Nanofiber Microenvironment Effectively Restores Angiogenic Potential of Diabetic Endothelial Cells

Abstract

Objective: The effect of chronic hyperglycemic exposure on endothelial cell (EC) phenotype, impaired wound neovascularization, and healing is not completely understood. The hypotheses are: 1) chronic exposure to diabetic conditions in vivo impairs the angiogenic potential of ECs and 2) this deficiency can be improved by an extracellular microenvironment of angiogenic peptide nanofibers. Approach: Angiogenic potential of microvascular ECs isolated from diabetic (db/db) and wild type (wt) mice was assessed by quantifying migration, proliferation, apoptosis, capillary morphogenesis, and vascular endothelial growth factor (VEGF) expression for cell cultures on Matrigel (Millipore, Billerica, MA) or nanofibers under normoglycemic conditions. The in vivo effects of nanofiber treatment on wound vascularization were determined using two mouse models of diabetic wound healing. Results: Diabetic ECs showed significant impairments in migration, VEGF expression, and capillary morphogenesis. The nanofiber microenvironment restored capillary morphogenesis and VEGF expression and significantly increased proliferation and decreased cell apoptosis of diabetic cells versus wt controls. In diabetic wounds, nanofibers significantly enhanced EC infiltration, neovascularization, and VEGF protein levels, as compared to saline treatment; this effect was observed even in MMP9 knockout mice with endothelial progenitor cell (EPC) deficiency. Innovation: The results suggest a novel approach for correcting diabetes-induced endothelial deficiencies via cell interactions with a nanofiber-based provisional matrix in the absence of external angiogenic stimuli. Conclusion: Impaired endothelial angiogenic potential can be restored by angiogenic cell stimulation in the nanofiber microenvironment; this suggests that nanofiber technology for diabetic wound healing and treatment of other diabetes-induced vascular deficiencies is promising.

Angiopoietin-1 improves endothelial progenitor cell–dependent neovascularization in diabetic wounds

“…EPCs contribute to vessel growth in embryonic and damaged tissues in adults (50). One of the more potent factors that mobilize EPCs from their BM niche is VEGF (51–53).…”

Multifunctional Antimicrobial Nanofiber Dressings Containing ε-Polylysine for the Eradication of Bacterial Bioburden and Promotion of Wound Healing in Critically Colonized Wounds

“…Electrospinning is a versatile method for the production of nanofiber scaffolds for tissue engineering and regenerative medicine. − We have recently demonstrated the utility of polydopamine-crosslinked electrospun nanofibers containing vancomycin in accelerating the wound healing in a porcine model of cutaneous wound healing. , The antibiotic laden nanofiber mats had wound healing properties comparable with silver dressings but increased wound closure and wound healing rates when compared to untreated wounds and nanofiber mats without vancomycin. We present here the use of nanofiber dressings containing ε-polylysine (εPL) with a broad spectrum of antimicrobial properties, low innate resistance development by Gram-negative bacteria, and excellent biocompatibility for skin cells.…”

Adipose tissue from subjects with type 2 diabetes exhibits impaired capillary formation in response to GROα: involvement of MMPs-2 and -9

“…Altered behaviour of T2D-EC would agree with multiple in vitro studies showing that endothelial progenitor cells (EPC) from individuals with T2D generated EC with reduced proliferation, adhesion, and capacity to form tubes, thereby inhibiting their ability to re-vascularize damaged tissue [ 7 ]. Additionally, such behaviour is observed in EC isolated from db/db mice [ 39 ] and can also be generated in vitro by culture of EC under hyperglycaemic conditions [ 40 ]. Furthermore, Gealekman and colleagues have reported that the angiogenic capacity and CD of SAT is decreased with morbid obesity [ 3 ].…”