Dual-Peptide-Functionalized Nanofibrous Scaffolds Recruit Host Endothelial Progenitor Cells for Vasculogenesis to Repair Calvarial Defects

Abstract

Vasculogenesis (de novo formation of vessels) induced by endothelial progenitor cells (EPCs) is requisite for vascularized bone regeneration. However, there exist few available options for promoting vasculogenesis within artificial bone grafts except for exogenous EPC transplantation, which suffers from the source of EPC, safety, cost, and time concerns in clinical applications. This study aimed at endogenous EPC recruitment for vascularized bone regeneration by using a bioinspired EPCinduced graft. The EPC-induced graft was created by immobilizing two bioactive peptides, WKYMVm and YIGSR, on the surface of poly(εcaprolactone) (PCL)/poliglecaprone (PGC) nanofibrous scaffolds via a polyglycolic acid (PGA)-binding peptide sequence. Remarkable immobilization efficacy of WKYMVm and YIGSR peptides and their sustained release (over 14 days) from scaffolds were observed. In vivo and in vitro studies showed robust recruitment of EPCs, which subsequently contributed to early vasculogenesis and ultimate bone regeneration. The dual-peptide-functionalized nanofibrous scaffolds proposed in this study provide a promising therapeutic strategy for vasculogenesis in bone defect repair.

Mechanic-Driven Biodegradable Polyglycolic Acid/Silk Fibroin Nanofibrous Scaffolds Containing Deferoxamine Accelerate Diabetic Wound Healing

“…PGA/SF nanofibrous scaffolds were fabricated by electrostatic spinning using the 10% ( w / v ) PGA/SF mixture solution according to our previous study with slight modifications [ 40 ]. Briefly, 0.25 g of PGA and 0.25 g SF were dissolved in 5 mL hexafluoroisopropanol (HFIP) and then the mixture was stirred for three days at room temperature.…”

“…To evaluate the mechanical properties of scaffolds, an electromechanical dynamic/static testing system (Instron E1000, High Wycombe, UK) was chosen to measure the macro-tensile with pneumatic grips as a previous study described, with slight modifications [ 40 ]. Briefly, all the scaffolds were firstly folded into a rectangular strip with a size of 2.5 cm (length) × 0.4–0.5 cm (width) × 0.03–0.04 cm (thickness) and subsequently loaded in the machine.…”

Recent advance in treatment of atherosclerosis: Key targets and plaque-positioned delivery strategies

“…A 12-mer peptide, termed as TPS (TPSLEQRTVYAK), an EPC-specific ligand, also unfolds high affinity and specific binding ability for human endothelial progenitor cells (EPCs). 352 WKYMVm (Trp-Lys-Tyr-Met-Val-D-Met), a hexapeptide, according to Li’s group, 353 possessed a fixed characteristics showing up remarkable EPC-induced recruitment for vasculogenesis guided by activating the formyl peptide receptor. Newly, HGGVRLY, hemocompatible peptide-1 (HCP-1), α4β1 integrin ligand, a recently defined stem cell homing peptide, could combine with EPCs and boost them spreading, which confirmed by Hsu et al 354 Going further, HGGVRLY also fastened a high proportion of BMSC (bone marrow stromal cells) having VCAM-1.…”

A Review Into the Insights of the Role of Endothelial Progenitor Cells on Bone Biology

“…Consistent with the work of Li et al, EPC transplantation increased neovascularization and BMP-2 gene edition in MSCs, and EPCs significantly promoted bone regeneration ( He et al, 2013 ). Moreover, grafted EPCs released VEGF to recruit host EPCs and induced angiogenesis in the bone defect, which is an important indirect effect ( Li et al, 2020 ). EPCs accelerated bone fracture healing and regeneration via the SDF-1/CXCR4 axis, an essential interaction in vascular development ( Zhang R. et al, 2019 ).…”