First Author (year)

Study type/Details

Type of Scar/Cell

Toxin Application


Xiao Z et al. (2009) [44]

Prospective uncontrolled trial. 6 months follow-up

Active HTS from 19 patients

Intralesional BTX-A injection of 2.5 U per cubic cm of lesion, once monthly for 3 months

All patients showed acceptable improvement and high rate of therapeutic satisfaction. Scores for erythema, itching sensation, and pliability post BTX-A injections were significantly lower than prior to BTX-A injections (p < 0.01).

Xiao Z et al. (2011) [40]

In-vitro/cell culture study

HTS derived FBs from 8 different patients

3 groups; cells treated with BTX-A in concentrations of 1 U/106 cells vs. 2.5 U/106 cells vs. control

Proliferation of FBs treated with BTX-A was slower than of FBs without BTX-A (p < 0.01). Compared with FBs without BTX-A, BTX-A at 1 U/106 cells decreased expression of CTGF by 49.2% ± 12.5% (p < 0.01), and BTX-A at 2.5 U/106 cells, decreased CTGF expression by 56.9% (p < 0.01).

Zhibo X et al. (2008) [45]

In-vitro/cell culture study

FBs cultured from HTS of 8 different patients

FBs in 1 U/106 BTX-A vs. control FBs

Significant differences in cell cycle distribution between experimental (64% in G0 - G1, 6.4% in G2-M, 29% in S phase), compared to control FBs (36% in G0 - G1; majority in proliferative phase; 21% in G2-M, 43% in S), (p < 0.01).

Jeong HS et al. (2015) [37]

In-vitro/cell culture study

HTS derived FBs vs. normal mature scar derived FBs

FBs treated with BTX-A 4 U/ml vs. control

FB proliferation in both normal mature scar and hypertrophic scar tissue decreased significantly after treatment with 4 U/ml BTX-A (p < 0.001). α-smooth muscle actin mRNA and proteins also decreased in BTX-A treated group compared to control (TGF-β1 only) of FBs derived from HTS, but not FBs derived from normal mature scars. FBs to myofibroblasts differentiation decreased in FBs of HTS after BTX-A treatment.

Xiao Z Qu G. (2012) [39]

In-vivo experiment (animal model)

HTS of 8 different rabbits ears.

Rt. ear injected with BTX-A (0.5 U per cubic cm, once a month for 3 months), Lt. ear as control

Thicknesses of HTS in BTXA group were lower than in control groups (P < 0.01). Collagen fibers were thicker and arrangement of fibers was disordered in control group than in BTXA group.

Xiao Z et al. (2010) [42]

In-vitro/cell culture study

HTS tissue obtained from 8 different patients

FBs treated with BTX-A concentration of 1 U/106 cells, 2.5 U/106 cells, and control

TGF-β1 concentration per cell in FBs without BTX-A was higher than in FBs with BTX-A (p < 0.01). Significant difference noted in TGF-β1 production per cell between FBs treated with 1 U/106 cells of BTX-A and FBs treated with 2.5 U/106 cells of BTX-A (p < 0.01).

Hao R et al. (2018) [46]

In-vitro study

Human Keloid FBs vs. Normal FBs

FBs treated with different concentrations of BTX-A (0.01, 0.1, 1 and 10 U/L)

Viability of Keloid FBs decreased with increasing BTXA dose. BTXA inhibited proliferation, and S phase of Keloid FBs. MMP-1, -2 RNA and protein showed high expression, but TGF-β1 and MMP-9 showed low expression than control.

Chen M et al. (2016) [47]

In-vitro/cell culture study

Scar contracture tissue from 10 patients

BTX-A concentrations of 1 U/106 cells, 2.5 U/106 cells, and control

FBs without BTX-A treatment had higher proliferation than groups with BTX-A; proliferation of FBs significantly inhibited by BTX-A (p < 0.05). BTX-A also inhibited protein of α-SMA and myosin II in FBs treated with BTX-A compared to FBs without BTXA (p < 0.05).

Liu DQ et al. (2017) [72]

In-vivo experiment (animal model)

HTS of 18 different rabbit ears

4 groups: 12 ears as BTX-A (0.5, 1.0, 1.5, 2.0 IU), 12 ears as triamcinolone acetonide (TAC) group, 12 ears phosphate-buffered saline (PBS), and healthy skin as control

Mean hypertrophic index of HTS with BTX-A (2.0 IU) were lower than that of control (p < 0.05).

BTX-A and the TAC group showed significantly less expression of collagen fibrils compared to PBS. BTXA (2.0 IU) and TAC significantly reduced FBs compared to control group.

Lee BJ et al. 2009 [73]

Prospective randomized experimental study

Surgical skin wounding on the dorsum of rat

10 U, 0.5 mL BTXA injected in one wound and normal saline injected into adjacent wound as control

Significant differences in wound size at 3rd and 4th week between BTXA and control (p < 0.05). Less inflammatory cells in BTXA group than control at 2nd week (p < 0.05). BTXA group showed less FBs and fibrosis than control at 4th week (p < 0.05). BTX-A group had strong collagen density than control at 8th week (p < 0.05). At 4th week, BTX-A group had lower TGF-β1 expression than control (p < 0.05).