Temporal Immunomodulation via Wireless Programmed Electric Cues Achieves Optimized Diabetic Bone Regeneration.

Mimicking the temporal pattern of biological behaviors during the natural repair process is a promising strategy for biomaterial-mediated tissue regeneration. However, precise regulation of dynamic cell behaviors allocated in a microenvironment post-implantation remains challenging until now. Here, remote tuning of electric cues is accomplished by wireless ultrasound stimulation (US) on an electroactive membrane for bone regeneration under a diabetic background. Programmable electric cues mediated by US from the piezoelectric membrane achieve the temporal regulation of macrophage polarization, satisfying the pattern of immunoregulation during the natural healing process and effectively promoting diabetic bone repair. Mechanistic insight reveals that the controllable decrease in AKT2 expression and phosphorylation could explain US-mediated macrophage polarization. This study exhibits a strategy aimed at precisely biosimulating the temporal regenerative pattern by controllable and programmable electric output for optimized diabetic tissue regeneration and provides basic insights into bionic design-based precision medicine achieved by intelligent and external field-responsive biomaterials.

Corrosion fatigue behavior and anti-fatigue mechanisms of an additively manufactured biodegradable zinc-magnesium gyroid scaffold.

Additively manufactured biodegradable zinc (Zn) alloy scaffolds constitute an important branch in orthopedic implants because of their moderate degradation behavior and bone-mimicking mechanical properties. This work investigated the corrosion fatigue response of a zinc-magnesium (Zn-Mg) alloy gyroid scaffold fabricated via laser-powder-bed-fusion additive manufacturing at the first time. The high-cycle compression-compression fatigue testing of the printed Zn-Mg scaffold was conducted in simulated body fluid, showing its favorable fatigue strength, structural reliability, and anti-fatigue capability. The printed Zn-Mg scaffold obtained a 227% higher fatigue strength than that of the printed Zn scaffold but 17% lower strain accumulation at 106 cycles. The accumulative strain of the Zn-Mg scaffold at its fatigue strength was dominant by fatigue ratcheting, since the fatigue damage strain of the scaffold was approximately zero. The corrosion products (ZnO and Zn(OH)2) were conducive to the inhibition of fatigue ratcheting and fatigue damage. Dislocation pile-up and solid solution phases at the grain boundaries of the Zn-Mg scaffold could retard the spreading of the crack tip and impede excessive grain coarsening, improving its fatigue endurance limit. Notably, the printed Zn-Mg scaffold could dissipate the fatigue energy through moderate grain boundary migration, thus reducing its plastic deformation. These findings illuminated the anti-fatigue mechanisms related to microstructural features and corrosive environments and highlighted the promising prospects of additively manufactured Zn-Mg scaffolds in orthopedic applications. STATEMENT OF SIGNIFICANCE: Additive manufacturing (AM) of biodegradable metals shows unprecedented prospects for bone tissue regeneration medicine. The corrosion fatigue property is one of the key determinants in the performance of AM biodegradable scaffolds. In this study, a Zn-Mg gyroid scaffold was additively manufactured with admirable fatigue endurance limit and anti-fatigue capability. We reported that the corrosion fatigue performance was highly relevant to the microstructural features, validating that the grain boundary engineering strategy improved fatigue strength and inhibited crack penetration. Notably, moderate grain boundary migration could dissipate fatigue energy and reduce plastic deformation. Furthermore, corrosion products were conducive to impeding fatigue ratcheting and fatigue damage, indicating the promising potential of AM Zn-Mg scaffolds in treating load-bearing bone defects.

Electrophoretic deposition of novel semi-permeable coatings on 3D-printed Ti-Nb alloy meshes for guided alveolar bone regeneration.

OBJECTIVE: Guided bone regeneration (GBR) techniques use barrier membranes to augment the alveolar ridge for the site-specific growth of bone defects. However, current approaches using cast metal substructures exhibit poor adaptation to the surgical site and increased risk of infection. This study aimed to fabricate multi-functional coatings with 3D-printed porous titanium-niobium (Ti-Nb) alloy meshes to maintain space, prevent the ingrowth of fibroblasts and inhibit the colonization of bacteria for GBR. METHODS: Ti-Nb alloy meshes were prepared by selective laser melting (SLM) and used as substrates for novel surface coatings. Porous chitosan (CS)/ gelatin (G)/ doxycycline (Dox) coatings were formed on the meshes using electrophoretic deposition (EPD) and freeze-drying. The process of EPD was characterized through Fourier transform infrared spectroscopy (FT-IR), zeta potential, and particle size analysis. The cytotoxicity of the coatings was evaluated through the culture of osteoblasts and immunostaining. The antibacterial activity of the coatings was tested using inhibition zone tests against Staphylococcus aureus (S. aureus) and scanning electron microscope (SEM). The inhibition of fibroblasts infiltration and nutrients transfer properties were analyzed using immunostaining and permeability tests. RESULTS: High yield strength (567.5 ± 3.5 MPa) and low elastic modulus (65.5 ± 0.2 GPa) were achieved in Ti-Nb alloy bulk samples. The data of zeta potential, FT-IR and SEM indicated that porous spongy coatings were chemically bonded following EPD. In vitro analysis of CSGDox1 (containing Dox at 1 mg·mL-1) coating revealed its antibacterial effect and biocompatibility. Moreover, the CSGDox1 coating was proved to be effective for preventing the ingrowth of fibroblasts, whilst allowing the infiltration of nutrients. SIGNIFICANCE: This study verified that the EPD of CSGDox coatings on the 3D-printed Ti-Nb meshes can maintain space, provide antibiotic release whilst maintaining a barrier against soft-tissue growth, which is essential for the success of GBR treatment.

In situ fabrication of a titanium-niobium alloy with tailored microstructures, enhanced mechanical properties and biocompatibility by using selective laser melting.

A titanium-niobium (Ti-Nb) alloy with tailored microstructures, enhanced mechanical properties and biocompatibility was in situ fabricated by selective laser melting (SLM) using a blended powder with 25 wt.% Nb content. The effect of laser energy density from 70 J/mm3 to 110 J/mm3 on the phase transformation, microstructure, and mechanical properties of the SLM-printed Ti-25Nb alloy was investigated. The results indicate that the energy density of 110 J/mm3 results in the highest relative density and homogeneous element distributions in the alloy. The α' and ß phases with an orientation relationship of [023]ß//[-12-16]α' were identified through X-ray diffraction and transmission electron microscopy, and their proportions are crucially determined by the laser energy density. With an increase in the energy density, the microstructure of the Ti-25Nb alloy varies from acicular-shaped grains to coarsened lath-shaped grains and to lath-shaped grain + cellular-shaped subgrains, due to the decrease in cooling rate and the rise in temperature gradient. The yield strength and microhardness of the printed Ti-25Nb alloy decrease with the increase in energy density from 70 J/mm3 to 100 J/mm3, and then increase to the highest values of 645 MPa and 264 HV at 110 J/mm3, respectively. This variation of mechanical properties is dependent on both the coarsening of α' phase and the formation of ß (Ti, Nb) solid solution. Besides, the SLM-printed Ti-25Nb alloy exhibits both the excellent in vitro apatite-forming capability and better cell spread and proliferation compared to pure Ti.

Effect of pore geometry on the fatigue properties and cell affinity of porous titanium scaffolds fabricated by selective laser melting.

Porous titanium scaffolds with different unit cell type (tetrahedron and octahedron) and pore size (500 µm and 1000 µm) were fabricated by selective laser melting (SLM), and the effects of unit cell type and pore size on their fatigue properties and cell affinity were studied. The fatigue properties were performed by static and dynamic mechanical testing, while the cell affinity was evaluated in vitro with mouse osteoblast cells. It was found that octahedron scaffolds exhibited superior static mechanical properties, longer fatigue lives and higher fatigue strength in comparison to those of tetrahedron ones. As expected, scaffolds with 1000 µm pore resulted in lower compressive properties and shorter fatigue lives compared to those with 500 µm pore. The differences were analyzed based on the unit cell structure, porosity, and manufacturing imperfections. Scanning electron microscopy (SEM) and immunofluorescence showed that cells spread better on octahedron scaffolds than those on tetrahedron ones. Meanwhile, the scaffolds with 1000 µm pore were more suitable for cell attachment and growth within the same unit cell owing to higher porosity. The comparison of different pore geometry on the mechanical and biological property provided further insight into designing an optimal porous scaffold.

[Quantitative analysis of age-related changes of human major salivary glands using magnetic resonance imaging].

OBJECTIVE: To analyze the age-related characteristics of volumes, signal intensities (SIs) of T1-weighted images (T1WI), T2-weighted images (T2WI) and apparent diffusion coefficients (ADCs) of three major salivary glands. METHODS: A total of 300 subjects with normal salivary glands were divided into 4 different age groups and examined with a 1.5 T magnetic resonance (MR) unit. T1WI, T2WI and diffusion-weighted MR images (DW MRI) were obtained and bilateral parotid, submandibular and sublingual glands segmented manually. The volumes, T1WI, T2WI SIs and ADCs of three major salivary glands were measured. And the relative SIs (RSIs) were assessed by comparing with cerebrospinal fluid. RESULTS: The volumes, T1WI and T2WI RSIs of parotid glands were significantly correlated with age (P < 0.01) and showed similar significant tendencies of growing from minority to middle age and decreasing slightly after old age. Significant differences existed between minority and middle age groups in all above-mentioned parameters (P < 0.01). The ADCs of submandibular glands also showed that there was a significant difference between the minority and middle age groups (P < 0.01). CONCLUSION: MRI may be applied for studying the morphological and functional changes of normal major salivary glands with aging. Thus clinical rationales can be provided for assessing the subjects of any age during salivary gland imaging and aging-related researches.