A spatiotemporal drug release scaffold with antibiosis and bone regeneration for osteomyelitis

Abstract

Introduction: Scaffolds loaded with antibacterial agents and osteogenic drugs are considered essential tools for repairing bone defects caused by osteomyelitis. However, the simultaneous release of two drugs leads to premature osteogenesis and subsequent sequestrum formation in the pathological situation of unthorough antibiosis.

Objectives: In this study, a spatiotemporal drug-release polydopamine-functionalized mesoporous silicon nanoparticle (MSN) core/shell drug delivery system loaded with antibacterial silver (Ag) nanoparticles and osteogenic dexamethasone (Dex) was constructed and introduced into a poly-l-lactic acid (PLLA) scaffold for osteomyelitis therapy.

Methods: MSNs formed the inner core and were loaded with Dex through electrostatic adsorption (MSNs@Dex), and then polydopamine was used to seal the core through the self-assembly of dopamine as the outer shell (pMSNs@Dex). Ag nanoparticles were embedded in the polydopamine shell via an in situ growth technique. Finally, the Ag-pMSNs@Dex nanoparticles were introduced into PLLA scaffolds (Ag-pMSNs@Dex/PLLA) constructed by selective laser sintering (SLS).

Results: The Ag-pMSNs@Dex/PLLA scaffold released Ag⁺ at the 12th hour, followed by the release of Dex starting on the fifth day. The experiments verified that the scaffold had excellent antibacterial performance against Escherichia coli and Staphylococcus aureus. Moreover, the scaffold significantly enhanced the osteogenic differentiation of mouse bone marrow mesenchymal stem cells.

Conclusion: The findings suggested that this spatiotemporal drug release scaffold had promising potential for osteomyelitis therapy.

Keywords: Antibiosis; Bone regeneration; Core/shell drug delivery system; Osteomyelitis; Selective laser sintering; Spatiotemporal drug release.

Graphical abstract

Fig. 1

Schematic diagram of the overall study design. A. The synthesis of Ag-pMSNs@Dex nanoparticles. B. The construction of the Ag-pMSNs@Dex/PLLA scaffold. C. Experiments on antibacterial and osteogenic properties.

Fig. 2

Characteristics of Ag-pMSNs@Dex. A. N₂ adsorption–desorption curve of MSNs. B. FTIR of nanoparticles, C. XPS spectra of Ag-pMSNs@Dex. D. High-resolution XPS spectra of Ag3d.

Fig. 3

Characteristics of Ag-pMSNs@Dex. TEM (A), high-resolution TEM (B), SEAD (C) and inverse fast Fourier transform (D) of Ag-pMSNs@Dex.

Fig. 4

Spatiotemporal drug release of the PLLA/Ag-pMSNs@Dex scaffold. Drug release (A) and degradation (C) of the PLLA/Ag-pMSNs@Dex scaffold and the corresponding drug release rate (B) and degradation rate (D).

Fig. 5

The antibacterial properties of the scaffolds against S. aureus. A. Inhibition zone. B1&2. Bacterial turbidity and corresponding absorbance values. C1&2. SEM of normal S. aureus and debris of S. aureus. D1&2. Live/dead bacteria staining of different scaffolds. E1-4. Crystal violet staining of bacterial biofilm and corresponding absorbance values. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 6

Cell proliferation and adhesion properties of mBMSCs on different scaffolds. Live/dead cell staining (A1 - A4, C1 - C4) and cell morphologies (B1 - B4, D1 - D4) of mBMSCs on different scaffolds and the corresponding standard CCK-8 assay (E) on day 3 and day 7.

Fig. 7

Osteogenesis experiments of mBMSCs on different scaffolds. ALP staining (A1 - A4, B1 - B4) on Day 7 and Day 14 and Alizarin red staining (C1 - C4, D1 - D4) on Day 7 and Day 21 of mBMSCs on different scaffolds and the corresponding quantitative analysis (E, F). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 8

Schematic illustration of the spatiotemporal effects of antibiosis and bone regeneration scaffolds in infected bone defects. A-D. The four phases of bone regeneration. E-F. The spatiotemporal effects of antibiosis and bone regeneration.