Construction of injectable, pH sensitive, antibacterial, mineralized amino acid yolk-shell microspheres for potential minimally invasive treatment of bone infection

Abstract

IntroductionTreatment of infection within bone is difficult, and conventional surgical treatment brings intense pain to the patients physically and mentally. There is an urgent need to develop injectable nano- and/or micro-medicine for minimally invasive treatment of osteomyelitis.MethodsIn this paper, amino acid (L-lysine [Lys]) was mineralized into yolk-shell structured CaCO3 microspheres (MSs). The morphologies of the obtained MSs were investigated by scanning electron microscopy and transmission electron microscopy. The composition of CaCO3 MSs was identified by using Fourier transform infrared spectroscopy. The as-prepared CaCO3 MSs were examined with power X-ray diffraction analysis to obtain the crystallographic structure of the MSs.ResultsThe as prepared Lys encapsulated CaCO3 MSs (Lys@CaCO3 MSs) were used as micro-drug to improve acidic environment of osteomyelitis caused by bacterial infection and promote osteoblast proliferation under oxidative stress. These pH responsive Lys@CaCO3 MSs have a drug loading efficiency of 89.8 wt % and drug loading content (DLC) of 22.3 wt %.ConclusionOur results demonstrated that Lys@CaCO3 MSs can effectively kill Staphylococcus aureus and promote proliferation and differentiation of osteoblasts under stimulation of H2O2 at pH = 5.5.

Elevated lymphotoxin-α (TNFβ) is associated with intervertebral disc degeneration

“…: 10270-HNAE; Sino Biological, China) were added to the experimental group and incubated for 72 h. To evaluate the time dependence, LTα (5 μg/ml) was added to the experimental group and incubated for 24 h, 48 h, and 72 h. Equal volumes of sterile phosphate buffered saline (PBS) were added to the control group. MTT (Sigma) solution and dimethyl sulfoxide (DMSO) (Sigma) were added in turns, and the optical density (OD) values were tested as reported in previous method [ 21 ].…”

Recent Innovations in Bacterial Infection Detection and Treatment

“…The high metabolic rate and rapid proliferation of bacteria generally create an acidic environment within infected regions . Biomaterials can be designed to respond to this low pH, including disruption of biomaterials in the carrier system ,, or release of active therapeutics from a pro-drug formulation . Various pH-responsive antimicrobial biomaterials have recently been reported, including electrospun fibers, NPs, hydrogels, and microspheres .…”

Intrinsic stimuli‐responsive nanocarriers for smart drug delivery of antibacterial agents—An in‐depth review of the last two decades

“…To date, only two reports of intrinsic stimuli‐responsive nanocrystals synthesized for antibacterial use have been published. The first report was of a pH‐responsive yolk‐shell spherical CaCO 3 nanocrystal with antibacterial activity, which was reported by Z. Chen, Zhao, et al (2018). The nanocrystal was formed from the mineralization of amino acid lysine, to improve the acidic environment of bacterial infection‐caused osteomyelitis and to enhance the proliferation of osteoblasts exposed to H 2 O 2 .…”

“…Moreover, in vitro antibacterial tests confirmed the pH‐responsive antibiotic activity of the nanocarriers to S. aureus and E. coli . These lysine‐mineralized nanocrystals are a promising antibacterial option for the treatment of osteomyelitis (Z. Chen, Zhao, et al, 2018).…”

“…These lysinemineralized nanocrystals are a promising antibacterial option for the treatment of osteomyelitis (Z. Chen, Zhao, et al, 2018).…”