First Author (year) | Study type/Details | Type of Scar/Cell | Toxin Application | Results |
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). |