Multiscale architecture design of 3D printed biodegradable Zn-based porous scaffolds for immunomodulatory osteogenesis
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE262010 | GEO | 2024/03/23
REPOSITORIES: GEO
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Project description: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.
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Project description: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.
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Project description: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.
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Project description:In order to increase the bone forming ability of MBG-PCL composite scaffold, microporosity was created in the struts of 3D-printed MBG-PCL scaffolds for the manufacturing of a construct with a multiscale porosity consisting of meso- micro- and macropores. 3D-printing imparted macroporosity while the microporosity was created by porogen removal from the struts, and the MBG particles were responsible for the mesoporosity. The scaffolds were 3D-printed using a mixture of PCL, MBG and phosphate buffered saline (PBS) particles, subsequently leached out. Microporous-PCL (pPCL) as a negative control, microporous MBG-PCL (pMBG-PCL) and non-microporous-MBG-PCL (MBG-PCL) were investigated. Scanning electron microscopy, mercury intrusion porosimetry and micro-computed tomography demonstrated that the PBS removal resulted in the formation of micropores inside the struts with porosity of around 30% for both pPCL and pMBG-PCL, with both constructs displaying an overall porosity of 8090%. In contrast, the MBG-PCL group had a microporosity of 6% and an overall porosity of 70%. Early mineralisation was found in the pMBG-PCL post-leaching out and this resulted in the formation a more homogeneous calcium phosphate layer when using a biomimetic mineralisation assay. Mechanical properties ranged from 5 to 25 MPa for microporous and non-microporous specimens, hence microporosity was the determining factor affecting compressive properties. MC3T3-E1 metabolic activity was increased in the pMBG-PCL along with an increased production of RUNX2. Therefore, the microporosity within a 3D-printed bioceramic composite construct may result in additional physical and biological benefits.
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Project description:Introduction: Simulating hydrophobic-hydrophilic composite face with hierarchical porous and fibrous architectures of bone extracellular matrix (ECM) is a key aspect in bone tissue engineering. This study focused on the fabrication of new three-dimensional (3D) scaffolds containing polytetrafluoroethylene (PTFE), and polyvinyl alcohol (PVA), with and without graphene oxide (GO) nanoparticles using the chemical cross-linking and freeze-drying methods for bone tissue application. The effects of GO on physicochemical features and osteoinduction properties of the scaffolds were evaluated through an in vitro study. Methods: After synthesizing the GO nanoparticles, two types of 3D scaffolds, PTFE/PVA (PP) and PTFE/PVA/GO (PPG), were developed by cross-linking and freeze-drying methods. The physicochemical features of scaffolds were assessed and the interaction of the 3D scaffold types with human adipose mesenchymal stem cells (hADSCs) including attachment, proliferation, and differentiation to osteogenic like cells were investigated. Results: GO nanoparticles were successfully synthesized with no agglomeration. The blending of PTFE as a hydrophobic polymer with PVA polymer and GO nanoparticles (hydrophilic compartments) were successful. Two types of 3D scaffolds had nano topographical structures, good porosities, hydrophilic surfaces, thermal stabilities, good stiffness, as well as supporting the cell attachments, proliferation, and osteogenic differentiation. Notably, GO incorporating scaffolds provided a better milieu for cell behaviors. Conclusion: Novel multiscale porous nanofibrous 3D scaffolds made from PTFE/ PVA polymers with and without GO nanoparticles could be an ideal candidate for bone tissue engineering as a 3D template.
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Project description:Over the past two decades, electrospinning has emerged as a common technique to produce biomedical scaffolds composed of ultrafine fibers formed from many natural and synthetic polymers. A major advantage of this technique is the ability to produce scaffolds that resemble the native extracellular matrix in physical, chemical, and topological properties. However, scaffolds fabricated via electrospinning are not formed with a controlled architecture and typically do a poor job of directing cell growth into prescribed structures for tissue/organ development. To address these weaknesses, 3D bioprinting has recently been used to develop scaffolds that have a highly organized and precise global topology. Unfortunately, these 3D bioprinted scaffolds do not typically resemble the native extracellular matrix in physical properties, such as porosity, fiber diameter, and pore size (e.g., the microarchitecture). Thus, the goal of the current study was to develop a technique that harnesses the intrinsic advantages of both conventional electrospinning and 3D bioprinting techniques to produce scaffolds that have the potential to be used within biomedical applications. The physical properties of formed 3D printed electrospun scaffolds were compared with conventional electrospun and 3D printed scaffolds. Further, we conducted initial proof-of-concept biocompatibility studies to illustrate the applicability of the scaffolds within vascular applications. Our results illustrate that 3D printed electrospun scaffolds can be developed, via our technique, that have highly tailored and organized arbitrary geometries with scaffold properties in the range of the innate extracellular matrix. In addition, these scaffolds were shown to support endothelial cell growth. Therefore, we illustrate the development and testing of a novel bioscaffold fabrication technique that may be used for many tissue engineering and regenerative medicine applications, which allows for the direct printing of electrospun scaffolds into well-defined macro-scale geometries that also retain the micro-structures commonly observed in electrospun scaffolds.
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