Front Bioeng Biotechnol ; 2020 Nov 23



Cornea is located on the outermost layer of the eye and is easily injured. Ocular chemical burns are responsible for 11.5–22.1% of ocular injuries. Alkali burn is the most common among chemical burns and considered as ophthalmic emergencies. Amniotic membrane (AM) is the innermost layer of the placenta and protects a fetus during pregnancy. Currently, AM products were approved by the Food and Drug Administrationthat are clinically used to help the ocular surface reconstruction due to its unique biological characteristics. AM transplantation is an effective medical therapy for corneal alkali burn due to its outstanding biological performances. As a temporary covering material, AM can promote corneal epithelialization and inhibit inflammation. The biological performances of AM are due to various growth factors from amniotic epithelial cells. However, growth factors will be gradually lost and insufficient and cannot maintain the activity after AM preparation process and long-time storage. The advantage of fresh AM is the growth factors is abundant, so it has more significant effects in anti-inflammatory, inhibiting scar formation, inhibiting neovascularization, and promoting epithelial cell proliferation.

Professor Yuan Jin and his group from Sun yat-sen university ophthalmology center presented a modified AM (AMHEP) for the supplement and sustained release of growth factor by surface grafting heparin for treatment of ocular chemical burns. Heparin grafting rate and stability, microstructure, physical property, and sustained release of epithelial growth factor (EGF) of AM-HEP were characterized. Biocompatibility and ability to promote corneal epithelial cell growth and migration were evaluated and compared with a biological amnion, which is available on the market in vitro. The therapeutic effects of AM-HEP combined with EGF (AM-HEP@EGF) in vivo had been evaluated in a model of mouse corneal alkali burn. The results indicated that heparin was introduced into AM and maintain stability over 3 weeks at 37◦C. The modification process of AM-HEP did not affect microstructure and physical property after comparing with non-modified AM. EGF could be combined quickly and effectively with AM-HEP; the sustained release could last for more than 14 days. AM-HEP@EGF could significantly promote corneal epithelial cell growth and migration, compared with non-modified AM and control group. Faster corneal epithelialization was observed with the transplantation of AM-HEP@EGF in vivo, compared with the untreated control group. The corneas in the AM-HEP@EGF group have less inflammation and were more transparent than those in the control group. The results from in vitro and in vivo experiments demonstrated that AM-HEP@EGF could significantly enhance the therapeutic effects. Taken together, AM-HEP@EGF is exhibited to be a potent clinical application in corneal alkali burns through accelerating corneal epithelial wound healing.

DOI: 10.3389/fbioe.2020.599800