Reactive Microneedle Patches with Antibacterial and Dead Bacteria-Trapping Abilities for Skin Infection Treatment

Abstract

Bacterial skin infections are highly prevalent and pose a significant public health threat. Current strategies are primarily focused on the inhibition of bacterial activation while disregarding the excessive inflammation induced by dead bacteria remaining in the body and the effect of the acidic microenvironment during therapy. In this study, a novel dual-functional MgB₂ microparticles integrated microneedle (MgB₂ MN) patch is presented to kill bacteria and eliminate dead bacteria for skin infection management. The MgB₂ microparticles not only can produce a local alkaline microenvironment to promote the proliferation and migration of fibroblasts and keratinocytes, but also achieve >5 log bacterial inactivation. Besides, the MgB₂ microparticles effectively mitigate dead bacteria-induced inflammation through interaction with lipopolysaccharide (LPS). With the incorporation of these MgB₂ microparticles, the resultant MgB₂ MN patches effectively kill bacteria and capture dead bacteria, thereby mitigating these bacteria-induced inflammation. Therefore, the MgB₂ MN patches show good therapeutic efficacy in managing animal bacterial skin infections, including abscesses and wounds. These results indicate that reactive metal borides-integrated microneedle patches hold great promise for the treatment of clinical skin infections.

Keywords: eliminate dead bacteria; microenvironment; microneedle; reactive metal boride; skin infection.

Figure 1

Schematic illustration of MgB₂ microparticles (MPs) integrated microneedle (MgB₂ MN) patches with multiple functions to kill bacteria, eliminate dead bacteria, and regulate pH microenvironment for treating bacterial skin infection.

Figure 2

Characterization of defect‐rich MgB₂ MPs. A) SEM image of MgB₂ MPs. B) TEM image of MgB₂ MPs. C) HRTEM image of MgB₂ MPs. D) STEM and elemental mapping images of MgB₂ MPs. E) XRD pattern of MgB₂ MPs. F,G) XPS spectra of (F) Mg 2p and (G) B 1s orbitals for MgB₂ MPs.

Figure 3

Functional characterization of MgB₂ MPs. Changes of pH after MgB₂ MPs with different concentrations hydrolysis under A) pH 5.5 or B) pH 7.5 solution. Expression of C) TNF‐α and D) IL‐6 in LPS induced Raw 264.7 cells treated with MgB₂ MPs for 6 h via quantitative polymerase chain reaction (QPCR). Expression of E) TNF‐α and F) IL‐6 in HIB (HIB, heat inhibited MRSA) treated with MgB₂ MPs for 6 h via QPCR. G) FT‐IR spectra of MgB₂ MPs before and after incubation with HIB. XPS spectra of H) Mg 2p and I) B 1s orbitals for MgB₂ MPs after incubation with HIB. Data represents mean ± SD, ^**** p < 0.0001, ^*** p < 0.001, ^** p < 0.01, ^* p < 0.05, n = 3.

Figure 4

Antibacterial ability of MgB₂ MPs. A) CFU counts of E. coli treated by MgB₂ MPs. B) The inactivation efficiency of E. coli treated with MgB₂ MPs. C) CFU counts of S. aureus treated by MgB₂ MPs. D) The inactivation efficiency of S. aureus treated with MgB₂ MPs. E) CFU counts of MRSA treated by MgB₂ MPs. F) The inactivation efficiency of MRSA treated with MgB₂ MPs. SEM images of G) E. coli, H) S. aureus, and I) MRSA subjected to MgB₂ MPs for 60 min.

Figure 5

Characterization and property investigations of MgB₂ MN. A) Photograph of MgB₂ MN. B) SEM image of MgB₂ MN. C) SEM and elemental mapping images of a single needle in MgB₂ MN. D) CFU counts of bacteria treated by MgB₂ MN over time. The inactivation efficiency of E) E. coli and F) MRSA after incubated with MgB₂ MN. G) SEM and elemental mapping images of bacteria after treatment with MgB₂ MN. H) Change of pH after MgB₂ MN hydrolysis in bacterial solutions. Data represents mean ± SD, ^**** p < 0.0001, ^** p < 0.01, n = 3.

Figure 6

The dead bacteria‐trapping ability of MgB₂ MN. A) Scheme of MN (needles down) for trapping dead bacteria. B) SEM image of empty MN (control) and MgB₂ MN after incubation with dead E. coli. C) SEM image of empty MN (control) and MgB₂ MN after incubation with dead MRSA. D) Scheme of MN (needles upward) for trapping dead bacteria. E) SEM image of empty MN (control) and MgB₂ MN after incubation with dead E. coli. F) SEM image of empty MN (control) and MgB₂ MN after incubation with dead MRSA.

Figure 7

Treatment of subcutaneous abscess. A) Scheme of MgB₂ MN for treating subcutaneous abscess. B) The pH values of infected tissues on the 8th day. C) Photographs of mice with subcutaneous abscesses for different days. D) SEM images of MgB₂ MN after treating subcutaneous abscess on the 8th day. E) H&E staining photomicrographs of the infected tissues. F) The lesion areas of the infected site. G) Quantitative bacterial colonies from the infected tissues. Secretion level of H) TNF‐α, I) IL‐6, J) IL‐1β, and K) iNOS in infected tissues after 16 days of treatment. Data were based on mean ± SD (^*** p < 0.0001, ^* p < 0.01, n = 3 in G, n = 5 in F and H–K).

Figure 8

Treatment of MRSA infected wounds. A) Photographs of wounds on mice after treatment of different groups. B) Area changes of wounds treated by different groups of mice. C) H&E staining images of wound tissues. D) Photograph of CFU counts and E) quantitative bacterial CFU from wound tissues after 9 days of treatment. Secretion level of F) TNF‐α, G) IL‐6, H) IL‐1β, and I) iNOS from MRSA infected wound tissues after 9 days of treatment. Data were based on mean ± SD (^**** p < 0.0001, n = 3 in E, n = 5 in B and F–I).