Additively Manufactured Zn-2Mg Alloy Porous Scaffolds with Customizable Biodegradable Performance and Enhanced Osteogenic Ability.

The combination of bioactive Zn-2Mg alloy and additively manufactured porous scaffold is expected to achieve customizable biodegradable performance and enhanced bone regeneration. Herein, Zn-2Mg alloy scaffolds with different porosities, including 40% (G-40-2), 60% (G-60-2), and 80% (G-80-2), and different unit sizes, including 1.5 mm (G-60-1.5), 2 mm (G-60-2), and 2.5 mm (G-60-2.5), are manufactured by a triply periodic minimal surface design and a reliable laser powder bed fusion process. With the same unit size, compressive strength (CS) and elastic modulus (EM) of scaffolds substantially decrease with increasing porosities. With the same porosity, CS and EM just slightly decrease with increasing unit sizes. The weight loss after degradation increases with increasing porosities and decreasing unit sizes. In vivo tests indicate that Zn-2Mg alloy scaffolds exhibit satisfactory biocompatibility and osteogenic ability. The osteogenic ability of scaffolds is mainly determined by their physical and chemical characteristics. Scaffolds with lower porosities and smaller unit sizes show better osteogenesis due to their suitable pore size and larger surface area. The results indicate that the biodegradable performance of scaffolds can be accurately regulated on a large scale by structure design and the additively manufactured Zn-2Mg alloy scaffolds have improved osteogenic ability for treating bone defects.

In vitro and in vivo studies on biodegradable Zn porous scaffolds with a drug-loaded coating for the treatment of infected bone defect.

Additively manufactured biodegradable zinc (Zn) scaffolds have great potential to repair infected bone defects due to their osteogenic and antibacterial properties. However, the enhancement of antibacterial properties depends on a high concentration of dissolved Zn2+, which in return deteriorates osteogenic activity. In this study, a vancomycin (Van)-loaded polydopamine (PDA) coating was prepared on pure Zn porous scaffolds to solve the above dilemma. Compared with pure Zn scaffolds according to comprehensive in vitro tests, the PDA coating resulted in a slow degradation and inhibited the excessive release of Zn2+ at the early stage, thus improving cytocompatibility and osteogenic activity. Meanwhile, the addition of Van drug substantially suppressed the attachment and proliferation of S. aureus and E. coli bacterial. Furthermore, in vivo implantation confirmed the simultaneously improved osteogenic and antibacterial functions by using the pure Zn scaffolds with Van-loaded PDA coating. Therefore, it is promising to employ biodegradable Zn porous scaffolds with the proposed drug-loaded coating for the treatment of infected bone defects.

Multiscale architecture design of 3D printed biodegradable Zn-based porous scaffolds for immunomodulatory osteogenesis.

Reconciling the dilemma between rapid degradation and overdose toxicity is challenging in biodegradable materials when shifting from bulk to porous materials. Here, we achieve significant bone ingrowth into Zn-based porous scaffolds with 90% porosity via osteoinmunomodulation. At microscale, an alloy incorporating 0.8 wt% Li is employed to create a eutectoid lamellar structure featuring the LiZn4 and Zn phases. This microstructure optimally balances high strength with immunomodulation effects. At mesoscale, surface pattern with nanoscale roughness facilitates filopodia formation and macrophage spreading. At macroscale, the isotropic minimal surface G unit exhibits a proper degradation rate with more uniform feature compared to the anisotropic BCC unit. In vivo, the G scaffold demonstrates a heightened efficiency in promoting macrophage polarization toward an anti-inflammatory phenotype, subsequently leading to significantly elevated osteogenic markers, increased collagen deposition, and enhanced new bone formation. In vitro, transcriptomic analysis reveals the activation of JAK/STAT pathways in macrophages via up regulating the expression of Il-4, Il-10, subsequently promoting osteogenesis.

Mechanical properties, in vitro biodegradable behavior, biocompatibility and osteogenic ability of additively manufactured Zn-0.8Li-0.1Mg alloy scaffolds.

Alloying and structural design provide flexibility to modulate performance of biodegradable porous implants manufactured by laser powder bed fusion (L-PBF). Herein, bulk Zn-0.8Li-0.1Mg was first fabricated to indicate the influence of the ternary alloy system on strengthening effect. Porous scaffolds with different porosities, including 60 % (P60), 70 % (P70) and 80 % (P80), were designed and fabricated to study the influence of porosity on mechanical properties, in vitro degradation behavior, biocompatibility and osteogenic ability. Pure Zn (Zn-P70) scaffolds with a porosity of 70 % were utilized for the comparison. The results showed Zn-0.8Li-0.1Mg bulks had an ultimate tensile strength of 460.78 ± 5.79 MPa, which was more than 3 times that of pure Zn ones and was the highest value ever reported for Zn alloys fabricated by L-PBF. The compressive strength (CS) and elastic modulus (E) of scaffolds decreased with increasing porosities. The CS of P70 scaffolds was 24.59 MPa, more than 2 times that of Zn-P70. The weight loss of scaffolds during in vitro immersion increased with increasing porosities. Compared with Zn-P70, a lower weight loss, better biocompatibility and improved osteogenic ability were observed for P70 scaffolds. P70 scaffolds also exhibited the best biocompatibility and osteogenic ability among all the used porosities. Influence mechanism of alloying elements and structural porosities on mechanical behaviors, in vitro biodegradation behavior, biocompatibility and osteogenic ability of scaffolds were discussed using finite element analysis and the characterization of degradation products. The results indicated that the proper design of alloying and porosity made Zn-0.8Li-0.1Mg scaffolds promising for biodegradable applications.

Machine learning-enabled constrained multi-objective design of architected materials.

Architected materials that consist of multiple subelements arranged in particular orders can demonstrate a much broader range of properties than their constituent materials. However, the rational design of these materials generally relies on experts' prior knowledge and requires painstaking effort. Here, we present a data-efficient method for the high-dimensional multi-property optimization of 3D-printed architected materials utilizing a machine learning (ML) cycle consisting of the finite element method (FEM) and 3D neural networks. Specifically, we apply our method to orthopedic implant design. Compared to uniform designs, our experience-free method designs microscale heterogeneous architectures with a biocompatible elastic modulus and higher strength. Furthermore, inspired by the knowledge learned from the neural networks, we develop machine-human synergy, adapting the ML-designed architecture to fix a macroscale, irregularly shaped animal bone defect. Such adaptation exhibits 20% higher experimental load-bearing capacity than the uniform design. Thus, our method provides a data-efficient paradigm for the fast and intelligent design of architected materials with tailored mechanical, physical, and chemical properties.

A drug-loaded composite coating to improve osteogenic and antibacterial properties of Zn-1Mg porous scaffolds as biodegradable bone implants.

Zinc (Zn) alloy porous scaffolds produced by additive manufacturing own customizable structures and biodegradable functions, having a great application potential for repairing bone defect. In this work, a hydroxyapatite (HA)/polydopamine (PDA) composite coating was constructed on the surface of Zn-1Mg porous scaffolds fabricated by laser powder bed fusion, and was loaded with a bioactive factor BMP2 and an antibacterial drug vancomycin. The microstructure, degradation behavior, biocompatibility, antibacterial performance and osteogenic activities were systematically investigated. Compared with as-built Zn-1Mg scaffolds, the rapid increase of Zn2+, which resulted to the deteriorated cell viability and osteogenic differentiation, was inhibited due to the physical barrier of the composite coating. In vitro cellular and bacterial assay indicated that the loaded BMP2 and vancomycin considerably enhanced the cytocompatibility and antibacterial performance. Significantly improved osteogenic and antibacterial functions were also observed according to in vivo implantation in the lateral femoral condyle of rats. The design, influence and mechanism of the composite coating were discussed accordingly. It was concluded that the additively manufactured Zn-1Mg porous scaffolds together with the composite coating could modulate biodegradable performance and contribute to effective promotion of bone recovery and antibacterial function.

Processing optimization, mechanical properties, corrosion behavior and cytocompatibility of additively manufactured Zn-0.7Li biodegradable metals.

Biodegradable Zn-Li alloys exhibit superior mechanical performance and favorable osteogenic capability for load-bearing bone devices. Additive manufacturing (AM) endows freedom for the fabrication of bone implants of personalized structure to satisfy patient-specific needs. In this paper, AM of Zn-Li alloys was attempted for the first-time using laser powder bed fusion (LPBF), and the fabricated samples exhibited good fusion quality and high dimensional accuracy. The processing optimization, mechanical properties, in vitro corrosion behavior and cytocompatibility were investigated by using Zn-0.7Li bulk and porous samples. The ultimate tensile strength and elastic modulus of bulk samples respectively reached 416.5 MPa and 83.3 GPa, and both were the highest among various additively manufactured Zn alloys reported so far. Porous samples achieved compressive strength (18.2 MPa) and elastic modulus (298.0 MPa), which were comparable to those of cancellous bone. Porous samples exhibited a higher corrosion rate and alleviated the problem of slow degradation of Zn-Li alloys. Nevertheless, osteoblastic cells showed a more spreading and healthier morphology when adhering to the porous samples compared to the bulk samples, thus a better cytocompatibility was confirmed. This work shows tremendous potential to precisely design and modulate biodegradable Zn alloys to fulfill clinical needs by using AM technology. STATEMENT OF SIGNIFICANCE: This paper firstly studied processing optimization during laser powder bed fusion of Zn-Li alloy. Bulk and porous Zn-0.7Li samples in customized design were obtained with high formation quality. The tensile strength of bulk samples reached 416.5 MPa, while the compressive strength and modulus of porous samples reduced to 18.2 MPa and 298.0 MPa, comparable to those of bone. The weight loss of porous samples was roughly 5 times that of bulk samples; osteoblastic cells showed a more spreading and healthier morphology at porous samples, indicating improved biodegradation rate and cytocompatibility. This work shows tremendous potential to precisely design and modulate biodegradable Zn alloy porous scaffolds to fulfill clinical needs by using additive manufacturing technology.

Effect of sleep deprivation on general anesthesia in rats.

OBJECTIVE: To explore the effects of sleep deprivation on perioperative general anesthesia in rats. METHODS: 45 healthy male Sprague-Dawley (SD) rats were randomly divided into 3 groups, the control group (Group A), the anesthesia group (Group B) and the sleep deprivation anesthesia group (Group C), 15 in each group. The sleep deprivation model was established by improving multi-platform water environment method. The group B and C were received propofol 80 mg/kg by intraperitoneally, the group A was given the same dose of normal saline. The EEG in each group was measured. The GABAa R-ß3 protein in cerebral cortex was detected by Western Blot. The rats were treated with Brennan incision, and the changes of thermal pain sensitive (PWL) and open field behavior were measured in each group. RESULTS: In group C, the δ band of brainwave of EEG increased significantly, the disappearance time of righting reflex shortened significantly, the recovery time prolonged significantly, the GABAa R-ß3 protein was significantly increased, and the time of passing through the central area before operation was significantly decreased. CONCLUSION: Sleep deprivation can significantly inhibit the electrical activity of rat cerebral cortex induced by propofol, up-regulating the GABAa R-ß3 protein in cortex.