Bioactive glass (BG) is a frequently used biomaterial applicable in bone tissue engineering and known to be particularly effective when applied in nanoscopic dimensions. In this work, we employed the scalable reactive laser fragmentation in liquids method to produce nanosized 45S5 BG in the presence of light-absorbing Fe and Cu ions. Here, the function of the ions was twofold: (i) increasing the light absorption and thus causing a significant increase in laser fragmentation efficiency by a factor of 100 and (ii) doping the BG with bioactive metal ions up to 4 wt%. Our findings reveal an effective downsizing of the BG from micrometer-sized educts into nanoparticles having average diameters of <50 nm. This goes along with successful elementspecific incorporation of the metal ions into the BG, inducing co-doping of Fe and Cu ions as verified by energy-dispersive X-ray spectroscopy (EDX). In this context, the overall amorphous structure is retained, as evidenced by X-ray powder diffraction (XRD). We further demonstrate that the level of doping for both elements can be adjusted by changing the BG/ion concentration ratio during laser fragmentation.Consecutive ion release experiments using inductively-coupled plasma mass spectrometry (ICP-MS) were conducted to assess the potential bioactivity of the doped nanoscopic BG samples, and cell culture experiments using MG-63 osteoblast-like cells demonstrated their cytocompatibility. The elegant method of in situ co-doping of Fe and Cu ions during BG nanosizing may provide functionality-advanced biomaterials for future studies on angiogenesis or bone regeneration, particularly as the level of doping may be adjusted by ion concentrations and ion type in solution.bioactive ion doped bioglass, biocompatibility, biomaterials, bone tissue, engineering, laser doping
| INTRODUCTION45S5 bioactive glass (BG) initially synthesized by Hench et al, 1 has advantages of controllable biodegradability, osteoconductivity and bioactivity. [2][3][4] BG can bind to bone tissue and stimulate bone regeneration by releasing Si 4+ , Ca 2+ , and PO 4 3À ions, 5 making it a successful bone graft. 6 To further enhance the dissolution, bioactivity, and protein-related bone therapeutics of BG, nanosized BG particle variants significantly increased in vitro