Inhibiting Postoperative Fibrosis in Glaucoma Filtration Surgery Through Porous PLLA/RGD Membrane Mediated Local/Sustained Delivery of Mitomycin C

通过多孔PLLA/RGD膜介导的丝裂霉素C局部/持续递送抑制青光眼滤过手术后的纤维化

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Abstract

PURPOSE: The purpose of this study was to investigate the characteristics of sustained drug release systems established by polylactic acid (PLLA)/RGD/mitomycin C (MMC) electrospun nanofiber membrane in vitro, and confirm its anti-scarring effect in a rabbit model of glaucoma filtration surgery (GFS). METHODS: In vitro experiments: (1) PLLA/RGD/MMC nanofiber membrane drug delivery system was prepared by electrospinning technology. (2) Characterization of nanofiber membrane. (3) Biocompatibility detection of nanofiber membrane. In vivo experiment: construct a surgical model for rabbit eye GFS, divided into four groups: the control group, the PLLA/RGD membrane group, the 0.4 mg/mL MMC group, and the PLLA/RGD/MMC membrane group. The morphology of filtering blebs and wound healing were observed on the 7th, 14th, and 28th days after the operation. At 28 days after the operation, histological and immunohistochemical staining were performed to observe the scar formation. Finally, the results were statistically analyzed. RESULTS: The composition, structure, hydrophily, thermal behaviors, degradability, and mechanical properties of the membrane were investigated in detail. In vitro cell culture assay indicated that the PLLA/RGD/MMC2 membrane could release MMC in a sustained manner for over 25 days. In vitro cell culture assay proved the superior cytocompatibility of the membrane with Human embryonic Tenon's capsule fibroblasts (HFTFs). Histology and immunohistochemistry indicated that the membrane could efficiently inhibit scaring formation after GFS and showed significant advantage over the conventional MMC cotton pad. CONCLUSIONS: The as-prepared PLLA/RGD/MMC membrane could be a potential candidate for inhibiting scaring formation after GFS in the future. TRANSLATIONAL RELEVANCE: This work shed some light to the developments and applications of MMC loaded electrospinning membrane for inhibiting postoperative fibrosis in GFS.

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