Introduction: Few effective treatments are currently available for mucosal injuries caused by irritant chemicals or surgical removal of cancer. The goal of this study is to develop an approach in which the injured mucosa can be coated with a polymer hydrogel layer to allow tissue regeneration. In the present study, a phospholipid polymer was designed to chemically bind with the tissue surface and to form a biocompatible polymer hydrogel encapsulating cells tc be delivered to the target area. The synthesized polymers were characterized using NMR and rheological analysis and evaluated for cytocompatibility. Materials and Methods: The polymer was synthesized using radical random copolymerization of monomer units poly(2-methacryloyloxyethyl[MPC]-co-n-butyl methacrylate[BMA]-co-p-vinylphenylboronic acid[VPBA]-co-N-hydroxysuccinimide oligo[ethylene glycol] methacrylaye[PENHS]) in two forms with (PMBVS) or without BMA (PMVS). The hydrogel was formed by reaction with polyvinyl alcohol(PVA) in neutral conditions (PBS pH 7.4). The stability of the protein-binding hydrogels in vitro was evaluated by layering the polymers with fluorescently labeled PMBV on top of epithelial cells. After 1, and 72 hours of incubation, wells were washed with PBS and each well was imaged to analyze for fluorescence intensity. The viability of corneal epithelial cells was assessed using the LIVE/DEAD assay and following the manufacturer's instructions. Migration of fluorescently labeled cells and microspheres mimicking viral particles was also quantified. Results and Discussion: The NMR analysis for PMVS and PMBVS revealed similar percentage contents of NHS (10-12%)and VPBA (17-18%) in both polymers, and the difference was made up by the amount of MPC for PMVS lacking BMA. When the polymer hydrogel stability on the epithelial surface was compared for different formulations, both the NHS-containing tissue-binding polymers were present after 1 hour of incubation and saline wash, while polymer lacking PENHS (PMBV) was absent. After 72 hours, however, only the formulation containing BMA (PMBVS) was still present on the cell surface indicating that PMVS (without BMA) degraded during this time period. Moreover, the encapsulated cells were shown to migrate out of the hydrogel successfully using PMBVS with low stiffness, indicating a loose network. Finally, examining the microparticle migration through hydrogels and subsequent cellular uptake demonstrated that both PMBVS and PMVS provided a barrier function, which was absent in PMBV. Conclusion: The results of the present study provided evidence that our novel phospholipid polymer not only exhibits tissue-binding property, but also functions well as a cell-delivery device that forms a protective layer on the epithelial tissue surface. Further study, however, is necessary to confirm the long-term safety and efficacy of the novel polymer in treatment of mucosal injuries.
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