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.

Wenpei Dong,Yan Gu,Suihong Liu,Jianjun Yang,Dongchao Yang,Qinxi Hu,Haiguang Zhang,Zhipeng Shen,Ping Yu,Zhicheng Song

doi:10.3389/fbioe.2021.676409

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.

Highlights

The abdominal wall has a significant protective effect on abdominal organs
For the study, adipose-derived stem cells (ADSCs) isolated from the adipose tissues of male SD rats were cultured and passaged to the third generation and identified by testing the cell phenotype and differentiation potential (Supplementary Figure 1)
We found the stiffness of the biomimetic scaffold increased when ascending the weight ratio of polylactic acid (PLA), reaching a maximum value of 4.248 ± 0.624 N/mm in PLA scaffold (Figure 1A) in the mechanical testing

Summary

Introduction

The abdominal wall has a significant protective effect on abdominal organs. Etiologic factors, including abdominal trauma, lead to abdominal wall defects. Electrospun scaffolds have comparatively weak mechanical characteristics of low strength and stiffness, which limit their application in the repair of abdominal wall defects for which a relatively high mechanical strength is needed (Khorshidi et al, 2016). To overcome this disadvantage, polylactic acid (PLA), a biodegradable polymer of lactic acid, has been reported to be applied in tissue engineering scaffolds for providing sufficient mechanical and tensile strength (Dinh Nguyen et al, 2018; Singhvi et al, 2019)

Methods

Results

Discussion

Conclusion