Review Article

The Application of Mechanical Stimulations in Tendon Tissue Engineering

Table 1

Dynamic uniaxial stretching used in tendon tissue engineering.

Cell typeParametersEffectsRef

Human BMSCs1% strain; 1 Hz; 30 min/day.Maintained the expression of SCX.[44]
Rat BMSCs2% strain; 0.5 cycles/min; 30 min/day.Increased cellularity and tensile strength; promoted ECM deposition and fiber alignment.[24]
Rat BMSCs2% strain; 0.5, 1, and 2 cycles/min; 0.5, 1, and 2 h/day.Significantly increased cellularity and tensile strength; further ECM deposition and fiber alignment.[43]
Rabbit TDSCs2% strain; 1 Hz; stretching and rest alternated.Promoted tenogenic differentiation (COL 3A1 and DCN).[37]
Rat BMSCs2.4% strain; 1 Hz; stretching for 20 s and resting for 100 s.Significantly promoted COL I expression; increased stiffness of construct.[45]
Rabbit MSCs2.4% strain; 1 Hz, 8 h/day.Significantly increased COL I expression. Increased the linear stiffness of construct.[46]
Dog BMSCs3.0% strain; 0.2 Hz; 20 min/h, 12 h/day.The elongated cell morphology; promoted cell infiltration and retained mechanical properties; promoted the tenogenic differentiation.[7, 47, 48]
Equine BMSCs, ASCs, TDSCs3% strain; 0.33 Hz; 1 h/day.Promoted cell infiltration and tenogenic differentiation; increased mechanical properties.[49]
Human ASCs4% strain; 0.5 Hz; 2 h/day.Significantly increased the tendon-related genes and proteins.[33]
Rabbit BMSCsA 5% translational strain and a 90° rotational strain; 0.1 Hz; 12 h/day.Upregulated the expression of tendon-related ECM proteins (COL I, TNC, and TNMD); promoted cell alignment.[50]
Human BMSCs5% strain; 1 Hz; 1 h/day.An upregulation in a number of key tendon genes (Col1a1, Col1a2, Col3a1, TNC, ELN, and FN).[51]
Rat TDSCs6% strain; 0.25 Hz; 8 h/day.Induced tenogenic-specific differentiation; aligned and compact F-actin network.[10]
Human fibroblasts10% strain; 0.25 Hz; 8 h/day.Significant increased cell proliferation and increased COL I, TFG-β1, and CTGF expression; increased COL I and FN deposition.[52]
Human BMSCs10% strain; 0.33 Hz.Increased COL I, COL III, and SCX expression compared to control group.[53]
Murine fibroblasts10% strain; 0.5 Hz.Better alignment of collagen fibers and proper organization of ECM.[15]
Human BMSCs10% strain; 1 Hz; 2 h/day.Enhanced expression of COL I, EphA4, and SCX; elongated cell morphology.[34, 54]
Human BMSCs10% strain; 1 Hz; 3 h of strain followed by 3 h rest.Significantly upregulated tendon related genes (COL I, COL III, and TNC).[55]
Human BMSCs10% strain and axial rotation; 1 Hz.Significantly enhanced cell infiltration, matrix synthesis (COL I and III and TNC), and ultimate tensile load of engineered tendons.[8]
Equine BMSCs3%, or 5% strain; 0.33 Hz; 1 h/day.3% strain promoted cell infiltration, tenogenic differentiation, and increased construct elastic modulus and ultimate tensile strength.[56]
Human BMSCs4, 8 or 12% strain; 0.5 or 1 Hz.The highest proliferation rate at 1 Hz and at 4% strain. The highest tenogenic expression at 8% and 12% strain.[27]
Human BMSCs4, 8 or 12% strain; 1 Hz.Higher tenogenic gene expressions at 8% (highest) and 12% strain (COL I, COL III, FN, and N-cadherin).[28]
Rabbit TDSCsIn vitro: 4% strain; 0.5 Hz; 2 h/day.
In vivo: implanted into the mouse back.
In vitro: promoted tendon-specific genes and protein expression.
In vivo: more parallelly arranged matrixes (COL I, COL III, and TNC); the mature engineered tendon.
Both: increased cell proliferation, elongated cell morphology, and mechanical properties.
[6]
Human ESC-MSCsIn vitro: 10% strain; 1 Hz; 2 h/day.
In vivo: implanted into the mouse back.
In vitro: unregulated the expression of tendon-related genes (SCX, COL I, COL III, and Epha4).
In vivo: elongated morphology of cells; promote more parallel alignment.
[57]
[58]
Rat BMSCsIn vitro: 15% strain; 1 Hz.
In vivo: implanted into the hind limbs of mice.
In vitro: increased cell viability and the expression of SCX and TNC; COL1a1 and TNC expression did not significantly change; increased pore size.
In vivo: better mechanical properties and cell alignment (after prestretching in vitro).
[35]