Enhancing calvarial defects repair with PDGF-BB mimetic peptide hydrogels

Xia Wu; Mingming Yan; Jun Shen; Yatong Xiang; Ke Jian; Xiaoyun Pan; Dan Yuan; Junfeng Shi

doi:10.1016/j.jconrel.2024.04.045

Enhancing calvarial defects repair with PDGF-BB mimetic peptide hydrogels

J Control Release. 2024 Apr 30:370:277-286. doi: 10.1016/j.jconrel.2024.04.045. Online ahead of print.

Authors

Xia Wu¹, Mingming Yan², Jun Shen³, Yatong Xiang³, Ke Jian³, Xiaoyun Pan⁴, Dan Yuan⁵, Junfeng Shi⁶

Affiliations

¹ The Affliated XiangTan Central Hospital of Hunan University, School of Biomedical Sciences, Hunan University, Changsha, Hunan 410082, China; Shenzhen International Institute for Biomedical Research, Longhua District, Shenzhen, Guangdong 518116, China.
² Department of Orthopaedic Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410082, China.
³ The Affliated XiangTan Central Hospital of Hunan University, School of Biomedical Sciences, Hunan University, Changsha, Hunan 410082, China; Shenzhen Research Institute, Hunan University, Shenzhen, Guangdong 518000, China.
⁴ Department of Orthopedics, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China. Electronic address: xiaoyunpan@wmu.edu.cn.
⁵ The Affliated XiangTan Central Hospital of Hunan University, School of Biomedical Sciences, Hunan University, Changsha, Hunan 410082, China; Shenzhen Research Institute, Hunan University, Shenzhen, Guangdong 518000, China. Electronic address: yuandan@hnu.edu.cn.
⁶ The Affliated XiangTan Central Hospital of Hunan University, School of Biomedical Sciences, Hunan University, Changsha, Hunan 410082, China; Shenzhen Research Institute, Hunan University, Shenzhen, Guangdong 518000, China. Electronic address: Jeff-Shi@hnu.edu.cn.

PMID: 38679161
DOI: 10.1016/j.jconrel.2024.04.045

Abstract

Addressing bone defects represents a significant challenge to public health. Localized delivery of growth factor has emerged as promising approach for bone regeneration. However, the clinical application of Platelet-Derived Growth Factor (PDGF) is hindered by its high cost and short half-life. In this work, we introduce the application of PDGF-mimicking peptide (PMP1) hydrogels for calvarial defect restoration, showcasing their remarkable effectiveness. Through osteogenic differentiation assays and q-PCR analyses, we demonstrate PMP1's substantial capacity to enhance osteogenic differentiation of bone marrow mesenchymal stem cell (BMSC), leading to increased expression of crucial osteogenic genes. Further molecular mechanistic investigations reveal PMP1's activation of the PI3K-AKT-mTOR signaling pathway, a key element of its osteogenic effect. In vivo experiments utilizing a rat calvaria critical-sized defect model underscore the hydrogels' exceptional ability to accelerate new bone formation, thereby significantly advancing the restoration of calvaria defects. This research provides a promising bioactive material for bone tissue regeneration.

Keywords: Calvarial defects repair; Osteogenic differentiation; PDGF; Peptide hydrogel; Self-assembly.