Cefazolin/BMP-2-Loaded Mesoporous Silica Nanoparticles for the Repair of Open Fractures with Bone Defects

Abstract

The study aimed to explore the feasibility of a nanodrug delivery system to treat open fractures with bone defects. We developed a cefazolin (Cef)/bone morphogenetic protein 2 (BMP-2)@mesoporous silica nanoparticle (MSN) delivery system; meanwhile, Cef/MBP-2@ poly(lactic-co-glycolic acid) (PLGA) was also developed as control. For the purpose of determining the osteogenic and anti-inflammatory actions of the nanodelivery system, we cultured bone marrow mesenchymal stem cells (BMSCs) and constructed a bone defect mouse model to evaluate its clinical efficacy. After physicochemical property testing, we determined that MSN had good stability and did not easily accumulate or precipitate and it could effectively prolong the Cef’s half-life by nearly eight times. In BMSCs, we found that compared with the PLGA delivery system, MSNs better penetrated into the bone tissue, thus effectively increasing BMSCs’ proliferation and migration ability to facilitate bone defect repair. Furthermore, the MSN delivery system could improve BMSCs’ mineralization indexes (alkaline phosphatase [ALP], osteocalcin [OCN], and collagen I [Col I]) to effectively improve its osteogenic ability. Moreover, the MSN delivery system could inhibit inflammation in bone defect mice, which was mainly reflected in its ability to reduce the release of IL-1β and IL-4 and increase IL-10 levels; it could also effectively reduce apoptosis of CD4+ and CD8+ T cells, thus improving their immune function. Furthermore, the percentage of new bones, bone mineral density, trabecular volume, and trabecular numbers in the fracture region were improved in mice treated with MSN, which allowed better repair of bone defects. Hence, Cef/BMP-2@MSN may be feasible for open fractures with bone defects.

Nanoparticle-Based Drug Delivery Systems for Enhancing Bone Regeneration

“…Based on the above advantages, MSN are often functionalized to form a multifunctional drug delivery system. Shen et al 69 developed an MSN-based dual drug delivery system that can simultaneously deliver cefazolin (Cef) and bone morphogenic protein-2 (BMP-2). Compared with a Poly-(D,L-lactide-co-glycolide) (PLGA) delivery system, the MSN group showed better permeability to the bone tissue and higher levels of bone marrow-derived MSC (BMSC) proliferation and migration ability, which is beneficial for accelerating bone repair.…”

“…Significant differences between groups are indicated as * P < 0.05, ** P < 0.01, *** P < 0.001. Reproduced with permission from ref . Copyright 2022 Hindawi.…”

Recent advances of nanoparticles on bone tissue engineering and bone cells

“…Yi et al 72 found that mesoporous silica nanoparticles-chitosan-loaded BMP-2 could effectively promote the repair of bone defects in chronic osteomyelitis and promote the osteogenic differentiation of BMSCs. Shen et al 73 found that Cefazolin/BMP-2 loaded mesoporous silica nanoparticles significantly promoted the repair of open fractures and reduced inflammation with bone defects in mice, and increased the osteogenic differentiation ability of BMSCs in vitro . Qiu et al 74 prepared silk fibroin/chitosan scaffolds containing mesoporous hydroxyapatite nanoparticles (mHANPs) of BMP-2 (SCH-L).…”

The Delivery and Activation of Growth Factors Using Nanomaterials for Bone Repair

“…Dentin matrix extract protein (DMEP) was identified as a complex GF mixture, and MSNs loaded with DMEP were demonstrated to promote cartilage regeneration in vitro and in vivo [ 97 ]. To mitigate the risk of infection in defective bone tissue, a study showed that co-loading the antibiotic cefazolin with BMP-2 into MSNs significantly increased new bone formation and reduced the release of inflammatory factors IL-1 and IL-4 in a mouse fracture model [ 98 ]. The flexible surface of MSNs also provides alternative loading methods for growth factors.…”