Functionalization of Silk Fibroin Electrospun Scaffolds via BMSC Affinity Peptide Grafting through Oxidative Self-Polymerization of Dopamine for Bone Regeneration

ACS Appl Mater Interfaces. 2019 Mar 6;11(9):8878-8895. doi: 10.1021/acsami.8b22123. Epub 2019 Feb 19.

Abstract

Electrospun scaffolds have been broadly studied to enhance bone regeneration because of the ability to simulate the structure and biological functions of the extracellular matrix. Polydopamine (PDA) is used to coat various surfaces at a slightly basic pH (8-8.5) and spontaneously reacts with nucleophilic functional groups. It is suitable for surface modifications of scaffolds correlated with bone formation. E7 is a newly discovered peptide with specific affinity for bone marrow mesenchymal stem cells (BMSCs). It can be useful for recruiting stem cells. Here, electrospun silk fibroin (SF) scaffolds were fabricated, and PDA was used for surface modification followed by grafting E7 (SF-PDA-E7). These composite SF-PDA-E7 electrospun scaffolds improved hydrophilicity, facilitated cell proliferation and adhesion, and boosted the osteogenic differentiation of BMSCs by creating osteoinduction conditions under the synergistic effects of PDA and E7. Moreover, the scaffolds showed high efficiency for recruiting BMSCs induced by E7 both in vitro and in vivo, which was associated with the SDF-1α/CXCR4 axis and the p38, extracellular signal-related kinase, and Akt signal transduction pathways. These functionalized electrospun scaffolds promoted regeneration of bone in the rat calvarial bone defect model. In general, this study verified that PDA could be a simple and efficient method for surface modification, and E7-grafted PDA-modified SF electrospun scaffolds were suitable for bone tissue engineering.

Keywords: E7 peptide; bone regeneration; cell recruitment; dopamine; electrospun scaffold; signal pathways; silk fibroin.

MeSH terms

  • Animals
  • Bone Diseases / pathology
  • Bone Diseases / therapy
  • Bone Marrow Cells / cytology
  • Bone Regeneration*
  • Bone and Bones / diagnostic imaging
  • Bone and Bones / pathology
  • Cell Culture Techniques / instrumentation
  • Cell Culture Techniques / methods
  • Cell Differentiation
  • Chemokine CXCL12 / metabolism
  • Fibroins / chemistry*
  • Hydrophobic and Hydrophilic Interactions
  • Indoles / chemistry*
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Mesenchymal Stem Cells / pathology
  • Osteocalcin / genetics
  • Osteocalcin / metabolism
  • Osteogenesis
  • Peptides / chemistry*
  • Peptides / metabolism
  • Polymers / chemistry*
  • Rats
  • Surface Properties
  • Tissue Engineering
  • Tissue Scaffolds / chemistry*

Substances

  • Chemokine CXCL12
  • Indoles
  • Peptides
  • Polymers
  • polydopamine
  • Osteocalcin
  • Fibroins