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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 element-specific 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., (© 2022 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)

Nanocomposites have been widely applied in medical device fabrication and tissue-engineering applications. In this context, the release of metal ions as well as protein adsorption capacity are hypothesized to be two key processes directing nanocomposite-cell interactions. The objective of this study is to understand the polymer-matrix effects on ion release kinetics and their relations with protein adsorption. Laser ablation in macromolecule solutions was employed for synthesizing Au and Fe nanoparticle-loaded nanocomposites based on thermoplastic polyurethane (TPU) and alginate. Confocal microscopy revealed a three-dimensional homogeneous dispersion of laser-generated nanoparticles in the polymer. The physicochemical properties revealed a pronounced dependence upon embedding of Fe and Au nanoparticles in both polymer matrices. Interestingly, the total Fe ion concentration released from alginate gels under static conditions decreased with increasing mass loadings, a phenomenon only found in the Fe-alginate system and not in the Cu/Zn-alginate and Fe-TPU control system (where the effects were proportioonal to the nanoparticle load). A detailed mechanistic examination of iron the ion release process revealed that it is probably not the redox potential of metals and diffusion of metal ions alone, but also the solubility of nano-metal oxides and affinity of metal ions for alginate that lead to the special release behaviors of iron ions from alginate gels. The amount of adsorbed bovine serum albumin (BSA) and collagen I on the surface of both the alginate and TPU composites was significantly increased in contrast to the unloaded control polymers and could be correlated with the concentration of released Fe ions and the porosity of composites, but was independent of the global surface charge. Interestingly, these effects were already highly pronounced at minute loadings with Fe nanoparticles down to 200 ppm. Moreover, the laser-generated Fe or Au nanoparticle-loaded alginate composites were shown to be a suitable bioink for 3D printing. These findings are potentially relevant for ion-sensitive bio-responses in cell differentiation, endothelisation, vascularisation, or wound healing.

Wound healing is a complex orchestration of processes involving cell proliferation, migration, differentiation, anabolism, and catabolism in order to restore skin continuity. Within these processes, elements such as metallic ions are involved due to their implications in cell behavior and enzymatic activity regulation. This study analyzed the kinetics of zinc, iron, copper and magnesium concentrations in a full thickness open wound rat model over 14 days. We made wounds with a diameter of 6 mm on the back of Lewis rats and let them heal naturally prior to analysis by histology and inductively coupled plasma mass spectrometry analysis. Histological and immunofluorescence analysis confirmed an inflammation phase until 7 days, epithelial proliferation phase from 16 h to 10 days, and remodeling phase from 7 days onward. These defined phases were correlated with the measured metal element kinetics. Zinc concentrations showed an inverted parabolic progression between 30.4 and a maximum of 39.9 μg/g dry weight. Magnesium values had a similar pattern between 283 and 499 μg/g dry weight. Copper concentrations, on the other hand, followed an inverted sigmoid trend with a decrease from 9.8 to 1.5 μg/g dry weight. Iron had a slight decrease in concentration for 24 h followed by an increase to a maximum of 466 μg/g dry weight. In conclusion, zinc, iron, and copper, even though differing in their total mass within the wound, exhibited concentration curve transitions at day 3. Interestingly, this time point correlates with the maximum proliferating keratinocyte rate during the proliferation phase.