Enhanced Neovascular Formation in a Novel Hydrogel Matrix Consisting of Citric Acid and Collagen

Abstract

Background: Three-dimensional regenerative tissue with large bulk generally requires blood perfusion through a vascular network to maintain its viability, and one promising approach is induction of neovascular growth from the recipient bed into the tissue. To induce ingrowth of a vascular network, it is necessary to furnish the regenerative tissue with a scaffold structure for neovasculature and a delivery system for an angiogenic growth factor. As such a scaffold structure, the present study created novel hydrogel materials by chemically cross-linking alkali-treated collagen (AlCol) with trisuccinimidyl citrate (TSC).
Materials and Methods: Many prototypes, consisting of several concentrations of TSC and AlCol, were implanted into the subfascial space of the rat rectus muscle, and 7 days later, the implanted materials were excised for histological analysis. Cross-sections were stained and neovascular development in the materials was evaluated by measuring vessel density, length and number of joints and branches.
Results: Significant ingrowth of vascularized granulation was observed in some materials, which surpassed the angiogenic ability of Matrigel^TM. Further, combination with basic fibroblast growth factor (bFGF) significantly increased the vascular formation in these gels.
Conclusions: The TSC-AlCol gel functioned as a favorable scaffold for neovascular formation and also as a reservoir for controlled delivery of bFGF.