Enhancing calvarial defects repair with PDGF-BB mimetic peptide hydrogels

J Control Release. 2024 Jun:370:277-286. doi: 10.1016/j.jconrel.2024.04.045. Epub 2024 May 1.

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.

MeSH terms

  • Animals
  • Becaplermin* / administration & dosage
  • Bone Regeneration* / drug effects
  • Cell Differentiation* / drug effects
  • Cells, Cultured
  • Hydrogels* / chemistry
  • Male
  • Mesenchymal Stem Cells* / drug effects
  • Osteogenesis* / drug effects
  • Peptides / administration & dosage
  • Peptides / chemistry
  • Peptides / pharmacology
  • Rats
  • Rats, Sprague-Dawley*
  • Skull* / drug effects
  • Skull* / injuries

Substances

  • Hydrogels
  • Becaplermin
  • Peptides