Table 2.
Studies Using Bioreactor Systems for Tendon/Ligament Engineering
| First author | Bioreactor type (Company) | Parameters of mechanical stimulation | Scaffold material (dimensions) | Cell source | Effect | Reference |
|---|---|---|---|---|---|---|
| Altman (2002) | Custom-made step motor bioreactor with environmental chamber | Cyclic stretching 2-mm, 90o rotation, 0.0167 Hz, 21 days | Collagen type I gels, Bombyx mori silkworm silk fiber matrices (length:30 mm) | Human bone marrow stromal cells (hBMSC) | Elongation of hBMSCs, cross-section cell density↑ | 76 |
| Juncosa-Melvin (2006) | Custom-made pneumatic cylinder bioreactor with LVDT for displacement monitoring | Cyclic stretching 2.4% strain, 0.0033 Hz, 8 h/day for 2 weeks | Type I collagen sponge (23±0.8 mm×9±0.8 mm ×3±0.1 mm) | Rabbit MSCs | Maximum force↑, linear stiffness↑, maximum stress↑, linear modulus↑ | 19 |
| Webb (2006) | Custom-made step motor bioreactor | Cyclic stretching 10% strain, 0.25 Hz, 8 h/day for 7 days | Polyurethane construct (20×10×2 mm) | Human tracheal fibroblasts | Type I collagen↑, TGFβ-1↑, CTGF, Elastin↑, alpha I↑, Procollagen↑, Fibronectin↑, MMP-1↑, elastic modulus↑ | 42 |
| Androjna (2007) | Custom-made bioreactor with load- displacement measure system | Cyclic stretching 9% strain, twice daily for 30 min each period separated by 8-h rest for 2 weeks | Small-intestine submucosa (3×5×95 μm) | Dog tenocytes | Cell density↑, stiffness↑ | 35 |
| Nirmalanandhan (2008) | Custom-made pneumatic cylinder bioreactor | Cyclic stretching 2.4% and 1.2% strain, 1 Hz, stimulation period: 8 h/day, 100 and 3000 cycles/day for 12 days | Type I collagen sponge | Rabbit iliac-crest MSCs | The stimulation pattern of 2.4% strain, 3000 cycles/day, 1 Hz has the best effect on increasing stiffness. | 21 |
| Nirmalanandhan (2008) | Custom-made pneumatic cylinder bioreactor | Cyclic stretching 2.4% strain, 0.0033 Hz, 8 h/day for 12 days | Type I purified bovine collagen gel, type I collagen sponges (length: 11 and 51 mm) | Rabbit MSCs | Stiffness↑ | 20 |
| Nguyen (2009) | Custom-made linear actuator bioreactor with load cell for force measurement | Preloaded with 0.05 N, cyclic stretching 10%, 0.5 Hz, 2 h stimulation—2 h rest—2 h stimulation—18 h rest for 5 days | Porcine small intestine submucosa (length: 2 cm and width: 1 cm) | Rabbit MCL fibroblasts | Improved fiber orientation, fiber angular dispersion↓, better organized collagen fiber, elongated cell morphology, | 22 |
| Abousleiman (2009) | Custom-made linear actuator bioreactor with medium circulation system | Cyclic stretching 2% strain, 1 h/day, 0.0167 Hz for 1 and 2 weeks. | Human umbilical veins (wall thickness: 0.75 mm, outer diameter: 6.75±0.25 mm, length: 8.5 cm) | Wistar Rat bone marrow MSCs | better cell distribution, more elongated cell morphology, cell proliferation↑, ultimate stress↑, elastic modulus↑ | 23 |
| Butler 2009) | Custom-made pneumatic cylinder bioreactor with LVDT for displacement monitoring | Cyclic stretching 2.4% strain, 0.0033 Hz, 8 h/day for 2 weeks | Type I collagen sponge (94% pore volume; 62-mm mean pore diameter) | Mouse mesenchymal stem cell | Type I collagen↑, linear stiffness↑ | 83 |
| Chen(2010) | Custom-made step motor bioreactor | Cyclic stretching 10% strain, 2 h/day, 1 Hz for 14 days | Knitted silk-collagen sponge scaffold (5×0.5×0.2 cm) | Human embryonic stem cell | Collagen I↑, Collagen III↑, Epha4↑, Scx↑, Sox9↓, Myosin↑, Integrin α1↑, Integrin α2↑, Integrin β1↑, Collagen content↑, Collagen diameter↑, better cell alignment | 2 |
| Doroski (2010) | Custom-made linear motor bioreactor | Cyclic stretching 10% strain (5% offset, 5% amplitude), 1 Hz, 3 h/day, 1. 7, 14, and 21 days | Poly(ethylene glycol)-based hydrogel material oligo(poly(ethylene glycol) fumarate) (12.5×9.5×1.6 mm) | MSCs (PT-2510; Lonza) | Collagen I↑, Collagen III↑, TNC↑, Tenascin-C↑ | 27 |
| Saber (2010) | Ligagen L30-4C (Tissue Growth Technologies) | Cyclic stretching 1.25 N, 1 cycle/min, 1 h/day for 5 days | Acellular rabbit hindpaw tendon (length: 5 cm) | Rabbit tenocytes | Ultimate tensile stress↑ (closed to fleshly harvested tendon), elastic modulus↑ | 36 |
| Issa (2011) | Custom-made bioreactor | Cyclic stretching 2% strain, 1 h/day, 0.0167 Hz for 1 and 2 weeks. | Human umbilical veins (wall thickness: 0.41 mm) with Wharton's jelly matrix as central portion (total thickness: 0.75 mm) | Wistar rat bone marrow MSCs | Cell proliferation↑, tensile strength↑ | 28 |
| Woon (2011) | Ligagen L30-1C & Ligagen L30-4C (Tissue Growth Technologies) | L30-1C: dynamic loading, 10 N, 1 h/day, 0.0167 Hz for 5 days L30-4C: dynamic loading, 0.625 N 1.25 N 2.5 N, 1 h/day, 0.0167 Hz for 3, 5, and 8 days |
Acellular human flexor tendon scaffolds | Human dermal fibroblasts | Ultimate tensile stress↑, elastic modulus↑ | 31 |
LVDT, linear variable differential transformers; ↑, up regulation; ↓, down regulation.