Graphene Oxide/Black Phosphorus Functionalized Collagen Scaffolds with Enhanced Near-Infrared Controlled In Situ Biomineralization for Promoting Infectious Bone Defect Repair through PI3K/Akt Pathway

ACS Appl Mater Interfaces. 2024 Sep 25;16(38):50369-50388. doi: 10.1021/acsami.4c10284. Epub 2024 Sep 12.

Abstract

Infectious bone defects resulting from surgery, infection, or trauma are a prevalent clinical issue. Current treatments commonly used include systemic antibiotics and autografts or allografts. Nevertheless, therapies come with various disadvantages, including multidrug-resistant bacteria, complications arising from the donor site, and immune rejection, which makes artificial implants desirable. However, artificial implants can fail due to bacterial infections and inadequate bone fusion after implantation. Thus, the development of multifunctional bone substitutes that are biocompatible, antibacterial, osteoconductive, and osteoinductive would be of great clinical importance. This study designs and prepares 2D graphene oxide (GO) and black phosphorus (BP) reinforced porous collagen (Col) scaffolds as a viable strategy for treating infectious bone defects. The fabricated Col-GO@BP scaffold exhibited an efficient photothermal antibacterial effect under near-infrared (NIR) irradiation. A further benefit of the NIR-controlled degradation of BP was to promote biomineralization by phosphorus-driven and calcium-extracted phosphorus in situ. The abundant functional groups in GO could synergistically capture the ions and enhance the in situ biomineralization. The Col-GO@BP scaffold facilitated osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSC) by leveraging its mild photothermal effect and biomineralization process, which upregulated heat shock proteins (HSPs) and activated PI3K/Akt pathways. Additionally, systematic in vivo experiments demonstrated that the Col-GO@BP scaffold obviously promotes infectious bone repair through admirable photothermal antibacterial performance and enhanced vascularization. As a result of this study, we provide new insights into the photothermal activity of GO@BP nanosheets, their degradation, and a new biological application for them.

Keywords: biomineralization; black phosphorus; graphene oxide; infectious bone repair; photothermal therapy; scaffold.

MeSH terms

  • Animals
  • Anti-Bacterial Agents* / chemistry
  • Anti-Bacterial Agents* / pharmacology
  • Biomineralization / drug effects
  • Bone Regeneration / drug effects
  • Collagen* / chemistry
  • Escherichia coli / drug effects
  • Graphite* / chemistry
  • Graphite* / pharmacology
  • Infrared Rays
  • Mesenchymal Stem Cells* / cytology
  • Mesenchymal Stem Cells* / drug effects
  • Mesenchymal Stem Cells* / metabolism
  • Osteogenesis / drug effects
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorus* / chemistry
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Staphylococcus aureus / drug effects
  • Tissue Scaffolds* / chemistry

Substances

  • Anti-Bacterial Agents
  • Collagen
  • graphene oxide
  • Graphite
  • Phosphatidylinositol 3-Kinases
  • Phosphorus
  • Proto-Oncogene Proteins c-akt