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: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:Biocatalysis is increasingly becoming an alternative method for the synthesis of industrially relevant complex molecules. This can be realized by using enzyme immobilized polysaccharide-based 3D scaffolds as compatible carriers, with defined properties. Especially, immobilization of either single or multiple enzymes on a 3D printed polysaccharide scaffold, exhibiting well-organized interconnected porous structure and morphology, is a versatile approach to access the performance of industrially important enzymes. Here, we demonstrated the use of nanocellulose-based 3D porous scaffolds for the immobilization of glycosyltransferases, responsible for glycosylation in natural biosynthesis. The scaffolds were produced using an ink containing nanofibrillated cellulose (NFC), carboxymethyl cellulose (CMC), and citric acid. Direct-ink-writing 3D printing followed by freeze-drying and dehydrothermal treatment at elevated temperature resulted in chemically cross-linked scaffolds, featuring tunable negative charges (2.2-5.0 mmol/g), pore sizes (10-800 μm), fluid uptake capacity, and exceptional dimensional and mechanical stability in the wet state. The negatively charged scaffolds were applied to immobilize two sugar nucleotide-dependent glycosyltransferases (C-glycosyltransferase, Zbasic2-CGT; sucrose synthase, Zbasic2-SuSy), each harboring a cationic binding module (Zbasic2) to promote charge-based enzyme adsorption. Both enzymes were immobilized at ∼30 mg of protein/g of dry carrier (∼20% yield), independent of the scaffold used. Their specific activities were 0.50 U/mg (Zbasic2-CGT) and 0.19 U/mg (Zbasic2-SuSy), corresponding to an efficacy of 37 and 18%, respectively, compared to the soluble enzymes. The glycosyltransferases were coimmobilized and shown to be active in a cascade reaction to give the natural C-glycoside nothofagin from phloretin (1.0 mM; ∼95% conversion). All enzyme bound scaffolds showed reusability of a maximum of 5 consecutive reactions. These results suggest that the 3D printed and cross-linked NFC/CMC-based scaffolds could present a class of solid carriers for enzyme (co)-immobilization, with promising applications in glycosyltransferase-catalyzed synthesis and other fields of biocatalysis.
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Project description:Polyetheretherketone (PEEK) constitutes a preferred alternative material for orthopedic implants owing to its good mechanical properties and biocompatibility. However, the poor osseointegration property of PEEK implants has limited their clinical applications. To address this issue, in this study, we investigated the mechanical and biological properties of fully porous PEEK scaffolds with different pore sizes both in vitro and in vivo. PEEK scaffolds with designed pore sizes of 300, 450, and 600 μm and a porosity of 60% were manufactured via fused deposition modeling (FDM) to explore the optimum pore size. Smooth solid PEEK cylinders (PEEK-S) were used as the reference material. The mechanical, cytocompatibility, proliferative, and osteogenic properties of PEEK scaffolds were characterized in comparison to those of PEEK-S. In vivo dynamic contrast-enhanced magnetic resonance imaging, microcomputed tomography, and histological observation were performed after 4 and 12 weeks of implantation to evaluate the microvascular perfusion and bone formation afforded by the various PEEK implants using a New Zealand white rabbit model with distal femoral condyle defects. Results of in vitro testing supported the good biocompatibility of the porous PEEK scaffolds manufactured via FDM. In particular, the PEEK-450 scaffolds were most beneficial for cell adhesion, proliferation, and osteogenic differentiation. Results of in vivo analysis further indicated that PEEK-450 scaffolds exhibited preferential potential for bone ingrowth and vascular perfusion. Together, our findings support that porous PEEK implants designed with a suitable pore size and fabricated via three-dimensional printing constitute promising alternative biomaterials for bone grafting and tissue engineering applications with marked potential for clinical applications.
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Project description:Rotator cuff tears are the most common conditions in sports medicine and attract increasing attention. Scar tissue healing at the tendon-bone interface results in a high rate of retears, making it a major challenge to enhance the healing of the rotator cuff tendon-bone interface. Biomaterials currently employed for tendon-bone healing in rotator cuff tears still exhibit limited efficacy. 3D printing, a promising technology, enables the customization of scaffold shapes and properties. Bone marrow mesenchymal stem cells (BMSCs) have multi-differentiation potential and valuable immunomodulatory effects. Basic fibroblast growth factor (bFGF), known for its role in proliferation, has been reported to promote osteogenesis. These properties make them applicable in tissue engineering. In this study, we developed a 3D-printed PCL scaffold loaded with bFGF and BMSCs (PCLMF) to restore the tendon-bone interface and regulate the local inflammatory microenvironment. The PCLMF scaffolds significantly improved the biomechanical strength, histological score, and local bone mineral density at regenerated entheses at 2 weeks post-surgery and achieved optimal performance at 8 weeks. Furthermore, PCLMF scaffolds facilitated BMSC osteogenic differentiation and suppressed adipogenic differentiation both in vivo and in vitro. In addition, RNA-seq showed that PCLMF scaffolds could regulate macrophage polarization and inflammation through the MAPK pathway. The implanted scaffold demonstrated excellent biocompatibility and biosafety. Therefore, this study proposes a promising and practical strategy for enhancing tendon-bone healing in rotator cuff tears.
2024-09-30 | GSE277270 | GEO
Project description:Regenerating critical-sized long bone defects poses substantial challenges due to limitations of autografts and processed allografts. Biomaterial scaffolds offer versatile alternatives, yet their effectiveness is often constrained by their limited innate osteoinductivity. While growth factors and cells can enhance osteoinduction, the inclusion of biologics in biomaterial scaffolds creates regulatory challenges for clinical translation. To address this, here we describe three-dimensional (3D) printed polycaprolactone (PCL) scaffolds for temporally controlled delivery of osteoimmunomodulatory amorphous calcium phosphate-chitosan nanoparticles (ACPC-NP). In vitro, the ACPC-NP exhibit concentration dependent effects on osteoblasts, monocytes, and osteoclasts. At increasing concentrations up to 500 μg/ml, these nanoparticles stimulate osteogenesis, modulate M2/M1 macrophage polarization, and inhibit osteoclast maturation and activity. Leveraging these concentration-dependent effects in vivo through temporally controlled release of ACPC-NP from 3D-printed PCL scaffolds, we observe the complete regeneration and the restoration of biomechanical strength of critically sized radial defects in rats. Such healing is absent in defects implanted with bare PCL scaffolds or those loaded with calcium-phosphate microparticles. The tunable osteoimmunomodulation by the NP underscore the translational potential of this technology to yield structurally sound and functionally robust bone regeneration outcomes.
2024-07-02 | GSE262295 | GEO
Project description:3D-printed Scaffolds to Regulate the Translational Balance between Vascularization and Bone Metabolism
| PRJNA1034004 | ENA