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Abstract Background The Naples Prognostic Score (NPS), integrating inflammatory and nutritional biomarkers, has been reported to be associated with the prognosis of various malignancies, but there is no report on intrahepatic cholangiocarcinoma (ICC). This study aimed to explore the prognostic value of NPS in patients with ICC. Methods Patients with ICC after hepatectomy were collected, and divided into three groups. The prognosis factors were determined by Cox regression analysis. Predictive efficacy was evaluated by the time-dependent receiver operating characteristic (ROC) curves. Results A total of 174 patients were included (Group 1: 33 (19.0%) patients; Group 2: 83 (47.7%) patients; and Group 3: 58 (33.3%) patients). The baseline characteristics showed the higher the NPS, the higher the proportion of patients with cirrhosis and Child-Pugh B, and more advanced tumors. The Kaplan-Meier curves reflect higher NPS were associated with poor survival. Multivariable analysis showed NPS was an independent risk factor of overall survival (NPS group 2 vs. 1: HR = 1.671, 95% CI: 1.022–3.027, p = 0.009; NPS group 3 vs. 1: HR = 2.208, 95% CI: 1.259–4.780, p = 0.007) and recurrence-free survival (NPS group 2 vs. 1: HR = 1.506, 95% CI: 1.184–3.498, p = 0.010; NPS group 3 vs. 1: HR = 2.141, 95% CI: 2.519–4.087, P = 0.001). The time ROC indicated NPS was superior to other models in predicting prognosis. Conclusions NPS is a simple and effective tool for predicting the long-term survival of patients with ICC after hepatectomy. Patients with high NPS require close follow-up, and improving NPS may prolong the survival time.

Abstract Background and aims Preoperative prediction of microvascular invasion (MVI) using a noninvasive method remain unresolved, especially in HBV-related in intrahepatic cholangiocarcinoma (ICC). This study aimed to build and validate a preoperative prediction model for MVI in HBV-related ICC. Methods Patients with HBV-associated ICC undergoing curative surgical resection were identified. Univariate and multivariate logistic regression analyses were performed to determine the independent risk factors of MVI in the training cohort. Then, a prediction model was built by enrolling the independent risk factors. The predictive performance was validated by receiver operator characteristic curve (ROC) and calibration in the validation cohort. Results Consecutive 626 patients were identified and randomly divided into the training (418, 67%) and validation (208, 33%) cohorts. Multivariate analysis showed that TBIL, CA19-9, tumor size, tumor number, and preoperative image lymph node metastasis were independently associated with MVI. Then, a model was built by enrolling former fiver risk factors. In the validation cohort, the performance of this model showed good calibration. The area under the curve was 0.874 (95% CI: 0.765–0.894) and 0.729 (95%CI: 0.706–0.751) in the training and validation cohort, respectively. Decision curve analysis showed an obvious net benefit from the model. Conclusion Based on clinical data, an easy model was built for the preoperative prediction of MVI, which can assist clinicians in surgical decision-making and adjuvant therapy.

Background: The long-term prognosis of patients with hepatocellular carcinoma (HCC) after surgery remains far from satisfactory, especially in patients with microvascular invasion (MVI). This study aimed to evaluate the potential survival benefit from adjuvant lenvatinib for patients with HCC and MVI. Methods: Patients with HCC after curative hepatectomy were reviewed. All patients were divided into 2 groups according to adjuvant lenvatinib. Propensity score matching (PSM) analysis was used to reduce selection bias and make the results more robust. Survival curves are shown by the Kaplan-Meier (K-M) analysis and compared by the Log-rank test. Univariate and multivariate Cox regression analyses were performed to determine the independent risk factors. Results: Of 179 patients enrolled in this study, 43 (24%) patients received adjuvant lenvatinib. After PSM analysis, 31 pairs of patients were enrolled for further analysis. Survival analysis before and after PSM analysis showed a better prognosis in the adjuvant lenvatinib group (all P < .05). The adverse events associated with oral lenvatinib were acceptable. Multivariate Cox regression analysis showed that adjuvant lenvatinib was an independent protective factor for improving overall survival (OS) (hazard ratio [HR] = 0.455, 95% confidence interval [CI] = 0.249-0.831, P = .001) and recurrence-free survival (RFS) (HR = 0.523, 95% CI = 0.308-0.886, P = .016). Conclusions: Postoperative adjuvant targeted therapy can improve the long-term prognosis of patients with HCC and MVI. Therefore, in clinical practice, oral lenvatinib should be recommended for patients with HCC and MVI to decrease tumor recurrence and improve long-term survival.

PurposeWe evaluated he effects of molecular guided-targeted therapy for intractable cancer. Also, the epidemiology of druggable gene alterations in Chinese population was investigated.Materials and methodsThe Long March Pathway (ClinicalTrials.gov identifier: NCT03239015) is a non-randomized, open-label, phase II trial consisting of several basket studies examining the molecular profiles of intractable cancers in the Chinese population. The trial aimed to 1) evaluate the efficacy of targeted therapy for intractable cancer and 2) identify the molecular epidemiology of the tier II gene alterations among Chinese pan-cancer patients.ResultsIn the first stage, molecular profiles of 520 intractable pan-cancer patients were identified, and 115 patients were identified to have tier II gene alterations. Then, 27 of these 115 patients received targeted therapy based on molecular profiles. The overall response rate (ORR) was 29.6% (8/27), and the disease control rate (DCR) was 44.4% (12/27). The median duration of response (DOR) was 4.80 months (95% CI, 3.33−27.2), and median progression-free survival (PFS) was 4.67 months (95% CI, 2.33−9.50). In the second stage, molecular epidemiology of 17,841 Chinese pan-cancer patients demonstrated that the frequency of tier II gene alterations across cancer types is 17.7%. Bladder cancer had the most tier-II alterations (26.1%), followed by breast cancer (22.4%), and non-small cell lung cancer (NSCLC; 20.2%).ConclusionThe Long March Pathway trial demonstrated a significant clinical benefit for intractable cancer from molecular-guided targeted therapy in the Chinese population. The frequency of tier II gene alterations across cancer types supports the feasibility of molecular-guided targeted therapy under basket trials.

Background & aimsThe long-term prognosis of patients with metabolic syndrome (MS) and hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) after radical hepatectomy remains unclear. The purpose of this study was to elucidate the effect of MS on long-term survival for patients with HBV-related HCC after hepatectomy.MethodsPatients with HBV-HCC after hepatectomy were included. Patients were stratified into MS-HBV-HCC and HBV-HCC groups. Clinical features and surgical outcomes were compared between the two groups, and COX regression analysis was used to determine independent risk factors associated with overall survival (OS) and recurrence-free survival (RFS).Result389 patients (MS-HBV-HCC group: n=50, HBV-HCC group: n=339) were enrolled for further analysis. Baseline characteristics showed that patients with MS-HBV-HCC were associated with a high rate of elderly patients, ASA score, and co-morbid illness, but a lower rate of anatomy hepatectomy. There were no significant differences in perioperative complications. After excluding patients who relapsed or died within 90 days after surgery, multivariate Cox regression analysis showed MS was an independent risk factor of OS (HR 1.68, 95% CI 1.05-2.70, P = 0.032) and RFS (HR 1.78, 95% CI 1.24-2.57, P = 0.002).ConclusionMS is an independent risk factor for poor OS and RFS in HBV-infected HCC patients after radical hepatectomy. This suggests that we need to strengthen postoperative follow-up of the relevant population and encourage patients to develop a healthy lifestyle.

Abstract Background Patients with lung adenocarcinoma (LUAD) have high mortality rate and poor prognosis. The LUAD cells display increased aerobic glycolysis, which generates energy required for their survival and proliferation. Deregulation of Wnt/β-catenin signaling pathway induces the metabolism switching and oncogenesis in tumor cells. RING finger protein 115 (RNF115) is an E3 ligase for ubiquitin-mediated degradation. Although the oncogenic functions of RNF115 have been revealed in breast tumor cells, the effect of RNF115 on lung cancer is still not clear. Methods RNF115 expression and its correlation with the features of LUAD patients were analyzed by using public database and our own cohort. The functions of RNF115 in proliferation and energy metabolism in LUAD cells were explored by downregulating or upregulating RNF115 expression. Results We demonstrated that RNF115 was overexpressed in LUAD tissues and its expression was positively correlated with the poor overall survival of LUAD patients. Moreover, RNF115 overexpression inhibited LUAD cell apoptosis and promoted cellular proliferation and metabolism in LUAD cells. On the contrary, RNF115 knockdown displayed reverse effects. Furthermore, the underlying mechanism of the biological function of RNF115 in LUAD was through regulating Wnt/β-catenin pathway via ubiquitination of adenomatous polyposis coli (APC). Conclusion The current study reveals a close association between RNF115 expression and prognostic conditions in LUAD patients and the oncogenic roles of RNF115 in LUAD at the first time. These findings may help establish the foundation for the development of therapeutics strategies and clinical management for lung cancer in future.

Chromia-forming ferritic stainless steel (FSS) is a highly promising interconnect material for application in solid oxide fuel cells. In this study, initial oxidation of chromium oxides was performed at 500–800 °C to understand the evolution of materials at an early stage. The structural variations in oxide scales were analyzed through scanning electron microscopy, energy dispersive spectroscopy (EDS), transmission electron microscopy (TEM), X-ray diffractometry (XRD), laser confocal microscopy (LSCM), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy. Surface electrochemical properties were investigated through electrochemical impedance spectroscopy to understand how the heat treatment temperature affected surface impedance. Treatment temperatures higher than 700 °C facilitate the diffusion of Cr and Mn, thus allowing ferritic spinels to form on the surface and leading to high electrical conductivity.

Traditional intelligent product design usually focuses on functional design, aiming to generate appropriate structures that would provide required functions. Design specifications are mainly formulized into technical descriptions or values that are related to certain functional or usability requirements. In today’s global market, to in-crease user satisfaction, the appearance design of a product become vital for users to make purchasing decisions. This is particularly true of today’s consumer products such as mobile phones, digital cameras, and other electronic products. In intelligent product appearance design, design specifications are merely described as basic geometric dimensions and types of surface materials. Additionally, the aesthetic considerations and emotional needs of product appearance are seldom discussed when establishing design specifications for product appearance design. In this regard, the objective of this study is to propose a design specification representation framework for intelligent product appearance design considering both emotional and aesthetic aspects. The framework be-gins to investigate user needs by acquiring user aesthetic experience. Based on the notion of aesthetic experience, a detailed representation model of appearance design specifications is provided for satisfying user emotional and aesthetic needs. Finally, a case study of the appearance design of digital cameras is provided to demonstrate the acquisition of user needs and establishment of design specifications based on the proposed framework.

NGCs are considered as an alternative treatment method for treating peripheral nerve injuries in place of nerve autografts. Biomimicry, conductivity, and biodegradability are the properties expected of an ideal NGC. PCL/PAA NGCs with three different concentrations of PAA (2.5, 5 and 7.5%) were fabricated using EHD-jet 3D printing. The mechanical properties of the PCL/PAA NGCs mimic the native human nerve properties (ultimate tensile strength of 6.5 to 11.7 MPa) and the conductivity match that of the amphibian motor nerve fiber myelin sheath (10−6 S/cm). The in vitro degradation studies reveal that they are biodegradable and injury/site-specific biodegradability can be obtained by tuning the PCL/PAA concentration ratio. In addition, PAA being a polyanionic polymer has the potential to act as a cation-exchanger, mimicking the functions of the nerve cortical gel layer, thereby influencing the electrophysiological phenomena called nerve excitation and conduction. Neural differentiation studies with PC12 cells assessed by the Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and immunocytochemistry showed enhanced gene expression with the presence of PAA. Our results suggest that the EHD-jet 3D printed porous conductive PCL/PAA NGCs has the potential to be used in the treatment of peripheral nerve injuries. Keywords: 3D printing, Tissue engineering scaffolds, Peripheral nerve injury, Nerve guide conduits, Electrohydrodynamic jet, Conductive scaffolds

Overlapping melting trajectories and partially-melted powders result in poor surface morphology and high surface roughness values (Ra = ~13.34 μm) of selective laser melted (SLMed) Ti6Al4V alloy. Secondary processing of SLMed components is thus an essential finishing operation to produce functional SLMed parts in precision engineering. This paper investigates the effects of laser scanning strategies (0°, 67.5° and 90° laser scanning schemes) and machining surfaces (top and front surfaces) on the machining performance of SLMed Ti6Al4V alloy in milling, compared with that of annealed ASTM B265 Ti6Al4V alloy. High degree of anisotropy of SLMed Ti6Al4V alloy is reflected in cutting force, surface morphology and surface roughness on different machining surfaces. The machining anisotropy is dominated by the anisotropy of microstructure and mechanical properties of SLMed Ti6Al4V alloy, where the anisotropy weakens following the sequence of 0°, 90° and 67.5° SLMed samples. It is verified that high cutting speed can improve machining anisotropy features of SLMed titanium alloy. The chip shape of SLMed Ti6Al4V alloy is a typical conical spiral chip, and the bending degree and length of chips produced by SLMed Ti6Al4V alloy are larger than those produced by annealed Ti6Al4V alloy.

This paper aims to improve the surface quality of 316L stainless steel parts manufactured by selective laser melting (SLM) using dry mechanical-electrochemical polishing (DMECP). DMECP is an advanced surface finishing method combining the advantages of both mechanical and electrochemical polishing techniques in a more environmentally friendly manner. In this paper, the SLM process-related defects causing poor surface quality are analysed first. The material removal mechanism of DMECP is investigated to continuously remove the oxide layers formed during polishing. Surface morphology and roughness evolution under different polishing conditions are characterised. The top surface roughness can be reduced by over 91% from 8.72 μm to 0.75 μm compared to side surface by over 93% from 12.10 to 0.80 μm. The material removal on the top surface is more efficient than that on the side surface under the same polishing condition. The secondary defects formed during polishing can be removed using mechanical polishing mode. The chemical element composition of the polished surface exhibits almost identical content to the initial 316L powders. Compared with the initial dark and rough surfaces, the results validate the capability of DMECP as an effective tool to improve the SLM surface quality and achieve a mirror finish.

Conductivity is a desirable property of an ideal nerve guide conduit (NGC) that is being considered for peripheral nerve regeneration. Most of the conductive polymers reported in use for fabrication of tissue engineering scaffolds such as polypyrrole (PPy), polyaniline, polythiophene, and poly(3,4-ethylenedioxythiophene) are non-biodegradable and possess weak mechanical properties to be fabricated into 3D structures. In this study, a biodegradable and conductive block copolymer of PPy and Polycaprolactone (PPy-b-PCL) was used to fabricate 3D porous NGCs using a novel electrohydrodynamic jet 3D printing process which offers superior control over fiber diameter, pore size, porosity, and fiber alignment. PCL/PPy scaffolds with three different concentrations of PPy-b-PCL (0.5, 1, and 2% v/v) were fabricated as a mesh (pore size 125 ± 15 μm) and the effect of incorporation of PPy-b-PCL on mechanical properties, biodegradability, and conductivity of the NGCs were studied. The mechanical properties of the scaffolds decreased with the addition of PPy-b-PCL which aided the ability to fabricate softer scaffolds that are closer to the properties of the native human peripheral nerve. With increasing concentrations of PPy-b-PCL, the scaffolds displayed a marked increase in conductivity (ranging from 0.28 to 1.15 mS/cm depending on concentration of PPy). Human embryonic stem cell-derived neural crest stem cells (hESC-NCSCs) were used to investigate the impact of PPy-b-PCL based conductive scaffolds on the growth and differentiation to peripheral neuronal cells. The hESC-NCSCs were able to attach and differentiate to peripheral neurons on PCL and PCL/PPy scaffolds, in particular the PCL/PPy (1% v/v) scaffolds supported higher growth of neural cells and a stronger maturation of hESC-NCSCs to peripheral neuronal cells. Overall, these results suggest that PPy-based conductive scaffolds have potential clinical value as cell-free or cell-laden NGCs for peripheral neuronal regeneration.

The prevalence of peripheral nerve injuries resulting in loss of motor function, sensory function, or both, is on the rise. Artificial Nerve Guide Conduits (NGCs) are considered an effective alternative treatment for autologous nerve grafts, which is the current gold-standard for treating peripheral nerve injuries. In this study, Polycaprolactone-based three-dimensional porous NGCs are fabricated using Electrohydrodynamic jet 3D printing (EHD-jetting) for the first time. The main advantage of this technique is that all the scaffold properties, namely fibre diameter, pore size, porosity, and fibre alignment, can be controlled by tuning the process parameters. In addition, EHD-jetting has the advantages of customizability, repeatability, and scalability. Scaffolds with five different pore sizes (125 to 550 μm) and porosities (65 to 88%) are fabricated and the effect of pore size on the mechanical properties is evaluated. In vitro degradation studies are carried out to investigate the degradation profile of the scaffolds and determine the influence of pore size on the degradation rate and mechanical properties at various degradation time points. Scaffolds with a pore size of 125 ± 15 μm meet the requirements of an optimal NGC structure with a porosity greater than 60%, mechanical properties closer to those of the native peripheral nerves, and an optimal degradation rate matching the nerve regeneration rate post-injury. The in vitro neural differentiation studies also corroborate the same results. Cell proliferation was highest in the scaffolds with a pore size of 125 ± 15 μm assessed by the PrestoBlue assay. The Reverse Transcription-Polymerase Chain Reaction (RT-PCR) results involving the three most important genes concerning neural differentiation, namely β3-tubulin, NF-H, and GAP-43, confirm that the scaffolds with a pore size of 125 ± 15 μm have the highest gene expression of all the other pore sizes and also outperform the electrospun Polycaprolactone (PCL) scaffold. The immunocytochemistry results, expressing the two important nerve proteins β3-tubulin and NF200, showed directional alignment of the neurite growth along the fibre direction in EHD-jet 3D printed scaffolds.

Additive manufacturing, commonly referred to as 3D printing, is a technology that builds three-dimensional structures and components layer by layer. Bioprinting is the use of 3D printing technology to fabricate tissue constructs for regenerative medicine from cell-laden bio-inks. 3D printing and bioprinting have huge potential in revolutionizing the field of tissue engineering and regenerative medicine. This paper reviews the application of 3D printing and bioprinting in the field of pediatrics.

Fe-rich intermetallics, especially β-Fe phase, usually forming in the microstructure of cast aluminum alloys, are very detrimental to mechanical properties. In the present work, the effects of Fe content on phase transformation and microstructures were analyzed using a 3D X-ray microscope. Based on the high-resolution 3D X-ray computed tomography, the 3D characteristics of Fe-rich intermetallics and micropores in the gravity-cast Al-6Si alloys with different Fe contents were investigated. In addition, the effect of intermetallics on the microporosity was discussed. The results show that with increasing the Fe content from 0.10wt.% to 0.60wt.%, the volume fraction of Fe-rich intermetallics and the volume of the largest size Fe-rich intermetallic increased, and the 3D morphology of intermetallics changed from fine flake to network aggregation. As the Fe contents increased, the shrinkage pores were characterized, which were rather complex due to the micropores promoted by the intermetallics interactions.

Characterization of the mechanical properties plays an essential role in the post-processing and evaluation of the functionality of the additively manufactured metallic parts. A number of studies have been focused on the tensile properties of additively manufactured metals. However, the quasi-static compression test of the additively manufactured 316L blocks with different heat-treatment conditions and scanning strategies seems to be overlooked in the literature. This paper aims to provide a comprehensive study of compressive mechanical response in plastic deformation of SS316L fabricated by selective laser melting (SLM). The mechanical response and microstructures in compressive deformation is analyzed for three printing strategies with 0°-, 90°- and 67.5°- scanning and three heat treatment conditions (450 °C for 3 h, 1100 °C for 1 h with furnace cool and 1100 °C for 1 h with water quenching) for selective laser melted (SLMed) stainless steel 316L in comparison with wrought stainless steel 316L in this work. Alteration of mechanical properties, microstructure evolution and compressive deformation mechanism is studied. Melt pool features are not significantly affected by low-temperature heat treatment (450 °C for 3 h) but fully dissolved through high-temperature heat treatment (1100 °C for 1 h). High-temperature heat treatment provides a higher resistance to compressive plastic deformation for SLMed 316L compared with the low-temperature heat-treated and as-built samples where more twinnings are observed. The compressive plastic deformation mechanism of 90°- and 67.5°-scanning samples is similar, which mainly results from twinning-induced plasticity. For 0°-scanning samples, the strong crystallographic texture is the main cause of anisotropic deformation. Modelling and simulation have been conducted to explain the anisotropic deformation mechanism of the 0°-scanning strategy. Simulation results suggest that the morphology difference of laser-scanning tracks and melt pools, which leads to material flow along the laser scanning direction, explains the anisotropic deformation mechanism.

ABSTRACTWith the prosperity of laser powder bed fusion (LPBF) technology, post-processing tends to be increasingly attractive in further improving the performance of the LPBFed parts. In this study, post-heat treatment and electroless plating were performed on the LPBFed 316L stainless steel to investigate the evolution of surface topography, mechanical property and corrosion behaviour. The results show that the as-built part features melt tracks and fine cellular substructures, which presents higher deformation resistance than the cast and recrystallized counterparts. The uniform amorphous Ni-P coating can significantly increase microhardness of as-built 316L stainless steel from ∼300 to ∼800 HV. In addition, the as-built parts with/without coatings have better corrosion resistance than the corresponding cast ones, which can be further improved through 450°C annealing. Moreover, the coatings can also prevent the localised corrosion effectively. Therefore, this study provides available post-processing methods for further improve the performance of LPBFed 316L stainless steel.

Wound healing is a dynamic process that involves a series of molecular and cellular events aimed at replacing devitalized and missing cellular components and/or tissue layers. Recently, extracellular vesicles (EVs), naturally cell-secreted lipid membrane-bound vesicles laden with biological cargos including proteins, lipids, and nucleic acids, have drawn wide attention due to their ability to promote wound healing and tissue regeneration. However, current exploitation of EVs as therapeutic agents is limited by their low isolation yields and tedious isolation processes. To circumvent these challenges, bioinspired cell-derived nanovesicles (CDNs) that mimic EVs were obtained by shearing mesenchymal stem cells (MSCs) through membranes with different pore sizes. Physical characterisations and high-throughput proteomics confirmed that MSC-CDNs mimicked MSC-EVs. Moreover, these MSC-CDNs were efficiently uptaken by human dermal fibroblasts and demonstrated a dose-dependent activation of MAPK signalling pathway, resulting in enhancement of cell proliferation, cell migration, secretion of growth factors and extracellular matrix proteins, which all promoted tissue regeneration. Of note, MSC-CDNs enhanced angiogenesis in human dermal microvascular endothelial cells in a 3D PEG-fibrin scaffold and animal model, accelerating wound healing in vitro and in vivo. These findings suggest that MSC-CDNs could replace both whole cells and EVs in promoting wound healing and tissue regeneration.

The effect of cold metal transfer (CMT) mode on ultra-precision machining (UPM) was investigated to explore phase transformation and potential improvements of surface integrity for a wire and arc additive manufactured (WAAMed)Ti–6Al–4V alloy part. Both CMT and CMT + Pulse (CMT + P) modes are taken into account, which is proved to be the stable methods to fabricate Ti–6Al–4V components. The calculation result shows that the heat input of the CMT + P mode is higher than that of the CMT mode. In the reheated conditions of the CMT + P mode, the α′ → α+β phase transformation occurs, which leads to a decrease in the number of acicular α′ martensite phases decreased and an increase in the size of the lamellar α+β phases. The UPM results showed that the cutting force increase with the cutting speed increases. In addition, the cutting force of the specimens fabricated in CMT mode is a little larger than that in CMT + P mode due to the higher strength and more α′ martensite phases. UPM can create a better surface finish with a reduction of surface roughness up to ∼90%. Moreover, the machine surface quality of the specimens in CMT mode is much better with the surface roughness of ∼0.1 μm at a low cutting speed.

Stress shielding is one of the main problems that lead to bone resorption and revision surgery after implantation. Most of the commercially available metallic non-porous bone implants have a much greater stiffness than the native human bones and are prone to cause stress-shielding. With an open cell structure and intricate architecture, hyperbolic minimal surfaces offer several advantages such as less stress concentration, high permeability and high surface area to volume ratio, thus providing an ideal environment for cell adhesion, migration, and proliferation. This paper explores the use of porous bone implant design based on Triply Periodic Minimal Surfaces (TPMS) which is additively manufactured with ceramic material (Alumina) using Lithography-based Ceramics Manufacturing (LCM) technology. A total of 12 different primitive surface structure unit cells with pore size in the range of 500–1000 μm and porosity above 50% were considered. This is one of the earliest studies reporting the 3D printing of TPMS-based structures using ceramic material. Our results suggest that the choice of material and a porous TPMS-based design led to fabrication of structures with a much lesser compressive modulus comparable with the native bone and hence could potentially be adopted for bone implant design to mitigate the stress-shielding effect.

In this study, polycaprolactone/mineral trioxide aggregate (PCL/MTA) scaffolds were successfully fabricated via an electrohydrodynamic jet (or E-jet) 3D printing system developed by our group. The viscosity of the composited solutions and the key process parameters (i.e. applied voltage and feed rate) were investigated to achieve an optimal process condition. To investigate the potential of PCL/MTA scaffolds to support regeneration ability for dentin related tissue, we seeded dental pulp stem cells on the scaffolds, and compared the results with cell-seeded PCL scaffolds. Assessment of cell viability and proliferation using live/dead cell staining and MTS assay showed compatibility of PCL and PCL/MTA scaffolds for cellular attachment and growth. These scaffolds could be used for fabrication of three-dimensional tissues and in future could be applied to dentin and periodontal tissue engineering applications.

Tissue engineering is a multi-disciplinary area of research bringing together the fields of engineering and life sciences with the aim of fabricating tissue constructs aiding in the regeneration of damaged tissues and organs. Scaffolds play a key role in tissue engineering, acting as the templates for tissue regeneration and guiding the growth of new tissue. The use of stem cells in tissue engineering and regenerative medicine becomes indispensable, especially for applications involving successful long-term restoration of continuously self-renewing tissues, such as skin. The differentiation of stem cells is controlled by a number of cues, of which the nature of the substrate and its innate stiffness plays a vital role in stem cell fate determination. By tuning the substrate stiffness, the differentiation of stem cells can be directed to the desired lineage. Many studies on the effect of substrate stiffness on stem cell differentiation has been reported, but most of those studies are conducted with two-dimensional (2D) substrates. However, the native in vivo tissue microenvironment is three-dimensional (3D) and life science researchers are moving towards 3D cell cultures. Porous 3D scaffolds are widely used by the researchers for 3D cell culture and the properties of such scaffolds affects the cell attachment, proliferation, and differentiation. To this end, the design of porous scaffolds directly influences the stem cell fate determination. There exists a need to have 3D scaffolds with tunable stiffness for directing the differentiation of stem cells into the desired lineage. Given the limited number of biomaterials with all the desired properties, the design of the scaffolds themselves could be used to tune the matrix stiffness. This paper is an in silico study, investigating the effect of various scaffold parameter, namely fiber width, porosity, number of unit cells per layer, number of layers, and material selection, on the matrix stiffness, thereby offering a guideline for design of porous tissue engineering scaffolds with tunable matrix stiffness for directing stem cell lineage specification.