A Collagen–Chitosan Hydrogel for Endothelial Differentiation and Angiogenesis

Abstract

Cell therapy for the treatment of cardiovascular disease has been hindered by low cell engraftment, poor survival, and inadequate phenotype and function. In this study, we added chitosan to a previously developed injectable collagen matrix, with the aim of improving its properties for cell therapy and neovascularization. Different ratios of collagen and chitosan were mixed and chemically crosslinked to produce hydrogels. Swell and degradation assays showed that chitosan improved the stability of the collagen hydrogel. In culture, endothelial cells formed significantly more vascular-like structures on collagen–chitosan than collagen-only matrix. While the differentiation of circulating progenitor cells to CD31+ cells was equal on all matrices, vascular endothelial-cadherin expression was increased on the collagen–chitosan matrix, suggesting greater maturation of the endothelial cells. In addition, the collagen–chitosan matrix supported a significantly greater number of CD133+ progenitor cells than the collagen-only matrix. In vivo, subcutaneously implanted collagen–chitosan matrices stimulated greater vascular growth and recruited more von Willebrand factor (vWF+) and CXCR4+ endothelial/angiogenic cells than the collagen-only matrix. These results indicate that the addition of chitosan can improve the physical properties of collagen matrices, and enhance their ability to support endothelial cells and angiogenesis for use in cardiovascular tissue engineering applications.

A stromal cell-derived factor-1 releasing matrix enhances the progenitor cell response and blood vessel growth in ischaemic skeletal muscle

“…The rheological properties of the collagen matrix were measured using a Brookfield R/S Plus Rheometer as previously described (Deng et al, 2010). Samples of collagen matrix or microsphere-collagen matrix (1.5 mL) were subjected to a constant shear rate of 5 s -1 for 20-30 min using a C50-2 spindle (spindle gap of 4 μm, according to the spindle specifi cations), and the temperature was maintained at 37 °C.…”

Synthesis and Characterization of Tunable Poly(Ethylene Glycol): Gelatin Methacrylate Composite Hydrogels

“…[8][9][10] This has resulted in a wide variety of hydrogels developed from both synthetic and naturally derived polymers. 6,[11][12][13] Interestingly, both cell fate and cell function can be influenced by the hydrogel microenvironment. [14][15][16] Thus, ideally the hydrogel microenvironment should mimic the mechanical and biological demands and requirements of the tissues being replicated.…”

Hydrogels With Integrin-Binding Angiopoietin-1–Derived Peptide, QHREDGS, for Treatment of Acute Myocardial Infarction

“…[4][5][6][7][8][9] Typically, collagen and chitosan, alone or in combination, are crosslinked using exogenous, sometimes toxic, chemical crosslinkers to improve the hydrogel mechanical properties. 4,10,11 However, we have previously shown that chitosan-collagen composites gel because of ionic interactions at physiological temperature and pH to form mechanically stable hydrogels that are appropriate for in vivo application.12 Furthermore, the collagen-chitosan interaction within the gels resembles the collagen-glycosaminoglycan interaction found in vivo in the extracellular matrix. 13 Thus, chitosan-collagen may mediate physiological cell-matrix interactions.…”