A pilot study investigating basic fibroblast growth factor for the repair of chronic tympanic membrane perforations in pediatric patients

Acharya, Aanand; Coates, Harvey; Távora-Vieira, Dayse; Rajan, Gunesh

doi:10.1016/j.ijporl.2014.12.014

Cited by 27 publications

(33 citation statements)

References 14 publications

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“…Although a majority of studies reported encouraging outcomes, this is mainly in the setting of acute or traumatic TM perforation models. For chronic TM perforation, bFGF has been used in combination with a graft material such as Gelfoam (23,38,39) or a collagen patch (6,40), thus the direct effectiveness of bFGF in chronic perforation is unclear. In addition, the most effective dosage (12,41), duration and frequency of application (42), and presence of patching materials (43) have yet to be fully investigated (44).…”

Section: Discussionmentioning

confidence: 99%

“…Although otorrhoea was reported with excessive application of a single dosage, it only prolonged the closure time and did not affect the closure rate (12). The safety of bFGF has been investigated extensively in the literature (23,38,45). In addition, Lou et al (12) reported that patching materials were not necessary for topical application of bFGF in acute TM perforation.…”

Section: Discussionmentioning

confidence: 99%

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The Effectiveness of bFGF in the Treatment of Tympanic Membrane Perforations: A Systematic Review and Meta-Analysis

Huang

Teh

Eikelboom

et al. 2020

Otology &Amp; Neurotology

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Objective: To investigate the effectiveness of basic fibroblast growth factor (bFGF) versus placebo or no intervention in the treatment of tympanic membrane (TM) perforations from randomized controlled trials (RCTs), prospective and retrospective studies. Data Sources: PubMed, EMBASE, and Cochrane databases were screened from their inceptions to June 2019. Study Selection: Inclusion criteria: 1) English language; 2) observational (retrospective or prospective) or treatment (RCT) studies; 3) reported the outcomes on the application of bFGF in adult or pediatric population. Exclusion criteria: 1) studies without a control group; 2) animal studies, in vitro studies, review studies, and case reports. Data Extraction: Number of patients, cause of TM perforation, perforation size, treatment, mean age, follow-up time, sex, closure rate, healing time, mean air-bone gap improvement. Data Synthesis: A total of 14 studies were included, including seven RCTs and seven non-RCTs with a total of 1,072 participants. The odds ratio for closure rate of bFGF treatment was 7.33 (95% confidence interval [CI], 4.65 to 11.53; p < 0.01; I 2 ¼ 44%) and the standardized mean difference (SMD) for healing time was-5.89 (95% CI:-7.85 to-3.93, p < 0.01, I 2 ¼ 98%), suggesting bFGF application has a significant effect on closure of TM perforations. However, no significant change in hearing (SMD: 0.08, 95% CI:-0.11 to 0.27, p ¼ 0.39, I 2 ¼ 0%) was seen as a result of bFGF treatment. Conclusions: Our meta-analysis has revealed that the application of bFGF can significantly enhance the closure rate as well as shorten the healing time for TM perforations. In terms of hearing, there is as yet no evidence that bFGF has a significant effect. Given its ease, availability, and safety, bFGF can be used effectively for TM repair.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Effectiveness of bFGF in the Treatment of Tympanic Membrane Perforations: A Systematic Review and Meta-Analysis

Huang

Teh

Eikelboom

et al. 2020

Otology &Amp; Neurotology

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“…(Santa Maria et al, Santa Maria et al, 2015) The other concern for growth factor treatments for the tympanic membrane is the potential to induce cholesteatoma or malignancy formation, but this is yet to be observed in any animal or human studies of tympanic membrane growth factor treatment. (Acharya et al, 2015, Hakuba et al, 2010, Hakuba et al, 2014, Hakuba et al, 2003, Kanemaru et al, 2011, Ramalho and Bento, 2006, Ma et al, 2002, Dvorak et al, 1995, Santa Maria et al, 2015) Based on all available research to date, the application of trans tympanic HB-EGF is safe to the local tissues. A phase one clinical trial will be needed to definitively answer this question.…”

Section: Discussionmentioning

confidence: 99%

No systemic exposure of transtympanic heparin-binding epidermal growth factor like growth factor

Maria

Kim

Yang

2016

Drug and Chemical Toxicology

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Context Heparin binding epidermal growth factor like growth factor (HB-EGF) is an emerging therapeutic for the regeneration of the tympanic membrane. Objective Our aim was to determine whether the doses of HB-EGF delivered in a sustained release hydrogel into a middle ear mouse model, would be measurable in the systemic circulation. We also aimed to observe, in the scenario that the intended dose was absorbed directly into the circulation, whether these levels could be measured above the background levels of HB-EGF in the circulation. Methods A total of 12 mice had trans tympanic injections of 5ug/ml of HB-EGF contained within a previously described novel hydrogel vehicle, while another 12 mice had intravenous delivery of 10ug/kg of HB-EGF. Intravenous blood samples were collected at 0, 3, 24, 168, 288 and 720 hours post injection. A double-antibody sandwich one-step process enzyme-linked immunosorbent assay (ELISA) was used to determine the level of HB-EGF in the serum. Results No mice in the trans tympanic administration group and no mice in the intravenous administration group were found to have blood level measured above that in the controls. Discussion The inability of the positive control to measure levels above background, suggest the total dose used in our studies, even if 100% absorbed into the system circulation is insignificant. Conclusions HB-EGF at the doses and delivery method proposed for treatment of chronic TM perforation in a mouse model are likely to have no measurable systemic effect.

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“…To date, the efficacy of medicinal products incorporating FGF-2 into novel tissue engineering constructs has primarily been investigated using cellular or animal models of human disease [ 15 , 16 ]. The limited clinical translation of these studies may be evidenced by the small number of recently published human clinical trials in the literature [ 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. Most of these focused on wound healing, with a majority on the repair of traumatic tympanic membrane (TM) perforations by Lou et al The effectiveness of FGF-2 for the treatment of traumatic tympanic membrane is controversial due to the high rate of spontaneous closure for acute traumatic perforations [ 31 , 32 ].…”

Section: Introductionmentioning

confidence: 99%

Fibroblast Growth Factor 2—A Review of Stabilisation Approaches for Clinical Applications

et al. 2020

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Basic fibroblast growth factor (FGF)-2 has been shown to regulate many cellular functions including cell proliferation, migration, and differentiation, as well as angiogenesis in a variety of tissues, including skin, blood vessel, muscle, adipose, tendon/ligament, cartilage, bone, tooth, and nerve. These multiple functions make FGF-2 an attractive component for wound healing and tissue engineering constructs; however, the stability of FGF-2 is widely accepted to be a major concern for the development of useful medicinal products. Many approaches have been reported in the literature for preserving the biological activity of FGF-2 in aqueous solutions. Most of these efforts were directed at sustaining FGF-2 activity for cell culture research, with a smaller number of studies seeking to develop sustained release formulations of FGF-2 for tissue engineering applications. The stabilisation approaches may be classified into the broad classes of ionic interaction modification with excipients, chemical modification, and physical adsorption and encapsulation with carrier materials. This review discusses the underlying causes of FGF-2 instability and provides an overview of the approaches reported in the literature for stabilising FGF-2 that may be relevant for clinical applications. Although efforts have been made to stabilise FGF-2 for both in vitro and in vivo applications with varying degrees of success, the lack of comprehensive published stability data for the final FGF-2 products represents a substantial gap in the current knowledge, which has to be addressed before viable products for wider tissue engineering applications can be developed to meet regulatory authorisation.

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A pilot study investigating basic fibroblast growth factor for the repair of chronic tympanic membrane perforations in pediatric patients

Cited by 27 publications

References 14 publications

The Effectiveness of bFGF in the Treatment of Tympanic Membrane Perforations: A Systematic Review and Meta-Analysis

The Effectiveness of bFGF in the Treatment of Tympanic Membrane Perforations: A Systematic Review and Meta-Analysis

No systemic exposure of transtympanic heparin-binding epidermal growth factor like growth factor

Fibroblast Growth Factor 2—A Review of Stabilisation Approaches for Clinical Applications

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