Smart coating by thermo-sensitive Pluronic F-127 for enhanced corneal healing via delivery of biological macromolecule progranulin

• Published in: International journal of biological macromolecules 2023-12, Vol.253 (Pt 8), p.127586, Article 127586
• Main Authors: Yan, Dan, Ouyang, Weijie, Lin, Jinyou, Liu, Zuguo
• Format: Article
• Language: English
• Subjects: Axon growth; Cornea; Corneal Injuries - therapy; Corneal wound healing; Humans; Hydrogels - chemistry; Hydrogels - pharmacology; Poloxamer; Progranulin (PGRN); Progranulins; Thermo-sensitive hydrogel; Wound Healing
• ISSN: 0141-8130; 1879-0003; 1879-0003
• DOI: 10.1016/j.ijbiomac.2023.127586

As a leading cause of vision impairment and blindness, corneal alkali burns lead to long-term visual deterioration or even permanent visual impairment while effective treatment strategies remain a challenge. Herein, a thermo-sensitive hydrogel with the combination of multi-functional protein progranulin (PGRN), a biological macromolecule consisting of several hundred amino acids and possessing a high molecular weight, is efficiently prepared through a convenient stirring and mixing at the low temperature. The hydrogel can be easily administrated to the ocular surface contacting with the cornea, which can be immediately transformed into gel-like state due to the thermo-responsive behavior, realizing a site-specific coating to isolate further external stimulation. The smart coating not only exhibits excellent transparency and biocompatibility, but also presents a constant delivery of PGRN, creating a nutritious and supportive micro-environment for the ocular surface. The results show that the prepared functional hydrogel can efficiently suppress inflammation, accelerate re-epithelization, and intriguingly enhance axonal regeneration via modulation of multiple signaling pathways, indicating the novel designed HydrogelPGRN is a promising therapy option for serious corneal injury. Schematic illustration of the thermo-sensitive Pluronic F-127 HydrogelPGRN formation for treating corneal alkali injury. The hydrogel could easily encapsulate therapeutic macromolecule progranulin (PGRN), and be administrated onto the ocular surface. Upon contact with the cornea, the hydrogel quickly gelatinized and coated the whole ocular surface. It exhibited great therapeutic efficacy and massively restored the structural and function of the ocular surface, which not only accelerated the re-epithelization process of the cornea, but also significantly suppressed stromal inflammation. [Display omitted]