Monocyte chemoattractant protein-1 released from polycaprolactone/chitosan hybrid membrane to promote angiogenesis in vivo

We have fabricated a hybrid membrane composed of polycaprolactone and a natural polysaccharide, chitosan. The incorporation of chitosan enabled heparinization of the material via electrostatic interaction between heparin and chitosan. More importantly, since multiple cytokines have exhibited binding affinity towards heparin, heparinization of the polycaprolactone/chitosan compound also facilitated immobilization of monocyte chemoattractant protein-1, which is a well-reported pro-angiogenic chemokine. Results demonstrated that the heparinized polycaprolactone/chitosan membrane with monocyte chemoattractant protein-1 immobilization was able to release monocyte chemoattractant protein-1 in a controlled and sustained manner. Bioactivity of the released monocyte chemoattractant protein-1 was uncompromised as shown by a chemotaxis chamber assay using isolated rat peripheral blood mononuclear cells. Enhanced local angiogenesis was subsequently observed in vivo after subcutaneous implantation of the heparinized polycaprolactone/chitosan membrane with monocyte chemoattractant protein-1-releasing property and the mechanisms underlying the angiogenic role of monocyte chemoattractant protein-1 were also investigated. We propose that the monocyte chemoattractant protein-1-induced local capillary formation is attributable to increased recruitment of macrophages, particularly the alternatively activated M-2 macrophages, which have been implicated in wound healing. Moreover, a direct effect of monocyte chemoattractant protein-1 on angiogenesis was also observed, mainly via monocyte chemoattractant protein-1-stimulated vascular endothelial growth factor expression and activity. In summary, we report here a feasible way to fabricate a polycaprolactone/chitosan hybrid material that could be functionalized with angiogenic signalling agents, such as monocyte chemoattractant protein-1. Implantation of this material promoted angiogenesis and may therefore be developed into scaffold or dressing materials in treating local ischemia injuries or cutaneous wound.