Treatment of microbial keratitis and corneal wound healing

微生物性角膜炎的治疗和角膜伤口愈合

基本信息

批准号：
10317792
负责人：
Manav Mehta
金额：
$ 2.97万
依托单位：
GEL4MED, INC.
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2021-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10317792
关键词：
Affect Animal Model Anti-Bacterial Agents Antibiotics Antimicrobial Resistance Artificial Tears Autologous Bacteria Bacterial Eye Infections Bacterial conjunctivitis Bandage Blindness Cell Proliferation Cell-Matrix Junction Cicatrix Clinical Complex Contact Lenses Cornea Corneal Injury Corneal Neovascularization Defect Development Dyes Edema Endophthalmitis Epithelial Epithelial Cells Exhibits Extracellular Matrix Eye Eye Infections Eye Injuries Eyedrops Failure Fluorescein Formulation Gel Goals Hospitals Hydrogels Hydrophilic Contact Lenses Iatrogenesis Immune response Implant In Situ In Vitro Infection Intervention Keratitis Knowledge Lead Legal patent Licensing Life Lubrication Mammalian Cell Measures Membrane Natural regeneration Ointments Opportunistic Infections Oryctolagus cuniculus Pathogenicity Patients Peptides Perforation Phase Preparation Property Pseudomonas aeruginosa Resistance development Risk Safety Serum Shapes Site Small Business Innovation Research Grant Staphylococcus aureus Steroids Swelling Technology Testing Time TimeLine Tissues Topical Antibiotic United States Validation Vision Visit Visual impairment Work antimicrobial biomaterial compatibility cell growth corneal epithelial wound healing corneal epithelium corneal regeneration cost design dosage effective therapy epithelial wound feasibility testing hydrogel scaffold improved in vivo innovation manufacturing scale-up microbial novel pathogen pathogenic bacteria phase 2 study pressure prevent regenerative scaffold self assembly skin ulcer technological innovation tissue regeneration tissue support frame transmission process treatment strategy visual control wound wound closure wound healing wound treatment

项目摘要

The goal of this Phase I SBIR proposal is to test the feasibility of an antimicrobial tissue scaffolding hydrogel matrix in eliminating infections of the eye and promoting corneal epithelial wound regeneration. There are approximately 2.4 million eye injuries each year in the United States alone and a failure to promote re-epithelialization in corneal wounds within normal two-week time frame causes persistent corneal epithelial defects (PCED’s). Such defects lead to compromised vision or loss, ocular discomfort, infection, scarring, corneal neovascularization, opacification and perforations. Current treatment strategies for PCED’s involve aggressive lubrication with artificial tears/ointments, bandage contact lens, tarsorrhaphy, topical antibiotics, steroids and amniotic membrane grafting or autologous serum and scleral contact lenses. However, neither antibiotics nor amniotic membrane are sufficient to promote corneal re-epithelialization and wound healing in wounds associated with infections. Hence, there is an unmet clinical need to develop a product to promote corneal wound healing while preventing and eliminating infections. Therefore, we propose here a novel self-assembling tissue scaffolding matrix – G4I to (i) prevent infectious pathogens through a unique mechanism of action that is broad spectrum antibacterial, and (2) promoting tissue regeneration by providing cell attachment sites within the scaffolding matrix. Additionally, G4I can gel in situ and conforms to unique wound shapes and depths easily thereby enabling easy administration. Phase I hypothesis. The Phase I SBIR hypothesis is that G4I antimicrobial regenerative matrix can treat microbial keratitis while promoting corneal epithelial wound healing in vitro and in vivo. Phase I Specific Aims. SA1. Demonstrate safety and biocompatibility of G4I to confirm its safety by performing the Draize rabbit eye test and quantifying gel dwell time in the rabbit cornea. Criterion for acceptance: Demonstrate G4I is safe and biocompatible throughout the in-life period, as measured by a Draize score with swelling, edema, and discharge with a score less than 3. SA2. Demonstrate in vivo antimicrobial efficacy of G4I to eliminate Pseudomonas aeruginosa from infected corneal wounds. Criterion for acceptance: Demonstrate effective clearing of P. aeruginosa from wounds by at least 3 log reductions in G4I treated groups on Day 1, 3 and 7. SA3. Demonstrate in vivo efficacy of G4I to promote healing of corneal epithelial wounds. Criterion for acceptance: Improved rate of wound closure in G4I treated groups compared to controls by visual examination, photographs and a histopathological assessment on Day 14.

第一阶段 SBIR 提案的目标是测试抗菌组织支架的可行性水凝胶基质对抗眼部感染并促进角膜上皮伤口仅在美国，每年就有大约 240 万人眼部受伤且失败。在正常两周时间内促进角膜伤口的上皮化，导致持续性角膜上皮细胞缺陷（PCED）会导致视力受损或丧失、眼部不适、感染、 PCED 目前的治疗策略包括疤痕、角膜新生血管、混浊和穿孔。涉及使用人工泪液/软膏进行积极润滑、绷带隐形眼镜、睑板缝合术、局部用药然而，抗生素、类固醇和羊膜移植或自体血清和巩膜隐形眼镜。抗生素和羊膜都不足以促进角膜上皮再生和伤口因此，开发一种产品来治疗与感染相关的伤口尚未得到满足。促进角膜伤口愈合，同时预防和消除感染。因此，我们在这里提出一种新型自组装组织支架基质——G4I，以（i）防止通过独特的广谱抗菌作用机制对抗传染性病原体，以及 (2) 另外，G4I 通过在支架基质内提供细胞附着位点来促进组织再生。可以原位凝胶并符合独特的伤口形状和深度，从而轻松实现轻松管理。 I 期假设。 I 期 SBIR 假设是 G4I 抗菌再生基质可以治疗。微生物角膜炎，同时促进体外和体内角膜上皮伤口愈合。第一阶段的具体目标。 SA1。通过 Draize 兔眼演示 G4I 的安全性和生物相容性以确认其安全性测试并量化凝胶在兔角膜中的停留时间验收标准：证明 G4I 是安全且有效的。通过肿胀、水肿和分泌物的 Draize 评分来衡量，在整个生命周期内具有生物相容性分数低于3。 SA2 证明 G4I 消除铜绿假单胞菌的体内抗菌功效。接受标准：证明有效清除铜绿假单胞菌。 G4I 治疗组在第 1、3 和 7 天的伤口减少至少 3 个对数。 SA3. 证明 G4I 促进角膜上皮伤口愈合的体内功效。接受：通过目视检查，与对照组相比，G4I 治疗组的伤口闭合率有所提高，第 14 天的照片和组织病理学评估。