Adipose-Derived Stem Cells Based on Electrospun Biomimetic Scaffold Mediated Endothelial Differentiation Facilitating Regeneration and Repair of Abdominal Wall Defects via HIF-1α/VEGF Pathway

Abstract

Application of synthetic or biological meshes is the main therapy for the repair and reconstruction of abdominal wall defects, a common disease in surgery. Currently, no ideal materials are available, and there is an urgent need to find appropriate ones to satisfy clinical needs. Electrospun scaffolds have drawn attention in soft tissue reconstruction. In this study, we developed a novel method to fabricate a composite electrospun scaffold using a thermoresponsive hydrogel, poly (N-isopropylacrylamide)-block-poly (ethylene glycol), and a biodegradable polymer, polylactic acid (PLA). This scaffold provided not only a high surface area/volume ratio and a three-dimensional fibrous matrix but also high biocompatibility and sufficient mechanical strength, and could simulate the native extracellular matrix and accelerate cell adhesion and proliferation. Furthermore, rat adipose-derived stem cells (ADSCs) were seeded in the composite electrospun scaffold to enhance the defect repair and regeneration by directionally inducing ADSCs into endothelial cells. In addition, we found early vascularization in the process was regulated by the hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathway. In our study, overexpression of HIF-1α/VEGF in ADSCs using a lentivirus system promoted early vascularization in the electrospun scaffolds. Overall, we expect our composite biomimetic scaffold method will be applicable and useful in abdominal wall defect regeneration and repair in the future.

Potential of Electrospun Fibrous Scaffolds for Intestinal, Skin, and Lung Epithelial Tissue Modeling

“…[119][120][121] To address this potential cytotoxicity of PCL and PCL:cellulose derivative electrospun scaffolds, LIVE/DEAD assays based on viable and nonviable cell-selective permeability to fluorescent dyes could be performed at several timepoints during in vitro culture. [119,122] Moreover, it would be beneficial to incubate all cells with leachates from all scaffold formulations, in order to assess whether any toxic products are released from the nanofibers into the culture media. [119] Of note, only basic biocompatibility analyses were conducted, and it would be interesting to further evaluate the performance of these formulations in terms of tissue functionality (i.e., gene and protein expression, tight junction formation).…”

Abdominal wall hernia repair: from prosthetic meshes to smart materials

“…7 D). In a study by Dong et al., a novel electrospun composite scaffold was developed by culturing the rat adipose-derived stem cells (ADSCs), which can be induced into endothelial cells in vivo to enhance regeneration capacity when used in an abdominal wall defect [ 260 ]. The 3D porous structure with sufficient mechanical strength provided a high surface area and volume ratio for native tissue ingrowth while maintaining the structural integrity of the defect area.…”

Novel Material Optimization Strategies for Developing Upgraded Abdominal Meshes

“…For instance, Dong et al [ 98 ] fabricated a composite scaffold through the combination of PLA with a thermo-responsive hydrogel (i.e., poly ( N -isopropylacrylamide)-block-poly (ethylene glycol)) and seeded it with rat adipose-derived stem cells (ADSCs). The 3D matrix offered a high surface area/volume ratio, exceptional biocompatibility, adequate mechanical strength, ability to stimulate native ECM, and capacity to accelerate cell adhesion and proliferation.…”