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Biocompatibility and osteointegration capability of β-TCP manufactured by stereolithography 3D printing: In vitro study

  • Jialiang Li , Jiaxi Li , Yubing Yang , Xijing He EMAIL logo , Xinyu Wei , Qinghua Tan , Yiqun Wang , Siyue Xu , Sue Chang and Weiwei Liu
Published/Copyright: January 24, 2023
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Open Life Sciences
From the journal Open Life Sciences Volume 18 Issue 1

Abstract

Beta-tricalcium phosphate (β-TCP) bioceramics have an inorganic composition similar to the human bone. While conventional methods can only produce ceramic scaffolds with poor controllability, the advancement of 3D-printing, especially stereolithography, made it possible to manufacture controllable, highly precise, micropore ceramic scaffolds. In this study, the stereolithography was applied to produce β-TCP bioceramics, while ZrO2, Al2O3, Ti6Al4V, and polyetheretherketone (PEEK) were used as controls. Phase analysis, water contact angle tests, and Micro-CT were applied to evaluate the surface properties and scaffold. Hemolytic toxicity, cell proliferation, and morphological assessment were performed to evaluate the biocompatibility. Alkaline phosphatase (ALP) level, mineralization, and qRT-PCR were measured to evaluate the osteointegration. During the manufacturing of β-TCP, no evident impurity substance and hemolytic toxicity was found. Cells on β-TCP had good morphologies, and their proliferation capability was similar to Ti6Al4V, which was higher than the other materials. Cells on β-TCP had higher ALP levels than PEEK. The degree of mineralization was significantly higher on β-TCP. The expression of osteogenesis-related genes on β-TCP was similar to Ti6Al4V and higher than the other materials. In this study, the β-TCP produced by stereolithography had no toxicity, high accuracy, and excellent osteointegration capability, thus resulting as a good choice for bone implants.

Graphical abstract

Keywords: β-TCP; bioceramics; stereolithography; biocompatibility; osteogenesis

1 Introduction

The incidence of bone diseases, such as trauma, tumor, and degeneration, has been gradually increasing every year, resulting in ever-higher requirements for bone substitutes in clinical practice [1,2], and stem cell-based bone regeneration [3,4]. Autogenous bone graft is the gold standard of the bone implant; however, the source of autogenous bone is limited, and harvesting could induce secondary injuries. Therefore, an autogenous bone graft is rarely used to treat large segmental bone defects [5]. Metal bone implants, such as Ti–6Al–4V (Ti6Al4V, a class of medical titanium alloys), could provide stable mechanical support and good clinical effects [1,6,7]. According to Wolff’s Law (the growth, absorption, and reconstruction of bone are related to the mechanical stress of bone), however, metal has a far higher elastic modulus than human bones and thus could lead to stress-shielding, consequently inducing osteoporosis [8–10]. In addition, metal debris could also induce the aseptic loosening of implants [11]. Polymer materials such as polyetheretherketone (PEEK) have a similar elastic modulus as human bones and have been widely applied in spinal, oral, and maxillofacial surgeries [12,13]. Yet, PEEK could promote the formation of fibrous tissue with surrounding tissues, thus influencing the efficiency of osteointegration of bone implants [14,15].

The major inorganic components of human bone are calcium phosphate (CaP), which makes it possible to treat bone defects by bioceramics [16]. Some commonly used bioceramic materials, such as ZrO2 and Al2O3, are characterized by high toughness, corrosion resistance, and wearing resistance and are mainly used in oral and maxillofacial surgeries [17,18]. Hydroxyapatite (HA) is one of the components of human bone that has high biocompatibility and osteogenesis capability. However, HA is difficult to process and has poor degradability, which challenges its use as a bone implant [19,20]. On the other hand, beta-tricalcium phosphate (β-TCP), one of the CaP ceramics, has better osteogenesis capability and degradability than HA, making it to become a good choice for bioceramic material of bone implants [21,22].

Micropore structures are required for bone implants as they provide spaces for the growth of cells and blood vessels and consequently maintain long-term stability [23–25]. Due to the high melting point and toughness, as well as poor flexibility, the sophisticated micropore structures are difficult to be manufactured for bioceramics. The conventional methods, which include gas foaming, particulate leaching, and freeze-drying, can be used to produce ceramic scaffolds with high porosity. Nonetheless, the morphological parameters of micropores are uncontrollable, and the interconnection of micropores cannot be guaranteed, which is unfavorable for the growth of cells and tissues [26–28]. Fortunately, the advancement of 3D printing (3DP) techniques has made it possible to manufacture sophisticated, highly precise micropore structures [29–33]. The layer-by-layer printing also favors maintaining the integrity of micropore structures. In order to improve the mechanical properties, it is necessary to increase the solid components of the ceramic powder-photosensitive resin composite slurry in the printing process. However, this inevitably increases the viscosity of the slurry, consequently reducing the controllability of printing [34].

The application of stereolithography (SLA) technique allows for the rapid whole-surface curing of ceramic slurry and thus ensures the controllability and precision of printing with high-viscosity ceramic slurry. In this study, SLA was applied for the processing of β-TCP material, while ZrO2 and Al2O3 ceramics, Ti6Al4V, and PEEK materials that are commonly used in clinical practices were selected as controls. Phase analysis and surface properties assay, as well as cellular, biochemical, and molecular biological experiments, were performed to evaluate the biocompatibility and osteointegration capability of β-TCP produced by SLA, thus providing evidence for its application in bone implants.

2 Materials and methods

2.1 Sample preparation and scaffold structure observation

As shown in Figure 1a, the micrometer-scale β-TCP powder and photosensitive resin (National Innovation Institute of Additive Manufacturing, China) were mixed, stirred, ground, and then filtered to acquire the composite slurry (solid content >50%). The CAD models were designed in 3-Matic (Materialise Inc., Leuven, Belgium), and then 3DP was performed by the SLA equipment (Ceramaker, 3D Ceram, France). The printing process was as follows: first, the slurry storage was elevated, and the composite slurry was brought into the printing bed and smoothed by a scraper; then laser shooting, curing, and molding were performed; after that, the printing bed was downshifted to repeat the previous steps; finally, the 3D curing printing layer by layer was completed. The printed ceramic was further processed by defatting and sintering to remove the chemical additives. ZrO2 and Al2O3 ceramics were also manufactured by SLA technique (Xi’an Particle Cloud Biotechnology Co., Ltd, China). Ti6Al4V was printed by selective laser melting technique (National Innovation Institute of Additive Manufacturing, China). PEEK was manufactured by fused deposition modeling (College of Mechanical Engineering, Xi’an Jiaotong University, China). All materials were processed into thin plates for subsequent tests, and β-TCP was processed into a scaffold to preliminarily detect its possibility as a microporous bone implant. The structure of β-TCP scaffold was scanned by Micro-CT (YXLON, Germany) and reconstructed by VGstudio Max 3.0 (Volume Graphics, Germany) software. The scanning parameters were set as follows: X-ray source voltage, 90 kV; beam current, 50 μA; and scanning resolution, 12 μm. Meanwhile, the surface morphology of scaffold was observed using scanning electron microscope (SEM) (JSM-7900F, JEOL, Japan) after gold spraying. The size of the plates was 10 mm for length and width and 1 mm for thickness. All the plates were washed and sterilized before being used in the experiments. Three repeats of plates for each material were used in this study.

Figure 1 Schematic of the SLA system and example of plates and scaffold used in this experiment. (a) Schematic of SLA 3DP process of β-TCP bioceramics: the composite slurry of β-TCP powder and photosensitive resin was evenly distributed on the printing bed; then laser shooting, curing, and molding were performed according to the CAD models; after that, the 3DP of the next layer continued; finally, the printed ceramic was further processed by defatting and sintering. (b) Thin plates of PEEK, ZrO2, Al2O3, β-TCP, and Ti6Al4V. (c) β-TCP scaffold printed by SLA.
Figure 1

Schematic of the SLA system and example of plates and scaffold used in this experiment. (a) Schematic of SLA 3DP process of β-TCP bioceramics: the composite slurry of β-TCP powder and photosensitive resin was evenly distributed on the printing bed; then laser shooting, curing, and molding were performed according to the CAD models; after that, the 3DP of the next layer continued; finally, the printed ceramic was further processed by defatting and sintering. (b) Thin plates of PEEK, ZrO2, Al2O3, β-TCP, and Ti6Al4V. (c) β-TCP scaffold printed by SLA.

2.2 X-ray diffraction (XRD)

The β-TCP plates produced by SLA 3DP were carefully washed and dried. Then XRD analysis (Empyrean, PANalytical, Netherlands) was used to scan the β-TCP plates. The scanning range was 4–75°.

2.3 Water contact angle measurement

The water contact angle was measured and recorded using a dynamic photography system (JC2000DM, Powereach, China). The contact angles were measured and calculated when the water droplets just contacted (0 s water contact angles) and at 1 s after contacting the surface of a material (1 s water contact angles). Three points were selected for detection on each plate, and three replicates were set for each group.

2.4 Hemolytic toxicity

A total of 2% rabbit red blood cell (RBC) suspension was centrifuged and resuspended by an equal volume of PBS as the negative control group or resuspended by distilled water as the positive control group. The different material plates were added to the negative group as the experimental group. The tubes were placed at 37°C for 1 h, after which they were centrifuged, and the optical density (OD) of the supernatant was assessed by a microplate reader (SYNERGY, BioTek, USA) (n = 3). The hemolysis rates were calculated as the ratio of the difference between the experimental group and the negative group and the difference between the experimental group and the positive group.

2.5 Culture and differentiation of MC3T3 E1 cells

MC3T3-E1 cells were provided by the Procell Life Science & Technology Co., Ltd (Wuhan, China), and cultured in alpha-minimum essential medium (α-MEM) containing 10% fetal bovine serum (Gibco, USA). A total of 1 mL of cell suspension with a density of 10,000 cells/mL medium was added to the surface of the plates in a 24-well culture plate. The cell proliferation capability and morphologies were observed on 1, 3, 5, and 7 days of culture, and the cell differentiation induction began on the seventh day after culture. The cell differentiation-inducing system (Gibco, USA) was the α-MEM, which consisted of 10% fetal bovine serum, 10–8 mol/L dexamethasone, 10 mmol/L β-sodium 3-phosphoglycerate, and 50 mg/L vitamin C. The osteogenesis capability was measured on 7, 14, and 21 days of differentiation induction. All the cells were cultured at 37°C, 5% CO2, and the culture medium was changed every other day.

2.6 Proliferation and morphologies of MC3T3 E1 cells

Cell Counting Kit-8 (CCK8; KeyGEN BioTECH, China) was used to assess the proliferation capability of the cultured cells (n = 3). In brief, 500 µL highly sensitive CCK8 work solution was added to the 24-well culture plate to immerse the plates, which were then incubated at 37°C in dark. After 2 h, the reaction solution was thoroughly mixed and 100 µL was absorbed into a 96-well plate. The OD of each well was measured at 450 nm. The plates with cells were added into 2.5% glutaraldehyde (Solarbio Science & Technology, China) and then placed at 4°C for 4 h. Ethanol solution of 30, 50, 70, 80, 90, and 100% was added sequentially for gradient dehydration. Afterward, the plates were dried under vacuum and gold-sputtered. The morphology of plates and attached cells were visualized by SEM (TM4000, Hitachi, Japan).

2.7 Cell differentiation

Cells on plates were digested by trypsin (Solarbio Science & Technology, China) and collected into an Eppendorf centrifugal tube (EP) tube, centrifuged, and then resuspended by double distilled water. The EP tubes were sequentially placed in liquid nitrogen, −20°C, and room temperature, so as to lyse the cells by repeated freezing and thawing. After centrifugation at 4°C, the alkaline phosphatase (ALP) levels were measured by the Alkaline Phosphatase Assay Kit (Beyotime, China) (n = 3). The extracellular matrix mineralization was detected by the quantitative method (n = 3). In brief, the cells were fixed by 4% paraformaldehyde, after which alizarin red S (Solarbio Science & Technology, China) was added to stain the mineralized nodules. Next, the mineralized nodules were dissolved by 10% hexadecylpyridinium chloride sodium phosphate solution (Solarbio Science & Technology, China), incubated at room temperature for 10 min, and then measured at 562 nm. At the same time, the same quantitative analysis was used for materials without seed cells to eliminate the effect of calcium ion released by the material itself on the results.

2.8 qRT-PCR

Osteogenesis-related genes, including bone morphogenetic protein-2 (BMP-2), ALP, Collagen I α1 (COL-1), Runt-related transcription factor 2 (Runx-2), Osteopontin (OPN), and Osteocalcin (OCN), were measured. Cells on plates were collected, and 1 mL TRNzol was added to lyse the cells. The top 400 μL of liquid was collected and an equal volume of chloroform was added, then thoroughly mixed and centrifuged again, and the upper layer was harvested. Isopropanol and 75% ethanol were sequentially added and then dried to acquire the precipitate. Next, RNase-free ddH2O was added to dissolve the precipitate, and the concentration and purity of the extracted nucleic acid were measured (Thermo Fisher Scientific, USA). Reverse transcription was performed by using a kit (HiFiScript cDNA Synthesis Kit, Cowin Bio, China), and the primers are shown in Table 1. The amplification system was prepared according to the real-time PCR kit (UltraSYBR Mixture, Cowin Bio, China), and the amplification conditions were as follows: initial denaturation at 95°C for 10 min, denaturation at 95°C for 15 s, and annealing and extension at 60°C for 40 s. Forty cycles of PCR reactions were performed. The relative level of the target gene to the housekeeping gene GAPDH (2−ΔΔt) was calculated for statistical analysis (n = 3).

Table 1

Primer sequences for RT-qPCR

Gene Forward primer Reversed primer
BMP-2 5′-AAGCGTCAAGCCAAACACAAACAG-3′ 5′-GAGGTGCCACGATCCAGTCATTC-3′
ALP 5′-CTTGGTGGTCACAGCAGTTGGTAG-3′ 5′-CCAGGCGACAGGTGAAGAAACAG-3′
OPN 5′-ATGGACGACGATGATGACGATGATG-3′ 5′-CTTGTGTACTAGCAGTGACGGTCTC-3′
OCN 5′-CAAGCAGGAGGGCAATAAGGTAGTG-3′ 5′-CGGTCTTCAAGCCATACTGGTCTG-3′
COL-1 5′-AACTTTGCTTCCCAGATGTCCTAT-3′ 5′-CTCGGTGTCCCTTCATTCCAG-3′
RUNX-2 5′-TCCCGTCACCTCCATCCTCTTTC-3′ 5′-GAATACGCATCACAACAGCCACAAG-3′
GAPDH 5′-GGTGAAGGTCGGTGTGAACG-3′ 5′-CTCGCTCCTGGAAGATGGTG-3′

2.9 Statistical analysis

SPSS 19.0 software (SPSS Inc., Chicago, IL, USA) was used for statistical analysis. Quantitative data were described by mean ± standard deviation. One-way analysis of variance followed by Tukey’s post hoc tests was used to analyze the statistically significant differences. P < 0.05 was considered statistically significant.

3 Results

3.1 Characterization of plate samples and porous β-TCP scaffolds

Figure 1b shows the plates of β-TCP, ZrO2, Al2O3, Ti6Al4V, and PEEK. All the plates had morphological integrity and a sophisticated surface. β-TCP scaffold (Figure 1c) had a complete physical structure and regular micropore morphology. The XRD phase analysis of β-TCP produced by SLA 3DP showed that the distribution of peaks was highly consistent with the characteristics of Ca3(PO4)2 and in agreement with the characteristics of β-TCP of CaP materials (Figure 2). No characteristic peaks of new materials were found. In the Micro-CT reconstruction model (Figure 3a) and the SEM observation (Figure 3b), we can find that the morphology of the β-TCP scaffold is intact and the scaffold has good connectivity and no micropore obstruction. Moreover, we can find that the parameters of the scanning model are consistent with those of the CAD model, which indicates that SLA technology has high accuracy in manufacturing β-TCP scaffold (Table 2).

Figure 2 XRD analysis of the β-TCP plates produced by SLA 3DP.
Figure 2

XRD analysis of the β-TCP plates produced by SLA 3DP.

Figure 3 Characteristics of β-TCP scaffold and water contact angle measurement. (a) Micro-CT reconstructed model of β-TCP scaffold. (b) SEM observation of β-TCP scaffold. (c) Comparison of water contact angles of different material plates. (d) Water contact angle recorded and measured 0 and 1 s after contacting the material surface. P(a) < 0.05 and P(a * ) < 0.01 compared with PEEK; P(b) < 0.05 compared with ZrO2; P(c) < 0.05 and P(c * ) < 0.01 compared with Al2O3; P(d * ) < 0.01 compared with β-TCP.
Figure 3

Characteristics of β-TCP scaffold and water contact angle measurement. (a) Micro-CT reconstructed model of β-TCP scaffold. (b) SEM observation of β-TCP scaffold. (c) Comparison of water contact angles of different material plates. (d) Water contact angle recorded and measured 0 and 1 s after contacting the material surface. P(a) < 0.05 and P(a * ) < 0.01 compared with PEEK; P(b) < 0.05 compared with ZrO2; P(c) < 0.05 and P(c * ) < 0.01 compared with Al2O3; P(d * ) < 0.01 compared with β-TCP.

Table 2

Comparison of micropore parameters between Micro-CT and CAD models

Porosity (%) Volume (mm3) Specific surface area (mm−1)
CAD model 66.13 373.42 7.77
Micro-CT model 64.37 374.12 8.59

3.2 Water contact angle

The 0 s water contact angles for bioceramics were relatively small, i.e., 93.32 ± 3.62° and 89.00 ± 6.76° for Al2O3 and ZrO2, respectively. The 0 s water contact angle of β-TCP was the smallest (78.00 ± 2.29°), and significantly lower than PEEK (109.82 ± 13.50°) and Ti6Al4V (106.82 ± 10.40°) (P < 0.05) (Figure 3c). After the water droplet contacted the materials, the contact angle reduced due to various causes, such as the water adsorption by porous materials and diffusion of water droplets (Figure 3d). At 1 s after contact, the water contact angle of PEEK (52.02 ± 5.54°) was significantly larger than in other materials, and the water contact angle of Ti6Al4V (38.65 ± 4.17°) was also significantly larger than the other three bioceramics (P < 0.05). Among the bioceramics, the water contact angle of β-TCP (9.26 ± 2.57°) was significantly smaller than ZrO2 (23.99 ± 4.88°) and Al2O3 (26.43 ± 4.35°) (P < 0.05).

3.3 Hemolytic toxicity

The supernatant of the negative group and experimental groups showed lucid and transparent supernatant, and no hemolysis was found, while the supernatant in the positive group was bright red and showed evident hemolysis (Figure 4a). The hemolytic toxicity assay (Figure 4b) showed that the hemolysis rates of PEEK, ZrO2, Al2O3, β-TCP, and Ti6Al4V, which were all <5% (0.92 ± 0.08, 0.79 ± 0.19, 0.97 ± 0.03, 0.72 ± 0.08, and 1.21 ± 0.07%, respectively), met the requirement of hemolytic toxicity.

Figure 4 Hemolytic toxicity of different materials. (a) Supernatant of RBCs in the experimental groups, negative control group (NC, with PBS), and positive control group (PC, with distilled water). (b) Hemolysis rates of different materials (<5%) and positive control group (100%).
Figure 4

Hemolytic toxicity of different materials. (a) Supernatant of RBCs in the experimental groups, negative control group (NC, with PBS), and positive control group (PC, with distilled water). (b) Hemolysis rates of different materials (<5%) and positive control group (100%).

3.4 Cell proliferation

As shown in Figure 5, the cells on PEEK, ZrO2, Al2O3, β-TCP, and Ti6Al4V all increased with the time of culture. However, the proliferation of cells on PEEK was significantly lower than on the other four materials (P < 0.05). Among ceramics, the proliferation of cells on Al2O3 occurred earlier than on ZrO2; however, with the increase of culture time, the cell proliferation on Al2O3 was lower compared to other ceramics and Ti6Al4V (P < 0.05). The proliferation of cells on ZrO2 gradually increased on 3 days of culture and was higher than on Ti6Al4V. The proliferation of cells on β-TCP was relatively high and was significantly higher than on other materials on 5 days of culture (P < 0.05).

Figure 5 Cell proliferation at different culture times. P(a) < 0.05 and P(a * ) < 0.01 compared with PEEK; P(b * ) < 0.01 compared with ZrO2; P(c * ) < 0.01 compared with Al2O3; P(d * ) < 0.01 compared with β-TCP.
Figure 5

Cell proliferation at different culture times. P(a) < 0.05 and P(a * ) < 0.01 compared with PEEK; P(b * ) < 0.01 compared with ZrO2; P(c * ) < 0.01 compared with Al2O3; P(d * ) < 0.01 compared with β-TCP.

3.5 SEM observation

The low vacuum field emission SEM was used to assess the cell morphology. As shown in Figure 6, cells could adhere to and grow on all plates, but cells that adhered to PEEK had fewer pseudopodia, which had sharp morphologies, while the background was the PEEK material, showing clear texture and smooth surface (Figure 6a). Figure 6b–d shows the ZrO2, Al2O3, and β-TCP. The particulates on the surfaces of the three bioceramics were all evenly distributed, showing porous structures. Cells were completely expanded and flat on the surface of all bioceramics; numerous pseudopodia were extended from the cells, while the bases were wide and with irregular morphologies. Cells on Ti6Al4V material (Figure 6e) showed the adhesive morphologies of the fusion of metal spheres of Ti6Al4V and the ability of cells to grow between the Ti6Al4V sphere particulates. Cells adhered to the adjacent Ti6Al4V sphere particulates and extended numerous processes to adjacent particulates; the bases of cells were wide, and the cells showed plump morphologies.

Figure 6 Representative SEM images of the growth of MC3T3 cells on the plates surface. (a) Cells on PEEK had sharp morphologies and fewer pseudopodia. (b–d) Cells with numerous extended pseudopodia were completely expanded and flat on ZrO2, Al2O3, and β-TCP. (e) Cells extend and grow between the sphere particulates on Ti6Al4V.
Figure 6

Representative SEM images of the growth of MC3T3 cells on the plates surface. (a) Cells on PEEK had sharp morphologies and fewer pseudopodia. (b–d) Cells with numerous extended pseudopodia were completely expanded and flat on ZrO2, Al2O3, and β-TCP. (e) Cells extend and grow between the sphere particulates on Ti6Al4V.

3.6 ALP level

The synthesis and secretion of ALP by osteoblasts are the markers of early osteogenesis. As shown in Figure 7a, the ALP levels did not significantly differ at the early stage of induction. However, the ALP secretion reached the peak level on 14 days of induction. The ALP level on ZrO2 and β-TCP were significantly higher than on PEEK (P < 0.05). However, on 21 days of induction, ALP levels of cells on all materials decreased and were not significantly different. The ALP level of cells on β-TCP was not significantly different from Ti6Al4V at any time.

Figure 7 Cell differentiation and osteogenic ability at different culture times. (a) ALP level and (b) the mineralization of extracellular matrix. P(a) < 0.05 and P(a * ) < 0.01 compared with PEEK; P(b * ) < 0.01 compared with ZrO2; P(c * ) < 0.01 compared with Al2O3; P(d * ) < 0.01 compared with β-TCP.
Figure 7

Cell differentiation and osteogenic ability at different culture times. (a) ALP level and (b) the mineralization of extracellular matrix. P(a) < 0.05 and P(a * ) < 0.01 compared with PEEK; P(b * ) < 0.01 compared with ZrO2; P(c * ) < 0.01 compared with Al2O3; P(d * ) < 0.01 compared with β-TCP.

3.7 Mineralization

The degree of extracellular matrix mineralization could reflect the maturation of the osteoblast matrix. As shown in Figure 7b, the mineralization was significantly higher on Ti6Al4V than PEEK, ZrO2, and Al2O3, and also significantly higher on β-TCP than PEEK and other ceramics on 7 days of differentiation induction (P < 0.05). On 14 days of differentiation induction, the mineralization on PEEK was significantly lower compared to other materials; the mineralization on Al2O3 was relatively low among ceramics; while the Ti6Al4V had the highest mineralization degree (P < 0.05). On 21 days of differentiation induction, the mineralization degree on Ti6Al4V and β-TCP was significantly higher than on other materials (P < 0.05).

3.8 RT-qPCR

Real-time quantitative PCR was used to measure the expression of osteogenesis-related genes after differentiation induction. As shown in Figure 8, the BMP-2 and ALP gene expression on β-TCP and Ti6Al4V were significantly higher compared to other groups and also significantly higher on β-TCP than Ti6Al4V (P < 0.05). Compared to PEEK and Al2O3, cells on ZrO2, β-TCP, and Ti6Al4V had significantly higher Col1α1 and Runx2 gene expression (P < 0.05). The expression of OPN and OCN genes was significantly higher on β-TCP compared to other materials (P < 0.05).

Figure 8 RT-qPCR analysis of osteogenesis-related genes of cells on different material plates. Osteogenesis-related genes including BMP-2, ALP, COL-1, Runx-2, OPN, and OCN. P(a) < 0.05 and P(a * ) < 0.01 compared with PEEK; P(b) < 0.05 and P(b * ) < 0.01 compared with ZrO2; P(c) < 0.05 and P(c * ) < 0.01 compared with Al2O3; P(d) < 0.05 and P(d * ) < 0.01 compared with β-TCP.
Figure 8

RT-qPCR analysis of osteogenesis-related genes of cells on different material plates. Osteogenesis-related genes including BMP-2, ALP, COL-1, Runx-2, OPN, and OCN. P(a) < 0.05 and P(a * ) < 0.01 compared with PEEK; P(b) < 0.05 and P(b * ) < 0.01 compared with ZrO2; P(c) < 0.05 and P(c * ) < 0.01 compared with Al2O3; P(d) < 0.05 and P(d * ) < 0.01 compared with β-TCP.

4 Discussion

There are various materials for bone implants, among which metal materials have good mechanical performances, but their elastic modulus is relatively high. Polymer materials have similar mechanical performances as human bones; however, their osteogenesis and osteointegration capability are relatively low. Bioceramic has good osteogenesis capability, especially the degradable CaP materials such as β-TCP, which have excellent biocompatibility and osteointegration capability, making them good choices for bone implants [35–37]. Despite the good osteogenesis capability of CaP bioceramics, the micropore structures required for osteogenesis are difficult to be manufactured for CaP due to the limitations of conventional manufacturing techniques. Following the advancements of additive manufacturing techniques, SLA has become one of the effective methods in manufacturing bioceramics with high viscosity and controllable structures. In this study, β-TCP ceramic powder and photosensitive resin were mixed and then printed by SLA 3DP technique to improve the final structure’s precision and controllability. The sizes of printed plates were in agreement with the designed sizes, which had a smooth surface, no fracture, and no burr or protrusion, indicating that the printing had good overall effects. And β-TCP scaffold printed by SLA 3DP had a complete physical structure, regular micropore morphology, and showed good pore connectivity in Micro-CT scan, which means it could be used for the microporous bone implant.

The chemical structures and surface characteristics of materials substantially impact the biological properties [38]. The phase analysis of the β-TCP produced by SLA demonstrated that the chemical additives introduced by 3DP and temperature change for defatting and sintering did not change the phase structures of β-TCP material.

The water contact angle is one of the indexes reflecting the hydrophilic property of the material surface. When the water contact angle is relatively low, water tends to diffuse and adhere to the material, thus indirectly reflecting that the material could favor the cell adhesion, while a high water contact angle reflects the opposite property of the material [39]. When the water droplet immediately contacts the material surface, it becomes plump and larger than the hemisphere. However, the water droplets on β-TCP were relatively flat and lower than the droplets on PEEK and Ti6Al4V. Observation at 1 s after water droplet contact the surface showed that the water droplets diffused on PEEK and Ti6Al4V and water droplet permeation and adsorption were found on the three bioceramics due to the porous structures, which is why the water droplets showed flat morphologies. PEEK had the largest water contact angle than other materials because of the smooth surface and lack of hydrophilic groups, indicating that PEEK had relatively poor cell affinity. Of the three bioceramics, β-TCP had the smallest water contact angle due to the characteristics of the material, as well as the porous structure, which indicated that the material structures of β-TCP could endow it with better cell affinity, favoring the cell adhesion, growth, and proliferation.

The first and foremost biological characteristic of materials for implants is biocompatibility [40]. The effects of materials on blood should first be verified in vitro [41]. Several previous studies have reported the clinical application of β-TCP; still, few studies have reported β-TCP produced by steerable SLA 3DP. Therefore, its hemolytic toxicity should be further investigated. The hemolysis rate was <1.5% for all the materials used in the present study. After co-incubation and centrifugation, the RBC aggregated at the bottom of the tube. Although there were several RBC suspended in the supernatant, no hemolysis occurred. Therefore, the β-TCP produced by SLA had no hemolytic toxicity and met the basic clinical application requirements.

The basic biocompatibility of materials is high cell affinity, which allows the cell to adhere, grow, and proliferate on the surface [42–44]. In this study, cells on all materials showed proliferation, but the morphology and proliferation capability varied. PEEK had lower proliferation capability, and cells did not extend fully on its surface, which could be associated with the fact that there were large amounts of hydrophobic groups on the PEEK surface that made cells difficult to grow and proliferate [45]. Ti6Al4V showed good cell proliferation capability and had a high capability of promoting cell adhesion and growth. In comparison to the high cell proliferation rate at an early stage of Al2O3, ZrO2 showed less cell proliferation at the early stage of culture; however, it gradually showed higher cell proliferation with the increase of culture time, which was even higher than Ti6Al4V at the late stage. The relatively lower proliferation of ZrO2 at the early stage could be explained by the higher smoothness of the surface [46]. Although the two ceramics had relatively good cell proliferation capability, their toughness and wearing resistance were more prominent, which is why they were mainly used in studies of teeth and joints. β-TCP bioceramic had better cell proliferation capability than Ti6Al4V, which could be attributed to the high similarities of chemical components with human bones, and thus could favor the adhesion and proliferation of osteogenic precursor cells [47]. SEM showed that the surface of β-TCP was unsmooth and had porous structures caused by defatting and sintering. Such structures endow certain water adsorption capability of the material and thus can promote cell adhesion, proliferation, and growth [48].

In addition to the high biocompatibility, bone implant materials also need to have the ability to promote bone formation. Bone-derived ALP mainly binds to the cellular membrane and is closely associated with bone formation, promotion of cell maturation, and mineralization and is the marker of transformation from preosteoblasts to mature osteoblasts. Elevation of ALP activity indicates the initiation of early differentiation. Osteoblasts can absorb the ions and induce mineralization to form calcium nodules. Due to the optical opacity of materials used in this study, quantitative measurements were used to assess the maturity of cell differentiation and mineralization. In the early differentiation induction phase, some preosteoblasts gradually matured, while some other preosteoblasts did not fully differentiate to mature osteoblasts, thus resulting in a lack of significant difference among ALP levels in different groups. At this time, the mature osteoblasts already could integrate the intra- and extracellular ions to induce extracellular matrix mineralization. Therefore, on 7 days of differentiation induction, some mineralized calcium nodules were already detected on the surfaces of Ti6Al4V and β-TCP, indicating that Ti6Al4V and β-TCP could promote extracellular matrix maturation in the early stage. The ALP level peaked with the increase of induction time, and the preosteoblasts generally completed the differentiation to mature osteoblasts. At 2 weeks of induction, β-TCP bioceramic already showed higher osteogenesis capability than PEEK, while the capability of promoting ALP expression in cells was comparable with Ti6Al4V. With the increase of mature osteoblasts, the extracellular matrix gradually matured, and the degree of mineralization also increased. However, PEEK showed lower mineralization compared to other materials. Of the three ceramics, Al2O3 had the lowest mineralization degree. Although β-TCP had the highest mineralization degree in ceramic materials, it was still lower than Ti6Al4V. Afterward, with the increase of induction time, ALP level gradually reduced, and extracellular matrix mineralization substantially accumulated. After 3 weeks of induction, the degree of extracellular matrix mineralization was still higher on Ti6Al4V and β-TCP than other materials. β-TCP had substantially higher osteogenesis capability at the early stage of osteogenesis than other ceramics and PEEK, and similar excellent performance as Ti6Al4V. In addition, β-TCP had the fastest mineralization speed, suggesting that with the increase of differentiation induction time, β-TCP could have the earliest bone mass formation.

Osteogenesis-related genes are expressed differently to exert the osteogenesis and regulation effects. Such genes include BMP-2, ALP, OPN, OCN, COL-1, and RUNX-2 genes. BMP-2 and analogues can bind to HA and promote the formation of a mineralization core [49]. ALP can degrade inorganic pyrophosphate (PPi) and increase the concentration of inorganic phosphate (Pi), thus promoting the formation of HA crystals and regulating the expression of Runx2 to promote osteogenesis. Previous studies have demonstrated that the ALP gene showed high expression in osteoblasts and vesicles [50]. RUNX-2 is a transcription factor expressed in the early stage of osteogenesis, which could affect cell nuclei to promote the expression of osteogenesis-related genes, such as OPN and OCN, and consequently promote the differentiation of preosteoblasts to osteoblasts [51]. OCN is the major component of non-collagen and the specific marker of bone that is secreted by osteoblasts and promotes calcification. COL1 is the major collagen in the process of osteogenesis that can promote calcification [52]. In this study, the expression of ALP, Col1α1, and Runx2 genes was the early signal of osteogenesis, which indicated the maturation of preosteoblasts to osteoblasts. Such genes had similar expression levels on β-TCP bioceramic and Ti6Al4V. In addition, cells growing on β-TCP bioceramic showed significantly higher levels of BMP-2, OPN, and OCN genes than other materials at different induction phases. With reference to the mineralization, the findings further indicated that β-TCP bioceramic had more powerful capability of promoting the maturation and mineralization of the extracellular matrix of osteoblasts.

In this study, β-TCP produced by SLA has excellent effect in promoting osteogenesis, so it can be used as one of the choice of orthopedic implant in the future. At the same time, SLA method can realize the accurate preparation of high viscosity bioceramics. From this point of view, combined with the fact that the main inorganic components of bone are CaP, this is the key to further promote the application of bioceramics in bone plants, because biodegradable bioceramics scaffolds with fine porous structures are a good choice for artificial bones. Therefore, the results of this study provide a direction for the selection of bone implant materials.

This study has a few limitations. First, due to the optical opacity of materials, some cell markers that should be observed by staining were not involved or were tested and explained by quantitative methods. In addition, more in vivo experiments are needed to fully prove the biocompatibility and osteogenic ability of these materials. Finally, our next step is to use SLA technology to process β-TCP bone scaffolds, and study the effects of microporous parameters and morphology of bone scaffolds on osteogenesis.

5 Conclusions

During the process of manufacturing and post-processing of SLA 3DP of degradable β-TCP bioceramic in the present study, no evident impurity substance was introduced. In addition, β-TCP plate and scaffold produced by SLA had good integrity and high hydrophilic property. β-TCP produced by SLA had no evident hemolytic toxicity but powerful cell proliferation capability. Cells on β-TCP bioceramic could express higher osteogenesis-related ALP levels, and the mineralization of the extracellular matrix occurred earlier on β-TCP and the maturity was higher. In addition, the expression of osteogenesis-related genes was also very high on β-TCP. These findings demonstrate that the degradable β-TCP bioceramic produced by SLA 3DP has high biocompatibility and osteogenesis capability and could be used as a choice for bone implants in future clinical practice.

  1. Funding information: This work was financially supported by the Key Research Project of Shaanxi Province (grant no. 2017ZDCXL-SF-01-05) and the National Key Research and Development Project of the People’s Republic of China (grant no. 2018YFE0114200).

  2. Author contributions: All authors participated in the design, interpretation of the studies, analysis of the data, and manuscript review. J.L., J.L., X.H., W.L., and X.W. conducted the experiments, Q.T., Y.W., and Y.Y. wrote the manuscript. S.X. and S.C. supervised this study.

  3. Conflict of interest: Authors state no conflict of interest.

  4. Data availability statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Received: 2022-08-10
Revised: 2022-09-27
Accepted: 2022-11-02
Published Online: 2023-01-24

© 2023 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  62. The influence and mechanistic action of sperm DNA fragmentation index on the outcomes of assisted reproduction technology
  63. Novel compound heterozygous mutations in TELO2 in an infant with You-Hoover-Fong syndrome: A case report and literature review
  64. ctDNA as a prognostic biomarker in resectable CLM: Systematic review and meta-analysis
  65. Diagnosis of primary amoebic meningoencephalitis by metagenomic next-generation sequencing: A case report
  66. Phylogenetic analysis of promoter regions of human Dolichol kinase (DOLK) and orthologous genes using bioinformatics tools
  67. Collagen changes in rabbit conjunctiva after conjunctival crosslinking
  68. Effects of NM23 transfection of human gastric carcinoma cells in mice
  69. Oral nifedipine and phytosterol, intravenous nicardipine, and oral nifedipine only: Three-arm, retrospective, cohort study for management of severe preeclampsia
  70. Case report of hepatic retiform hemangioendothelioma: A rare tumor treated with ultrasound-guided microwave ablation
  71. Curcumin induces apoptosis in human hepatocellular carcinoma cells by decreasing the expression of STAT3/VEGF/HIF-1α signaling
  72. Rare presentation of double-clonal Waldenström macroglobulinemia with pulmonary embolism: A case report
  73. Giant duplication of the transverse colon in an adult: A case report and literature review
  74. Ectopic thyroid tissue in the breast: A case report
  75. SDR16C5 promotes proliferation and migration and inhibits apoptosis in pancreatic cancer
  76. Vaginal metastasis from breast cancer: A case report
  77. Screening of the best time window for MSC transplantation to treat acute myocardial infarction with SDF-1α antibody-loaded targeted ultrasonic microbubbles: An in vivo study in miniswine
  78. Inhibition of TAZ impairs the migration ability of melanoma cells
  79. Molecular complexity analysis of the diagnosis of Gitelman syndrome in China
  80. Effects of maternal calcium and protein intake on the development and bone metabolism of offspring mice
  81. Identification of winter wheat pests and diseases based on improved convolutional neural network
  82. Ultra-multiplex PCR technique to guide treatment of Aspergillus-infected aortic valve prostheses
  83. Virtual high-throughput screening: Potential inhibitors targeting aminopeptidase N (CD13) and PIKfyve for SARS-CoV-2
  84. Immune checkpoint inhibitors in cancer patients with COVID-19
  85. Utility of methylene blue mixed with autologous blood in preoperative localization of pulmonary nodules and masses
  86. Integrated analysis of the microbiome and transcriptome in stomach adenocarcinoma
  87. Berberine suppressed sarcopenia insulin resistance through SIRT1-mediated mitophagy
  88. DUSP2 inhibits the progression of lupus nephritis in mice by regulating the STAT3 pathway
  89. Lung abscess by Fusobacterium nucleatum and Streptococcus spp. co-infection by mNGS: A case series
  90. Genetic alterations of KRAS and TP53 in intrahepatic cholangiocarcinoma associated with poor prognosis
  91. Granulomatous polyangiitis involving the fourth ventricle: Report of a rare case and a literature review
  92. Studying infant mortality: A demographic analysis based on data mining models
  93. Metaplastic breast carcinoma with osseous differentiation: A report of a rare case and literature review
  94. Protein Z modulates the metastasis of lung adenocarcinoma cells
  95. Inhibition of pyroptosis and apoptosis by capsaicin protects against LPS-induced acute kidney injury through TRPV1/UCP2 axis in vitro
  96. TAK-242, a toll-like receptor 4 antagonist, against brain injury by alleviates autophagy and inflammation in rats
  97. Primary mediastinum Ewing’s sarcoma with pleural effusion: A case report and literature review
  98. Association of ADRB2 gene polymorphisms and intestinal microbiota in Chinese Han adolescents
  99. Tanshinone IIA alleviates chondrocyte apoptosis and extracellular matrix degeneration by inhibiting ferroptosis
  100. Study on the cytokines related to SARS-Cov-2 in testicular cells and the interaction network between cells based on scRNA-seq data
  101. Effect of periostin on bone metabolic and autophagy factors during tooth eruption in mice
  102. HP1 induces ferroptosis of renal tubular epithelial cells through NRF2 pathway in diabetic nephropathy
  103. Intravaginal estrogen management in postmenopausal patients with vaginal squamous intraepithelial lesions along with CO2 laser ablation: A retrospective study
  104. Hepatocellular carcinoma cell differentiation trajectory predicts immunotherapy, potential therapeutic drugs, and prognosis of patients
  105. Effects of physical exercise on biomarkers of oxidative stress in healthy subjects: A meta-analysis of randomized controlled trials
  106. Identification of lysosome-related genes in connection with prognosis and immune cell infiltration for drug candidates in head and neck cancer
  107. Development of an instrument-free and low-cost ELISA dot-blot test to detect antibodies against SARS-CoV-2
  108. Research progress on gas signal molecular therapy for Parkinson’s disease
  109. Adiponectin inhibits TGF-β1-induced skin fibroblast proliferation and phenotype transformation via the p38 MAPK signaling pathway
  110. The G protein-coupled receptor-related gene signatures for predicting prognosis and immunotherapy response in bladder urothelial carcinoma
  111. α-Fetoprotein contributes to the malignant biological properties of AFP-producing gastric cancer
  112. CXCL12/CXCR4/CXCR7 axis in placenta tissues of patients with placenta previa
  113. Association between thyroid stimulating hormone levels and papillary thyroid cancer risk: A meta-analysis
  114. Significance of sTREM-1 and sST2 combined diagnosis for sepsis detection and prognosis prediction
  115. Diagnostic value of serum neuroactive substances in the acute exacerbation of chronic obstructive pulmonary disease complicated with depression
  116. Research progress of AMP-activated protein kinase and cardiac aging
  117. TRIM29 knockdown prevented the colon cancer progression through decreasing the ubiquitination levels of KRT5
  118. Cross-talk between gut microbiota and liver steatosis: Complications and therapeutic target
  119. Metastasis from small cell lung cancer to ovary: A case report
  120. The early diagnosis and pathogenic mechanisms of sepsis-related acute kidney injury
  121. The effect of NK cell therapy on sepsis secondary to lung cancer: A case report
  122. Erianin alleviates collagen-induced arthritis in mice by inhibiting Th17 cell differentiation
  123. Loss of ACOX1 in clear cell renal cell carcinoma and its correlation with clinical features
  124. Signalling pathways in the osteogenic differentiation of periodontal ligament stem cells
  125. Crosstalk between lactic acid and immune regulation and its value in the diagnosis and treatment of liver failure
  126. Clinicopathological features and differential diagnosis of gastric pleomorphic giant cell carcinoma
  127. Traumatic brain injury and rTMS-ERPs: Case report and literature review
  128. Extracellular fibrin promotes non-small cell lung cancer progression through integrin β1/PTEN/AKT signaling
  129. Knockdown of DLK4 inhibits non-small cell lung cancer tumor growth by downregulating CKS2
  130. The co-expression pattern of VEGFR-2 with indicators related to proliferation, apoptosis, and differentiation of anagen hair follicles
  131. Inflammation-related signaling pathways in tendinopathy
  132. CD4+ T cell count in HIV/TB co-infection and co-occurrence with HL: Case report and literature review
  133. Clinical analysis of severe Chlamydia psittaci pneumonia: Case series study
  134. Bioinformatics analysis to identify potential biomarkers for the pulmonary artery hypertension associated with the basement membrane
  135. Influence of MTHFR polymorphism, alone or in combination with smoking and alcohol consumption, on cancer susceptibility
  136. Catharanthus roseus (L.) G. Don counteracts the ampicillin resistance in multiple antibiotic-resistant Staphylococcus aureus by downregulation of PBP2a synthesis
  137. Combination of a bronchogenic cyst in the thoracic spinal canal with chronic myelocytic leukemia
  138. Bacterial lipoprotein plays an important role in the macrophage autophagy and apoptosis induced by Salmonella typhimurium and Staphylococcus aureus
  139. TCL1A+ B cells predict prognosis in triple-negative breast cancer through integrative analysis of single-cell and bulk transcriptomic data
  140. Ezrin promotes esophageal squamous cell carcinoma progression via the Hippo signaling pathway
  141. Ferroptosis: A potential target of macrophages in plaque vulnerability
  142. Predicting pediatric Crohn's disease based on six mRNA-constructed risk signature using comprehensive bioinformatic approaches
  143. Applications of genetic code expansion and photosensitive UAAs in studying membrane proteins
  144. HK2 contributes to the proliferation, migration, and invasion of diffuse large B-cell lymphoma cells by enhancing the ERK1/2 signaling pathway
  145. IL-17 in osteoarthritis: A narrative review
  146. Circadian cycle and neuroinflammation
  147. Probiotic management and inflammatory factors as a novel treatment in cirrhosis: A systematic review and meta-analysis
  148. Hemorrhagic meningioma with pulmonary metastasis: Case report and literature review
  149. SPOP regulates the expression profiles and alternative splicing events in human hepatocytes
  150. Knockdown of SETD5 inhibited glycolysis and tumor growth in gastric cancer cells by down-regulating Akt signaling pathway
  151. PTX3 promotes IVIG resistance-induced endothelial injury in Kawasaki disease by regulating the NF-κB pathway
  152. Pancreatic ectopic thyroid tissue: A case report and analysis of literature
  153. The prognostic impact of body mass index on female breast cancer patients in underdeveloped regions of northern China differs by menopause status and tumor molecular subtype
  154. Report on a case of liver-originating malignant melanoma of unknown primary
  155. Case report: Herbal treatment of neutropenic enterocolitis after chemotherapy for breast cancer
  156. The fibroblast growth factor–Klotho axis at molecular level
  157. Characterization of amiodarone action on currents in hERG-T618 gain-of-function mutations
  158. A case report of diagnosis and dynamic monitoring of Listeria monocytogenes meningitis with NGS
  159. Effect of autologous platelet-rich plasma on new bone formation and viability of a Marburg bone graft
  160. Small breast epithelial mucin as a useful prognostic marker for breast cancer patients
  161. Continuous non-adherent culture promotes transdifferentiation of human adipose-derived stem cells into retinal lineage
  162. Nrf3 alleviates oxidative stress and promotes the survival of colon cancer cells by activating AKT/BCL-2 signal pathway
  163. Favorable response to surufatinib in a patient with necrolytic migratory erythema: A case report
  164. Case report of atypical undernutrition of hypoproteinemia type
  165. Down-regulation of COL1A1 inhibits tumor-associated fibroblast activation and mediates matrix remodeling in the tumor microenvironment of breast cancer
  166. Sarcoma protein kinase inhibition alleviates liver fibrosis by promoting hepatic stellate cells ferroptosis
  167. Research progress of serum eosinophil in chronic obstructive pulmonary disease and asthma
  168. Clinicopathological characteristics of co-existing or mixed colorectal cancer and neuroendocrine tumor: Report of five cases
  169. Role of menopausal hormone therapy in the prevention of postmenopausal osteoporosis
  170. Precisional detection of lymph node metastasis using tFCM in colorectal cancer
  171. Advances in diagnosis and treatment of perimenopausal syndrome
  172. A study of forensic genetics: ITO index distribution and kinship judgment between two individuals
  173. Acute lupus pneumonitis resembling miliary tuberculosis: A case-based review
  174. Plasma levels of CD36 and glutathione as biomarkers for ruptured intracranial aneurysm
  175. Fractalkine modulates pulmonary angiogenesis and tube formation by modulating CX3CR1 and growth factors in PVECs
  176. Novel risk prediction models for deep vein thrombosis after thoracotomy and thoracoscopic lung cancer resections, involving coagulation and immune function
  177. Exploring the diagnostic markers of essential tremor: A study based on machine learning algorithms
  178. Evaluation of effects of small-incision approach treatment on proximal tibia fracture by deep learning algorithm-based magnetic resonance imaging
  179. An online diagnosis method for cancer lesions based on intelligent imaging analysis
  180. Medical imaging in rheumatoid arthritis: A review on deep learning approach
  181. Predictive analytics in smart healthcare for child mortality prediction using a machine learning approach
  182. Utility of neutrophil–lymphocyte ratio and platelet–lymphocyte ratio in predicting acute-on-chronic liver failure survival
  183. A biomedical decision support system for meta-analysis of bilateral upper-limb training in stroke patients with hemiplegia
  184. TNF-α and IL-8 levels are positively correlated with hypobaric hypoxic pulmonary hypertension and pulmonary vascular remodeling in rats
  185. Stochastic gradient descent optimisation for convolutional neural network for medical image segmentation
  186. Comparison of the prognostic value of four different critical illness scores in patients with sepsis-induced coagulopathy
  187. Application and teaching of computer molecular simulation embedded technology and artificial intelligence in drug research and development
  188. Hepatobiliary surgery based on intelligent image segmentation technology
  189. Value of brain injury-related indicators based on neural network in the diagnosis of neonatal hypoxic-ischemic encephalopathy
  190. Analysis of early diagnosis methods for asymmetric dementia in brain MR images based on genetic medical technology
  191. Early diagnosis for the onset of peri-implantitis based on artificial neural network
  192. Clinical significance of the detection of serum IgG4 and IgG4/IgG ratio in patients with thyroid-associated ophthalmopathy
  193. Forecast of pain degree of lumbar disc herniation based on back propagation neural network
  194. SPA-UNet: A liver tumor segmentation network based on fused multi-scale features
  195. Systematic evaluation of clinical efficacy of CYP1B1 gene polymorphism in EGFR mutant non-small cell lung cancer observed by medical image
  196. Rehabilitation effect of intelligent rehabilitation training system on hemiplegic limb spasms after stroke
  197. A novel approach for minimising anti-aliasing effects in EEG data acquisition
  198. ErbB4 promotes M2 activation of macrophages in idiopathic pulmonary fibrosis
  199. Clinical role of CYP1B1 gene polymorphism in prediction of postoperative chemotherapy efficacy in NSCLC based on individualized health model
  200. Lung nodule segmentation via semi-residual multi-resolution neural networks
  201. Evaluation of brain nerve function in ICU patients with Delirium by deep learning algorithm-based resting state MRI
  202. A data mining technique for detecting malignant mesothelioma cancer using multiple regression analysis
  203. Markov model combined with MR diffusion tensor imaging for predicting the onset of Alzheimer’s disease
  204. Effectiveness of the treatment of depression associated with cancer and neuroimaging changes in depression-related brain regions in patients treated with the mediator-deuterium acupuncture method
  205. Molecular mechanism of colorectal cancer and screening of molecular markers based on bioinformatics analysis
  206. Monitoring and evaluation of anesthesia depth status data based on neuroscience
  207. Exploring the conformational dynamics and thermodynamics of EGFR S768I and G719X + S768I mutations in non-small cell lung cancer: An in silico approaches
  208. Optimised feature selection-driven convolutional neural network using gray level co-occurrence matrix for detection of cervical cancer
  209. Incidence of different pressure patterns of spinal cerebellar ataxia and analysis of imaging and genetic diagnosis
  210. Pathogenic bacteria and treatment resistance in older cardiovascular disease patients with lung infection and risk prediction model
  211. Adoption value of support vector machine algorithm-based computed tomography imaging in the diagnosis of secondary pulmonary fungal infections in patients with malignant hematological disorders
  212. From slides to insights: Harnessing deep learning for prognostic survival prediction in human colorectal cancer histology
  213. Ecology and Environmental Science
  214. Monitoring of hourly carbon dioxide concentration under different land use types in arid ecosystem
  215. Comparing the differences of prokaryotic microbial community between pit walls and bottom from Chinese liquor revealed by 16S rRNA gene sequencing
  216. Effects of cadmium stress on fruits germination and growth of two herbage species
  217. Bamboo charcoal affects soil properties and bacterial community in tea plantations
  218. Optimization of biogas potential using kinetic models, response surface methodology, and instrumental evidence for biodegradation of tannery fleshings during anaerobic digestion
  219. Understory vegetation diversity patterns of Platycladus orientalis and Pinus elliottii communities in Central and Southern China
  220. Studies on macrofungi diversity and discovery of new species of Abortiporus from Baotianman World Biosphere Reserve
  221. Food Science
  222. Effect of berrycactus fruit (Myrtillocactus geometrizans) on glutamate, glutamine, and GABA levels in the frontal cortex of rats fed with a high-fat diet
  223. Guesstimate of thymoquinone diversity in Nigella sativa L. genotypes and elite varieties collected from Indian states using HPTLC technique
  224. Analysis of bacterial community structure of Fuzhuan tea with different processing techniques
  225. Untargeted metabolomics reveals sour jujube kernel benefiting the nutritional value and flavor of Morchella esculenta
  226. Mycobiota in Slovak wine grapes: A case study from the small Carpathians wine region
  227. Elemental analysis of Fadogia ancylantha leaves used as a nutraceutical in Mashonaland West Province, Zimbabwe
  228. Microbiological transglutaminase: Biotechnological application in the food industry
  229. Influence of solvent-free extraction of fish oil from catfish (Clarias magur) heads using a Taguchi orthogonal array design: A qualitative and quantitative approach
  230. Chromatographic analysis of the chemical composition and anticancer activities of Curcuma longa extract cultivated in Palestine
  231. The potential for the use of leghemoglobin and plant ferritin as sources of iron
  232. Investigating the association between dietary patterns and glycemic control among children and adolescents with T1DM
  233. Bioengineering and Biotechnology
  234. Biocompatibility and osteointegration capability of β-TCP manufactured by stereolithography 3D printing: In vitro study
  235. Clinical characteristics and the prognosis of diabetic foot in Tibet: A single center, retrospective study
  236. Agriculture
  237. Biofertilizer and NPSB fertilizer application effects on nodulation and productivity of common bean (Phaseolus vulgaris L.) at Sodo Zuria, Southern Ethiopia
  238. On correlation between canopy vegetation and growth indexes of maize varieties with different nitrogen efficiencies
  239. Exopolysaccharides from Pseudomonas tolaasii inhibit the growth of Pleurotus ostreatus mycelia
  240. A transcriptomic evaluation of the mechanism of programmed cell death of the replaceable bud in Chinese chestnut
  241. Melatonin enhances salt tolerance in sorghum by modulating photosynthetic performance, osmoregulation, antioxidant defense, and ion homeostasis
  242. Effects of plant density on alfalfa (Medicago sativa L.) seed yield in western Heilongjiang areas
  243. Identification of rice leaf diseases and deficiency disorders using a novel DeepBatch technique
  244. Artificial intelligence and internet of things oriented sustainable precision farming: Towards modern agriculture
  245. Animal Sciences
  246. Effect of ketogenic diet on exercise tolerance and transcriptome of gastrocnemius in mice
  247. Combined analysis of mRNA–miRNA from testis tissue in Tibetan sheep with different FecB genotypes
  248. Isolation, identification, and drug resistance of a partially isolated bacterium from the gill of Siniperca chuatsi
  249. Tracking behavioral changes of confined sows from the first mating to the third parity
  250. The sequencing of the key genes and end products in the TLR4 signaling pathway from the kidney of Rana dybowskii exposed to Aeromonas hydrophila
  251. Development of a new candidate vaccine against piglet diarrhea caused by Escherichia coli
  252. Plant Sciences
  253. Crown and diameter structure of pure Pinus massoniana Lamb. forest in Hunan province, China
  254. Genetic evaluation and germplasm identification analysis on ITS2, trnL-F, and psbA-trnH of alfalfa varieties germplasm resources
  255. Tissue culture and rapid propagation technology for Gentiana rhodantha
  256. Effects of cadmium on the synthesis of active ingredients in Salvia miltiorrhiza
  257. Cloning and expression analysis of VrNAC13 gene in mung bean
  258. Chlorate-induced molecular floral transition revealed by transcriptomes
  259. Effects of warming and drought on growth and development of soybean in Hailun region
  260. Effects of different light conditions on transient expression and biomass in Nicotiana benthamiana leaves
  261. Comparative analysis of the rhizosphere microbiome and medicinally active ingredients of Atractylodes lancea from different geographical origins
  262. Distinguish Dianthus species or varieties based on chloroplast genomes
  263. Comparative transcriptomes reveal molecular mechanisms of apple blossoms of different tolerance genotypes to chilling injury
  264. Study on fresh processing key technology and quality influence of Cut Ophiopogonis Radix based on multi-index evaluation
  265. An advanced approach for fig leaf disease detection and classification: Leveraging image processing and enhanced support vector machine methodology
  266. Erratum
  267. Erratum to “Protein Z modulates the metastasis of lung adenocarcinoma cells”
  268. Erratum to “BRCA1 subcellular localization regulated by PI3K signaling pathway in triple-negative breast cancer MDA-MB-231 cells and hormone-sensitive T47D cells”
  269. Retraction
  270. Retraction to “Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats”
https://doi.org/10.1515/biol-2022-0530
Keywords for this article
β-TCP; bioceramics; stereolithography; biocompatibility; osteogenesis
Creative Commons
BY 4.0

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  2. Systemic investigation of inetetamab in combination with small molecules to treat HER2-overexpressing breast and gastric cancers
  3. Immunosuppressive treatment for idiopathic membranous nephropathy: An updated network meta-analysis
  4. Identifying two pathogenic variants in a patient with pigmented paravenous retinochoroidal atrophy
  5. Effects of phytoestrogens combined with cold stress on sperm parameters and testicular proteomics in rats
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  7. Neutrophilia with subclinical Cushing’s disease: A case report and literature review
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  10. Novel CPLANE1 c.8948dupT (p.P2984Tfs*7) variant in a child patient with Joubert syndrome
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  13. High glucose and high lipid induced mitochondrial dysfunction in JEG-3 cells through oxidative stress
  14. Pharmacological inhibition of the ubiquitin-specific protease 8 effectively suppresses glioblastoma cell growth
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  16. Age-related changes in peripheral T-cell subpopulations in elderly individuals: An observational study
  17. Single-cell transcription analysis reveals the tumor origin and heterogeneity of human bilateral renal clear cell carcinoma
  18. Identification of iron metabolism-related genes as diagnostic signatures in sepsis by blood transcriptomic analysis
  19. Long noncoding RNA ACART knockdown decreases 3T3-L1 preadipocyte proliferation and differentiation
  20. Surgery, adjuvant immunotherapy plus chemotherapy and radiotherapy for primary malignant melanoma of the parotid gland (PGMM): A case report
  21. Dosimetry comparison with helical tomotherapy, volumetric modulated arc therapy, and intensity-modulated radiotherapy for grade II gliomas: A single‑institution case series
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  25. 6-Phosphogluconate dehydrogenase inhibition arrests growth and induces apoptosis in gastric cancer via AMPK activation and oxidative stress
  26. Experimental study on the optimization of ANM33 release in foam cells
  27. Primary retroperitoneal angiosarcoma: A case report
  28. Metabolomic analysis-identified 2-hydroxybutyric acid might be a key metabolite of severe preeclampsia
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  30. Effect of spaceflight on the phenotype and proteome of Escherichia coli
  31. Comparison of immunotherapy combined with stereotactic radiotherapy and targeted therapy for patients with brain metastases: A systemic review and meta-analysis
  32. Activation of hypermethylated P2RY1 mitigates gastric cancer by promoting apoptosis and inhibiting proliferation
  33. Association between the VEGFR-2 -604T/C polymorphism (rs2071559) and type 2 diabetic retinopathy
  34. The role of IL-31 and IL-34 in the diagnosis and treatment of chronic periodontitis
  35. Triple-negative mouse breast cancer initiating cells show high expression of beta1 integrin and increased malignant features
  36. mNGS facilitates the accurate diagnosis and antibiotic treatment of suspicious critical CNS infection in real practice: A retrospective study
  37. The apatinib and pemetrexed combination has antitumor and antiangiogenic effects against NSCLC
  38. Radiotherapy for primary thyroid adenoid cystic carcinoma
  39. Design and functional preliminary investigation of recombinant antigen EgG1Y162–EgG1Y162 against Echinococcus granulosus
  40. Effects of losartan in patients with NAFLD: A meta-analysis of randomized controlled trial
  41. Bibliometric analysis of METTL3: Current perspectives, highlights, and trending topics
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  43. PI3K/AKT/mTOR pathway and its related molecules participate in PROK1 silence-induced anti-tumor effects on pancreatic cancer
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  45. Effects of pegylated recombinant human granulocyte colony-stimulating factor on lymphocytes and white blood cells of patients with malignant tumor
  46. Prostatitis as initial manifestation of Chlamydia psittaci pneumonia diagnosed by metagenome next-generation sequencing: A case report
  47. NUDT21 relieves sevoflurane-induced neurological damage in rats by down-regulating LIMK2
  48. Association of interleukin-10 rs1800896, rs1800872, and interleukin-6 rs1800795 polymorphisms with squamous cell carcinoma risk: A meta-analysis
  49. Exosomal HBV-DNA for diagnosis and treatment monitoring of chronic hepatitis B
  50. Shear stress leads to the dysfunction of endothelial cells through the Cav-1-mediated KLF2/eNOS/ERK signaling pathway under physiological conditions
  51. Interaction between the PI3K/AKT pathway and mitochondrial autophagy in macrophages and the leukocyte count in rats with LPS-induced pulmonary infection
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  53. Cloning, subcellular localization and expression of phosphate transporter gene HvPT6 of hulless barley
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  55. Significant elevated CXCL14 and decreased IL-39 levels in patients with tuberculosis
  56. Whole-exome sequencing applications in prenatal diagnosis of fetal bowel dilatation
  57. Gemella morbillorum infective endocarditis: A case report and literature review
  58. An unusual ectopic thymoma clonal evolution analysis: A case report
  59. Severe cumulative skin toxicity during toripalimab combined with vemurafenib following toripalimab alone
  60. Detection of V. vulnificus septic shock with ARDS using mNGS
  61. Novel rare genetic variants of familial and sporadic pulmonary atresia identified by whole-exome sequencing
  62. The influence and mechanistic action of sperm DNA fragmentation index on the outcomes of assisted reproduction technology
  63. Novel compound heterozygous mutations in TELO2 in an infant with You-Hoover-Fong syndrome: A case report and literature review
  64. ctDNA as a prognostic biomarker in resectable CLM: Systematic review and meta-analysis
  65. Diagnosis of primary amoebic meningoencephalitis by metagenomic next-generation sequencing: A case report
  66. Phylogenetic analysis of promoter regions of human Dolichol kinase (DOLK) and orthologous genes using bioinformatics tools
  67. Collagen changes in rabbit conjunctiva after conjunctival crosslinking
  68. Effects of NM23 transfection of human gastric carcinoma cells in mice
  69. Oral nifedipine and phytosterol, intravenous nicardipine, and oral nifedipine only: Three-arm, retrospective, cohort study for management of severe preeclampsia
  70. Case report of hepatic retiform hemangioendothelioma: A rare tumor treated with ultrasound-guided microwave ablation
  71. Curcumin induces apoptosis in human hepatocellular carcinoma cells by decreasing the expression of STAT3/VEGF/HIF-1α signaling
  72. Rare presentation of double-clonal Waldenström macroglobulinemia with pulmonary embolism: A case report
  73. Giant duplication of the transverse colon in an adult: A case report and literature review
  74. Ectopic thyroid tissue in the breast: A case report
  75. SDR16C5 promotes proliferation and migration and inhibits apoptosis in pancreatic cancer
  76. Vaginal metastasis from breast cancer: A case report
  77. Screening of the best time window for MSC transplantation to treat acute myocardial infarction with SDF-1α antibody-loaded targeted ultrasonic microbubbles: An in vivo study in miniswine
  78. Inhibition of TAZ impairs the migration ability of melanoma cells
  79. Molecular complexity analysis of the diagnosis of Gitelman syndrome in China
  80. Effects of maternal calcium and protein intake on the development and bone metabolism of offspring mice
  81. Identification of winter wheat pests and diseases based on improved convolutional neural network
  82. Ultra-multiplex PCR technique to guide treatment of Aspergillus-infected aortic valve prostheses
  83. Virtual high-throughput screening: Potential inhibitors targeting aminopeptidase N (CD13) and PIKfyve for SARS-CoV-2
  84. Immune checkpoint inhibitors in cancer patients with COVID-19
  85. Utility of methylene blue mixed with autologous blood in preoperative localization of pulmonary nodules and masses
  86. Integrated analysis of the microbiome and transcriptome in stomach adenocarcinoma
  87. Berberine suppressed sarcopenia insulin resistance through SIRT1-mediated mitophagy
  88. DUSP2 inhibits the progression of lupus nephritis in mice by regulating the STAT3 pathway
  89. Lung abscess by Fusobacterium nucleatum and Streptococcus spp. co-infection by mNGS: A case series
  90. Genetic alterations of KRAS and TP53 in intrahepatic cholangiocarcinoma associated with poor prognosis
  91. Granulomatous polyangiitis involving the fourth ventricle: Report of a rare case and a literature review
  92. Studying infant mortality: A demographic analysis based on data mining models
  93. Metaplastic breast carcinoma with osseous differentiation: A report of a rare case and literature review
  94. Protein Z modulates the metastasis of lung adenocarcinoma cells
  95. Inhibition of pyroptosis and apoptosis by capsaicin protects against LPS-induced acute kidney injury through TRPV1/UCP2 axis in vitro
  96. TAK-242, a toll-like receptor 4 antagonist, against brain injury by alleviates autophagy and inflammation in rats
  97. Primary mediastinum Ewing’s sarcoma with pleural effusion: A case report and literature review
  98. Association of ADRB2 gene polymorphisms and intestinal microbiota in Chinese Han adolescents
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  100. Study on the cytokines related to SARS-Cov-2 in testicular cells and the interaction network between cells based on scRNA-seq data
  101. Effect of periostin on bone metabolic and autophagy factors during tooth eruption in mice
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  103. Intravaginal estrogen management in postmenopausal patients with vaginal squamous intraepithelial lesions along with CO2 laser ablation: A retrospective study
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  106. Identification of lysosome-related genes in connection with prognosis and immune cell infiltration for drug candidates in head and neck cancer
  107. Development of an instrument-free and low-cost ELISA dot-blot test to detect antibodies against SARS-CoV-2
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  109. Adiponectin inhibits TGF-β1-induced skin fibroblast proliferation and phenotype transformation via the p38 MAPK signaling pathway
  110. The G protein-coupled receptor-related gene signatures for predicting prognosis and immunotherapy response in bladder urothelial carcinoma
  111. α-Fetoprotein contributes to the malignant biological properties of AFP-producing gastric cancer
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  114. Significance of sTREM-1 and sST2 combined diagnosis for sepsis detection and prognosis prediction
  115. Diagnostic value of serum neuroactive substances in the acute exacerbation of chronic obstructive pulmonary disease complicated with depression
  116. Research progress of AMP-activated protein kinase and cardiac aging
  117. TRIM29 knockdown prevented the colon cancer progression through decreasing the ubiquitination levels of KRT5
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  120. The early diagnosis and pathogenic mechanisms of sepsis-related acute kidney injury
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  122. Erianin alleviates collagen-induced arthritis in mice by inhibiting Th17 cell differentiation
  123. Loss of ACOX1 in clear cell renal cell carcinoma and its correlation with clinical features
  124. Signalling pathways in the osteogenic differentiation of periodontal ligament stem cells
  125. Crosstalk between lactic acid and immune regulation and its value in the diagnosis and treatment of liver failure
  126. Clinicopathological features and differential diagnosis of gastric pleomorphic giant cell carcinoma
  127. Traumatic brain injury and rTMS-ERPs: Case report and literature review
  128. Extracellular fibrin promotes non-small cell lung cancer progression through integrin β1/PTEN/AKT signaling
  129. Knockdown of DLK4 inhibits non-small cell lung cancer tumor growth by downregulating CKS2
  130. The co-expression pattern of VEGFR-2 with indicators related to proliferation, apoptosis, and differentiation of anagen hair follicles
  131. Inflammation-related signaling pathways in tendinopathy
  132. CD4+ T cell count in HIV/TB co-infection and co-occurrence with HL: Case report and literature review
  133. Clinical analysis of severe Chlamydia psittaci pneumonia: Case series study
  134. Bioinformatics analysis to identify potential biomarkers for the pulmonary artery hypertension associated with the basement membrane
  135. Influence of MTHFR polymorphism, alone or in combination with smoking and alcohol consumption, on cancer susceptibility
  136. Catharanthus roseus (L.) G. Don counteracts the ampicillin resistance in multiple antibiotic-resistant Staphylococcus aureus by downregulation of PBP2a synthesis
  137. Combination of a bronchogenic cyst in the thoracic spinal canal with chronic myelocytic leukemia
  138. Bacterial lipoprotein plays an important role in the macrophage autophagy and apoptosis induced by Salmonella typhimurium and Staphylococcus aureus
  139. TCL1A+ B cells predict prognosis in triple-negative breast cancer through integrative analysis of single-cell and bulk transcriptomic data
  140. Ezrin promotes esophageal squamous cell carcinoma progression via the Hippo signaling pathway
  141. Ferroptosis: A potential target of macrophages in plaque vulnerability
  142. Predicting pediatric Crohn's disease based on six mRNA-constructed risk signature using comprehensive bioinformatic approaches
  143. Applications of genetic code expansion and photosensitive UAAs in studying membrane proteins
  144. HK2 contributes to the proliferation, migration, and invasion of diffuse large B-cell lymphoma cells by enhancing the ERK1/2 signaling pathway
  145. IL-17 in osteoarthritis: A narrative review
  146. Circadian cycle and neuroinflammation
  147. Probiotic management and inflammatory factors as a novel treatment in cirrhosis: A systematic review and meta-analysis
  148. Hemorrhagic meningioma with pulmonary metastasis: Case report and literature review
  149. SPOP regulates the expression profiles and alternative splicing events in human hepatocytes
  150. Knockdown of SETD5 inhibited glycolysis and tumor growth in gastric cancer cells by down-regulating Akt signaling pathway
  151. PTX3 promotes IVIG resistance-induced endothelial injury in Kawasaki disease by regulating the NF-κB pathway
  152. Pancreatic ectopic thyroid tissue: A case report and analysis of literature
  153. The prognostic impact of body mass index on female breast cancer patients in underdeveloped regions of northern China differs by menopause status and tumor molecular subtype
  154. Report on a case of liver-originating malignant melanoma of unknown primary
  155. Case report: Herbal treatment of neutropenic enterocolitis after chemotherapy for breast cancer
  156. The fibroblast growth factor–Klotho axis at molecular level
  157. Characterization of amiodarone action on currents in hERG-T618 gain-of-function mutations
  158. A case report of diagnosis and dynamic monitoring of Listeria monocytogenes meningitis with NGS
  159. Effect of autologous platelet-rich plasma on new bone formation and viability of a Marburg bone graft
  160. Small breast epithelial mucin as a useful prognostic marker for breast cancer patients
  161. Continuous non-adherent culture promotes transdifferentiation of human adipose-derived stem cells into retinal lineage
  162. Nrf3 alleviates oxidative stress and promotes the survival of colon cancer cells by activating AKT/BCL-2 signal pathway
  163. Favorable response to surufatinib in a patient with necrolytic migratory erythema: A case report
  164. Case report of atypical undernutrition of hypoproteinemia type
  165. Down-regulation of COL1A1 inhibits tumor-associated fibroblast activation and mediates matrix remodeling in the tumor microenvironment of breast cancer
  166. Sarcoma protein kinase inhibition alleviates liver fibrosis by promoting hepatic stellate cells ferroptosis
  167. Research progress of serum eosinophil in chronic obstructive pulmonary disease and asthma
  168. Clinicopathological characteristics of co-existing or mixed colorectal cancer and neuroendocrine tumor: Report of five cases
  169. Role of menopausal hormone therapy in the prevention of postmenopausal osteoporosis
  170. Precisional detection of lymph node metastasis using tFCM in colorectal cancer
  171. Advances in diagnosis and treatment of perimenopausal syndrome
  172. A study of forensic genetics: ITO index distribution and kinship judgment between two individuals
  173. Acute lupus pneumonitis resembling miliary tuberculosis: A case-based review
  174. Plasma levels of CD36 and glutathione as biomarkers for ruptured intracranial aneurysm
  175. Fractalkine modulates pulmonary angiogenesis and tube formation by modulating CX3CR1 and growth factors in PVECs
  176. Novel risk prediction models for deep vein thrombosis after thoracotomy and thoracoscopic lung cancer resections, involving coagulation and immune function
  177. Exploring the diagnostic markers of essential tremor: A study based on machine learning algorithms
  178. Evaluation of effects of small-incision approach treatment on proximal tibia fracture by deep learning algorithm-based magnetic resonance imaging
  179. An online diagnosis method for cancer lesions based on intelligent imaging analysis
  180. Medical imaging in rheumatoid arthritis: A review on deep learning approach
  181. Predictive analytics in smart healthcare for child mortality prediction using a machine learning approach
  182. Utility of neutrophil–lymphocyte ratio and platelet–lymphocyte ratio in predicting acute-on-chronic liver failure survival
  183. A biomedical decision support system for meta-analysis of bilateral upper-limb training in stroke patients with hemiplegia
  184. TNF-α and IL-8 levels are positively correlated with hypobaric hypoxic pulmonary hypertension and pulmonary vascular remodeling in rats
  185. Stochastic gradient descent optimisation for convolutional neural network for medical image segmentation
  186. Comparison of the prognostic value of four different critical illness scores in patients with sepsis-induced coagulopathy
  187. Application and teaching of computer molecular simulation embedded technology and artificial intelligence in drug research and development
  188. Hepatobiliary surgery based on intelligent image segmentation technology
  189. Value of brain injury-related indicators based on neural network in the diagnosis of neonatal hypoxic-ischemic encephalopathy
  190. Analysis of early diagnosis methods for asymmetric dementia in brain MR images based on genetic medical technology
  191. Early diagnosis for the onset of peri-implantitis based on artificial neural network
  192. Clinical significance of the detection of serum IgG4 and IgG4/IgG ratio in patients with thyroid-associated ophthalmopathy
  193. Forecast of pain degree of lumbar disc herniation based on back propagation neural network
  194. SPA-UNet: A liver tumor segmentation network based on fused multi-scale features
  195. Systematic evaluation of clinical efficacy of CYP1B1 gene polymorphism in EGFR mutant non-small cell lung cancer observed by medical image
  196. Rehabilitation effect of intelligent rehabilitation training system on hemiplegic limb spasms after stroke
  197. A novel approach for minimising anti-aliasing effects in EEG data acquisition
  198. ErbB4 promotes M2 activation of macrophages in idiopathic pulmonary fibrosis
  199. Clinical role of CYP1B1 gene polymorphism in prediction of postoperative chemotherapy efficacy in NSCLC based on individualized health model
  200. Lung nodule segmentation via semi-residual multi-resolution neural networks
  201. Evaluation of brain nerve function in ICU patients with Delirium by deep learning algorithm-based resting state MRI
  202. A data mining technique for detecting malignant mesothelioma cancer using multiple regression analysis
  203. Markov model combined with MR diffusion tensor imaging for predicting the onset of Alzheimer’s disease
  204. Effectiveness of the treatment of depression associated with cancer and neuroimaging changes in depression-related brain regions in patients treated with the mediator-deuterium acupuncture method
  205. Molecular mechanism of colorectal cancer and screening of molecular markers based on bioinformatics analysis
  206. Monitoring and evaluation of anesthesia depth status data based on neuroscience
  207. Exploring the conformational dynamics and thermodynamics of EGFR S768I and G719X + S768I mutations in non-small cell lung cancer: An in silico approaches
  208. Optimised feature selection-driven convolutional neural network using gray level co-occurrence matrix for detection of cervical cancer
  209. Incidence of different pressure patterns of spinal cerebellar ataxia and analysis of imaging and genetic diagnosis
  210. Pathogenic bacteria and treatment resistance in older cardiovascular disease patients with lung infection and risk prediction model
  211. Adoption value of support vector machine algorithm-based computed tomography imaging in the diagnosis of secondary pulmonary fungal infections in patients with malignant hematological disorders
  212. From slides to insights: Harnessing deep learning for prognostic survival prediction in human colorectal cancer histology
  213. Ecology and Environmental Science
  214. Monitoring of hourly carbon dioxide concentration under different land use types in arid ecosystem
  215. Comparing the differences of prokaryotic microbial community between pit walls and bottom from Chinese liquor revealed by 16S rRNA gene sequencing
  216. Effects of cadmium stress on fruits germination and growth of two herbage species
  217. Bamboo charcoal affects soil properties and bacterial community in tea plantations
  218. Optimization of biogas potential using kinetic models, response surface methodology, and instrumental evidence for biodegradation of tannery fleshings during anaerobic digestion
  219. Understory vegetation diversity patterns of Platycladus orientalis and Pinus elliottii communities in Central and Southern China
  220. Studies on macrofungi diversity and discovery of new species of Abortiporus from Baotianman World Biosphere Reserve
  221. Food Science
  222. Effect of berrycactus fruit (Myrtillocactus geometrizans) on glutamate, glutamine, and GABA levels in the frontal cortex of rats fed with a high-fat diet
  223. Guesstimate of thymoquinone diversity in Nigella sativa L. genotypes and elite varieties collected from Indian states using HPTLC technique
  224. Analysis of bacterial community structure of Fuzhuan tea with different processing techniques
  225. Untargeted metabolomics reveals sour jujube kernel benefiting the nutritional value and flavor of Morchella esculenta
  226. Mycobiota in Slovak wine grapes: A case study from the small Carpathians wine region
  227. Elemental analysis of Fadogia ancylantha leaves used as a nutraceutical in Mashonaland West Province, Zimbabwe
  228. Microbiological transglutaminase: Biotechnological application in the food industry
  229. Influence of solvent-free extraction of fish oil from catfish (Clarias magur) heads using a Taguchi orthogonal array design: A qualitative and quantitative approach
  230. Chromatographic analysis of the chemical composition and anticancer activities of Curcuma longa extract cultivated in Palestine
  231. The potential for the use of leghemoglobin and plant ferritin as sources of iron
  232. Investigating the association between dietary patterns and glycemic control among children and adolescents with T1DM
  233. Bioengineering and Biotechnology
  234. Biocompatibility and osteointegration capability of β-TCP manufactured by stereolithography 3D printing: In vitro study
  235. Clinical characteristics and the prognosis of diabetic foot in Tibet: A single center, retrospective study
  236. Agriculture
  237. Biofertilizer and NPSB fertilizer application effects on nodulation and productivity of common bean (Phaseolus vulgaris L.) at Sodo Zuria, Southern Ethiopia
  238. On correlation between canopy vegetation and growth indexes of maize varieties with different nitrogen efficiencies
  239. Exopolysaccharides from Pseudomonas tolaasii inhibit the growth of Pleurotus ostreatus mycelia
  240. A transcriptomic evaluation of the mechanism of programmed cell death of the replaceable bud in Chinese chestnut
  241. Melatonin enhances salt tolerance in sorghum by modulating photosynthetic performance, osmoregulation, antioxidant defense, and ion homeostasis
  242. Effects of plant density on alfalfa (Medicago sativa L.) seed yield in western Heilongjiang areas
  243. Identification of rice leaf diseases and deficiency disorders using a novel DeepBatch technique
  244. Artificial intelligence and internet of things oriented sustainable precision farming: Towards modern agriculture
  245. Animal Sciences
  246. Effect of ketogenic diet on exercise tolerance and transcriptome of gastrocnemius in mice
  247. Combined analysis of mRNA–miRNA from testis tissue in Tibetan sheep with different FecB genotypes
  248. Isolation, identification, and drug resistance of a partially isolated bacterium from the gill of Siniperca chuatsi
  249. Tracking behavioral changes of confined sows from the first mating to the third parity
  250. The sequencing of the key genes and end products in the TLR4 signaling pathway from the kidney of Rana dybowskii exposed to Aeromonas hydrophila
  251. Development of a new candidate vaccine against piglet diarrhea caused by Escherichia coli
  252. Plant Sciences
  253. Crown and diameter structure of pure Pinus massoniana Lamb. forest in Hunan province, China
  254. Genetic evaluation and germplasm identification analysis on ITS2, trnL-F, and psbA-trnH of alfalfa varieties germplasm resources
  255. Tissue culture and rapid propagation technology for Gentiana rhodantha
  256. Effects of cadmium on the synthesis of active ingredients in Salvia miltiorrhiza
  257. Cloning and expression analysis of VrNAC13 gene in mung bean
  258. Chlorate-induced molecular floral transition revealed by transcriptomes
  259. Effects of warming and drought on growth and development of soybean in Hailun region
  260. Effects of different light conditions on transient expression and biomass in Nicotiana benthamiana leaves
  261. Comparative analysis of the rhizosphere microbiome and medicinally active ingredients of Atractylodes lancea from different geographical origins
  262. Distinguish Dianthus species or varieties based on chloroplast genomes
  263. Comparative transcriptomes reveal molecular mechanisms of apple blossoms of different tolerance genotypes to chilling injury
  264. Study on fresh processing key technology and quality influence of Cut Ophiopogonis Radix based on multi-index evaluation
  265. An advanced approach for fig leaf disease detection and classification: Leveraging image processing and enhanced support vector machine methodology
  266. Erratum
  267. Erratum to “Protein Z modulates the metastasis of lung adenocarcinoma cells”
  268. Erratum to “BRCA1 subcellular localization regulated by PI3K signaling pathway in triple-negative breast cancer MDA-MB-231 cells and hormone-sensitive T47D cells”
  269. Retraction
  270. Retraction to “Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats”
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