A novel approach in biomedical engineering: The use of polyvinyl alcohol hydrogel encapsulating human umbilical cord mesenchymal stem cell-derived exosomes for enhanced osteogenic differentiation and angiogenesis in bone regeneration

Longlong He; Hengwei Zhang; Ningbo Zhao; Lifan Liao

doi:10.1016/j.ijbiomac.2024.132116

A novel approach in biomedical engineering: The use of polyvinyl alcohol hydrogel encapsulating human umbilical cord mesenchymal stem cell-derived exosomes for enhanced osteogenic differentiation and angiogenesis in bone regeneration

Int J Biol Macromol. 2024 May 7;270(Pt 2):132116. doi: 10.1016/j.ijbiomac.2024.132116. Online ahead of print.

Authors

Longlong He¹, Hengwei Zhang², Ningbo Zhao¹, Lifan Liao³

Affiliations

¹ Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an 710004, PR China; Department of Implant Dentistry, College of Stomatology, Xi'an Jiaotong University, Xi'an 710004, PR China.
² Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an 710004, PR China.
³ Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an 710004, PR China; Department of Implant Dentistry, College of Stomatology, Xi'an Jiaotong University, Xi'an 710004, PR China. Electronic address: liaolifan2016@xjtu.edu.cn.

PMID: 38723803
DOI: 10.1016/j.ijbiomac.2024.132116

Abstract

Developing effective methods for alveolar bone defect regeneration is a significant challenge in orthopedics. Exosomes from human umbilical cord mesenchymal stem cells (HUMSC-Exos) have shown potential in bone repair but face limitations due to undefined application methods and mechanisms. To address this, HUMSC-Exos were encapsulated in polyvinyl alcohol (PVA) hydrogel (Exo@PVA) to create a novel material for alveolar bone repair. This combination enhanced the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs) more effectively than Exos alone. Additionally, Exo@PVA significantly improved alveolar bone regeneration and defect repair in rats. The microRNA-21-5p (miR-21-5p) in Exo@PVA, identified through the GEO database and analyzed via in silico methods, played a crucial role. miR-21-5p promoted BMSC osteogenic differentiation by inhibiting WWP1-mediated KLF5 ubiquitination and enhanced HUVEC angiogenesis by targeting ATP2B4. These findings underscore the potential of an Exo-based approach with PVA hydrogel scaffolds for bone defect repair, operating through the miR-21-5p/WWP1/ATP2B4 signaling axis.

Keywords: ATP2B4; Alveolar bone defect; Exosomes; Human umbilical cord mesenchymal stem cells; KLF5 ubiquitination; Polyvinyl alcohol hydrogel; WWP1; miR-21-5p.