Enhanced Adsorption Stability and Biofunction Durability with Phosphonate-Grafted, PEGylated Copolymer on Hydroxyapatite Surface.

Nonfouling surfaces are crucial in applications such as biosensors, medical implants, marine coatings, and drug delivery vehicles. However, their long-term coating stability and robust surface binding strength in physiological media remain challenging. Herein, a phosphonate-grafted, PEGylated copolymer on the hydroxyapatite (HA) surface is proposed to significantly improve the adsorption stability and thus enhance the biofunction durability accordingly. The phosphoryl (-PO3) grafted branch is employed in the functional polymer to facilitate attaching to the HA substrate. In addition, the polymer integrates the nonfouling polymer brushes of poly(ethylene glycol) (PEG) with the cell-adhesive moiety of cyclic Arg-Gly-Asp-d-Phe-Cys peptides (cRGD). A systematic study on the as-synthesized PEGylated graft copolymer indicates a synergistic binding mechanism of the NH2 and PO3 groups to HA, achieving a high surface coverage with desirable adsorption stability. The cRGD/PEGylated copolymers of optimized grafting architecture are proven to effectively adsorb to HA surfaces as a self-assembled copolymer monolayer, showing stability with minimal desorption even in a complex, physiological medium and effectively preventing nonspecific protein adsorption as examined with X-ray photoelectron spectroscopy (XPS) and a quartz crystal microbalance with dissipation (QCM-D). Direct adhesion assays further confirm that the enhanced coating stability and biofunction durability of the phosphonate-grafted, cRGD-PEGylated copolymer can considerably promote osteoblast attachment on HA surfaces, meanwhile preventing microbial adhesion. This research has resulted in a solution of self-assembly polymer structure optimization that exhibits stable nonfouling characteristics.

Efficacy and Safety of Absorb Everolimus-Eluting Bioresorbable Vascular Scaffold in Peripheral Artery Disease: A Single-Arm Meta-Analysis.

PURPOSE: This study aimed to evaluate the benefits and risks of patients with peripheral artery disease (PAD) treated with Absorb everolimus-eluting bioresorbable vascular scaffold (BVS) by analyzing all the published studies on the clinical characteristics of patients with PAD. MATERIALS AND METHODS: PubMed, Embase, and the Cochrane Library were searched for relevant studies. Efficacy, safety, and basic characteristics were analyzed. RESULTS: Four studies were included in meta-analysis, including a total number of 155 patients with PAD. The pooled overall primary patency, freedom from target lesion revascularization (TLR), symptom resolution, and wound healing were 90%, 96%, 94%, and 86%, respectively. The pooled perioperative complication and all-cause mortality were 4% and 9%, respectively. Preoperative total occlusion was detected in 43 of 192 lesions (22%). The mean lesion length was 27.26 mm. In terms of comorbidities, the pooled percentage of hypertension, hyperlipidemia, diabetes mellitus, coronary artery disease, chronic kidney disease history, and smoking were 65%, 74%, 49%, 43%, 20%, and 57%, respectively. CONCLUSION: Among these studies, hypertension, hyperlipidemia, and diabetes mellitus were the most common comorbidities in patients with PAD. The Absorb everolimus-eluting BVS was safe and showed the favorable clinical outcomes in both patency and TLR, especially in infrapopliteal disease with heavy calcification. The conclusions of this meta-analysis still needed to be verified by more relevant studies with more careful design, more rigorous execution, and larger sample size.

Intermediate analysis of magnesium alloy covered stent for a lateral aneurysm model in the rabbit common carotid artery.

OBJECTIVE: To analyze the outcomes of a magnesium alloy covered stent (MACS) for a lateral aneurysm model in common carotid artery (CCA). METHODS: In 32 rabbits, a MACS (group A, n = 17) or a Willis covered stent (WCS; group B, n = 15) was inserted and the rabbits were sacrificed 1, 3, 6, or 12 months after stenting. Angiography and intravascular ultrasound (IVUS) were performed at 3, 6, and 12 months. Scanning electron microscopy was performed for six stents in each group at 1, 3, and 6 months, and histopathology and histomorphology were conducted at 3 (n = 4), 6 (n = 4), and 12 (n = 12) months. RESULTS: Final angiography showed complete occlusion of the aneurysms in 12 cases. IVUS at 6 and 12 months revealed a significant increase in mean lumen area of the stented CCA in group A and also showed greater mean lumen area in group A than in group B. The endothelialization process was quicker in group A than in group B. CONCLUSION: MACS is effective for occlusion of lateral aneurysms and is superior to WCS in growth of the stented CCA and endothelialization. Further work is needed to make this device available for human use. KEY POINTS: • The MACS is an effective approach for occlusion of a lateral aneurysm. • IVUS showed that the CCA could grow following degradation of the MACS. • The lumen area of the stented CCA was excellent in MACS. • HE staining displayed the degradation of the magnesium alloy stent. • Combination of IVUS and DSA were applied in this study.

Influence of fluoride treatment on surface properties, biodegradation and cytocompatibility of Mg-Nd-Zn-Zr alloy.

Fluoride treatment is a commonly used technique or pre-treatment to optimize the degradation kinetic and improve the biocompatibility of magnesium-based implant. The influence of changed surface properties and degradation kinetics on subsequent protein adsorption and cytocompatibility is critical to understand the biocompatibility of the implant. In this study, a patent magnesium alloy Mg-Nd-Zn-Zr alloy (JDBM) designed for cardiovascular stent application was treated by immersion in hydrofluoric acid. A 1.5 µm thick MgF2 layer was prepared. The surface roughness was increased slightly while the surface zeta potential was changed to a much more negative value after the treatment. Static contact angle test was performed, showing an increase in hydrophilicity and surface energy after the treatment. The MgF2 layer slowed down in vitro degradation rate, but lost the protection effect after 10 days. The treatment enhanced human albumin adsorption while no difference of human fibrinogen adsorption amount was observed. Direct cell adhesion test showed many more live HUVECs retained than bare magnesium alloy. Both treated and untreated JDBM showed no adverse effect on HUVEC viability and spreading morphology. The relationship between changed surface characteristics, degradation rate and protein adsorption, cytocompatibility was also discussed.

[Finite element analysis for compression and expansion behavior of magnesium stent].

Magnesium stents have gained increasing interest as an ideal stent of future intervention. In order to study the deformation behavior of magnesium alloy stents in the interventional treatment, the finite element method was used to analysis the effects of different crimp and expansion dimensions on the mechanical properties (maximum stress, radial recoil rate, longitudinal shortening rate and radial strength). The results showed that crimping and expanding have a minimal influence on the stent radial strength. When the expansion size is same, the maximum equivalent stress and recoil rate decrease with the crimp size. When the crimp size is same, in contrast with the radial recoil rate, the maximum equivalent stress and longitudinal shortening rate increase with the expansion size. In addition the paper verified the radial strength-radial displacement curve obtained by FEM. Results are basically consistent, indicating the finite element method can efficiently provide researchers with reliable, high-quality design.

Smart stimuli-responsive strategies for titanium implant functionalization in bone regeneration and therapeutics.

With the increasing and aging of global population, there is a dramatic rise in the demand for implants or substitutes to rehabilitate bone-related disorders which can considerably decrease quality of life and even endanger lives. Though titanium and its alloys have been applied as the mainstream material to fabricate implants for load-bearing bone defect restoration or temporary internal fixation devices for bone fractures, it is far from rare to encounter failed cases in clinical practice, particularly with pathological factors involved. In recent years, smart stimuli-responsive (SSR) strategies have been conducted to functionalize titanium implants to improve bone regeneration in pathological conditions, such as bacterial infection, chronic inflammation, tumor and diabetes mellitus, etc. SSR implants can exert on-demand therapeutic and/or pro-regenerative effects in response to externally applied stimuli (such as photostimulation, magnetic field, electrical and ultrasound stimulation) or internal pathology-related microenvironment changes (such as decreased pH value, specific enzyme secreted by bacterial and excessive production of reactive oxygen species). This review summarizes recent progress on the material design and fabrication, responsive mechanisms, and in vitro and in vivo evaluations for versatile clinical applications of SSR titanium implants. In addition, currently existing limitations and challenges and further prospective directions of these strategies are also discussed.

Advancing Scaffold-Assisted Modality for In Situ Osteochondral Regeneration: A Shift From Biodegradable to Bioadaptable.

Over the decades, the management of osteochondral lesions remains a significant yet unmet medical challenge without curative solutions to date. Owing to the complex nature of osteochondral units with multi-tissues and multicellularity, and inherently divergent cellular turnover capacities, current clinical practices often fall short of robust and satisfactory repair efficacy. Alternative strategies, particularly tissue engineering assisted with biomaterial scaffolds, achieve considerable advances, with the emerging pursuit of a more cost-effective approach of in situ osteochondral regeneration, as evolving toward cell-free modalities. By leveraging endogenous cell sources and innate regenerative potential facilitated with instructive scaffolds, promising results are anticipated and being evidenced. Accordingly, a paradigm shift is occurring in scaffold development, from biodegradable and biocompatible to bioadaptable in spatiotemporal control. Hence, this review summarizes the ongoing progress in deploying bioadaptable criteria for scaffold-based engineering in endogenous osteochondral repair, with emphases on precise control over the scaffolding material, degradation, structure and biomechanics, and surface and biointerfacial characteristics, alongside their distinguished impact on the outcomes. Future outlooks of a highlight on advanced, frontier materials, technologies, and tools tailoring precision medicine and smart healthcare are provided, which potentially paves the path toward the ultimate goal of complete osteochondral regeneration with function restoration.

Developing Zn-2Cu-xLi (x < 0.1 wt %) alloys with suitable mechanical properties, degradation behaviors and cytocompatibility for vascular stents.

Biodegradable Zn alloys show great potential for vascular stents due to their moderate degradation rates and acceptable biocompatibility. However, the poor mechanical properties limit their applications. In this study, low alloyed Zn-2Cu-xLi (x = 0.004, 0.01, 0.07 wt %) alloys with favorable mechanical properties were developed. The microstructure consists of fine equiaxed η-Zn grains, micron, submicron-sized and coherent nano ε-CuZn4 phases. The introduced Li exists as a solute in the η-Zn matrix and ε-CuZn4 phase, and results in the increase of ε-CuZn4 volume fraction, the refinement of grains and more uniform distribution of grain sizes. As Li content increases, the strength of alloys is dramatically improved by grain boundary strengthening, precipitate strengthening of ε-CuZn4 and solid solution strengthening of Li. Zn-2Cu-0.07Li alloy has the optimal mechanical properties with a tensile yield strength of 321.8 MPa, ultimate tensile strength of 362.3 MPa and fracture elongation of 28.0 %, exceeding the benchmark of stents. It also has favorable mechanical property stability, weak tension compression yield asymmetry and strain rate sensitivity. It exhibits uniform degradation and a little improved degradation rate of 89.5 µm∙year-1, due to the improved electrochemical activity by increased ε-CuZn4 volume fraction, and generates Li2CO3 and LiOH. It shows favorable cytocompatibility without adverse influence on endothelial cell viability by trace Li+. The fabricated microtubes show favorable mechanical properties, and stents exhibit an average radial strength of 118 kPa. The present study indicates that Zn-2Cu-0.07Li alloy is a potential and promising candidate for vascular stent applications. STATEMENT OF SIGNIFICANCE: Zn alloys are promising candidates for biodegradable vascular stents. However, improving their mechanical properties is challenging. Combining the advantages of Cu and trace Li, Zn-2Cu-xLi (x < 0.1 wt %) alloys were developed for stents. As Li increases, the strength of alloys is dramatically improved by refined grains, increased volume fraction of ε-CuZn4 and solid solution of Li. Zn-2Cu-0.07Li alloy exhibits a TYS exceeding 320 MPa, UTS exceeding 360 MPa and fracture EL of nearly 30 %. It shows favorable mechanical stability, degradation behaviors and cytocompatibility. The alloy was fabricated into microtubes and stents for mechanical property tests to verify application feasibility for the first time. This indicates that Zn-2Cu-0.07Li alloy has great potential for vascular stent applications.

Anatomical Brushite-Coated Mg-Nd-Zn-Zr Alloy Cage Promotes Cervical Fusion: One-Year Results in Goats.

In this study, an anatomical brushite-coated Mg-Nd-Zn-Zr alloy cage was fabricated for cervical fusion in goats. The purpose of this study was to investigate the cervical fusion effect and degradation characteristics of this cage in goats. The Mg-Nd-Zn-Zr alloy cage was fabricated based on anatomical studies, and brushite coating was prepared. Forty-five goats were divided into three groups, 15 in each group, and subjected to C2/3 anterior cervical decompression and fusion with tricortical bone graft, Mg-Nd-Zn-Zr alloy cage, or brushite-coated Mg-Nd-Zn-Zr alloy cage, respectively. Cervical radiographs and computed tomography (CT) were performed 3, 6, and 12 months postoperatively. Blood was collected for biocompatibility analysis and Mg2+ concentration tests. The cervical spine specimens were obtained at 3, 6, and 12 months postoperatively for biomechanical, micro-CT, scanning electron microscopy coupled with energy dispersive spectroscopy, laser ablation-inductively coupled plasma-time-of-flight mass spectrometry, and histological analysis. The liver and kidney tissues were obtained for hematoxylin and eosin staining 12 months after surgery for biosafety analysis. Imaging and histological analysis showed a gradual improvement in interbody fusion over time; the fusion effect of the brushite-coated Mg-Nd-Zn-Zr alloy cage was comparable to that of the tricortical bone graft, and both were superior to that of the Mg-Nd-Zn-Zr alloy cage. Biomechanical testing showed that the brushite-coated Mg-Nd-Zn-Zr alloy cage achieved better stability than the tricortical bone graft at 12 months postoperatively. Micro-CT showed that the brushite coating significantly decreases the corrosion rate of the Mg-Nd-Zn-Zr alloy cage. In vivo degradation analysis showed higher Ca and P deposition in the degradation products of the brushite-coated Mg-Nd-Zn-Zr alloy cage, and no hyperconcentration of Mg was detected. Biocompatibility analysis showed that both cages were safe for cervical fusion surgery in goats. To conclude, the anatomical brushite-coated Mg-Nd-Zn-Zr alloy cage can promote cervical fusion in goats, and the brushite-coated Mg-Nd-Zn-Zr alloy is a potential material for developing absorbable fusion cages.

Concerting magnesium implant degradation facilitates local chemotherapy in tumor-associated bone defect.

Effective management of malignant tumor-induced bone defects remains challenging due to severe systemic side effects, substantial tumor recurrence, and long-lasting bone reconstruction post tumor resection. Magnesium and its alloys have recently emerged in clinics as orthopedics implantable metals but mostly restricted to mechanical devices. Here, by deposition of calcium-based bilayer coating on the surface, a Mg-based composite implant platform is developed with tailored degradation characteristics, simultaneously integrated with chemotherapeutic (Taxol) loading capacity. The delicate modulation of Mg degradation occurring in aqueous environment is observed to play dual roles, not only in eliciting desirable osteoinductivity, but allows for modification of tumor microenvironment (TME) owing to the continuous release of degradation products. Specifically, the sustainable H2 evolution and Ca2+ from the implant is distinguished to cooperate with local Taxol delivery to achieve superior antineoplastic activity through activating Cyt-c pathway to induce mitochondrial dysfunction, which in turn leads to significant tumor-growth inhibition in vivo. In addition, the local chemotherapeutic delivery of the implant minimizes toxicity and side effects, but markedly fosters osteogenesis and bone repair with appropriate structure degradation in rat femoral defect model. Taken together, a promising intraosseous administration strategy with biodegradable Mg-based implants to facilitate tumor-associated bone defect is proposed.

A Novel Scaffold of Icariin/Porous Magnesium Alloy-Repaired Knee Cartilage Defect in Rat by Wnt/ß-Catenin Signaling Pathway.

Cartilage defects caused by joint diseases are difficult to treat clinically. Tissue engineering materials provide a new means to promote the repair of cartilage defects. The purpose of this study is to design a novel scaffold of porous magnesium alloy loaded with icariin and sustained release in order to explore the effect and possible mechanism of this scaffold in repairing SD rat knee articular cartilage defect. We constructed a novel type of icariin/porous magnesium alloy scaffold, observed the structure of the scaffold by electron microscope, detected the drug release of icariin in the scaffold and the biological safety, and established an animal model of cartilage defect in the femoral intercondylar fossa of the knee joint in rats; the scaffold was placed in the defect. After 12 weeks of repair, the rat knee articular cartilage repair was evaluated by gross specimens and micro-CT, HE, safranin O-fast green, and toluidine blue staining combined with the modified Mankin's score. The protein expressions of the Wnt/ß-catenin signaling pathway-related factors (ß-catenin, Wnt5a, Wnt1, sFRP1) and chondrogenic differentiation-related factors (Sox9, Aggrecan, Col2α1) were detected by immunohistochemical staining. We found that the novel scaffold of icariin/porous magnesium alloy can release icariin slowly and has biosafety in rats. Compared with other groups, icariin/porous magnesium alloy can significantly promote the repair of cartilage defects and the expressions of ß-catenin, Wnt5a, Wnt1, Sox9, Aggrecan, and Col2α1 (P < 0.05). This novel scaffold can promote the repair of rat knee cartilage defects, and this process may be achieved by activating the Wnt/ß-catenin signaling pathway.

Long-Service-Life Rigid Polyurethane Foam Fillings for Spent Fuel Transportation Casks.

Soft materials bearing rigid, lightweight, and vibration-dampening properties offer distinct advantages over traditional wooden and metal-based fillings for spent fuel transport casks, due to their low density, tunable structure, excellent mechanical properties, and ease of processing. In this study, a novel type of rigid polyurethane foam is prepared using a conventional polycondensation reaction between isocyanate and hydroxy groups. Moreover, the density and size of the pores in these foams are precisely controlled through simultaneous gas generation. The as-prepared polyurethane exhibits high thermal stability exceeding 185 °C. Lifetime predictions based on thermal testing indicate that these polyurethane foams could last up to over 60 years, which is double the lifetime of conventional materials of about 30 years. Due to their occlusive structure, the mechanical properties of these polymeric materials meet the design standards for spent fuel transport casks, with maximum compression and tensile stresses of 6.89 and 1.37 MPa, respectively, at a testing temperature of -40 °C. In addition, these polymers exhibit effective flame retardancy; combustion ceased within 2 s after removal of the ignition source. All in all, this study provides a simple strategy for preparing rigid polymeric foams, presenting them as promising prospects for application in spent fuel transport casks.

Mg-based implants with a sandwiched composite coating simultaneously facilitate antibacterial and osteogenic properties.

Insufficient antibacterial effects and over-fast degradation are the main limitations of magnesium (Mg)-based orthopedic implants. In this study, a sandwiched composite coating containing a triclosan (TCS)-loaded poly(lactic acid) (PLA) layer inside and brushite (DCPD) layer outside was prepared on the surface of the Mg-Nd-Zn-Zr (denoted as JDBM) implant. In vitro degradation tests revealed a remarkable improvement in the corrosion resistance and moderate degradation rate. The drug release profile demonstrated a controllable and sustained TCS release for at least two weeks in vitro. The antibacterial rates of the implant were all over 99.8% for S. aureus, S. epidermidis, and E. coli, demonstrating superior antibacterial effects. Additionally, this coated JDBM implant exhibited no cytotoxicity but improved cell adhesion and proliferation, indicating excellent cytocompatibility. In vivo assays were conducted by implant-related femur osteomyelitis and osseointegration models in rats. Few bacteria were attached to the implant surface and the surrounding bone tissue. Furthermore, the coated JDBM implant exhibited more new bone formation than other groups due to the synergistic biological effects of released TCS and Mg2+, revealing excellent osteogenic ability. In summary, the JDBM implant with the sandwiched composite coating could significantly enhance the antibacterial activities and osteogenic properties simultaneously by the controllable release of TCS and Mg2+, presenting great potential for clinical transformation.

Brushite-coated Mg-Nd-Zn-Zr alloy promotes the osteogenesis of vertebral laminae through IGF2/PI3K/AKT signaling pathway.

Biodegradable magnesium (Mg) alloys have been extensively investigated in orthopedic implants due to their suitable mechanical strength and high biocompatibility. However, no studies have reported whether Mg alloys can be used to repair lamina defects, and the biological mechanisms regulating osteogenesis are not fully understood. The present study developed a lamina reconstruction device using our patented biodegradable Mg-Nd-Zn-Zr alloy (JDBM), and brushite (CaHPO4·2H2O, Dicalcium phosphate dihydrate, DCPD) coating was developed on the implant. Through in vitro and in vivo experiments, we evaluated the degradation behavior and biocompatibility of DCPD-JDBM. In addition, we explored the potential molecular mechanisms by which it regulates osteogenesis. In vitro, ion release and cytotoxicity tests revealed that DCPD-JDBM had better corrosion resistance and biocompatibility. We found that DCPD-JDBM extracts could promote MC3T3-E1 osteogenic differentiation via the IGF2/PI3K/AKT pathway. The lamina reconstruction device was implanted on a rat lumbar lamina defect model. Radiographic and histological analysis showed that DCPD-JDBM accelerated the repair of rat lamina defects and exhibited lower degradation rate compared to uncoated JDBM. Immunohistochemical and qRT-PCR results showed that DCPD-JDBM promoted osteogenesis in rat laminae via IGF2/PI3K/AKT pathway. This study shows that DCPD-JDBM is a promising biodegradable Mg-based material with great potential for clinical applications.

Biomimetic Porous Magnesium Alloy Scaffolds Promote the Repair of Osteoporotic Bone Defects in Rats through Activating the Wnt/ß-Catenin Signaling Pathway.

In this study, biomimetic porous magnesium alloy scaffolds were prepared to repair femoral bone defects in ovariectomized osteoporotic rats. The purpose of the study was to investigate the effect of biomimetic porous magnesium alloy scaffolds on repairing osteoporotic bone defects and possible mechanisms. The animal model of osteoporosis was established in female SD rats. Three months later, a bone defect of 3 mm in diameter and 3 mm in depth was created in the lateral condyle of the right femur. The rats were then randomly divided into two groups: an experimental group and a control group. Four weeks after surgery, gross specimens were observed and micro-CT scans were performed. The repair of osteoporotic femoral defects in rats was studied histologically using HE staining, Masson staining, and Goldner staining. The expression of Wnt5a, ß-catenin, and BMP-2 was measured between groups by immunohistochemical staining. The bone defect was repaired better after the application of biomimetic porous magnesium alloy scaffolds. Immunohistochemical results showed significantly higher expression of Wnt5a, ß-catenin, and BMP-2. To conclude, the biomimetic porous magnesium alloy scaffolds proposed in this paper might promote the repair of osteoporotic femoral bone defects in rats possibly through activating the Wnt/ß-catenin signaling pathway.

Biodegradable Zn-Cu-Mn alloy with suitable mechanical performance and in vitro degradation behavior as a promising candidate for vascular stents.

Recently, zinc (Zn) alloy has been considered as a promising biodegradable material due to its excellent physiological degradable behavior and acceptable biocompatibility. However, poor mechanical performance limits its application as vascular stents. In this study, novel biodegradable Zn-2.2Cu-xMn (x = 0.4, 0.7, and 1.0 wt%) alloys with suitable mechanical performance were investigated. The effects of Mn addition on microstructure, mechanical properties, and in vitro degradation of Zn-2.2Cu-xMn alloys were systematically investigated. After adding Mn, dynamic recrystallization (DRX) during hot extrusion was promoted, resulting in slightly finer grain size, higher DRXed regions ratio, and weaker texture. And volume fraction and number density of second phase precipitates (micron, submicron, and nano-sized ε and MnZn13 phase) and the concentration of (Cu, Mn) in the matrix were increased. Therefore, Zn-2.2Cu-xMn alloys exhibited suitable mechanical performances (strength >310 MPa, elongation >30%) mainly due to the combination effects of grain refinement, solid solution strengthening, second phase precipitation hardening, and texture weakening. Moreover, the alloys maintained good stability of mechanical properties within 18 months and good elongation over 15% even at a high strain rate of 0.1 s-1. In addition, the alloys presented appropriate in vitro degradation rates in a basically uniform degradation mode and acceptable in vitro cytocompatibility. The above results indicated that the newly designed biodegradable Zn-2.2Cu-0.4Mn alloy with suitable comprehensive mechanical properties, appropriate degradation behavior, and acceptable cytocompatibility is a promising candidate for vascular stents.

Fabrication and characterization of biodegradable Zn-Cu-Mn alloy micro-tubes and vascular stents: Microstructure, texture, mechanical properties and corrosion behavior.

Zinc (Zn) alloys are a promising biodegradable material for vascular stent applications. This study aimed to fabricate biodegradable Zn-2.0Cu-0.5Mn alloy micro-tubes and vascular stents with high dimensional accuracy and suitable mechanical properties, and to investigate their microstructure, texture, mechanical properties and corrosion behavior. The micro-tubes and vascular stents were successfully fabricated by a combined process of extrusion, drawing, laser cutting and electrochemical polishing. The microstructures of as-extruded and as-drawn micro-tubes consisted of Zn matrix with near-equiaxed grains (average grain size: ∼2 µm) and second phases of ε (CuZn4) and MnZn13 with different sizes. The texture evolved from basal planes approximately paralleling to deformation direction for as-extruded micro-tube to approximately perpendicular to deformation direction for as-drawn micro-tube, because predominant deformation mechanisms changed from basal dislocation slip during tube extrusion to prismatic dislocation, pyramidal dislocations, and {101¯2} twins during tube drawing. As-drawn micro-tube exhibited suitable mechanical properties with an ultimate tensile strength of about 298 MPa and elongation of about 26% as a stent material. Moreover, the processed stent with a thickness of about 125 µm possessed sufficient radial strength of about 150 kPa and good balloon expandability. In addition, as-drawn tube exhibited an in vitro corrosion rate of about 158 µm/year with a basically uniform corrosion morphology. These results indicated that biodegradable Zn-2.0Cu-0.5Mn alloy is a promising vascular stent material candidate, and the procedure for processing the micro-tube and stent is practical and effective. STATEMENT OF SIGNIFICANCE: Fabrication of micro-tubes followed by laser cutting and polishing is a common way to prepare metallic vascular stents. However, it is quite challenging to fabricate Zn-based stents using this standard method, and there is a lack of studies reporting processing details in the past. Biodegradable Zn-2.0Cu-0.5Mn alloy micro-tubes and vascular stents with high dimensional accuracy and suitable mechanical properties were successfully fabricated by a combined process in this study. As-drawn micro-tube exhibited an ultimate tensile strength of about 298 MPa and elongation of about 26%. The stent possessed sufficient radial strength of about 150 kPa and good balloon expandability. We demonstrated a practical method to fabricate biodegradable Zn-based micro-tubes and stents with high dimensional accuracy and mechanical properties.

The beneficial potential of magnesium-based scaffolds to promote chondrogenesis through controlled Mg2+ release in eliminating the destructive effect of activated macrophages on chondrocytes.

Chondral defects caused by osteoarthritis (OA) are common but difficult to manage due to their limited capacity for self-repair. Further, the activated macrophages induced by OA stimulates chondrocytes degradation and inhibits regeneration, further impeding cartilage repair. Therefore, biomaterials with the potential for blocking vicious cycles between activated macrophages and chondrocytes would be promising for use in the treatment of chondral defects caused by OA. In this study, we fabricated porous Mg-Nd-Zn-Zr alloy (denoted JDBM) scaffolds coated with polydopamine (PDA) and investigated their cytocompatibility and impact on immunoregulation. Mesenchymal stem cells (MSCs) were co-cultured in supernatant from M1-polarized macrophages pretreated with extracts from JDBM scaffolds and the anti-inflammatory effect on the NF-κB pathway and reactive oxygen species (ROS) evaluated. JDBM scaffolds could reduce M1 macrophage numbers, while promoting those of M2 macrophages; recruit MSCs; and enhance chondrogenesis. Furthermore, lipopolysaccharide (LPS)-induced p65 translocation to the nucleus was inhibited by JDBM scaffolds, with ROS production and matrix metalloproteinase (MMP) expression also suppressed. These findings suggest that JDBM scaffolds can both promote chondrogenesis and effectively attenuate local inflammatory responses by transforming macrophages from the M1 to M2 subtype and down-regulating NF-κB signaling. Hence, JDBM scaffolds could promote chondrogenesis under inflammatory microenvironment and represent a promising material for treatment of chondral defects caused by OA.

Fatigue and dynamic biodegradation behavior of additively manufactured Mg scaffolds.

Additive manufacturing (AM) has enabled the fabrication of biodegradable porous metals to satisfy the desired characteristics for orthopedic applications. The geometrical design on AM biodegradable metallic scaffolds has been found to offer a favorable opportunity to regulate their mechanical and degradation performance in previous studies, however mostly confined to static responses. In this study, we presented the effect of the geometrical design on the dynamic responses of AM Mg scaffolds for the first time. Three different types of porous structures, based on various unit cells (i.e., biomimetic, diamond, and sheet-based gyroid), were established and then subjected to selective laser melting (SLM) process using group-developed Mg-Nd-Zn-Zr alloy (JDBM) powders. The topology after dynamic electropolishing, dynamic compressive properties, and dynamic biodegradation behavior of the AM Mg scaffolds were comprehensively evaluated. It was found that dynamic electropolishing effectively removed the excessive adhered powders on the surfaces and resulted in similar geometrical deviations amongst the AM Mg scaffolds, independent of their porous structures. The geometrical design significantly affected the compressive fatigue properties of the AM Mg scaffolds, of which the sheeted-based gyroid structure demonstrated a superior fatigue endurance limit of 0.85 at 106 cycles. Furthermore, in vitro dynamic immersion behaviors of the AM Mg scaffolds revealed a decent dependence on local architectures, where the sheeted-based gyroid scaffold experienced the lowest structural loss with a relatively uniform degradation mode. The obtained results indicate that the geometrical design could provide a promising strategy to develop desirable bone substitutes for the treatment of critical-size load-bearing defects. STATEMENT OF SIGNIFICANCE: Additive manufacturing (AM) has provided unprecedented opportunities to fabricate geometrically complex biodegradable scaffolds where the topological design becomes a key determinant on comprehensive performance. In this paper, we fabricate 3 AM biodegradable Mg scaffolds (i.e., biomimetic, diamond, and sheet-based gyroid) and report the effect of the geometrical design on the dynamic responses of AM Mg scaffolds for the first time. The results revealed that the sheeted-based gyroid scaffold exhibited the best combination of superior compressive fatigue properties and relatively uniform dynamic biodegradation mode, suggesting that the regulation of the porous structures could be an effective approach for the optimization of AM Mg scaffolds as to satisfy clinical requirements in orthopedic applications.

The effects of alignment and diameter of electrospun fibers on the cellular behaviors and osteogenesis of BMSCs.

Electrospun fiber scaffolds, due to their mimicry of bone extracellular matrix (ECM), have become an important biomaterial widely applied in bone tissue engineering in recent years. While topographic cues of electrospun membranes such as alignment and diameter played vital roles in determining cellular behaviors. Yet few researches about the effects of these two significant parameters on osteogenesis have been reported. Thus, the present work explored the influence of aligned and random poly (L-lactic acid) (PLLA) fiber matrices with diameters of nanoscale (0.6 µm) and microscale (1.2 µm), respectively, on cellular responses of bone marrow mesenchymal stem cells (BMSCs), such as cell adhesion, migration, proliferation and osteogenesis. Our results revealed that aligned nanofibers (AN) could affect cell morphology and promote the migration of BMSCs after 24 h of cell culturing. Besides, AN group was observed to possess excellent biocompatibility and have significantly improved cell growth comparing with random nanofibers. More importantly, in vitro osteogenesis researches including ALP and Alizarin Red S staining, qRT-PCR and immunofluorescence staining demonstrated that BMSCs culturing on AN group exhibited higher osteogenic induction proficiency than that on aligned microfibers (AM) and random fiber substrates (RN and RM). Accordingly, aligned nanofiber scaffolds have greater application potential in bone tissue engineering.