Systematic in vitro and in vivo study on biodegradable binary Zn-0.2 at% Rare Earth alloys (Zn-RE: Sc, Y, La-Nd, Sm-Lu).

Biomedical implants and devices for tissue engineering in clinics, mainly made of polymers and stiff metallic materials, require possibly secondary surgery or life-long medicine. Biodegradable metals for biomedical implants and devices exhibit huge potential to improve the prognosis of patients. In this work, we developed a new type of biodegradable binary zinc (Zn) alloys with 16 rare earth elements (REEs) including Sc, Y, La to Nd, and Sm to Lu, respectively. The effects of REEs on the alloy microstructure, mechanical properties, corrosion behavior and in vitro and in vivo biocompatibility of Zn were systematically investigated using pure Zn as control. All Zn-RE alloys generally exhibited improved mechanical properties, and biocompatibilities compared to pure Zn, especially the tensile strength and ductility of Zn-RE alloys were dramatically enhanced. Among the Zn-RE alloys, different REEs presented enhancement effects at varied extent. Y, Ho and Lu were the three elements displaying greatest improvements in majority of alloys properties, while Eu, Gd and Dy exhibited least improvement. Furthermore, the Zn-RE alloys were comparable with other Zn alloys and also exhibited superior properties to Mg-RE alloys. The in vivo experiment using Zn-La, Zn-Ce, and Zn-Nd alloys as tibia bone implants in rabbit demonstrated the excellent tissue biocompatibility and much more obvious osseointegration than the pure Zn control group. This work presented the significant potential of the developed Zn-RE binary alloys as novel degradable metal for biomedical implants and devices.

Blending with transition metals improves bioresorbable zinc as better medical implants.

Zinc (Zn) is a new class of bioresorbable metal that has potential for cardiovascular stent material, orthopedic implants, wound closure devices, etc. However, pure Zn is not ideal for these applications due to its low mechanical strength and localized degradation behavior. Alloying is the most common/effective way to overcome this limitation. Still, the choice of alloying element is crucial to ensure the resulting alloy possesses sufficient mechanical strength, suitable degradation rate, and acceptable biocompatibility. Hereby, we proposed to blend selective transition metals (i.e., vanadium-V, chromium-Cr, and zirconium-Zr) to improve Zn's properties. These selected transition metals have similar properties to Zn and thus are beneficial for the metallurgy process and mechanical property. Furthermore, the biosafety of these elements is of less concern as they all have been used as regulatory approved medical implants or a component of an implant such as Ti6Al4V, CoCr, or Zr-based dental implants. Our study showed the first evidence that blending with transition metals V, Cr, or Zr can improve Zn's properties as bioresorbable medical implants. In addition, three in vivo implantation models were explored in rats: subcutaneous, aorta, and femoral implantations, to target the potential clinical applications of bioresorbable Zn implants.

Improved mechanical, degradation, and biological performances of Zn-Fe alloys as bioresorbable implants.

Zinc (Zn) is a promising bioresorbable implant material with more moderate degradation rate compared to magnesium (Mg) and iron (Fe). However, the low mechanical strength and localized degradation behavior of pure Zn limit its clinical applications. Alloying is one of the most effective ways to overcome these limitations. After screening the alloying element candidates regarding their potentials for improvement on the degradation and biocompatibility, we proposed Fe as the alloying element for Zn, and investigated the in vitro and in vivo performances of these alloys in both subcutaneous and femoral tissues. Results showed that the uniformly distributed secondary phase in Zn-Fe alloys significantly improved the mechanical property and facilitated uniform degradation, which thus enhanced their biocompatibility, especially the Zn-0.4Fe alloy. Moreover, these Zn-Fe alloys showed outstanding antibacterial property. Taken together, Zn-Fe alloys could be promising candidates as bioresorbable medical implants for various cardiovascular, wound closure, and orthopedic applications.

UCNPs@gelatin-ZnPc nanocomposite: synthesis, imaging and anticancer properties.

To enhance the total emission intensity, particularly the red emission of Yb,Er co-doped nanoparticles for red light activated photodynamic therapy (PDT), we doped Mn2+ ions into the NaGdF4:Yb,Er core, and subsequently coated the NaGdF4:Yb active shell to fabricate core-shell structured, up-conversion nanoparticles of NaGdF4:Yb,Er,Mn@NaGdF4:Yb (abbreviated as UCNPs). A novel and facile encapsulation method with gelatin has been proposed to transfer oleic acid (OA) stabilized UCNPs into an aqueous solution and simultaneously decorate zinc phthalocyanine (ZnPc) photosensitizer molecules. In the encapsulation process, ZnPc molecules are wrapped in the interlaced net structure of the peptide chain from gelatin, forming the UCNPs@gel-ZnPc nanocomposite. The nanoplatform has high emission intensity and excellent biocompatibility, as was expected. More importantly, the enhanced red emission of UCNPs has significant overlap with the UV absorbance of ZnPc; therefore, it can effectively activate the sensitizer to produce a large amount of singlet oxygen reactive oxygen species (ROS, 1O2) to kill cancer cells, which has evidently been verified by the in vitro results. Combined with the inherent up-conversion luminescence (UCL) imaging properties, this UCNPs@gel-ZnPc nanoplatform could have potential application in PDT and imaging fields.

A core/shell/satellite anticancer platform for 808 NIR light-driven multimodal imaging and combined chemo-/photothermal therapy.

In this contribution, a novel multifunctional anti-cancer nanoplatform has been firstly constructed by conjugating a photothermal agent (CuS nanoparticles) and a cancer cell target agent (folic acid, FA) onto the surface of mesoporous silica coated core-shell-shell up-conversion nanoparticles (UCNPs). It was found that the doxorubicin (DOX) loaded system exhibits obvious pH and NIR-responsive release behaviour and the drug can be targetedly delivered to the cancer cells by a receptor mediated endocytosis manner. Furthermore, both photothermal therapy (PTT) and chemotherapy can be triggered simultaneously by a single 808 nm near infrared (NIR) light source, thus leading to a synergistic effect. The combined chemo- and NIR photothermal therapy can significantly improve the therapeutic efficacy compared to any single therapy, which has been evidenced by both in vitro and in vivo results. Besides, due to the doped rare earth ions, the platform also exhibits good up-conversion luminescence (UCL), computed tomography (CT) and magnetic resonance imaging (MRI) properties. Based on the excellent multimodal imaging and anti-tumor properties, the multifunctional nanoplatform should be a promising candidate for imaging-guided anti-cancer therapy.