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Establishing a valid in vitro model to represent tumor heterogeneity and biology is critical but challenging. Tumor organoids are self-assembled three-dimensional cell clusters which are of great significance for recapitulating the histopathological, genetic, and phenotypic characteristics of primary tissues. The organoid has emerged as an attractive in vitro platform for tumor biology research and high-throughput drug screening in cancer medicine. Organoids offer unique advantages over cell lines and patient-derived xenograft models, but there are no standardized methods to guide the culture of organoids, leading to confusion in organoid studies that may affect accurate judgments of tumor biology. This review summarizes the shortcomings of current organoid culture methods, presents the latest research findings on organoid standardization, and proposes an outlook for organoid modeling., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Phototherapy, which generally refers to photothermal therapy (PTT) and photodynamic therapy (PDT), has received significant attention over the past few years since it is non-invasive, has effective selectivity, and has few side effects. As a result, it has become a promising alternative to traditional clinical treatments. At present, two-dimensional materials (2D materials) have proven to be at the forefront of the development of advanced nanomaterials due to their ultrathin structures and fascinating optical properties. As a result, much work has been put into developing phototherapy platforms based on 2D materials. This review summarizes the current developments in 2D materials beyond graphene for phototherapy, focusing on the novel approaches of PTT and PDT. New methods are being developed to go above and beyond conventional treatment to fully use the potential of 2D materials. Additionally, the efficacy of cutting-edge phototherapy is assessed, and the existing difficulties and future prospects of 2D materials for phototherapy are covered., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tan, Khan, Sheikh, Sun, Zhang, Chen, Huang, Chen, Zhou and Sun.)

Currently, various bioceramics have been widely used in bone regeneration. However, it remains a huge challenge to remote isolation bone regeneration, such as severed finger regeneration. The remote isolation bone tissue has a poor regenerative microenvironment that lacks enough blood and nutrition supply. It is very difficult to repair and regenerate. In this study, well-controlled multi-level porous 3D-printed calcium phosphate (CaP) bioceramic scaffolds with precision customized structures were fabricated by high-resolution digital light projection (DLP) printing technology for remote isolation bone regeneration. In vitro results demonstrated that optimizing material processing procedures could achieve multi-level control of 3D-printed CaP bioceramic scaffolds and enhance the osteoinduction ability of bioceramics effectively. In vivo results indicated that 3D-printed CaP bioceramic scaffolds constructed by optimized processing procedure exhibited a promising ability of bone regeneration and osteoinduction in ectopic osteogenesis and in situ caudal vertebrae regeneration in beagles. This study provided a promising strategy based on 3D-printed CaP bioceramic scaffolds constructed by optimized processing procedures for remote isolation bone regeneration, such as severed finger regeneration., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier B.V.)

The delayed healing of diabetic wounds is directly affected by the disturbance of wound microenvironment, resulting from persistent inflammation, insufficient angiogenesis, and impaired cell functions. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) showed considerable therapeutic potential in diabetic wound healing. However, the low retention rate of MSC-EVs at wound sites hampers their efficacy. For skin wounds exposed to the outer environment, using a hydrogel with tissue adhesiveness under a moist wound condition is a promising strategy for wound healing. In this study, we modified methacryloyl-modified gelatin (GelMA) hydrogel with catechol motifs of dopamine to fabricate a GelMA-dopamine hydrogel. EVs isolated from MSCs were applied in the synthesized GelMA-dopamine hydrogel to prepare a GelMA-dopamine-EV hydrogel. The results demonstrated that the newly formed GelMA-dopamine hydrogel possessed improved properties of softness, adhesiveness, and absorptive capacity, as well as high biocompatibility in the working concentration (15% w/v). In addition, MSC-EVs were verified to promote cell migration and angiogenesis in vitro . In the skin wound model of diabetic rats, the GelMA-dopamine-EV hydrogel exerted prominent wound healing efficacy estimated by collagen deposition, skin appendage regeneration, and the expression of IL-6, CD31, and TGF-β. In conclusion, this combination of MSC-EVs and the modified hydrogel not only accelerates wound closure but also promotes skin structure normalization by rescuing the homeostasis of the healing microenvironment of diabetic wounds, which provides a potential approach for the treatment of diabetic wounds.

Three-dimensional (3D) printing technology provides advanced technical support for designing personalized bone tissue engineering scaffold. In this study, two porous diffusing models, namely, average and layered perforated cylindrical scaffolds, were designed for bone tissue engineering scaffold. The designed models were fabricated by liquid crystal display mask stereolithography printing. Structural design and finite element mechanical analysis were conducted. 45S5 bioglass was selected as the raw material for preparing the printing inks for bone tissue engineering scaffolds. By adjusting the viscosity and temperature of the slurry, the maximum proportion of 45S5 bioglass (40 wt%) was added into the photosensitive resin for preparing 3D printing slurry. Our results indicated that an optimized sintering condition includes the debinding rate (0.5°C/min), and temperature raising rate (5°C/min) and sintering temperature (1100°C) were proposed to sinter 45S5 bioceramic scaffolds. The amorphous 45S5 bioglass showed good crystallization after sintering, and the scaffold porous structure showed good integrity. Micropores were observed in the struts which interconnected with each other. Moreover, the porosities were tested as 57% and 45% with a uniform pore distribution. The shrinkage rate was about 10% during sintering process due to binder burning and crystallization shrinkage. The compressive strength of the sintered scaffold was 0.71 ± 0.048 MPa and 2.13 ± 0.054 MPa, respectively, which are consistent with the finite element mechanical analysis simulation results. In conclusion, the layered perforated 45S5 bioglass scaffold shows good mechanical properties and porosity, indicating that it could be a promising candidate for bone tissue engineering., Competing Interests: The authors declare no conflict of interest regarding the publication of this paper., (Copyright: © 2022 Dong et al.)

Once pulp necrosis or apical periodontitis occurs on immature teeth, the weak root and open root apex are challenging to clinicians. Berberine (BBR) is a potential medicine for bone disorders, therefore, we proposed to apply BBR in root canals to enhance root repair in immature teeth. An in vivo model of immature teeth with apical periodontitis was established in rats, and root canals were filled with BBR, calcium hydroxide or sterilized saline for 3 weeks. The shape of the roots was analyzed by micro-computed tomography and histological staining. In vitro, BBR was introduced into stem cells from apical papilla (SCAPs). Osteogenic differentiation of stem cells from apical papilla was investigated by alkaline phosphatase activity, mineralization ability, and gene expression of osteogenic makers. The signaling pathway, which regulated the osteogenesis of SCAPs was evaluated by quantitative real time PCR, Western blot analysis, and immunofluorescence. In rats treated with BBR, more tissue was formed, with longer roots, thicker root walls, and smaller apex diameters. In addition, we found that BBR promoted SCAPs osteogenesis in a time-dependent and concentration-dependent manner. BBR induced the expression of β-catenin and enhanced β-catenin entering into the nucleus, to up-regulate more runt-related nuclear factor 2 downstream. BBR enhanced root repair in immature teeth with apical periodontitis by activating the canonical Wnt/β-catenin pathway in SCAPs.

In this work, a strain-based degradation model was implemented and validated to better understand the dynamic interactions between the bioresorbable vascular scaffold (BVS) and the artery during the degradation process. Integrating the strain-modulated degradation equation into commercial finite element codes allows a better control and visualization of local mechanical parameters. Both strut thinning and discontinuity of the stent struts within an artery were captured and visualized. The predicted results in terms of mass loss and fracture locations were validated by the documented experimental observations. In addition, results suggested that the heterogeneous degradation of the stent depends on its strain distribution following deployment. Degradation is faster at the locations with higher strains and resulted in the strut thinning and discontinuity, which contributes to the continuous mass loss, and the reduced contact force between the BVS and artery. A nonlinear relationship between the maximum principal strain of the stent and the fracture time was obtained, which could be transformed to predict the degradation process of the BVS in different mechanical environments. The developed computational model provided more insights into the degradation process, which could complement the discrete experimental data for improving the design and clinical management of the BVS., Competing Interests: Conflict of interest: The authors declare no conflicts of interest regarding the publication of this paper.

As a well-known oncogene, B cell lymphoma-2 (BCL-2) can promote cancer cell survival through preventing their apoptosis. Several functional BCL-2 single nucleotide polymorphisms (SNPs), such as rs2279115, rs1801018, and rs1564483, have been identified and might contribute to cancer susceptibility. However, the involvement of these SNPs in small cell lung cancer (SCLC) was still unclear. As a result, we investigated associations between these three genetic variants and SCLC risk in a case-control design. Genotypes were determined in two independent case-control sets consisted of 520 SCLC patients and 1040 controls from two medical centers. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated utilizing unconditional logistic regression. We found that only BCL-2 rs2279115 genetic variant significantly contributed to decreased SCLC risk in Chinese Han populations, with the rs2279115 A allele as the protective allele. Stratified analyses of association between BCL2 rs2279115 SNP and SCLC risk indicated that the functional polymorphism was only significantly associated with decreased risk of the limited stage SCLC but not the extensive stage disease. Our results indicate that the BCL-2 rs2279115 genetic variant was associated with SCLC risk in Chinese populations and support the hypothesis that SNPs in regulatory regions of oncogenes might contribute to cancer susceptibility.

As a well-known DNA repair gene, RAD52 plays an essential role in homologous recombination repair of double strand break, maintenance of genomic stability and prevention of cell malignant transformation. Previous genome-wide association studies (GWASs) have identified common genetic variants at 12p13.33 RAD52 locus associated with lung cancer risk in Caucasians. However, little or nothing has been known about the RAD52 single nucleotide polymorphisms (SNPs) in small cell lung cancer (SCLC) in the Chinese population. As a result, we examined the association between six RAD52 SNPs (rs10849605, rs1051669, rs10774474, rs11571378, rs7963551 and rs6489769) and SCLC susceptibility in Chinese. After 520 SCLC cases and 1040 controls in two independent case-control sets were genotyped, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression. We found that only the RAD52 rs7963551 SNP was significantly associated with SCLC risk among six RAD52 SNPs genotyped. The odds of having the rs7963551 CA genotype in SCLC patients was 0.38 (95% CI = 0.24-0.62, P = 1.1×10(-4)) compared with the CC genotype. Stratified analyses of association between rs7963551 SNP and SCLC risk indicated that the functional polymorphism was only significantly associated with decreased risk among smokers but not nonsmokers. Our results demonstrated that the functional RAD52 rs7963551 SNP contributes to susceptibility to developing SCLC in the Chinese population.