Abstract
Abstract: :
Purpose: We are developing new surfaces based on covalent attachment of death receptor ligands via heterobifunctional PEG spacer chains. Potential medical applications for these surfaces include wound dressings to modify scarring, inflammatory, or neoplastic processes. We are exploring the development of these novel surfaces with the aim of inducing apoptosis in lens epithelial cells to prevent deleterious scarring responses to intraocular lens implantation after cataract surgery. Fas-mediated apoptosis has been demonstrated in a human lens epithelial cell line. Our initial aim was to demonstrate proof of effect for the new surfaces. Methods: Prototype death surfaces were prepared from HEMA, heterobifunctional PEG chains (Sheerwater Corp. Huntsville AL), and recombinant FAS (Alexis Biochemicals, San Diego, CA). Jurkat T cells, a well recognised FAS sensitive control, were incubated at equal densities with either no surface (-ve control), the prototype death surface, or fluid phase Fas stimulating IgM (CH11). An LDH release assay was used to quantify cell death for each condition at different time points. Results: The initial prototype death surface (Hydrogel-PEG-FAS ligand) caused increased LDH release (21.3%+/-4.5) compared to untreated controls (12.4+/-2.6) but less than unbound Fas stimulating antibody (38.8+/-2.5) 12 hours after treatment. Conclusion: We have demonstrated proof of effect for death surfaces - a new class of biomaterials with a wide range of potential medical applications. Further work is required to optimise the bioactivity of these new surfaces, to explore possibilities for enhancing their molecular design and to evaluate their efficacy in preventing posterior capsular opacification.
Keywords: 323 apoptosis/cell death • 522 posterior capsular opacification (PCO)