Osteoinductivity and Antibacterial Properties of Strontium Ranelate-Loaded Poly(Lactic-co-Glycolic Acid) Microspheres With Assembled Silver and Hydroxyapatite Nanoparticles

负载雷奈酸锶的聚乳酸-羟基磷灰石微球组装银纳米颗粒和羟基磷灰石纳米颗粒的骨诱导性和抗菌性能

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Abstract

Bone-related infection rates are 4-64% in long open bone fractures and nearly 1% in joint-related surgeries. Treating bone infections and infection-related bone loss is very important. The present study prepared strontium ranelate (SR)-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres (PM) with assembled silver nanoparticles (AgNPs) and hydroxyapatite nanoparticles (HANPs) (SR-PM-Ag-HA) through a novel solid-in-oil nanosuspension (S/O/N) method to achieve osteoinductivity and antibacterial properties. We evaluated the microstructure, drug release, biocompatibility, osteoinductivity, and antibacterial activity in vitro. The microspheres showed a stable shape and size. The cumulative drug release reached a maximum of ∼90% after 22 days. All groups loaded with SR enhanced MC3T3-E1 cell proliferation to a greater degree than pure PM. The osteoinductivity behavior was investigated by ALP staining and real-time PCR of osteogenic differentiation marker genes. The antibacterial activity was evaluated using antibacterial ability and biofilm formation assays. SR-PM-Ag-HA greatly enhanced osteogenic differentiation and showed excellent antibacterial properties. These results indicated that SR-PM-Ag-HA could be biocompatible and suitable for drug delivery, osteoinduction, and antibiosis, and therefore, have potential applications in the treatment of bone-related infections and promotion of bone formation at infected sites.

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