Application of Mesoporous Silica Nanoparticle-Chitosan-Loaded BMP-2 in the Repair of Bone Defect in Chronic Osteomyelitis

Abstract

In order to test the effectiveness of nanoparticle- (NP-) loaded bone morphogenetic protein 2 (BMP-2) in chronic osteomyelitis (CO) complicated with bone defect, a new nanodrug delivery system composed of mesoporous silica NP (MSN) and chitosan were used to load BMP-2 and transfer it to the target region. Bone marrow mesenchymal stem cells (BMSCs) were purchased and cultivated to detect the osteogenesis of chitosan-MSN (Chi-MSN) and polylactic acid glycolic acid (PLGA) delivery system. In addition, the osteogenesis of Chi-MSN was further determined by constructing a bone defect mouse model. In physicochemical property test, we found Chi-MSN NPs could effectively maintain stability in vivo and had pH response characteristics. As a result, the release efficiency of dexamethasone (Dex) and BMP-2 in the environment with pH 7.4 was less, while it increased significantly in pH 6, so as to reduce the BMP-2 and Dex loss during transportation in vivo. Otherwise, we found that the permeation efficiency of Chi-MSN was significantly higher than that of PLGA delivery system, so as to effectively transport BMP-2 and Dex to action target. In the BMSC test, we found that Chi-MSN could better promote their activity and osteogenesis, and the expression of osteogenesis-related genes (runt-related transcription factor 2 (RUNX-2), osteopontine (OPN), alkaline phosphatase (ALP), and osteopontine (OCN)) in the Chi-MSN group was higher. In the bone defect mouse model test, we also found obviously increased bone trabecula number and thickness by Chi-MSN, contributing to better repair of bone defects. Therefore, BMP-2@Chi-MSN may be a better choice for the therapy of CO complicated with bone defect in the future.

Nanoparticle-Based Drug Delivery Systems for Enhancing Bone Regeneration

“…148−150 Delivery systems equipped with proteins are instead prepared using mild methods such as low-temperature freeze-drying or coprecipitation, although these traditional methods may result in uneven coating thickness. 151 The adhesion of the coating depends on the chemical bond between the scaffold and NPs, surface free energy, cleanliness, roughness, and other factors. Therefore, chemical modification of the scaffold surface is often achieved through the use of acids or oxidants, which can increase surface polarity and thus improve the adhesive strength of the coating.…”

“…However, the physical and chemical properties of therapeutic factors inside the carrier must be fully considered, as some coating preparation conditions can easily lead to their deactivation, especially for protein drugs such as growth factors. Therefore, the electrostatic layer-by-layer self-assembly method using strong acid or strong alkali treatment and the vapor deposition method using high-temperature treatment are not considered suitable for a delivery system of protein molecules. − Delivery systems equipped with proteins are instead prepared using mild methods such as low-temperature freeze-drying or coprecipitation, although these traditional methods may result in uneven coating thickness …”

Advances of Antimicrobial Peptide‐Based Biomaterials for the Treatment of Bacterial Infections

“…[70] For example, the delivery of mesoporous silica nanoparticles (MSN) significantly improves the stability of BMP-2 and reduces its loss during in vivo transport. [71] Similarly, Atefyekta et al synthesized mesoporous titanium dioxide films with different pore sizes (4, 6, and 7 nm) and loaded them with three different antibiotics (vancomycin, gentamicin, and daptomycin), which could be successfully loaded and released from the surface. The results of counting bacterial colony-forming units showed reduced in bacterial adhesion to the loaded films.…”

Current research progress of local drug delivery systems based on biodegradable polymers in treating chronic osteomyelitis

“…The release and delivery of bone morphogenetic protein 2 (BMP-2) are critical for improving the clinical efficacy of bone healing and repair. To transfer BMP-2 to the target area, Yi et al (2022) constructed a novel nano-delivery system (Chi-MSN) composed of mesoporous silica nanoparticles (MSN) and chitosan. The study reported that the Chi-MSN system could effectively reduce drug loss and deliver BMP-2 to the lesion site due to its stable and pH-responsive properties.…”

“…FIGURE 4Mesoporous Silica Nanoparticle-Chitosan-Loaded BMP-2 in the Repair of Bone Defect in Chronic Osteomyelitis. Reproduced with permission fromYi et al (2022). Copyright © 2022 The Authors.…”