Preparation and application of collagen scaffold-encapsulated silver nanoparticles and bone morphogenetic protein 2 for enhancing the repair of infected bone

Abstract

The healing of contaminated/infected bone defects is a significant clinical challenge. Here, a novel collagen scaffold composite encapsulating silver nanoparticles (AgNP) and bone morphogenetic protein 2 (BMP-2) was prepared to enhance the healing of infected bone defects. Collagen scaffolds conjugated with AgNP possessed strong antibacterial properties that were dependent on the release rate of Ag(+). After introducing BMP-2, the BMP-2/AgNP/collagen scaffold composites did not adversely affect the adherence or proliferation of bone marrow-derived mesenchymal stromal cells (BMSCs). Differentiation of BMSCs toward osteoblasts was induced by the upregulation of RUNX2, osteopontin and osteonectin expression. BMP-2/AgNP/collagen scaffold composites, therefore, possess the antibacterial activity of AgNP and the osteoinductivity of BMP-2, making these composites an ideal pharmaceutical for the regeneration of bone in infected wounds.

Evaluation of Silver Ion-Releasing Scaffolds in a 3D Coculture System of MRSA and Human Adipose-Derived Stem Cells for Their Potential Use in Treatment or Prevention of Osteomyelitis

“…14 Cytotoxicity analyses of the scaffolds after 24 h showed that the scaffolds were not toxic to rat osteoprogenitor cells or human osteosarcoma cells. Although the short-term cell culture analyses in these studies, 13,14 and other similar studies 15,16 showed no cytotoxicity associated with the release of silver nanoparticles, concerns remain about the long-term effects of silver nanoparticles on host mammalian cells. 17 Some studies have shown that the very small size of nanoparticles allows them to diffuse within the cellular plasma membrane and interfere with a variety of cellular mechanisms.…”

Controlled release of drugs in electrosprayed nanoparticles for bone tissue engineering

“…Furthermore, use of PEG coating helps to maintain a sustained blood circulation of nanoparticle[117]. Sun et al used the same antibiotic vancomycin, which is resistant to Staphylococcus aureus and studied its antibacterial activity in collagen scaffolds encapsulated with silver nanoparticle and BMP-2 for infected bones in vitro[118]. Arya et al studied the synthesis of ampicillin loaded chitosan particles and found that it had targeted encapsulation efficiency of 80.4% and drug loading of 50.25% with a particle size of 520 nm.…”

“…Collagen scaffolds encapsulated with silver nanoparticles and growth factor BMP-2 was used to study the enhancement of healing process in infected bone defects. The differentiation of BMSCs into osteoblast was confirmed by Runx2 osteonectin and osteopontin protein marker expression[118]. Li et al, prepared BMP-2 loaded onto chitosan-stabilized bovine serum albumin nanoparticles (BNP) embedded to electrospun poly(ε-caprolactone)-co-poly(ethylene glycol) (PCE) copolymer scaffold loaded with DEX.…”

Advances of nanotechnology in osteochondral regeneration

“…In addition to growth factors, extracellular matrix proteins, such as collagen and osteopontin, have been introduced to nanoparticles to facilitate in situ bone regeneration (Jensen et al, ; C.‐Y. Sun, Che, & Lu, ). Although encapsulation in nanostructures can avoid acute toxicity and quick removal from the body, the drawbacks of a short lifetime in the bloodstream and unstable biological activity limit the application of growth factors and other proteins of interest in the clinic.…”