Water-soluble poly(ethylene glycol)-based mono- and di-saccharide block glycopolymers syntheses, biocompatibility and...

Novel approaches employing various polymer architectures and synthetic biomaterials are readily utilized for therapeutic angiogenesis. In this study, water-soluble glucose-based poly(1-O-methacryloyl-D-glucose) (PGl), maltose-based poly(1-O-methacryloyl-D-maltose) (PMa) homopolymers, and their corresponding poly(ethylene glycol) (PEG₂₀₀₀) based diblock copolymers PEG₂₀₀₀-b-PGl (PEG₂₀₀₀-PGl) and PEG₂₀₀₀-b-PMa (PEG₂₀₀₀-PMa) were prepared by deacetylation of acetylated polymers generated by the atom transfer radical polymerization (ATRP) method. The PMa and PGl homopolymers (T_d5%: 165, 160 °C) displayed higher thermal stability than the PEG₂₀₀₀-PMa and PEG₂₀₀₀-PGl diblock copolymers (T_d5%: 115, 130 °C). DSC studies indicate that the water-soluble diblock PEG₂₀₀₀-PMa and PEG₂₀₀₀-PGl show two melting and two crystallization temperatures on heating and cooling cycles, respectively. Initially, these homopolymers (PGl and PMa) and diblock copolymers (PEG₂₀₀₀-PGl and PEG₂₀₀₀-PMa) were evaluated for in vitro cell viability assay (using MTT reagent) and [methyl ³H]-thymidine incorporation experiment in HUVEC (human umbilical vein endothelial cells), which shows the proliferation of endothelial cells. CAM assay (in vivo experiment) in fertilized chicken eggs incubated with all these polymers exhibits neovascularization, suggesting the pro-angiogenic nature of these polymeric materials. This is further validated by the chick aortic arch experiment (ex vivo) that shows well-developed vascular sprouting. Considering all the above results, these synthesized glycopolymers show the pro-angiogenic nature. Ex vivo hemolysis assay using murine erythrocytes confirmed the biocompatibility of all the polymers. Furthermore, ELISA-based quantification of serum cytokines (IFN-γ and IL-6) revealed no significant alterations post-administration, indicating a non-inflammatory profile across all the polymeric formulations. Therefore, these pro-angiogenic, biocompatible polymeric compounds may be further investigated as an alternative potential treatment strategy for the treatment of different diseases (cardiovascular diseases, chronic wounds, ischemic diseases), where angiogenesis plays a critical role.