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Qiongyu Guo, Lucas Shores, Oliver Schein, Morgana Trexler, Jennifer Elisseeff; Regulation of collagen fibrillogenesis and alignment using cyclodextrin for corneal repair. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5188.
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© ARVO (1962-2015); The Authors (2016-present)
To engineer a thick, transparent and mechanically strong collagen-based membrane through regulating collagen fibrillogenesis and alignment using cyclodextrins for corneal repair.
Type I collagen-based membranes incorporated with different cyclodextrins (CDs) were prepared following a three-stage sequence: gelation, vitrification and rehydration. Three CDs were tested and compared, i.e. α-CD, β-CD and γ-CD. First, a type I collagen solution was quickly and thoroughly mixed at 1:1 v/v ratio with 2% HEPES solution containing CD. The mixed solution was gelled at 37 °C and 5% CO2 for 2 h. Second, the collagen-CD (col-CD) gels were vitrified in a humidifier at 39 °C and relative humidity of 40% for one week. Third, these col-CD membranes were rehydrated before usage. The nanoarchitectures of col-CD membranes were examined using TEM. The specific interactions between collagen and CD were evaluated using differential scanning calorimetry (DSC). An ophthalmic drug, indomethacin, was loaded into the col-CD membrane and the release kinetics were tested using HPLC.
Type I collagen-CD membranes were developed with optimized optical and mechanical properties for corneal regeneration. CDs represent a ring of six to eight glucose molecules with an inner hydrophobic core and an outer hydrophilic ring. All three CDs, especially α-CD, exhibited strong interactions with collagen triple helices, leading to formation of mechanically strong col-CD membranes. The col-CD membranes showed significantly higher transparency than conventional collagen membranes, which can be explained by the greatly reduced the collagen fibril diameter in col-CD membranes (~20 nm) compared to conventional collagen membranes (~80 nm). Furthermore, unlike conventional collagen membrane exhibiting a random fibrillar organization, the col-CD membranes demonstrated aligned fibrils in some regions probably due to reorganization of collagen triple helices by CD. In addition, we found that the col-CD membrane could absorb the ophthalmic drug, indomethacin, from eye drops and then slowly release the drug up to five hours.
The incorporation of cyclodextrin in type I collagen membranes regulated collagen fibrillogenesis and alignment and improved optical, mechanical and drug release properties in membranes.
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