Enhancing angiogenesis alleviates hypoxia and improves engraftment of enteric cells in polycaprolactone scaffolds

Abstract

We examined whether expediting angiogenesis in porous polycaprolactone (PCL) scaffolds could reduce hypoxia and consequently improve the survival of transplanted enteric cells. To accelerate angiogenesis, we delivered vascular endothelial growth factor (VEGF) using PCL scaffolds with surface cross-linked heparin. The scaffold fabrication and characterization has been reported in our previous study. Enteric cells, isolated from intestinal tissue of neonatal mice and expanded in vitro for 10 days, exhibited high expression levels for contractile protein alpha-smooth muscle actin and desmin. The cultured enteric cells were seeded in scaffolds and were implanted subcutaneously in immunodeficient mice for 7 and 14 days. At day 7, the heparin-modified PCL scaffolds with VEGF exhibited significantly increased angiogenesis and engraftment of enteric cells, with a simultaneous reduction in hypoxia. At day 14, the blood vessels grew across the entire thickness of the scaffold and resulted in significantly diminished hypoxic environment; however, the transplanted cell density did not increase further. In conclusion, the enhancement of angiogenesis reduced cellular hypoxia and improved engraftment of enteric cells.

Endotoxin hitchhiking on polymer nanoparticles

“…Concerns focus on any adverse environmental effects from the binding material. PCL is a biocompatible polymer [17,[30][31][32][33], providing us environmental benefit with significant reduction of undesired bacterial toxicity. We expect this study to offer a better understanding of the importance of specific endotoxin binding and material research.…”

In vitro and in vivo evaluation of heparin mediated growth factor release from tissue‐engineered constructs for anterior cruciate ligament reconstruction

“…In this study, heparin was cross‐linked onto an electrospun polycaprolactone graft using carbodiimide chemistry, where the amine groups reacts with the carboxylic groups in heparin. This technique has been widely used in a number of scaffolds for other tissue engineering applications …”

“…Heparin is a naturally occurring highly sulfated glycosaminoglycan. Because of its unique structure, and consequent ability to bind, release, and protect multiple growth factors, heparin has been investigated as a drug delivery mechanism . Our group has developed a method of immobilizing heparin onto a PCL scaffold for drug delivery and showed that immobilized heparin resulted in sustained release of VEGF, which resulted in a dose‐dependent angiogenic effect when implanted subcutaneously in mice …”

Actin grips: Circular actin-rich cytoskeletal structures that mediate the wrapping of polymeric microfibers by endothelial cells

“…Hybrid constructs containing cells and fibrillar scaffolds are increasingly used as models of cellular interaction with extracellular matrix [ 1 ], or for various bioengineering applications [ 2 , 3 ]. Because of their favorable biomimetic and biomechanical properties, cell-seeded fibrillar scaffolds are considered for vascular grafting [ 4 ], as cardiovascular patches [ 5 , 6 ], or for bone reconstruction [ 7 ].…”