A Review of 3D Printing Technology for Medical Applications

Scaffold design necessitates the consideration of mechanical properties and fluid flow dynamics as the main factors in the development of such materials. The mechanical behavior of bone scaffolds is characterized by properties such as elastic modulus and compressive strength. In terms of fluid flow dynamics, within bone scaffolds, permeability is an important parameter that affects cells' biological activities, and flow-induced shear stress is used as a mechanical stimulant of cell growth. In this study, two scaffold architectures with gyroid and lattice-based rectangular unit cells were designed to analysis the effective elastic moduli, compressive strength, permeability and fluid flow-induced wall shear stress as functions of porosity. Six levels of porosity (65%, 70%, 75%, 80%, 85% and 90%) were assigned to the scaffold architectures, and 12 models were developed. Scaffold deformation under static loading, compressive strength based on von Mises criteria, pressure drop, and fluid flow-induced wall shear stress in the scaffolds were then determined by finite element analysis. In both the scaffold types, models with higher porosity exhibited lower mechanical properties. Under the same porosity, the lattice-based scaffolds exhibited a Young's modulus and a compressive strength higher than those achieved by the gyroid scaffolds. With reference to geometrical parameters and the derived pressure drop from the computational fluid dynamics (CFD) analysis, scaffolds permeability was calculated using Darcy's law. In both the scaffold architectures, high porosity increased permeability and decreased wall shear stress. In the same porosity, the lattice-based models exhibited higher permeability and lower wall shear stress than did the gyroid models. On the basis of the results on elastic modulus and permeability, the models that most effectively mimic the properties of cancellous bones were identified.

Finite element analysis of mechanical behavior, permeability and fluid induced wall shear stress of high porosity scaffolds with gyroid and lattice-based architectures.

Mechanical and in vitro study of an isotropic Ti6Al4V lattice structure fabricated using selective laser melting

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Adiponectin increases bone mass by suppressing osteoclast and activating osteoblast

Recent studies have demonstrated the stimulatory effects of adiponectin on bone formation, but the mechanism underlying these effects remains unclear. The Wnt/β-catenin pathway, one of the most important pathways in osteogenesis, has rarely been associated with the osteogenic effects of adiponectin in previous studies. The present study was designed to investigate the effects of adiponectin on bone mesenchymal stem cell (BMSC) osteogenic differentiation and bone formation through the Wnt/β-catenin pathway. We detected adiponectin receptor expression in BMSCs, constructed a recombinant adenovirus containing the human adiponectin gene, and then used the adenovirus to transfect BMSCs in vitro or injected the adenovirus into bone defect areas in animal models. Wnt/β-catenin pathway and osteogenesis were detected by real-time PCR, western blotting, immunofluorescence, HE staining and micro-CT. In both our in vivo and in vitro experiments, we detected higher gene and protein expression levels of the Wnt/β-catenin pathway-related factors β-catenin and cyclinD1 in adiponectin transgenic BMSCs and rats. Similar results were noted regarding the gene and protein expression levels of osteogenesis-related genes. In addition, more new bone formation was observed in the adiponectin-treated groups. Our results indicate that adiponectin could facilitate BMSC osteogenic differentiation and osteogenesis, and the Wnt/β-catenin pathway was involved in the osteogenic effect of adiponectin.

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Adiponectin regulates BMSC osteogenic differentiation and osteogenesis through the Wnt/β-catenin pathway.

Fabrication and characterization of selective laser melting printed Ti–6Al–4V alloys subjected to heat treatment for customized implants design

Background:
The accuracy of three-dimensional (3D) reconstructions from cone-beam computed tomography (CBCT) has been particularly important in dentistry, which will affect the effectiveness of diagnosis, treatment plan, and outcome in clinical practice. The aims of this study were to assess the linear, volumetric, and geometric accuracy of 3D reconstructions from CBCT and to investigate the influence of voxel size and CBCT system on the reconstructions results.

Accuracy Assessment of Three-dimensional Surface Reconstructions of In vivo Teeth from Cone-beam Computed Tomography.

Human jaw bone marrow mesenchymal stem cells (h-JBMMSCs) are multipotent progenitor cells with osteogenic differentiation potential. The relationship between adiponectin (APN) and the metabolism of h-JBMMSCs has not been fully elucidated, and the underlying mechanism remains unclear. The aim of the study was to investigate the effect and mechanism of APN on h-JBMMSC metabolism. h-JBMMSCs were obtained from the primary culture of human jaw bones and treated with or without APN (1 µg/mL). Osteogenesis-related gene expression was evaluated by real-time polymerase chain reaction (PCR), alkaline phosphatase (ALP) activity assay, and enzyme-linked immunosorbent assay (ELISA). To further investigate the signaling pathway, mechanistic studies were performed using Western blotting, immunofluorescence, lentiviral transduction, and SB202190 (a specific p38 inhibitor). Alizarin Red staining showed that APN promoted h-JBMMSC osteogenesis. Real-time PCR, ALP assay, and ELISA showed that ALP, osteocalcin (OCN), osteopontin, and integrin-binding sialoprotein were up-regulated in APN-treated cells compared to untreated controls. Immunofluorescence revealed that adaptor protein containing a pleckstrin homology domain, phosphotyrosine domain, and leucine zipper motif (APPL1) translocated from the nucleus to the cytoplasm with APN treatment. Additionally, the phosphorylation of p38 mitogen-activated protein kinase (MAPK) increased over time with APN treatment. Moreover, knockdown of APPL1 or p38 MAPK inhibition blocked the expression of APN-induced calcification-related genes including ALP, Runt-related transcription factor 2 (RUNX2), and OCN. Furthermore, Alizarin Red staining of calcium nodes was not increased by the knockdown of APPL1 or p38 inhibition. Our data suggest that this regulation is mediated through the APPL1-p38 MAPK signaling pathway. These findings collectively provide evidence that APN induces the osteogenesis of h-JBMMSCs through APPL1-mediated p38 MAPK activation.

Adiponectin Promotes Human Jaw Bone Marrow Stem Cell Osteogenesis

A plastic and biodegradable bone substitute consists of poly (L-lactic-co-glycolic) acid and 30 wt % β-tricalcium phosphate has been previously fabricated, but its osteogenic capability required further improvement. We investigated the use of globular adiponectin (gAPN) as an anabolic agent for tissue-engineered bone using this scaffold. A qualitative analysis of the bone regeneration process was carried out using μCT and histological analysis 12 weeks after implantation. CBCT (Cone Beam Computed Tomography) superimposition was used to characterise the effect of the different treatments on bone formation. In this study, we also explored adiponectin's (APN) influence on primary cultured human jaw bone marrow mesenchymal stem cells gene expressions involved in the osteogenesis. We found OPEN ACCESS Int. J. Mol. Sci. 2015, 16 24947 that composite scaffolds loaded with gAPN or bone morphogenetic protein 2 (BMP2) exhibited significantly increased bone formation and mineralisation following 12 weeks in the extraction sockets of beagle dogs, as well as enhanced expression of osteogenic markers. In vitro investigation revealed that APN also promoted osteoblast differentiation of primary cultured human jaw bone marrow mesenchymal stem cells (h-JBMMSCs), accompanied by increased activity of alkaline phosphatase, greater mineralisation, and production of the osteoblast-differentiated genes osteocalcin, bone sialoprotein and collagen type I, which was reversed by APPL1 siRNA. Therefore, the composite scaffold loaded with APN exhibited superior activity for guided bone regeneration compared with blank control or Bio-Oss® (a commercially available product). The composite scaffold with APN has significant potential for clinical applications in bone tissue engineering.

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The Osteogenesis Effect and Underlying Mechanisms of Local Delivery of gAPN in Extraction Sockets of Beagle Dogs.

Implants treated by sandblasting acid etching (SLA) have been demonstrated to be capable of hastening the osseointegration process. However, they suffer from some shortcomings, which include contamination by the grit-blasting materials and residual acid solution, as well as limited satisfaction of certain requirements for oral use. As an alternative procedure that enables the fabrication of customized implants with complex geometries, the use of selective laser melting (SLM) to fabricate implants has recently drawn considerable attention. In the present work, SLM-printed substrates were compared with commercially available SLA-treated plates in terms of their surface characteristics and biological performance. The wettability and roughness of SLM-printed substrates were found to be significantly better. Moreover, in vitro evaluations revealed that the SLM surface facilitated the attachment and proliferation of human bone marrow mesenchymal stem cells (hBMSCs), and induced accelerated osteogenic progression, as indicated by the observed increased alkaline phosphatase (ALP) activity, elevated expression of osteo-related mRNA, and intense calcium deposition. Overall, the SLMbased substrates exhibited suitable cytocompatibility and osteophilic properties, which are expected to enhance in vivo bone-implant contact and osseointegration. A comprehensively optimized SLM-printed substrate mimics a more osteophilic environment and affords an alternative means of producing customized implants in oral implantology.

Songhe Lu

Papers

Fabrication and characterization of selective laser melting printed Ti–6Al–4V alloys subjected to heat treatment for customized implants design

Accuracy Assessment of Three-dimensional Surface Reconstructions of In vivo Teeth from Cone-beam Computed Tomography.

Adiponectin Promotes Human Jaw Bone Marrow Stem Cell Osteogenesis

The Osteogenesis Effect and Underlying Mechanisms of Local Delivery of gAPN in Extraction Sockets of Beagle Dogs.

Osteogenic Comparison on Selective Laser Melting Printed and Sandblasting-Acid-Etching Ti Substrates for Customized Implant Applications