FGF2 and EGF for the Regeneration of Tympanic Membrane: A Systematic Review

Table 1

Summary of FGF2 and EGF effects on experimental perforation.

Authors	Study subject	Treatment strategy	Vehicle	Healing outcome
Fina et al. [13] (1991)	GP-acute	1 μg FGF-2 vs. PBS only+Gel	Gel	1 mm TMPs: 55% in FGF-2 vs. 10% in PBS at 3 days; 2 mm TMPs: 87.5% in FGF-2 vs. 0% in PBS at 5 days
Fina et al. [14] (1993)	GP-acute	Group 1: 1 μg FGF-2 vs. 1 μg placebo (stabilizer solvent) alone; group 2: 1 μg FGF-2 vs. 1 μg stabilizers solvent	Group 1: no; group 2: Gel	Group 1. 1 mm TMPs: 60% in FGF-2 vs. 30% in placebo group by 7 days; 2 mm TMPs: 100% in FGF-2 vs. 33% in placebo group by 14 days; Group 2. 2 mm TMPs: 100% in FGF-2 vs. 100% in placebo group by 14 days
Vrabec et al. [15] (1994)	Rats-acute	100 μg/ml FGF-2 vs. Gly	Gly	days in FGF-2 vs. days in glycerol
Kato & Jackler [16] (1996)	Chinchillas-chronic	FGF-2 vs. buffer solution	Gel	81% by 4 weeks in FGF-2 vs. 41% by 6.5 weeks in buffer solution
Friedman et al. [17] (1997)	Chinchilla-acute	FGF-2 vs. sterile saline for 2 weeks	NO	100% in FGF-2 with 8-12 days vs. 100% in control group 6-18 days
Ozkaptan et al. [18] (1997)	GP-chronic	400 ng FGF-2 vs. saline solution	No	86.7% (13/15) in FGF-2 vs. 13.3% (2/15) in saline solution at 20 days
Chauvin et al. [19] (1999)	GP-acute	1 mg HA, 0.4 μg FGF-2, 1.0 μg EGF vs. 0.1 ml Vasocidin	Vasocidin	100% (7/7) in HA and 100% (7/7) in EGF at day 21, 85.7% (6/7) in FGF-2 and 63.6% (21/33) in Vasocidin at day 32
Hakuba et al. [20] (2014)	GP-acute	FGF-2 vs. saline vs. control (FGF-2 or saline alone)	Gelatin HG	100% in FGF2-HG, 62.5% in saline-HG, and 0% in no HG after 30 days
Zhang et al. [21] (2017)	SD rats-acute	FGF 2 vs. CM vs. SH	CM-CBD	100% (16/16) in CM-CBD-FGF2, 75%(12/16) in CM, and 68.8% (11/16) in SH at day 14
Santa Maria et al. [22] (2015)	Mice-chronic	HB-EGF, FGF-2, EGF, polymer	Polymer	83.3% (15/18) in HB-EGF; 31.6% (6/19) in FGF-2; 15.8% (3/19) in EGF; 27.8% (5/18) in polymer for 4 weeks
Yao et al. (2020) [23]	SD rats-acute	ACS vs. FGF-2 vs. ACS+FGF-2 vs. SP	ACS	At one week: 71.4% vs. 42.9% vs. 100% vs. 0; at 2 weeks: 100% vs. 100% vs. 100% vs. 42.9%
Seonwoo et al. [24] (2013)	SD-chronic	EGF-CPS vs. SH	CPS	56.5% (13/23) vs. 20.8% (4/24) for 10 weeks
Güneri et al. [25](2003)	SD rats-acute	10 μl of 1% HA vs. n 10 μl of 400 g/ml EGF vs. 10 μl of 2 mg/ml Mit C vs. SH	Gel	The mean closure time was days in HA-treated, days in EGF-treated, no healing in Mit C-treated for 60 days, and days in SH.
Ramalho and Bento et al. [26] (2006)	Chinchillas-subacute	EGF vs. PF vs. EGF+PF vs. DW	Gel	30.3% in EGF, 3.6% in PF, 16.5% in EGF+PF, and 8.7% in DW for 30 days
Amoils et al. [27] (1992)	Chinchilla-chronic	25 μl EGF vs. 25 μl PBS	Gel	81% (13/16) in EGF-treated ears vs. 25% (4/16) in PBS for 8 weeks
Lee et al. [28] (1994)	Chinchilla-chronic	50 μl EGF vs. 50 μl PBS	Gel	80% (12/15) in EGF and 20% (3/15) in PBS for 5 weeks
Dvorak et al. [29] (1995)	Chinchilla-chronic	50 μl of EGF vs. PBS+Gel 3 times/week for 6 weeks	Gel	100% (17/17) with 3.4 weeks in EGF vs. 80% (12/15) with 3.3 weeks in PBS
Santa Maria et al. [30] (2017)	Mice-chronic	5 mg/mL HB-EGF vs. polymer only	Polymer	CSOM+ET: 100% (16/16) vs. 41% (7/17); CSOM: 100% (8/8) vs. 33.3% (3/9)

CPS: chitosan patch scaffold; SD: Sprague-Dawle; GP: guinea pigs; ET: Eustachian tube; SH: spontaneous healing; HA: hyaluronic acid; CM: collagen membrane; CBD: collagen-binding domain; HG: hydrogel; Gly: glycerol; Gel: Gelfoam: HB: heparin binding; PF: pentoxifylline; DW: distilled water; ACS: acellular collagen scaffold; PBS: phosphate buffered saline; FGF2: fibroblast growth factor-2; EGF: epidermal growth factor; TMP: tympanic membrane perforation.