Gradient matters via filament diameter-adjustable 3D printing.

Gradient matters with hierarchical structures endow the natural world with excellent integrity and diversity. Currently, direct ink writing 3D printing is attracting tremendous interest, and has been used to explore the fabrication of 1D and 2D hierarchical structures by adjusting the diameter, spacing, and angle between filaments. However, it is difficult to generate complex 3D gradient matters owing to the inherent limitations of existing methods in terms of available gradient dimension, gradient resolution, and shape fidelity. Here, we report a filament diameter-adjustable 3D printing strategy that enables conventional extrusion 3D printers to produce 1D, 2D, and 3D gradient matters with tunable heterogeneous structures by continuously varying the volume of deposited ink on the printing trajectory. In detail, we develop diameter-programmable filaments by customizing the printing velocity and height. To achieve high shape fidelity, we specially add supporting layers at needed locations. Finally, we showcase multi-disciplinary applications of our strategy in creating horizontal, radial, and axial gradient structures, letter-embedded structures, metastructures, tissue-mimicking scaffolds, flexible electronics, and time-driven devices. By showing the potential of this strategy, we anticipate that it could be easily extended to a variety of filament-based additive manufacturing technologies and facilitate the development of functionally graded structures.

Fractal Design Boosts Extrusion-Based 3D Printing of Bone-Mimicking Radial-Gradient Scaffolds.

Although extrusion-based three-dimensional (EB-3D) printing technique has been widely used in the complex fabrication of bone tissue-engineered scaffolds, a natural bone-like radial-gradient scaffold by this processing method is of huge challenge and still unmet. Inspired by a typical fractal structure of Koch snowflake, for the first time, a fractal-like porous scaffold with a controllable hierarchical gradient in the radial direction is presented via fractal design and then implemented by EB-3D printing. This radial-gradient structure successfully mimics the radially gradual decrease in porosity of natural bone from cancellous bone to cortical bone. First, we create a design-to-fabrication workflow with embedding the graded data on basis of fractal design into digital processing to instruct the extrusion process of fractal-like scaffolds. Further, by a combination of suitable extruded inks, a series of bone-mimicking scaffolds with a 3-iteration fractal-like structure are fabricated to demonstrate their superiority, including radial porosity, mechanical property, and permeability. This study showcases a robust strategy to overcome the limitations of conventional EB-3D printers for the design and fabrication of functionally graded scaffolds, showing great potential in bone tissue engineering.

Biomaterials for bone tissue engineering scaffolds: a review.

Bone tissue engineering has been continuously developing since the concept of "tissue engineering" has been proposed. Biomaterials that are used as the basic material for the fabrication of scaffolds play a vital role in bone tissue engineering. This paper first introduces a strategy for literature search. Then, it describes the structure, mechanical properties and materials of natural bone and the strategies of bone tissue engineering. Particularly, it focuses on the current knowledge about biomaterials used in the fabrication of bone tissue engineering scaffolds, which includes the history, types, properties and applications of biomaterials. The effects of additives such as signaling molecules, stem cells, and functional materials on the performance of the scaffolds are also discussed.

HUWE1 upregulation has tumor suppressive effect in human prostate cancer cell lines through c-Myc.

PURPOSE: We investigated the regulatory function of HECT, UBA and WWE domain-containing protein 1, E3 ubiquitin protein ligase (HUWE1) in human prostate cancer (CaP). METHODS: HUWE1 was overexpressed (through transfection) or downregulated (through lentiviral transduction) in CaP cell lines, PC3 and DU145 cells. The functions of HUWE1 overexpression or downregulation on CaP cancer cell proliferation, migrationin vitro, and explant in vivo were examined. In addition, the regulatory effect of HUWE1 on c-Myc expression was assessed. In HUWE1-overexpressed CaP cells, c-Myc was further upregulated to assess whether c-Myc was directly involved in HUWE1-induced regulation in CaP. RESULTS: HUWE1 overexpression inhibited CaP proliferation and migrationin vitro, and explant growth in vivo. On the other hand, HUWE1 downregulation had no effects on CaP in vitro. C-Myc was downregulated in HUWE1-overexpressed, but un-changed in HUWE1-downregulated, CaP cells. Further upregulating c-Myc in HUWE1-overexpressed CaP cells reversed the tumor-suppressing effects by HUWE1-overexpression on cancer proliferation and migration in vitro. CONCLUSION: HUWE1 overexpression could functionally suppress CaP development bothin vitro and in vivo, possibly by inverse regulation on c-Myc.

PlncRNA-1 induces apoptosis through the Her-2 pathway in prostate cancer cells.

To determine whether PlncRNA-1 induces apoptosis in prostate cancer cells through the Her-2 pathway. The expression of PlncRNA-1, Her-2, and related cyclin proteins in 23 cases of prostate cancer and adjacent normal tissues was analyzed and compared. LNCaP cells were divided into a control group and an LNCaP-PlncRNA-1-siRNA experimental group. Normal prostate RWPE-1 cells were divided into an RWPE-1 control group and an RWPE-1-PlncRNA-1 experimental group. After PlncRNA-1 silencing and overexpression, changes in Her-2 and cyclinD1 expression levels were detected both in vivo and in vitro. In prostate cancer tissues, Her-2 and PlncRNA-1 were highly expressed and significantly correlated. In LNCaP cells, the expression of Her-2 and cyclinD1 decreased following the downregulation of PlncRNA-1 as assessed by real-time PCR and Western blotting. In RWPE-1 cells, the expression of Her-2 and cyclinD1 increased following PlncRNA-1 overexpression. Flow cytometry revealed that the proportion of LNCaP cells in G2/M phase was significantly increased after PlncRNA-1 silencing and that the proportion of RWPE-1 cells in G2/M phase was significantly decreased after PlncRNA-1 overexpression. Furthermore, animal experiments validated these results. In conclusion, in prostate cancer, PlncRNA-1 regulates the cell cycle and cyclinD1 levels and can also regulate proliferation and apoptosis in prostate cancer cells through the Her-2 pathway.

[Focusing on MRI-suspected lesions in targeted transrectal prostate biopsy guided by MRI-TRUS fusion imaging for the diagnosis of prostate cancer].

OBJECTIVE: To improve the accuracy of prostate cancer (PCa) detection by focusing biopsy on the suspected lesion manifested by MRI with the total number of biopsy cores relatively unchanged. METHODS: A prospective randomized analysis was performed on 262 cases of suspected PCa detected by multi-parametric MRI (mp-MRI), each with a single suspected lesion with 10 µg/L≤ PSA <20 µg/L. All the patients underwent targeted transrectal prostate biopsy guided by fusion imaging of MRI with transrectal ultrasonography (TRUS), using the 6X+6 strategy (6 cores in the suspected region and another 6 in the systematic prostate) for 134 cases and the traditional 12+2X method (12 cores in the systematic prostate and 2 in the suspected region) for the other 128. Comparisons were made between the two methods in the PCa detection rate in the cases of suspected lesion, total PCa detection rate, incidence of post-biopsy complications, and Gleason scores. Analyses were performed on the prostate imaging reporting and data system (PI-RADS) score, location, transverse section, and diameter of the suspected lesion. RESULTS: Both the total PCa detection rate and that in the cases of suspected lesion were significantly higher in the 6X+6 (44.8% and 37.3%) than in the 12+2X group (37.5% and 27.3%) (P<0.05). MRI showed that the suspected lesions were mostly (45%) located in the middle part of the prostate, the mean area of the transverse section was (0.48±0.11) cm2, and the mean diameter of the tumor was (8.51±2.21) mm. The results of biopsy showed that low-grade tumors (Gleason 3+3=6) accounted for 68% in the 6X+6 group and 71% in the 12+2X group. No statistically significant differences were found between the two groups in the incidence rate of post-biopsy complications. CONCLUSIONS: Compared with the traditional 12+2X method, for the suspected lesion manifested by mp-MRI, focusing biopsy on the suspected region with the 6X+6 strategy can achieve a higher PCa detection rate without increasing the incidence of complications.

Modified transurethral incision for primary bladder neck obstruction in women: a method to improve voiding function without urinary incontinence.

OBJECTIVE: To describe the modified surgical technique and report the long-term outcomes of modified transurethral incision for the treatment of primary bladder neck obstruction in women. METHODS: A total of 30 women were diagnosed with primary bladder neck obstruction from the videourodynamic study findings according to the Blaivas-Groutz nomogram for female bladder outlet obstruction. Patients with neurogenic, traumatic, anatomic, or iatrogenic causes of obstruction were excluded. The transurethral incision of the bladder neck was performed in all patients, with the modification of incising at 4 different sites on the bladder neck, at the 3-, 6-, 9-, and 12-o'clock positions. The urodynamic results and clinical improvement in voiding symptoms were assessed before surgery and 3, 48, and 60 months after treatment. RESULTS: Follow-up data were available for 30 (100%), 28 (93%), and 25 (83%) of the 30 patients at 3, 48, and 60 months postoperatively, respectively. During the 5-year follow-up, the mean International Prostate Symptom Score decreased from 23.3 to 5.9. The mean quality of life scores decreased from 4.4 to 2.1. The mean peak urinary flow rate increased from 7.61 to 17.53 mL/s. The mean postvoid residual urine volume decreased from 185.11 to 28.75 mL. The mean voiding detrusor pressure decreased from 62.12 to 21.92 cm H2O. All 25 patients had improvement in both objective and subjective voiding functions 5 years after this modified treatment. Only 1 woman (3%) had mild stress incontinence postoperatively and was cured after the patient performed levator ani exercises. CONCLUSION: The modified transurethral bladder neck incision is effective in the long term in relieving voiding difficulties owing to primary bladder neck obstruction in women without urinary incontinence.