||||
| Rat | Bone marrow | Col-glycoaminoglycan | Freeze-dried | OM | Steady | 1 ml/min for 1 hr followed by 0.05 ml/min for 7 hr |
< 0.09 Pa | Day 2 | NA | NA | NA | NA | NA | pgf, nox1↑ | [121] |
| Goat | Bone marrow | Starch-PCL | Melt-spun | OM | Steady | Continuous, 1 ml/min | NA | Day 14/21 | ↓ | NA | NA | ↑ | NA | Viability↓ ECM formation↑ | [122] |
| Human | Bone marrow | Chitosan-aldinate | Beads | CM | Steady | Continuous, 1 ml/min | NA | Day 28 | NA | NA | NA | NA | NA | COL2↑ Chondrogenesis↑ |
[123] |
| Human | Adipose | Sponceram® | Block | GM | Steady | Continuous, 1 ml/min | Mean: 0.467 mPa | Day 60 | NC | spp1, ocn | - | NA | ↑? | [124] | |
| Rat | Bone marrow | Polyamide-nHA | Sponge | OM | Steady | Continuous, 2 ml/min | NA | Day 21 | ↑ | OCN | - | ↑ | NA | [125] | |
| Human | hES (H9) | Decellularized bone | Block | OM | Steady | Continuous, 3.6 ml/min | Mean: 6 mPa | Week 5 | ↑ | OPN | - | ↑ | ↑ | in vivo bone formation↑ | [126] |
| Rat | Bone marrow | PLG | Salt-leached | OM | Steady | Continuous, 3.9 ml/min | 26.4 mPa | Day 15 | NC | opn, OPN | ocn | ↑? | NA | PGE2↑ | [127] |
| Pulsatile | 0.017 Hz, 3.1–6.1 ml/min (Mean: 3.9 ml/min) | 21–42 mPa | Day 15 | ↓? | opn, OPN | ocn | ↑? | NA | PGE2↑ | ||||||
| Pulsatile | 0.083 Hz, 3.1–6.1 ml/min (Mean: 3.9 ml/min) | 21–42 mPa | Day 15 | ↓? | opn, OPN | ocn | ↑? | NA | PGE2↑ | ||||||
| Human | Bone marrow | Pro Osteon® 200 µm pores |
Block | OM (VitD3) | Steady | Continuous, 0.1 ml/min | NA | Day 21 | ↓ |
alp, spp1 (Day 14), opn (Day 21) |
runx2, col1, ocn, bsp (Day 14, 21) |
↑(Day 7) ↓(Day 14, 21) | NA | No cell growth in dynamic culture with < 200 µm pores Rounded morphology↑ |
[129] |
| Pro Osteon® 500 µm pores |
Block | OM (VitD3) | Steady | Continuous, 0.1 ml/min | NA | Day 21 | ↓ |
spp1 (Day 14), opn, bmp2 (Day 21) |
alp, runx2, col1, ocn, bsp (Day 14, 21) |
↓(Day7–21) | NA | ||||
| Rat | Bone marrow | RGD modified PLA | Salt-leached | OM | Steady | Continuous, 0.1 and 1 ml/min | NA | Day 8/16 | ↑(Day8) ↓(Day 16) |
NA | NA | ↑ | ↑ | [130] | |
| Human | Bone marrow | Agalose | Casted | CM | Steady | Continuous, 400 µm/s | NA | Week 5 | NC | NA | NA | NA | NA | GAG↑ Col2↑ Cell distribution ↑ | [131] |
| Decellularized bone | Block | OM | Steady | Continuous, 400 µm/s | NA | Week 5 | NA | COL1, BSP | - | NA | NA | Cell distribution ↑ |
Search: ((Mesenchymal stem cells [MeSH Terms]) AND (Tissue engineering [MeSH Terms]) AND (Osteogenic OR Osteogenesis [MeSH Terms]) AND (Perfusion [MeSH Terms] OR Laminar flow) AND Bioreactors [MeSH Terms])
LTMC: Poly(L‐lactide) and Poly(L‐lactide-co-trimethylene carbonate, Col: Collagen, βTCP: Beta-tricalcium phosphate, PLA: Polylactic acid, nHA: Nano-hydroxyapatite, HA: hydroxyapatite, CaP: Calcium phosphate, PEG: Poly(ethylene glycol), PLG: Poly(lactide-co-glycolide), PLCL: Poly(l-lactide-co- ε -caprolactone), PU: Polyurethane, ECM: Extracellular matrix, HUVEC: Human umbilical vein endothelial cells, GM: Growth medium, OM: Osteogenic medium, NA: Not accessed, NC: No change