A novel strontium‐doped calcium polyphosphate/erythromycin/poly(vinyl alcohol) composite for bone tissue engineering

Abstract

It is our goal to develop bactericidal bone scaffolds with osteointegration potential. In this study, poly(vinyl alcohol) (PVA) coating (7%) was applied to an erythromycin (EM)-impregnated strontium-doped calcium polyphosphate (SCPP) scaffold using a simple slurry dipping method. MicroCT analysis showed that PVA coating reduced the average pore size and the percentage of pore interconnectivity to some extent. Compressive strength tests confirmed that the PVA coating significantly increased material elasticity and slightly enhanced the scaffold mechanical strength. It was also confirmed that the PVA coatings allowed a sustained EM release that is controlled by diffusion through the intact PVA hydrogel layer, irrespective of the drug solubility. PVA coating did not inhibit the EM bioactivity when the scaffolds were immersed in simulated body fluid for up to 4 weeks. EM released from SCPP-EM-PVA composite scaffolds maintained its capability of bacterial growth (S. aureus) inhibition. PVA coating is biocompatible and nontoxic to MC3T3 preosteoblast cells. Furthermore, we found that SCPP-EM-PVA composite scaffolds and their eluants remarkably inhibited RANKL-induced osteoclastogenesis in a murine RAW 264.7 macrophage cell line. Thus, this unique multifunctional bioactive composite scaffold has the potential to provide controlled delivery of relevant drugs for bone tissue engineering.

Effect of erythromycin‐doped calcium polyphosphate scaffold composite in a mouse pouch infection model

“…PVA is a water-soluble polymer that can firstly swell and then partly dissolve in water solution. Our in vitro study 7 revealed that SCPP EM -PVA composite scaffolds significantly reduced the EM burst release and extended the EM release time up to 150 h. EM released from SCPP EM -PVA composites maintained its capability of bacterial growth inhibition. PVA coating also increases the mechanical strength and reduces the material fragility.…”

“…We previously showed that SCPP scaffold with PVA coating extended the impregnated erythromycin (EM) release in vitro. 7 In this animal study, we found that the pouch infection was eliminated by the host immune surveillance in the absence of SCPP scaffolds. In the presence of SCPP scaffolds, both the pouch tissues and scaffolds were infected.…”

“…In addition, a quantitative bacterial growth assay was developed to measure bacterial growth. 7 Briefly, 2 mL of sterile broth with the addition of 50 mL of saline washout (from both the pouch tissue and removed scaffolds) were cultured at 37…”

“…3,4 Sr-doped CPP (SCPP) represents a promising bone graft because of its biocompatibility, mechanical strength, and stimulation of bone healing. [5][6][7] Tian et al 5 reported that SCPP has a much more new bone formation than CPP in a rabbit foreleg radius defect model. Sr enhances angiogenesis by stimulating the proliferation of endothelial cells 8 and increasing the production of vascular endothelial growth factor (VEGF).…”

“…27,29 We found that SCPP with PVA coating extended the impregnated EM release. 7 A murine air pouch model has been developed in our laboratory for the testing of in vivo biocompatibility 30 and drug efficacy. 13,31,32 Using this model, the presence of wear particles in such pouches were found to increase the air pouch membrane thickness, and the number of macrophages in the pouches as well as the cytokine production.…”