[Development and Challenges of Additive Manufactured Customized Implant].

Additive manufacturing (3D printing) technology aligns with the direction of precision and customization in future medicine, presenting a significant opportunity for innovative development in high-end medical devices. Currently, research and industrialization of 3D printed medical devices mainly focus on nondegradable implants and degradable implants. Primary areas including metallic orthopaedic implants, polyether-ether-ketone (PEEK) bone implants, and biodegradable implants have been developed for clinical and industrial application. Recent research achievements in these areas are reviewed, with a discussion on the additive manufacturing technologies and applications for customized implants. Challenges faced by different types of implants are analyzed from technological, application, and regulatory perspectives. Furthermore, prospects and suggestions for future development are outlined.

Prognostic and biological function value of OSBPL3 in colorectal cancer analyzed by multi-omic data analysis.

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies in the world. This study proposes to reveal prognostic biomarkers for the prognosis and treatment of CRC patients. METHODS: Differential analysis of OSBPL3 was performed in pan-cancer, and the correlation between clinical stage and OSBPL3 was analyzed. Multiple omics analysis was used to compare the relationship between survival of patients and copy number variation, single nucleotide variant, and methylation status. Survival differences between high and low OSBPL3 expression groups were analyzed. Differentially expressed genes (DEGs) between high and low OSBPL3 expression groups were obtained, and functional enrichment analysis was implemented. Correlations between immune cells and OSBPL3 was analyzed. Drug sensitivity between the two OSBPL3 expression groups was compared. Moreover, the expression of OSBPL3 was verified by immunohistochemistry and real-time quantitative PCR. RESULTS: OSBPL3 was differentially expressed in 13 tumors and had some correlations with T and N stages. OSBPL3 expression was regulated by methylation and higher OSBPL3 expression was associated with poorer prognosis in CRC. 128 DEGs were obtained and they were mainly involved in signaling receptor activator activity, aspartate and glutamate metabolism. T cell gamma delta and T cell follicular helper were significantly different in the high and low OSBPL3 expression groups. Moreover, OSBPL3 showed negative correlations with multiple drugs. OSBPL3 was significantly upregulated in CRC samples compared to normal samples. CONCLUSIONS: A comprehensive analysis demonstrated that OSBPL3 had potential prognostic value, and guiding significance for CRC chemotherapeutic.

Hsa-miR-1248 suppressed the proliferation, invasion and migration of colorectal cancer cells via inhibiting PSMD10.

BACKGROUND: Lymph node metastasis (LNM) is a critical event during the colorectal cancer (CRC) development and is indicative of poor prognosis. Identification of molecular markers of LNM may facilitate better therapeutic decision-making. METHODS: Six pairs of CRC tissues and corresponding adjacent tissues [3 pairs diagnosed as pT1N0M0 (M_Low group) and 3 pairs diagnosed as pT4N2M0 (M_High group)] collected from CRC patients who underwent surgical resection were used. MicroRNA sequencing was performed to screen differential microRNAs involved in CRC LNM. The selected microRNAs were validated in CRC tissues and cell lines using qRT-PCR. The functions of candidate hsa-miR-1248 were evaluated by CCK-8, colony formation, and Transwell assay. The binding of hsa-miR-1248 with its target PSMD10 was confirmed by luciferase activity assay, and the expression of PSMD10 in tissues was detected by droplet digital polymerase chain reaction. RESULTS: Ninety-five miRNAs were downregulated in carcinoma tissues (M_Low and M_high groups) compared with the normal group. Their expression in M_High group was significantly lower compared with M_Low group. The top 3 were hsa-miR-635, hsa-miR-1248, and hsa-miR-668-3p. After validation in tissues/cell lines, only hsa- hsa-miR-1248 was decreased in high metastatic tissues or SW620 cells compared to low metastatic tissues or SW480 cells. Hsa-miR-1248 was found to inhibit CRC cell viability, proliferation, invasion, and migration. The tumor suppressor effect of has-miR-1248 in CRC cells was attenuated or enhanced by up-regulating or down-regulating PSMD10, respectively. CONCLUSION: Hsa-miR-1248 may act as a tumor suppressor gene in CRC by targeting and inhibiting PSMD10, which provides a clue for CRC treatment.

Flexible fiber-shaped supercapacitors based on graphene/polyaniline hybrid fibers with high energy density and capacitance.

Fiber-shaped supercapacitors (FSCs) are promising energy storage devices for portable and wearable electronics due to their miniaturized size, flexibility, and knittability. Despite the significant progress in this area, it is still a challenge to develop large capacitance and high energy density FSCs for practical applications. In this work, a hybrid fiber composed of reduced graphene oxide and polyaniline nanoparticles (r-PANI-GOF) is synthesized viain situsynthesis of polyaniline nanoparticles both on the surface and inside of graphene fibers. The areal specific capacitance of a single r-PANI-GOF electrode is as large as 1755 mF cm-2in the three-electrode system. The r-PANI-GOF hybrid fibers were also used as electrodes for making an all-solid-state FSCs. This whole device has a specific areal capacitance of up to 481 mF cm-2and a high areal energy density of 42.76µWh cm-2. The hybrid fiber electrodes with a high capacitance, and excellent flexibility may become new candidates for the development of fiber-shaped high-performance energy storage devices.

Microphysiological systems inspired by leaf venation.

Nature-inspired microfluidic networks are revolutionizing microphysiological systems, allowing for the precise emulation of human physiology. This article delves into the fabrication techniques of leaf-venation-inspired (LVI) microfluidic networks and explores their transformative applications in organ-on-a-chip and tissue engineering, showcasing their pivotal role in advancing biomedical research.

Consecutive multimaterial printing of biomimetic ionic hydrogel power sources with high flexibility and stretchability.

Electric eel is an excellent example to harness ion-concentration gradients for sustainable power generation. However, current strategies to create electric-eel-inspired power sources commonly involve manual stacking of multiple salinity-gradient power source units, resulting in low efficiency, unstable contact, and poor flexibility. Here we propose a consecutive multimaterial printing strategy to efficiently fabricate biomimetic ionic hydrogel power sources with a maximum stretchability of 137%. The consecutively-printed ionic hydrogel power source filaments showed seamless bonding interface and can maintain stable voltage outputs for 1000 stretching cycles at 100% strain. With arrayed multi-channel printhead, power sources with a maximum voltage of 208 V can be automatically printed and assembled in parallel within 30 min. The as-printed flexible power source filaments can be woven into a wristband to power a digital wristwatch. The presented strategy provides a tool to efficiently produce electric-eel-inspired ionic hydrogel power sources with great stretchability for various flexible power source applications.

Coaxial Electrohydrodynamic Printing of Microscale Core-Shell Conductive Features for Integrated Fabrication of Flexible Transparent Electronics.

Reliable insulation of microscale conductive features is required to fabricate functional multilayer circuits or flexible electronics for providing specific physical/chemical/electrical protection. However, the existing strategies commonly rely on manual assembling processes or multiple microfabrication processes, which is time-consuming and a great challenge for the fabrication of flexible transparent electronics with microscale features and ultrathin thickness. Here, we present a novel coaxial electrohydrodynamic (CEHD) printing strategy for the one-step fabrication of microscale flexible electronics with conductive materials at the core and insulating material at the outer layer. A finite element analysis (FEA) method is established to simulate the CEHD printing process. The extrusion sequence of the conductive and insulating materials during the CEHD printing process shows little effect on the morphology of the core-shell filaments, which can be achieved on different flexible substrates with a minimum conductive line width of 32 ± 3.2 µm, a total thickness of 53.6 ± 4.8 µm, and a conductivity of 0.23 × 107 S/m. The thin insulating layer can provide the inner conductive filament enough protection in 3D, which endows the resultant microscale core-shell electronics with good electrical stability when working in different chemical solvent solutions or under large deformation conditions. Moreover, the presented CEHD printing strategy offers a unique capability to sequentially fabricate an insulating layer, core-shell conductive pattern, and exposed electrodes by simply controlling the material extrusion sequence. The resultant large-area transparent electronics with two-layer core-shell patterns exhibit a high transmittance of 98% and excellent electrothermal performance. The CEHD-printed flexible microelectrode array is successfully used to record the electrical signals of beating mouse hearts. It can also be used to fabricate large-area flexible capacitive sensors to accurately measure the periodical pressure force. We envision that the present CEHD printing strategy can provide a promising tool to fabricate complex three-dimensional electronics with microscale resolution, high flexibility, and multiple functionalities.

Development of Electro-Conductive Composite Bioinks for Electrohydrodynamic Bioprinting with Microscale Resolution.

Bioprinting has attracted extensive attention in the field of tissue engineering due to its unique capability in constructing biomimetic tissue constructs in a highly controlled manner. However, it is still challenging to reproduce the physical and structural properties of native electroactive tissues due to the poor electroconductivity of current bioink systems as well as the limited printing resolution of conventional bioprinting techniques. In this work, an electro-conductive hydrogel is prepared by introducing poly (3,4-ethylene dioxythiophene): poly (styrene sulfonate) (PEDOT: PSS) into an RGD (GGGGRGDSP)-functionalized alginate and fibrin system (RAF), and then electrohydrodynamic (EHD)-bioprinted to form living tissue constructs with microscale resolution. The addition of 0.1 (w/v%) PEDOT: PSS increases the electroconductivity to 1.95 ± 0.21 S m-1 and simultaneously has little effect on cell viability. Compared with pure RAF bioink, the presence of PEDOT: PSS expands the printable parameters for EHD-bioprinting, and hydrogel filaments with the smallest feature size of 48.91 ± 3.44 µm can be obtained by further optimizing process parameters. Furthermore, the EHD-bioprinted electro-conductive living tissue constructs with improved resolution show good viability (>85%). The synergy of the advanced electro-conductive hydrogel and EHD-bioprinting presented here may provide a promising approach for engineering electro-conductive and cell-laden constructs for electroactive tissue engineering.

A cell-free tissue-engineered tracheal substitute with sequential cytokine release maintained airway opening in a rabbit tracheal full circumferential defect model.

In this study, a cell-free tissue-engineered tracheal substitute was developed, which is based on a 3D-printed polycaprolactone scaffold coated with a gelatin-methacryloyl (GelMA) hydrogel, with transforming growth factor-ß1 (TGF-ß) and stromal cell-derived factor-1α (SDF-1) sequentially embedded, to facilitate cell recruitment and differentiation toward chondrocyte-phenotype. TGF-ß was loaded onto polydopamine particles, and then encapsulated into the GelMA together with SDF-1, and called G/S/P@T, which was used to coat 3D-printed PCL scaffold to form the tracheal substitute. A rapid release of SDF-1 was observed during the first week, followed by a slow and sustained release of TGF-ß for approximately four weeks. The tracheal substitute significantly promoted the recruitment of mesenchymal stromal cells (MSCs) or human bronchial epithelial cells in vitro, and enhanced the ability of MSCs to differentiate towards chondrocyte phenotype. Implantation of the tissue-engineered tracheal substitute with a rabbit tracheal anterior defect model improved regeneration of airway epithelium, recruitment of endogenous MSCs and expression of markers of chondrocytes at the tracheal defect site. Moreover, the tracheal substitute maintained airway opening for 4 weeks in a tracheal full circumferential defect model with airway epithelium coverage at the defect sites without granulation tissue accumulation in the tracheal lumen or underneath. The promising results suggest that this simple, cell-free tissue-engineered tracheal substitute can be used directly after tracheal defect removal and should be further developed towards clinical application.

Design of a Single-Channel Chaotic Secure Communication System Implemented by DNA Strand Displacement.

DNA strand displacement (DSD) is regarded as a foundation for the construction of biological computing systems because of the predictability of DNA molecular behaviors. Some complex system dynamics can be approximated by cascading DSD reaction modules with different functions. In this paper, four DSD reaction modules are used to realize chaotic secure communication based on drive-response synchronization of four-dimensional chaotic systems. The system adopts the communication technology of chaos masking and uses a single-channel synchronization scheme to achieve high accuracy. The simulation results demonstrate that encryption and decryption of the signal are achieved by the design. Moreover, the system is robust to noise signals and interference during the DNA reactions. This work provides a method for the application of DNA molecular computation in the communication field.

Embedded bioprinting for designer 3D tissue constructs with complex structural organization.

3D bioprinting has been developed as an effective and powerful technique for the fabrication of living tissue constructs in a well-controlled manner. However, most existing 3D bioprinting strategies face substantial challenges in replicating delicate and intricate tissue-specific structural organizations using mechanically weak biomaterials such as hydrogels. Embedded bioprinting is an emerging bioprinting strategy that can directly fabricate complex structures derived from soft biomaterials within a supporting matrix, which shows great promise in printing large vascularized tissues and organs. Here, we provide a state-of-the-art review on the development of embedded bioprinting including extrusion-based and light-based processes to manufacture complex tissue constructs with biomimetic architectures. The working principles, bioinks, and supporting matrices of embedded printing processes are introduced. The effect of key processing parameters on the printing resolution, shape fidelity, and biological functions of the printed tissue constructs are discussed. Recent innovations in the processes and applications of embedded bioprinting are highlighted, such as light-based volumetric bioprinting and printing of functional vascularized organ constructs. Challenges and future perspectives with regard to translating embedded bioprinting into an effective strategy for the fabrication of functional biological constructs with biomimetic structural organizations are finally discussed. STATEMENT OF SIGNIFICANCE: It is still challenging to replicate delicate and intricate tissue-specific structural organizations using mechanically-weak hydrogels for the fabrication of functional living tissue constructs. Embedded bioprinting is an emerging 3D printing strategy that enables to produce complex tissue structures directly inside a reservoir filled with supporting matrix, which largely widens the choice of bioprinting inks to ECM-like hydrogels. Here we aim to provide a comprehensive review on various embedded bioprinting techniques mainly including extrusion-based and light-based processes. Various bioinks, supporting matrices, key processing parameters as well as their effects on the structures and biological functions of resultant living tissue constructs are discussed. We expect that it can provide an important reference and generate new insights for the bioprinting of large vascularized tissues and organs with biological functions.

Enhanced Attachment and Collagen Type I Deposition of MC3T3-E1 Cells via Electrohydrodynamic Printed Sub-Microscale Fibrous Architectures.

Micro/sub-microscale fibrillar architectures of extracellular matrix play important roles in regulating cellular behaviors such as attachment, migration, and differentiation. However, the interactions between cells and organized micro/sub-microscale fibers have not been fully clarified yet. Here, the responses of MC3T3-E1 cells to electrohydrodynamic (EHD) printed scaffolds with microscale and/or sub-microscale fibrillar architectures were investigated to demonstrate their potential for bone tissue regeneration. Fibrillar scaffolds were EHD-fabricated with microscale (20.51 ± 1.70 µm) and/or sub-microscale (0.58 ± 0.51 µm) fibers in a controlled manner. The in vitro results showed that cells exhibited a 1.25-fold increase in initial attached cell number and 1.17-fold increase in vinculin expression on scaffolds with micro/sub-microscale fibers than that on scaffolds with pure microscale fibers. After 14 days of culture, the cells expressed 1.23 folds increase in collagen type I (COL-I) deposition compared with that on scaffolds with pure microscale fibers. These findings indicated that the EHD printed sub-microscale fibrous architectures can facilitate attachment and COL I secretion of MC3T3-E1 cells, which may provide a new insight to the design and fabrication of fibrous scaffolds for bone tissue engineering.

ALG8 Fuels Stemness Through Glycosylation of the WNT/Beta-Catenin Signaling Pathway in Colon Cancer.

Cancer stem cells (CSCs) drive tumor relapse, which is a major clinical challenge in colon cancer. Targeting CSCs presents a great opportunity in eradicating cancer cells and thus treatment of patients with cancer. However, the epigenetic control of the CSC signature and key molecules involved in colon cancer remains undefined. In this study, we demonstrated that alpha-1,3-glucosyltransferase (ALG8) is upregulated in colon cancer tissues compared with normal tissues. Overexpression of the ALG8 gene predicted poor overall survival and disease-free survival in colon cancer patients. Silencing of the ALG8 gene repressed the stemness of colon tumor cells. Xenograft mice transplanted with ALG8-deficient tumor cells significantly alleviated tumor burden and prolonged survival in comparison with control mice. Further analysis showed that ALG8 gene promoted cancer stemness through inducing glycosylation of LRP6, which activates the WNT/beta-catenin signaling pathway. Importantly, attenuation of the glycosylation using tunicamycin abrogated the effect of ALG8 gene on cancer stemness. Taken together, our findings demonstrated that ALG8 enhances colon tumorigenesis by activating the WNT/beta-catenin signaling pathway. Therefore, ALG8 gene is a potential therapeutic target in colon cancer.

Pulmonary Microbial Composition in Sepsis-Induced Acute Respiratory Distress Syndrome.

Background: Acute respiratory distress syndrome (ARDS) is an unresolved challenge in the field of respiratory and critical care, and the changes in the lung microbiome during the development of ARDS and their clinical diagnostic value remain unclear. This study aimed to explore the role of the lung microbiome in disease progression in patients with sepsis-induced ARDS and potential therapeutic targets. Methods: Patients with ARDS were divided into two groups according to the initial site of infection, intrapulmonary infection (ARDSp, 111 cases) and extrapulmonary infection (ARDSexp, 45 cases), and a total of 28 patients with mild pulmonary infections were enrolled as the control group. In this study, we sequenced the DNA in the bronchoalveolar lavage fluid collected from patients using metagenomic next-generation sequencing (mNGS) to analyze the changes in the lung microbiome in patients with different infectious site and prognosis and before and after antibiotic treatment. Results: The Shannon-Wiener index indicated a statistically significant reduction in microbial diversity in the ARDSp group compared with the ARDSexp and control groups. The ARDSp group was characterized by a reduction in microbiome diversity, mainly in the normal microbes of the lung, whereas the ARDSexp group was characterized by an increase in microbiome diversity, mainly in conditionally pathogenic bacteria and intestinal microbes. Further analysis showed that an increase in Bilophila is a potential risk factor for death in ARDSexp. An increase in Escherichia coli, Staphylococcus aureus, Candida albicans, enteric microbes, or conditional pathogens may be risk factors for death in ARDSp. In contrast, Hydrobacter may be a protective factor in ARDSp. Conclusion: Different initial sites of infection and prognoses are likely to affect the composition and diversity of the pulmonary microbiome in patients with septic ARDS. This study provides insights into disease development and exploration of potential therapeutic targets.

Bioprinted living tissue constructs with layer-specific, growth factor-loaded microspheres for improved enthesis healing of a rotator cuff.

Substantial challenges remain in constructing the native tendon-to-bone interface for rotator cuff healing owing to the enthesis tissues' highly organized structural and compositional gradients. Herein, we propose to bioprint living tissue constructs with layer-specific growth factors (GFs) to promote enthesis regeneration by guiding the zonal differentiation of the loaded stem cells in situ. The sustained release of tenogenic, chondrogenic, and osteogenic GFs was achieved via microsphere-based delivery carriers embedded in the bioprinted constructs. Compared to the basal construct without GFs, the layer-specific tissue analogs realized region-specific differentiation of stem cells in vitro. More importantly, bioprinted living tissue constructs with layer-specific GFs rapidly enhanced the enthesis regeneration in a rabbit rotator cuff tear model in terms of biomechanical restoration, collagen deposition, and alignment, showing gradient interface of fibrocartilage structures with aligned collagen fibrils and an ultimate load failure of 154.3 ± 9.5 N resembling those of native enthesis tissues in 12 weeks. This exploration provides a feasible strategy to engineer living tissue constructions with region-specific differentiation potentials for the functional repair of gradient enthesis tissues. STATEMENT OF SIGNIFICANCE: Previous studies that employed acellular layer-specific scaffolds or stem cells for the reconstruction of the rotator cuff faced challenges due to their insufficient capability to rebuild the anisotropic compositional and structural gradients of native enthesis tissues. This manuscript proposed a living tissue construct with layer-specific, GFs-loaded µS, which can direct in situ and region-specific differentiation of the embedded stem cells to tenogenic, chondrogenic, and osteogenic lineages for functional regeneration of the enthesis tissues. This bioprinted living tissue construct with the unique capability to reduce fibrovascular scar tissue formation and simultaneously facilitate enthesis tissue remodeling might provide a promising strategy to repair complex and gradient tissues in the future.

Identification and verification of the prognostic value of CUL7 in colon adenocarcinoma.

CUL7, a gene composed of 26 exons associated with cullin 7 protein, is also an E3 ligase that is closely related to cell senescence, apoptosis, and cell transformation and also plays an important role in human cancer. However, there is no systematic pan-cancer analysis has been performed to explore its role in prognosis and immune prediction. In this study, the expression of CUL7 in colon adenocarcinoma (COAD) was investigated to determine its prognosis value. First, based on the Cancer Genome Atlas (TCGA), Genotypic-Tissue Expression Project(GTEx), Cancer Cell Line Encyclopedias(CCLE), and TISIDB database, the potential role of CUL7 in different tumors was explored. Subsequently, the expression of CUL7 in COAD was explored and verified by Immunohistochemistry (IHC). Furthermore, the mutation frequency of CUL7 in COAD was analyzed, and the prognostic value of CUL7 in COAD was discussed. In addition, the nomogram was constructed, and its prognostic value was verified by follow-up data from Jiangmen Central Hospital. Finally, PPI network analysis explored the potential biological function of CUL7 in COAD. The results show that CUL7 is upregulated in most tumors, which is significantly associated with poor survival. At the same time, CUL7 is correlated with the clinical stage and immune landscape of various tumors. In colorectal cancer, CUL7 was overexpressed in tumor tissues by IHC with a mutation frequency of about 4%. CUL7 is an independent prognostic factor for colorectal cancer. The nomogram constructed has effective predictive performance, and external databases proved the prognostic value of CUL7. In addition, PPI network analysis showed that CUL7 was closely related to FBXW8, and further pathway enrichment analysis showed that CUL7 was mainly involved in ubiquitin-mediated proteolysis. Therefore, our study provides a comprehensive understanding of the potential role of CUL7 in different tumors, and CUL7 might be a prognostic marker for COAD.

The multimodal imaging characteristics of IRVAN syndrome: a case report.

BACKGROUND: In this case report, we aimed to describe the multimodal imaging characteristics and the successful treatment of idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome in a 39-year-old man. CASE PRESENTATION: His both eyes were diagnosed with IRVAN syndrome via multimodal imaging, including fundus color photograph, multicolor imaging, infrared ray, fundus autofluorescence, fundus fluorescence angiography and optical coherence tomography angiography. Both eyes were treated with vitrectomy and laser photocoagulation. The treatment was effective. Eighteen months after discharge, the patient had visual acuity of 20/20 in both eyes. CONCLUSIONS: This case report demonstrates that vitrectomy and retinal laser photocoagulation can be successful in treating a patient with IRVAN syndrome in both eyes.

In-situ re-melting and re-solidification treatment of selective laser sintered polycaprolactone lattice scaffolds for improved filament quality and mechanical properties.

Selective laser sintering (SLS) is a promising additive manufacturing technique that produces biodegradable tissue-engineered scaffolds with highly porous architectures without additional supporting. However, SLS process inherently results in partially melted microstructures which significantly impair the mechanical properties of the resultant scaffolds for potential applications in tissue engineering and regenerative medicine. Here, a novel post-treatment strategy was developed to endow the SLS-fabricated polycaprolactone (PCL) scaffolds with dense morphology and enhanced mechanical properties by embedding them in dense NaCl microparticles for in-situ re-melting and re-solidification. The effects of re-melting temperature and dwelling time on the microstructures of the SLS-fabricated filaments were studied. The results demonstrated that the minimum requirements of re-melting temperature and dwelling time for sufficient treatment were 65 °C and 5 min respectively and the size of the SLS-fabricated filaments was reduced from 683.3 ± 28.0 µm to 601.6 ± 17.4 µm. This method was also highly effective in treating three-dimensional (3D) PCL lattice scaffolds, which showed improved filament quality and mechanical properties after post-treatment. The treated PCL scaffolds with an initial compressive modulus and strength of 3027.8 ± 204.2 kPa and 208.8 ± 14.5 kPa can maintain their original shapes after implantation in vivo for 24 weeks. Extensive newly-grown tissues were found to gradually penetrate into the porous regions along the PCL filaments. Although degradation occurred, the mechanical properties of the implanted constructs stably maintained. The presented method provides an innovative, green and general post-treatment strategy to improve both the filament quality and mechanical properties of SLS-fabricated PCL scaffolds for various tissue engineering applications.