Local application of hepatocyte growth factor using gelatin hydrogels attenuates noise-induced hearing loss in guinea pigs

Abstract

Local HGF treatment significantly reduced the noise exposure-caused ABR threshold shifts and the loss of outer hair cells in the basal portion of the cochleae.

Growth factor-eluting cochlear implant electrode: impact on residual auditory function, insertional trauma, and fibrosis

“…ABR thresholds at 4, 8, and 16 kHz were recorded before, immediately after surgery, and 3, 7, 14, 21, and 28 days post-operatively (Figure 2). Pretreatment baseline ABR thresholds did not differ among the five groups and were consistent with data previously obtained in our laboratory [15]. Our surgical procedure caused average hearing loss around 61 dB, whereas noncoated, hydrogel-coated, IGF1, HGF, and IGF plus HGF electrodes shifted ABR thresholds by 70 ± 14, 57 ± 11, 52 ± 20, 62 ± 21, and 65 ± 26 dB (mean ± SD), respectively.…”

“…We found that local HGF treatment significantly reduced ABR threshold shifts and loss of outer hair cells in the basal portion of damaged cochleae due to noise exposure [15]. HGF activates ectodermal cell outgrowth in a similar pathway as IGF1 [27]; however, since HGF has different molecular weight (69 kDa for α-subunit and 34 kDa for β-subunit) compared to that of IGF1 (7.6 kDa), HGF may abundantly distribute in the basal portion of the cochlea in comparison with the distribution of IGF1.…”

“…The biodegradable hydrogels were prepared as described previously [15,20]. A previous analysis of in vitro HGFrelease profiles from hydrogels has demonstrated that a hydrogel, isoelectric point (IEP) 5.0, made with 5 wt% glutaraldehyde allows optimal HGF delivery [21].…”

“…We have developed insulin-like growth factor 1 (IGF1)-and hepatocyte growth factor (HGF)-containing hydrogels [13] and conducted a series of animal experiments, which revealed that topical growth factor application via gelatin hydrogels significantly improved hearing by protecting auditory hair cells (HCs) against damage caused by intense noise exposure [14,15], drug-induced hearing loss [16], or ischemic injury [17], with no adverse events. IGF1 inhibits apoptosis and promotes cell cycle progression to maintain HC numbers in the injured cochlea [18].…”

Dose-Dependent Sustained Release of Dexamethasone in Inner Ear Cochlear Fluids Using a Novel Local Delivery Approach

“…A number of investigators have started to explore their potential use in the middle ear, and findings to date have been encouraging Chen et al, 2006;Kitahara et al, 2008;Paulson et al, 2008;Inaoka et al, 2009]. Here, the potential of poloxamer 407 hydrogels as drug carriers for local delivery of dexamethasone to the inner ear was investigated.…”