Hierarchical Porous Scaffolds Research Articles

3D Cryo‐Printed Hierarchical Porous Scaffolds Harmonized with Hybrid Nanozymes for Combinatorial Mitochondrial Therapy: Enhanced Diabetic Bone Regeneration via Micromilieu Remodeling

AbstractRegeneration of bone defects in diabetic patients has always been a significant challenge in clinical treatment. The pathologic diabetic micromilieu, characterized by mitochondrial dysfunction, excessive reactive oxygen species (ROS) accumulation, cellular senescence, and chronic inflammation, compromises innate bone healing capacity. 3D cryo‐printing technology is utilized in bone tissue engineering to fabricate hierarchical porous scaffolds that promote a conducive microenvironment for cellular adhesion, migration, proliferation, and nutrient exchange. Nanozymes are used as synthetic mimics of natural enzymes to scavenge ROS, addressing the limitations of natural antioxidative enzymes. To remodel the diabetic bone regeneration micromilieu, a 3D cryo‐printed polyaryletherketone with carboxyl groups (PAEK‐COOH) and 45S5 bioactive glass (BG) hierarchical porous scaffold (PBG scaffold), harmonized with hybrid nanozymes comprising SS31‐enhanced manganese dioxide (MnO2)‐ferritin biomimetic nanozyme (MF@S nanozyme), is developed for combinatorial mitochondrial therapy. The MF@S nanozyme specifically targets mitochondria to enhance mitochondrial function, scavenge ROS accumulated in mitochondria, and suppress mitochondrial ROS (mtROS) production, and thus rejuvenate aging cells, regulate macrophage polarization, and modulate differentiation of osteoblasts and osteoclasts. This 3D cryo‐printed PBG‐MF@S hierarchical porous scaffold combines with a combinatorial mitochondrial therapy system to remodel the diabetic micromilieu and presents a promising therapeutic approach for the regeneration of bone defects in diabetes.

Study on the fabrication and performance of hierarchical porous 3D printed PCL-based artificial bone scaffold with anti-bacterial effect

Nonunion and large bone defects caused by trauma, tumor resection, and other bone diseases pose great challenges for clinical treatment. In this work, we fabricated a hierarchical porous scaffold mimicking the natural bone in structure and component. The inner MC/PCL/VCM (MCP-V) scaffold with pore sizes of 10–30 μm was prepared by vacuum freeze-drying, which has drug loading and mimics the bone component and structure. Then outer PT scaffold with pore sizes of 400–500 μm was prepared and a hole reserved for embedding the prepared MCP-V scaffold by 3D printing. The results showed that the compressive strength increased from 1.6 ± 0.01 MPa to 11.0 ± 0.38 MPa, and the compressive modulus increased from 1.1 ± 0.40 MPa to 12.4 ± 0.42 MPa, separately. As the variation of porosity for scaffolds, the cumulative drug release percentage decreased from (55.3 ± 1.43) % to (44.3 ± 2.47) % at 6 days. Furthermore, CCK-8 and the Live/Dead assay were utilized to assess the viability of MC3T3-E1 cells on scaffolds, which revealed no significant cytotoxicity. The hierarchical scaffold meets the mechanical requirement of cancellous bone, with slow drug release properties and excellent cytocompatibility, providing an effective repair strategy for clinical bone defects.

Nerve Growth Factor-Preconditioned Mesenchymal Stem Cell-Derived Exosome-Functionalized 3D-Printed Hierarchical Porous Scaffolds with Neuro-Promotive Properties for Enhancing Innervated Bone Regeneration.

The essential role of the neural network in enhancing bone regeneration has often been overlooked in biomaterial design, leading to delayed or compromised bone healing. Engineered mesenchymal stem cells (MSCs)-derived exosomes are becoming increasingly recognized as potent cell-free agents for manipulating cellular behavior and improving therapeutic effectiveness. Herein, MSCs are stimulated with nerve growth factor (NGF) to regulate exosomal cargoes to improve neuro-promotive potential and facilitate innervated bone regeneration. In vitro cell experiments showed that the NGF-stimulated MSCs-derived exosomes (N-Exos) obviously improved the cellular function and neurotrophic effects of the neural cells, and consequently, the osteogenic potential of the osteo-reparative cells. Bioinformatic analysis by miRNA sequencing and pathway enrichment revealed that the beneficial effects of N-Exos may partly be ascribed to the NGF-elicited multicomponent exosomal miRNAs and the subsequent regulation and activation of the MAPK and PI3K-Akt signaling pathways. On this basis, N-Exos were delivered on the micropores of the 3D-printed hierarchical porous scaffold to accomplish the sustained release profile and extended bioavailability. In a rat model with a distal femoral defect, the N-Exos-functionalized hierarchical porous scaffold significantly induced neurovascular structure formation and innervated bone regeneration. This study provided a feasible strategy to modulate the functional cargoes of MSCs-derived exosomes to acquire desirable neuro-promotive and osteogenic potential. Furthermore, the developed N-Exos-functionalized hierarchical porous scaffold may represent a promising neurovascular-promotive bone reparative scaffold for clinical translation.

Hierarchical Scaffold with Directional Microchannels Promotes Cell Ingrowth for Bone Regeneration.

Bone regenerative scaffolds with a bionic natural bone hierarchical porous structure provide a suitable microenvironment for cell migration and proliferation. Here, a bionic scaffold (DP-PLGA/HAp) with directional microchannels is prepared by combining 3D printing and directional freezing technology. The 3D printed framework provides structural support for new bone tissue growth, while the directional pore embedded in the scaffolds provides an express lane for cell migration and nutrition transport, facilitating cell growth and differentiation. The hierarchical porous scaffolds achieve rapid infiltration and adhesion of bone marrow mesenchymal stem cells (BMSCs) and improve the expression of osteogenesis-related genes. The rabbit cranial defect experiment presents significant new bone formation, demonstrating that DP-PLGA/HAp offers an effective means to guide cranial bone regeneration. The combination of 3D printing and directional freezing technology might be a promising strategy for developing bone regenerative biomaterials.

Synthesis of Bi2O3/hierarchical porous carbon composites for supercapacitor application

Bismuth oxide (Bi2O3) is considered a promising electrode material for supercapacitors boasting a high theoretical capacity. Its weak conductivity, limited rate performance, and poor cycling stability have significantly hindered practical applications. In this work, a simple precipitation and calcination method was used to prepare Bi2O3/hierarchical porous carbon composite materials (Bi2O3/N-HPC). The biomass-derived hierarchical porous carbon precursor was prepared through a process involving nitrogen doping and chemical activation. Comprehensive physical and chemical structure characterization results showed that a large number of spherical Bi2O3 particles were dispersed on the surface of the carbon material, providing numerous active sites for electrochemical reactions. The nitrogen-doped hierarchical porous carbon scaffold provided rapid pathways for charge transfer and restricted the aggregation of Bi2O3 particles. As an electrode material in a 6 M KOH electrolyte, Bi2O3/N-HPC exhibited a specific capacitance of 684.9 F g−1 at a current density of 0.5 A g−1, and even at an increased current density of 20 A g−1, the specific capacitance remained at 500.0 F g−1. After 10,000 cycles of charge and discharge, the capacitance retention rate of the Bi2O3/N-HPC electrode reached 85.2 %. This research offers a promising pathway for the development of high-performance supercapacitor electrode materials.

Direct ink writing of hierarchical porous SiC ceramics as catalyst support for hydrogen production

Due to the tunable porosity at multiple scales, hierarchical porous ceramics feature large specific surface area and excellent heat and mass transfer performance, which can effectively improve the catalytic reaction performance. This paper presents a method to fabricate SiC scaffolds with regular and hierarchical pore structures by direct ink writing (DIW) combined with sacrificial template technology, which can be used as methanol steam reforming (MSR) microreactor catalyst supports. Through printing along a defined path, primary pores with a regular pore structure were created. After sintering, the sacrificial template was removed and secondary pores appeared. Four different types of hierarchical porous SiC scaffolds were successfully prepared and the pore structure, total porosity, linear shrinkage and compressive strength of these scaffolds were investigated. The catalyst coating was then loaded onto the scaffold, and the microstructure characterization showed that the pore structure would not be damaged and blocked. Finally, the hydrogen production experiments were carried out on the MSR microreactor, and the results showed that the support with larger and denser secondary pores had the best fluid flow and hydrogen production characteristics. At the temperature of 280 °C and the gas hourly space velocity (GHSV) of 30000 ml g−1 h−1, the methanol conversion and hydrogen production of the best support can reach 90.95 % and 44.96 ml/min, respectively.

Biocompatible and bioactive PEG-Based resin development for additive manufacturing of hierarchical porous bone scaffolds

Bone diseases can often result in patient bone fragility. Different bone problems include low bone density, osteoporosis, and other bone diseases. Such bone diseases, ailments, and malfunctions often require complex and expensive treatments. In this study, we synthesized a new type of DLP resin for 3D printing purposes based on poly(ethylene glycol diacrylate) (PEGDA) and acrylic acid (AAc). In addition, using a porogen within the photopolymerizable resin allowed us to fabricate hierarchical interconnected porous structures. These structures combine the pores resulting from the CAD design with those obtained by the lixiviation of the porogen. Finally, bioactive particles were added to the mixture to increase the material's biocompatibility, thus proving the strategy's potential to include active compounds for particular purposes. Our results demonstrate that including the photoabsorber, Orange G, considerably increases the printing precision and resolution of the synthesized resin, making it possible to obtain printed parts with intricate and complex geometries with high accuracy and definition. Nano-hydroxyapatite (nHA) inclusion significantly increases the material's biocompatibility and mechanical stiffness (∼47 % increase, from 5.47 MPa to 8.02 MPa).

Beta-TCP scaffolds with rationally designed macro-micro hierarchical structure improved angio/osteo-genesis capability for bone regeneration

The design of hierarchical porous structure in scaffolds is crucial for bone defect regenerative repair. However, bioceramic materials present a challenge in precisely constructing designed micropores owing to the limitation of forming process. To investigate micropore shape influences bone regeneration in bioceramic scaffolds with macropores, hierarchical porous scaffolds with interconnective macropores (~400 μm) and two types of micropores (spherical and fibrous) were prepared using a combination of direct ink writing (DIW) and template sacrifice methods. Compared to the scaffold with spherical micropores, the scaffold with highly interconnected fibrous micropores significantly improved cell adhesion and upregulated osteogenic and angiogenetic-related gene expression in mBMSCs and HUVECs, respectively. Furthermore, in vivo implantation experiments showed that hierarchical scaffolds with fibrous micropores accelerated the bone repair process significantly. This result can be attributed to the high interconnectivity of fibrous micropores, which promotes the transportation of nutrients and waste during bone regeneration. Our work demonstrates that hierarchical porous scaffold design, especially one with a fibrous micropore structure, is a promising strategy for improving the bone regeneration performance of bioceramic scaffolds.Graphical

Hierarchical porous ECM scaffolds incorporating GDF-5 fabricated by cryogenic 3D printing to promote articular cartilage regeneration

BackgroundIn recent years, there has been significant research progress on in situ articular cartilage (AC) tissue engineering with endogenous stem cells, which uses biological materials or bioactive factors to improve the regeneration microenvironment and recruit more endogenous stem cells from the joint cavity to the defect area to promote cartilage regeneration.MethodIn this study, we used ECM alone as a bioink in low-temperature deposition manufacturing (LDM) 3D printing and then successfully fabricated a hierarchical porous ECM scaffold incorporating GDF-5.ResultsComparative in vitro experiments showed that the 7% ECM scaffolds had the best biocompatibility. After the addition of GDF-5 protein, the ECM scaffolds significantly improved bone marrow mesenchymal stem cell (BMSC) migration and chondrogenic differentiation. Most importantly, the in vivo results showed that the ECM/GDF-5 scaffold significantly enhanced in situ cartilage repair.ConclusionIn conclusion, this study reports the construction of a new scaffold based on the concept of in situ regeneration, and we believe that our findings will provide a new treatment strategy for AC defect repair.

3D Printed Hierarchical Porous Poly(ε-caprolactone) Scaffolds from Pickering High Internal Phase Emulsion Templating.

In the realm of biomaterials, particularly bone tissue engineering, there has been a great increase in interest in scaffolds with hierarchical porosity and customizable multifunctionality. Recently, the three-dimensional (3D) printing of biopolymer-based inks (solutions or emulsions) has gained high popularity for fabricating tissue engineering scaffolds, which optimally satisfies the desired properties and performances. Herein, therefore, we explore the fabrication of 3D printed hierarchical porous scaffolds of poly(ε-caprolactone) (PCL) using the water-in-oil (w/o) Pickering PCL high internal phase emulsions (HIPEs) as the ink in 3D printer. The Pickering PCL HIPEs stabilized using hydrophobically modified nanoclay comprised of aqueous poly(vinyl alcohol) (PVA) as the dispersed phase. Rheological measurements suggested the shear thinning behavior of Pickering HIPEs having a dispersed droplet diameter of 3-25 μm. The pore morphology resembling the natural extracellular matrix and the mechanical properties of scaffolds were customized by tuning the emulsion composition and 3D printing parameters. In vitro biomineralization and drug release studies proved the scaffolds' potential in developing the apatite-rich bioactive interphase and controlled drug delivery, respectively. During in vitro osteoblast (MG63) growth experiments for up to 7 days, good adhesion and proliferation on PCL scaffolds confirmed their cytocompatibility, assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) analysis. This study suggests that the assembly of HIPE templates and 3D printing is a promising approach to creating hierarchical porous scaffolds potentially suitable for bone tissue engineering and can be stretched to other biopolymers as well.

Hierarchical Macro-Mesoporous Silica Monolithic Tablets as a Novel Dose-Structure-Dependent Delivery System for the Release of Confined Dexketoprofen.

This study reports the application of hierarchical porous monoliths as carriers for controlled and dose-adjustable release of model pharmaceutical (dexketoprofen, DEX). The synthesis and detailed characterization of the hierarchical porous scaffolds are provided before and after the adsorption of three doses of DEX─a widely used nonsteroidal anti-inflammatory drug. The drug incorporated in the mesopores of silica was stabilized in an amorphous state, while the presence of macropores provided sufficient space for drug crystallization as we demonstrated via a combination of powder X-ray diffraction, differential scanning calorimetry, and imaging techniques (scanning electron microscopy and EDX analysis). Drug release from silica matrices was tested, and a mechanistic model of this release based on the Fick diffusion equation was proposed. The hierarchical structure of the carrier, due to the presence of micrometric macropores and nanometric mesopores, turned out to be critical for the control of the drug phase and drug release from the monoliths. It was found that at low drug content, the presence of an amorphous component in the pores promoted the rapid release of the drug, while at higher drug contents, the presence of macropores favored the crystallization of DEX, which naturally slowed down its release. Both the hierarchical porous structure and the control of the drug phase (amorphous and/or crystalline) were proven important for adjustable (fast or prolonged) release kinetics, desirable for effective pharmacotherapy and patient compliance. Therefore, the developed materials may serve as a versatile formulation platform for the smart manipulation of drug release kinetics.

Controlling the hierarchical microstructure of bioceramic scaffolds by 3D printing of emulsion inks

Mechanical and biological properties constitute the most fundamental requirements for bone tissue engineering (BTE) scaffolds. Nonetheless, existing fabrication strategies find it difficult to prepare highly porous BTE scaffolds for improved biological properties while also preserving sufficient mechanical properties that are compatible with the natural bone. Inspired by the hierarchical porous materials in Nature, hierarchical porous BTE scaffolds can achieve a combination of superior mechanical efficiency and biological functions. With this in mind, this study reports the fabrication of hierarchical porous hydroxyapatite (hpHA) scaffolds by 3D printing of emulsion inks. The scaffolds exhibit high porosity up to 73.7%, featuring 3D printed macropores of 300 – 400 µm and emulsion templated microporosity of < 20 µm. Via formulation of the emulsion inks, such as varying the oil volume and adding Pluronic® F-127, this process demonstrates effective control of the microporosity and pore morphology of the scaffolds. The scaffolds are mechanically compatible with the natural cancellous bone, with compressive strength in the range of 1.41 – 7.84 MPa and Young’s modulus of 57.3 – 304 MPa. Furthermore, the elastic admissible strain (EAS) and specific energy absorption (SEA) of the hpHA scaffolds can be increased up to 4.4% and 1.22 kJ/kg, respectively, indicating greatly enhanced mechanical performances owing to the hierarchical porous structure. Meanwhile, improved cell attachment, spreading and proliferation are observed in these scaffolds with their additional microporosity. Hence, the hpHA scaffolds in this study show great potential in BTE applications, and the reported process of 3D printing of emulsion inks is a promising fabrication strategy for further optimization of highly porous BTE scaffolds.

A novel hierarchical biofunctionalized 3D-printed porous Ti6Al4V scaffold with enhanced osteoporotic osseointegration through osteoimmunomodulation

BackgroundFemoral stem of titanium alloy has been widely used for hip arthroplasty with considerable efficacy; however, the application of this implant in patients with osteoporosis is limited due to excessive bone resorption. Macrophages participate in the regulation of inflammatory response and have been a topic of increasing research interest in implant field. However, few study has explored the link between macrophage polarization and osteogenic–osteoclastic differentiation. The present study aims to develop a novel hierarchical biofunctionalized 3D-printed porous Ti6Al4V scaffold with enhanced osteoporotic osseointegration through immunotherapy.MethodTo improve the osteointegration under osteoporosis, we developed a hierarchical biofunctionalized 3D-printed porous Ti6Al4V scaffold (PT). Biomimetic extracellular matrix (ECM) was constructed inside the interconnected pores of PT in micro-scale. And in nano-scale, a drug cargo icariin@Mg-MOF-74 (ICA@MOF) was wrapped in ECM-like structure that can control release of icariin and Mg2+.ResultsIn this novel hierarchical biofunctionalized 3D-printed porous Ti6Al4V scaffold, the macroporous structure provides mechanical support, the microporous structure facilitates cell adhesion and enhances biocompatibility, and the nanostructure plays a biological effect. We also demonstrate the formation of abundant new bone at peripheral and internal sites after intramedullary implantation of the biofunctionalized PT into the distal femur in osteoporotic rats. We further find that the controlled-release of icariin and Mg2+ from the biofunctionalized PT can significantly improve the polarization of M0 macrophages to M2-type by inhibiting notch1 signaling pathway and induce the secretion of anti-inflammatory cytokines; thus, it significantly ameliorates bone metabolism, which contributes to improving the osseointegration between the PT and osteoporotic bone.ConclusionThe therapeutic potential of hierarchical PT implants containing controlled release system are effective in geriatric orthopaedic osseointegration.Graphical

Construction of Bionic Porous Polyetherimide Structure by an In Situ Foaming Fused Deposition Modeling Process

The biological hierarchical porous structures have excellent properties that are unmatched by artificial fabrication and have great potential for applications in catalysis, adsorption, energy and biomedicine. However, the traditional fabrication methods are difficult to mimic finely hierarchical porous structures and involve complex solution handling and residues. 3D printing is limited by materials and resolution, making it difficult to achieve microporous preparation. Herein, an in situ foaming fusion deposition modeling (FDM) technology using environmentally friendly CO2 as blowing agent to fabricate polyetherimide bionic hierarchical porous structures is applied. The macroscopic pores are obtained by 3D design, while the microporous structure is regulated by changing foaming parameters such as saturation pressure, desorption time, and nozzle temperature. The cell size of the microextruded fibers by FDM nozzle vary from 1.3 to 5.3 μm and the cell density vary from 7.3 × 108 to 1.0 × 1010 cell cm−3 with the change of parameters. In addition, the deposited hierarchical porous scaffold with density of 0.89 g cm−3 possess a compressive strength of 78.9 MPa at 15% strain and a compressive modulus of 1454.3 MPa, which exhibits comparable mechanical property with that of bone.

Leather-like hierarchical porous composites with outstanding electromagnetic interference shielding effectiveness and durability

Delicate microstructure design and suitable matrixes are vital for attaining advanced electromagnetic interference (EMI) shielding materials with lightweight, flexible, durable, processible features. By mimicking natural leather, a three-dimensional (3D) hierarchical porous scaffold integrated with silver nanowires (AgNWs) and anti-abrasion polyurethane (PU) was constructed via a facile dip-coating method at ambient temperature. The interconnected micrometer-sized voids and unique hierarchical structure of this composite benefit uniform AgNWs anchored and the superior shielding performance by significantly enhancing the absorption loss of electromagnetic waves (98.5%). Intriguingly, the leather-like composite possesses the best EMI shielding effectiveness (~110 dB, 8.2–12.4 GHz) compared with reported natural leather-based shielding materials to date. Furthermore, the 3D PU network provides strong adhesion strength and mechanical properties, allowing the stable and durable EMI shielding performance of such composite to resist ultrasonic washing, strong acid, strong base, tape-peeling, bending, and abrasion.

Development of hierarchical porous bioceramic scaffolds with controlled micro/nano surface topography for accelerating bone regeneration

Mimicking hierarchical porous architecture of bone has been considered as a valid approach to promote bone regeneration. In this study, hierarchical porous β-tricalcium phosphate (β-TCP) scaffolds were constructed by combining digital light processing (DLP) printing technique and in situ growth crystal process. Macro/micro hierarchical scaffolds with designed macro pores for facilitating the ingrowth of bone tissue were fabricated by DLP printing. Three types of micro/nano surface topography were obtained by in situ growth crystal process to regulate stem cells behavior. The attachment and proliferation of rat bone marrow mesenchymal stem cells (rBMSCs) were strongly dependent on the surface roughness and the specific surface area. The micro/nano surface topography distinctly facilitated the differentiation of rBMSCs by targeting MAPK, STAT and AKT signaling pathways, in which the sodium hydroxide treatment group showed the highest promoting effect. Furthermore, in vivo results of skull defect repair model of rats indicated that hierarchical scaffolds with micro/nano topographies exhibited appealing bone regeneration capacity. The hierarchical porous bioceramic scaffolds constructed by integrating structural design and physical stimulation of the external surface topography have great potential for rapid bone repair via modulation of microenvironmental regulatory pathways at the bone defect site.

Intimately coupled Mn3O4 nanocrystalline@3D honeycomb hierarchical porous network scaffold carbon for high-performance cathode of aqueous zinc-ion batteries

Herein, 3D honeycomb hierarchical porous network scaffold carbon is synthesized by a unique PVP-SiO2-boiling method with the boiling bubbles as soft template and SiO2 nanospheres as hard template. Then MnO2 nanosheets intimately grow on the carbon matrix and are further decomposed to Mn3O4 nanocrystalline with size of 7–9 nm. The obtained Mn3O4 nanocrystalline@3D honeycomb hierarchical porous network scaffold carbon has abundant mesopores and large specific surface area (92 m2 g−1). When used as a cathode material for zinc-ion batteries, the synthesized composites exhibit high reversible capacity (546.2 mAh g−1 at 0.5 A g−1), remarkable cycling stability (discharge capacity of 97.8 mAh g−1 at 3 A g−1 after 600 cycles) and superior rate capability (15.7 mAh g−1 at 10 A g−1). The kinetics analyses indicate zinc storage mechanism includes diffusion process and capacitive process of Zn2+ and H+ ions, and the capacitive storage is dominant. The outstanding zinc storage performance benefits from the structural advantages. The unique carbon matrix improves electronic conductivity of Mn3O4, facilitates penetration of electrolyte, and well supports Mn3O4 nanocrystalline. The small size and large specific surface area of Mn3O4 nanocrystalline induce significant capacitive storage effect.

Praperation of magnetic Fe,N co-doped nano-sized graphitized carbon aerogel with hierarchical porous structure and its electrochemical and adsorption performance

<p indent=0mm>Nano-sized carbon materials have received intensive preoccupation owing to their extraordinary properties such as high specific surface area, abundant porous structure, and excellent electronic properties. Doping non-metallic element N can effectively modulate the electronic properties of graphene, and doping metallic element Fe can further improve their catalytic activity. To date, applications of Fe-N/C materials are mostly concentrated in supercapacitors, electrochemical double layer electrode materials or adsorption. In this communication, we present a novel route for fabricating Fe,N co-doped nano-sized graphitized carbon materials (FeNC aerogels) by a chelate-carbonization-activation process using chitosan-Fe³⁺ chelate and KOH as precursor and activator respectively. Chitosan-Fe³⁺ chelate aerogel was first formed via sol-gel process, and Fe³⁺ was chelated by chitosan and evenly distributed in 3D networks of aerogel. Then in a nitrogen atmosphere, Chitosan-Fe³⁺ chelate aerogel was pyrolyzed at elevated temperature, and Fe³⁺ was reduced to Fe nanoparticles under the control of chitosan molecular in this carbonization process. At the last stage of KOH activation process, most of the amorphous carbon was etched, and abundant nanoscale pores appeared. Upon mild heating at 70°C in air, core@shell Fe@Fe₃O₄ nanoparticles were formed due to the reaction of Fe nanoparticles inside the Fe-N/C aerogels with oxygen in air. The morphology, structure, and properties of the obtained FeNC aerogels were characterized using field emission scanning electron microscope (FESEM), high-resolution transmission electron microscope (HRTEM), element mapping, Raman spectra, X-ray diffraction analysis (XRD), X-ray photoelectron spectroscopy (XPS), and vibrating-sample-magnetometer (VSM). FeNC aerogels were confirmed to be Fe,N-contained carbon aerogels with 3D hierarchical porous scaffold including macropores, micropores and mesopores, displayed low density and good magnetic response. The as-prepared FeNC(1-100)-K800 showed extremely large specific surface area <sc>(3103 m²/g),</sc> low density <sc>(27 mg/cm³),</sc> and high nitrogen content (4%). The magnetic response ability of FeNC aerogels increased with the increase of Fe content, and Fe was doped as Fe@Fe₃O₄ and Fe-N. FeNC aerogels exhibited good electrocatalytic oxidation-reduction activity, which increased with the increase of Fe doping amount, graphitization degree, and specific surface area. The obtained FeNC(1-20)-K800 with the highest Fe doping amount showed the highest initial potential of <sc>0.98 V,</sc> half-wave potential of <sc>0.82 V</sc> in<sc>0.1 mol/L</sc> KOH electrolyte saturated with O₂, and the highest initial potential of <sc>0.92 V,</sc> half-wave potential of <sc>0.62 V</sc> in<sc>0.05 mol/L</sc> H₂SO₄ electrolyte, respectively. Meanwhile, FeNC aerogels showed good performance of the electric double layer capacity and good cycling stability, and the specific capacitance enhanced with the increase of specific surface area. The specific capacitance, energy density, and power density of FeNC(1-40)-K800 was <sc>253 F/g,</sc> 35.1 W h/kg, and <sc>249.7 W/kg</sc> respectively. And its specific capacitance retention rates were 92.9% and 88.6% respectively after 6000 times and 10000 times continuous charge-discharge cycles at a current density of <sc>10 A/g.</sc> Furthermore, The saturated adsorption capacities of four kinds of dyes: Methyl orange (anionic dye), Rhodamine B (neutral dye), crystal violet and malachite green (cationic dyes), on FeNC(1-20)-K800 all exceeded <sc>400 mg/g,</sc> and the saturated adsorption capacity of malachite green reached up to <sc>816 mg/g.</sc> FeNC aerogel prepared here is a new type of carbon materials with application potential in the field of new energy and environmental remediation. The novel aerogel preparation process we preposed is suitable for large-scale industrial preparation without environmental risks because complex nitrogen and iron treatment steps and expensive equipments are not needed.

A low-temperature-printed hierarchical porous sponge-like scaffold that promotes cell-material interaction and modulates paracrine activity of MSCs for vascularized bone regeneration

Mesenchymal stem cells (MSCs) secrete paracrine trophic factors that are beneficial for tissue regeneration. In this study, a sponge-like scaffold with hierarchical and interconnected pores was developed using low-temperature deposition modeling (LDM) printing. Its effects on the cellular behavior, especially on the paracrine secretion patterns of MSCs, were comprehensively investigated. We found that compared with the scaffolds printed via the fused deposition modeling (FDM) technique, the LDM-printed sponges enhanced the adhesion, retention, survival, and ingrowth of MSCs and promoted cell-material interactions. Moreover, the paracrine functions of the cultured MSCs on the LDM-printed sponges were improved, with significant secretion of upregulated immunomodulatory, angiogenic, and osteogenic factors. MSCs on the LDM-printed sponges exert beneficial paracrine effects on multiple regenerative processes, including macrophage polarization, tube formation, and osteogenesis, verifying the enhanced immunomodulatory, angiogenic, and osteogenic potential. Further protein function assays indicated that focal adhesion kinase (FAK), downstream AKT, and yes-associated-protein (YAP) signaling might participate in the required mechanotransductive pathways, through which the hierarchical porous structures stimulated the paracrine effects of MSCs. In a rat distal femoral defect model, the MSC-laden LDM-printed sponges significantly promoted vascularized bone regeneration. The results of the present study demonstrate that the hierarchical porous biomimetic sponges prepared via LDM printing have potential applications in tissue engineering based on their cell-material interaction promotion and MSC paracrine function modulation effects. Furthermore, our findings suggest that the optimization of biomaterial properties to direct the paracrine signaling of MSCs would enhance tissue regeneration.

Exploring the interconnectivity of biomimetic hierarchical porous Mg scaffolds for bone tissue engineering: Effects of pore size distribution on mechanical properties, degradation behavior and cell migration ability

Interconnectivity is the key characteristic of bone tissue engineering scaffold modulating cell migration, blood vessels invasion and transport of nutrient and waste. However, efforts and understanding of the interconnectivity of porous Mg is limited due to the diverse architectures of pore struts and pore size distribution of Mg scaffold systems. In this work, biomimetic hierarchical porous Mg scaffolds with tailored interconnectivity as well as pore size distribution were prepared by template replication of infiltration casting. Mg scaffold with better interconnectivity showed lower mechanical strength. Enlarging interconnected pores would enhance the interconnectivity of the whole scaffold and reduce the change of ion concentration, pH value and osmolality of the degradation microenvironment due to the lower specific surface area. Nevertheless, the degradation rates of five tested Mg scaffolds were no different because of the same geometry of strut unit. Direct cell culture and evaluation of cell density at both sides of four typical Mg scaffolds indicated that cell migration through hierarchical porous Mg scaffolds could be enhanced by not only bigger interconnected pore size but also larger main pore size. In summary, design of interconnectivity in terms of pore size distribution could regulate mechanical strength, microenvironment in cell culture condition and cell migration potential, and beyond that it shows great potential for personalized therapy which could facilitate the regeneration process.