3D bioprinting techniques have emerged as a flexible tool in tissue engineering and regenerative medicine to fabricate or pattern functional 3D bio-structures with precise geometric designs, bridging the divergence between engineered and natural tissue constructs. A significantly increasing development has been achieved in understanding the relationship between the 3D-printing process and the structures, properties, and applications of the objects created. The ongoing advancement of novel biomaterial inks has enabled manufacturing of models and in vitro implants capable of achieving some level of success in preclinical trials. Remarkable progress in cell biology and biology-inspired computational design has assisted in achieving the latest milestone with planned tissue- or organ-like constructs having specific levels of functionality. However, biofabricated constructs still have a long way to go before reaching clinics. This review presents a picture of 3D bioprinting in the context of tissue engineering and regenerative medicine, with focus on biomaterials-related and design-centred aspects. Biomedical applications are described in detail in relation to major tissues or organs considered in the human body. Current technical limitations, challenges, future prospects and improvements are critically outlined and discussed. 

Advancements in tissue and organ 3D bioprinting: Current techniques, applications, and future perspectives

Tissue engineering for injured tissue replacement and regeneration has been a subject of investigation over the last 30 years, and there has been considerable interest in using additive manufacturing to achieve these goals. Despite such efforts, many key questions remain unanswered, particularly in the area of biomaterial selection for these applications as well as quantitative understanding of the process science. The strategic utilization of biological macromolecules provides a versatile approach to meet diverse requirements in 3D printing, such as printability, buildability, and biocompatibility. These molecules play a pivotal role in both physical and chemical cross-linking processes throughout the biofabrication, contributing significantly to the overall success of the 3D printing process. Among the several bioprintable materials, gelatin methacryloyl (GelMA) has been widely utilized for diverse tissue engineering applications, with some degree of success. In this context, this review will discuss the key bioengineering approaches to identify the gelation and cross-linking strategies that are appropriate to control the rheology, printability, and buildability of biomaterial inks. This review will focus on the GelMA as the structural (scaffold) biomaterial for different tissues and as a potential carrier vehicle for the transport of living cells as well as their maintenance and viability in the physiological system. Recognizing the importance of printability toward shape fidelity and biophysical properties, a major focus in this review has been to discuss the qualitative and quantitative impact of the key factors, including microrheological, viscoelastic, gelation, shear thinning properties of biomaterial inks, and printing parameters, in particular, reference to 3D extrusion printing of GelMA-based biomaterial inks. Specifically, we emphasize the different possibilities to regulate mechanical, swelling, biodegradation, and cellular functionalities of GelMA-based bio(material) inks, by hybridization techniques, including different synthetic and natural biopolymers, inorganic nanofillers, and microcarriers. At the close, the potential possibility of the integration of experimental data sets and artificial intelligence/machine learning approaches is emphasized to predict the printability, shape fidelity, or biophysical properties of GelMA bio(material) inks for clinically relevant tissues.

Gelatin Methacryloyl (GelMA)-Based Biomaterial Inks: Process Science for 3D/4D Printing and Current Status.

Bone pain is one of the most common forms of pain reported by cancer patients with metastatic disease. We conducted a review of oncology literature to further understand the epidemiology of and treatment approaches for metastatic cancer-induced bone pain and the effect of treatment of painful bone metastases on the patient's quality of life. Two-thirds of patients with advanced, metastatic, or terminal cancer worldwide experience pain. Cancer pain due to bone metastases is the most common form of pain in patients with advanced disease and has been shown to significantly reduce patients' quality of life. Treatment options for cancer pain due to bone metastases include nonsteroidal anti-inflammatory drugs, palliative radiation, bisphosphonates, denosumab, and opioids. Therapies including palliative radiation and opioids have strong evidence supporting their efficacy treating cancer pain due to bone metastases; other therapies, like bisphosphonates and denosumab, do not. There is sufficient evidence that patients who experience pain relief after radiation therapy have improved quality of life; however, a substantial proportion are nonresponders. For those still requiring pain management, even with available analgesics, many patients are undertreated for cancer pain due to bone metastases, indicating an unmet need. The studies in this review were not designed to determine why cancer pain due to bone metastases was undertreated. Studies specifically addressing cancer pain due to bone metastases, rather than general cancer pain, are limited. Additional research is needed to determine patient preferences and physician attitudes regarding choice of analgesic for moderate to severe cancer pain due to bone metastases. 

The Burden of Metastatic Cancer–Induced Bone Pain: A Narrative Review

Corneal transplantation is considered a convenient strategy for various types of corneal disease needs. Even though it has been applied as a suitable solution for most corneal disorders, patients still face several issues due to a lack of healthy donor corneas, and rejection is another unknown risk of corneal transplant tissue. Corneal tissue engineering (CTE) has gained significant consideration as an efficient approach to developing tissue-engineered scaffolds for corneal healing and regeneration. Several approaches are tested to develop a substrate with equal transmittance and mechanical properties to improve the regeneration of cornea tissue. In this regard, bioprinted scaffolds have recently received sufficient attention in simulating corneal structure, owing to their spectacular spatial control which produces a three-cell-loaded-dimensional corneal structure. In this review, the anatomy and function of different layers of corneal tissue are highlighted, and then the potential of the 3D bioprinting technique for promoting corneal regeneration is also discussed.

/pdf/bioprinted-membranes-for-corneal-tissue-engineering-a-review-37q37afs.pdf

Bioprinted Membranes for Corneal Tissue Engineering: A Review

To evaluate retrospectively safety and effectiveness of cervical vertebroplasty (cVP) based on a single-center large cohort. All cVP performed at a single center from January 2001 to October 2014 were included and reviewed. Procedure-related complications (minor and major) were systematically recorded. Effectiveness in terms of analgesia was evaluated using a semi-quantitative grading scale at 1-month follow-up. Risk factors for the occurrence of a procedure-related complication or cement leakage, as well as factors influencing pain relief at 1-month follow-up, were evaluated using a multivariate analysis. One hundred and forty cVP procedures (176 vertebrae) were performed in 130 consecutive patients (88 female, 42 male; mean age = 56 years) during the inclusion period. Among the treated lesions, 80% were bone metastases (mostly from breast cancer), 8% were related to hematological malignancies, and 12% were non-malignant lesions. One fatal complication (0.7%) was related to cement migration in the vertebrobasilar system. Three cervical hematomas were recorded, one of them requiring prolonged oral intubation. The overall rate of major complications was 1.5%. At 1 month, pain reduction was observed in 76% of the cases. Additional surgical fixation was required in 6.1% of the cases. cVP of more than one vertebra during the same session was an independent risk factor for procedure-related complications. Cervical vertebroplasty is a safe technique with an acceptable major complication rate. Its effectiveness in terms of pain relief is good at mid-term follow-up. • Cervical vertebroplasty (cVP) is a safe procedure with a low rate of major complications (1.5%). • cVP provides pain relief in 76% of the cases. • Additional fixation surgery is rarely required after cVP (6.1% of the cases).

/pdf/safety-and-effectiveness-of-cervical-vertebroplasty-report-5bvs7a4rn1.pdf

Safety and effectiveness of cervical vertebroplasty: report of a large cohort and systematic review.

Percutaneous vertebroplasty (PVP) has been shown to release spinal pain and stabilize the vertebral body. PVP is suggested as an alternative treatment in spinal metastasis. Although cervical metastases is less prevalent than thoracic and lumbar spine, PVP procedure in cervical vertebrae remains technical challenging. We retrospectively analyzed the data from patients (n = 9) who underwent PVP using anterolateral approach to treat severe neck pain and restricted cervical mobility from metastatic disease. Patients were rated using modified Tokuhashi score and Tomita score before the procedure. Visual analog scale (VAS), neck disability index (NDI), analgesic use, and imaging (X-ray or CT) were evaluated before PVP and 3 days, 3 months, and 6 months after PVP. All patients were in late stage of cancer evaluated using modified Tokuhashi and Tomita score. The cement leakage rate was 63.6% (14 of the 22 vertebrae) with no severe complications. VAS, NDI, and analgesic use were significantly decreased 3 days after the procedure and remained at low level until 6 months of follow-up. Our result suggested PVP effectively released the pain from patients with cervical metastasis. The results warrant further clinical investigation.

/pdf/percutaneous-vertebroplasty-relieves-pain-in-cervical-spine-59ntd5guav.pdf

Percutaneous Vertebroplasty Relieves Pain in Cervical Spine Metastases.

Gelatin methacryloyl (GelMA) is a popular photocrosslinkable hydrogel that has been widely utilized in tissue engineering and regenerative medicine fields due to its excellent biocompatibility, biodegradability and cell response. However, the lack of mechanical properties limits its application. In the present study, a method for the preparation of a GelMA-GelMA (G-G) homogeneous double-network (DN) hydrogel to improve mechanical strength based on DLP 3D printing is proposed. The G-G DN hydrogel was fabricated and characterized in terms of microstructure, mechanical properties and rheological behavior. By modifying the degree of substitution (DS), the polymer concentration of double network crosslinking and the soak time, the novel G-G DN hydrogel could significantly improve the properties of strength, self-recovery and fatigue resistance. After all, the novel porous composite hydrogel (G-G DN hydrogel) could achieve more than twice that of the pure GelMA hydrogel, better fatigue resistance and printable ability. Therefore, it can be a potential choice of applications attracting great attention for its mechanical properties, great transmittance and biocompatibility.

A high-performance GelMA-GelMA homogeneous double-network hydrogel assisted by 3D printing.

Millions of individuals across the world suffer from corneal stromal diseases that impair vision. Fortunately, three-dimensional (3D) bioprinting technology which has revolutionized the field of regenerative tissue engineering makes it feasible to create personalized corneas. In this study, an artificial cornea with a high degree of precision, smoothness, and programmable curvature was prepared by using digital light processing (DLP) 3D bioprinting in one piece with no support structure, and the construct was then confirmed by optical coherence tomography (OCT). On the basis of this approach, we developed a novel corneal decellularized extracellular matrix/gelatin methacryloyl (CECM-GelMA) bioink that can produce complex microenvironments with highly tunable mechanical properties while retaining high optical transmittance. Furthermore, the composite hydrogel was loaded with human corneal fibroblasts (hCFs), and in vitro experiments showed that the hydrogel maintained high cell viability and expressed core proteins. In vivo tests revealed that the hydrogel might promote epithelial regeneration, keep the matrix aligned, and restore clarity. This demonstrates how crucial a role CECM plays in establishing a favorable environment that encourages the transformation of cell function. Therefore, artificial corneas that can be rapidly customized have a huge potential in the development of in vitro corneal matrix analogs. 

3D Bioprinting of Corneal Decellularized Extracellular Matrix (CECM): GelMA Composite Hydrogel for Corneal Stroma Engineering

Bladder cancer (BLCA) is the 10th most common form of cancer worldwide. Currently, the response rate of BLCA patients to novel immunotherapy and immune checkpoint inhibitor (ICI) treatment is around 30% or less. Therefore, there is an urgent clinical demand to understand the regulation of immune function in BLCA patients. LncRNAs are known to play fundamental roles in the regulation of the immune system in the tumor microenvironment. In this report, we performed a comprehensive analysis to identify immune-related lncRNAs (IRLs) in BLCA patients using The Cancer Genome Atlas (TCGA) databases. BLCA patients were divided into five TME subtypes. Subtype HMIE was strongly related to survival and high anti-tumor activity of patients. Through a four-step analysis, we identified 34 IRLs as subtype HMIE related lncRNAs (HMIE-lncs).The correlation analysis with immune cell infiltration and target gene pathway enrichment showed that 34 HMIE-lncs were correlated with immune cell activation and tumor cell killing. Among them, 24 lncRNAs were related to good prognosis. We constructed a risk model to predict BLCA. Cross tumor validation was performed, and the results showed that the 34 HMIE-lncs identified in the BLCA patients in this study were highly expressed in the immune-favorable TME subtype (IE) in most of the other cancer types. Graphical Abstract According to previous reports of four subtypes of tumor patients, we further divided subtype IE into two subtypes of HMIE and LMIE in bladder cancer. Further analysis through four steps identified 34 immune-related lncRNAs (IRLs) in the HMIE subtype. Of these, 24 lncRNAs are related to good prognosis. Following validation, a risk model was constructed to predict BLCA. Cross tumor type studies confirmed that 34 HMIE-lncs were highly expressed in immune-favorable TME subtype (IE) in most of cancers, and Imvigor210 immunotherapy cohort were used to validate these lncRNAs.

Characterization of the immune related lncRNAs in bladder cancer to aid immunotherapy

Objective Meningiomas are one of the most common primary tumors of the central nervous system. Most of them are benign and can be cured by surgery, while a few meningiomas are malignant. Ferroptosis gene characteristics might be associated with drug therapy and survival in patients with clinically aggressive, unresectable meningiomas. This study explored the mechanism of differentially expressed miRNAs and ferroptosis in meningioma to provide a new reference to treat meningioma. Methods Bioinformatics analysis of differential miRNA profiles and functions in patients with meningioma was performed. The contents of lactate dehydrogenase (LDH), malondialdehyde (MDA), and Fe2+ were determined. Reactive oxygen species (ROS) values, as well as cell cycle changes, were analyzed by flow cytometry. The targets of miR-127-5p and JAM3 were detected by dual luciferase assays. Cell counting kit-8 (CCK8) and Transwell assays were used to analyze cell activity. Ki67 expression was analyzed by immunohistochemistry. Expression levels of miR-127-5p and JAM3 were analyzed by RT-qPCR. GPX4 expression was quantified by western blotting. Results miR-127-5p was expressed at low levels in IOMM-Lee cells, while JAM3 was highly expressed in IOMM-Lee cells. A dual luciferase assay demonstrated that miR-127-5p could target JAM3. Upregulation of miR-127-5p in IOMM-Lee cells resulted in cell cycle arrest and inhibition of cell activity. Upregulation of miR-127-5p increased LDH, MDA, and ROS levels and Fe2+ content and inhibited the expression of GPX4 protein. Upregulation of JAM3 reversed the results of miR-127-5p upregulation. Conclusion miR-127-5p regulated meningioma formation and ferroptosis through JAM3, providing insights for the development of new treatments for meningioma.

/pdf/mir-127-5p-targets-jam3-to-regulate-ferroptosis-1qf6hxt3.pdf

miR-127-5p Targets JAM3 to Regulate Ferroptosis, Proliferation, and Metastasis in Malignant Meningioma Cells

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