Culture Platform Research Articles

Abstract A025: RNA-Based Therapeutics to target the p53 pathway in high-grade serous ovarian cancer: TAp63-Regulated Oncogenic LncRNAs (TROLLs) as novel therapeutic targets in cancer

Abstract High-grade serous ovarian cancer (HGSOC) is the most common and malignant type of ovarian cancer with a high frequency of p53 mutation and hyperactivation of the AKT pathway. Even though roughly 85% of patients achieve remission after initial surgical debulking and chemotherapy, four out of five HGSOC patients will experience disease recurrence, resulting in a 5-year survival rate of 43%. We have identified and characterized two TAp63 Regulated Oncogenic Long non-coding RNAs (TROLL-2 and TROLL-3) whose transcription is induced by mutant p53 and high expression level correlate with a more aggressive ovarian cancer grade and phosphorylation of AKT. In-depth analysis demonstrated that TROLL-2 and TROLL-3 directly activate AKT in tumor cells, thus linking p53 alterations to AKT activity. The use of AKT inhibitors in the clinic is limited because of frequent adverse effects, likely due to the constitutive expression of AKT in all cells. TROLL-2 and TROLL-3 expression is limited to tumor cells and provides a more specific target for decreasing AKT activation, potentially minimizing off-target effects. We have optimized reduction of TROLL-2 and TROLL-3 expression using antisense oligonucleotides (ASOs) in an ex vivo perfusion platform for 3D culture of microtumors from primary patient derived tumors. Samples show maximum reduction of proliferation (EdU) and phosphorylation of AKT when TROLL-2 and TROLL-3 ASOs are used concurrently. We also performed phospho-proteomics and single cell RNAseq to compare individual ASO-mediated knockdown of each lncRNA to combined targeted ASO treatments. We have developed primary patient derived xenograft models using ovarian tumors orthotopically implanted into NSG mice generating a relevant preclinical model to determine the efficacy of ASO treatment. To reduce the rapid degradation and clearance of ASOs in circulation, ASOs were encapsulated into lipid nanoparticles and metal-organic frameworks (MOFs) and we are currently testing these in vivo. Since AKT activation is associated with increased staging and resistance to platinum and targeted therapies in ovarian cancer patients, our data provides preclinical rationale for the implementation of ASOs and the use of new delivery methods as a relevant translational therapy and novel method to exploit the specificity of TROLL-2 and TROLL-3 expression in HGSOC. Citation Format: Ashley Lui, Marco Napoli, Jaden R Baldwin, Christina L Carr, Angie Rivera, Duy Nguyen, W. Gregory Sawyer, Michael R Dunne, Erin George, Omar K Farha, Michelle Teplensky, Elsa R Flores. RNA-Based Therapeutics to target the p53 pathway in high-grade serous ovarian cancer: TAp63-Regulated Oncogenic LncRNAs (TROLLs) as novel therapeutic targets in cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr A025.

Abstract A006: Development of a circulating tumor cell-derived cancer organoid platform for drug screening against metastatic tumors and longitudinal monitoring of drug resistance

Abstract Metastatic disease remains the primary cause of cancer-related deaths, presenting a significant challenge in oncology drug development. Current drug screening efforts often rely on cell lines or primary tumor-derived models, which may not adequately mimic the behavior of metastatic tumors. To address this, we aimed to develop a system that more accurately reflects metastatic tumors for improved drug screening. We leveraged a specialized culture platform featuring patented coated plates and proprietary media developed by AcroCyte (Taiwan) to cultivate circulating tumor cells (CTCs) into cancer organoids without pre-selection or enrichment. Building on our previous work, where we successfully cultivated CTCs from fresh blood and cryopreserved peripheral blood mononuclear cells (PBMCs) from renal, colon, and lung cancer patients into cancer organoids, we have now demonstrated the ability to freeze these CTC- derived organoids and thaw them for new culture when needed. We also present new data extending this success to breast and prostate cancers. CTCs from five frozen PBMC samples from breast cancer patients and three from prostate cancer patients formed visible colonies, with positive immunostaining for EpCAM, cytokeratin, and CD44. The immune cells in the PBMC samples gradually died off within three weeks of culture, as confirmed by the absence of CD45- positive cells. Interestingly, CTC-derived organoids from breast and prostate cancers did not form the spheroids observed in renal, colon, and lung cancer models. Instead, they appeared as colonies or clusters of CTCs. After 6-8 weeks of active growth, these clusters exhibited a slower growth rate, although they remained viable in the proprietary culture system. We are actively evaluating various culture media supplements, tailored to breast and prostate cancers, to extend the active growth period of these CTC-derived organoids for longer durations. Importantly, these CTC-derived colonies retained drug sensitivity, demonstrating the system's potential for effective drug screening against metastatic tumors. Our platform now supports organoid development from renal, colon, lung, breast, and prostate cancers, and we are actively expanding to include all major solid tumors. Since this technology uses blood, which can be obtained non-invasively, it enables longitudinal monitoring of CTCs as a functional liquid biopsy. Additionally, frozen PBMCs can be used as a source material for CTCs, and the resulting organoids can be utilized for drug sensitivity testing. This platform could be instrumental in oncology drug development and holds promise for monitoring emerging drug resistance in clinical trials by analyzing PBMC samples collected before and after treatment, offering a functional liquid biopsy-based approach to aid in developing therapies targeting metastatic disease. Citation Format: Yi-chun Han, David Hsieh, Ruobo Zhang, Emily Miyashita-Lin, Shian-Jiun Shih. Development of a circulating tumor cell-derived cancer organoid platform for drug screening against metastatic tumors and longitudinal monitoring of drug resistance [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A006.

Cultivating the Concept of the Chinese Ethnic Group Community from the Perspective of Cultural Identity

In the context of cultural diversity, cultivating a sense of shared identity among the Chinese ethnic group is not only crucial for national unity and ethnic solidarity but also promotes social harmony and development. Within the concept of the national community, cultural identity serves as a core element, playing an irreplaceable role in enhancing ethnic cohesion and centripetal force. Currently, China is in a crucial period of realizing the great rejuvenation of the Chinese ethnic group, facing various complex situations and challenges. To cultivate the concept of the Chinese ethnic group community and enhance the cultural identity and sense of belonging of all ethnic groups, efforts can be made to strengthen historical education, deepen understanding of Chinese ethnic group history and culture, and thereby enhance cultural identity among different ethnic groups. To promote cultural exchange and integration, cultural exchange platforms can be established to foster mutual respect and understanding of different ethnic cultures, promote the core socialist values, and advance the inheritance and innovation of Chinese excellent traditional culture, providing strong support for cultivating the concept of the Chinese ethnic group community.

Patient-Derived Organoids on a Microarray for Drug Resistance Study in Breast Cancer.

Drug resistance is always a challenge in cancer treatment, whether for chemotherapy, targeting, or immunotherapy. Although tumor cell lines are derived from cancer patients, they gradually lost the original characteristics, including heterogeneity and tumor microenvironment (TME), during the long period of in vitro culturing. Therefore, it is urgent to use patient-derived tumor models instead of cancer cell lines to study tumor drug resistance. Herein, we developed a microarray device that serves as a platform for high-throughput and three-dimensional culture of breast cancer patient-derived organoids (BCOs) and investigated their resistance to adriamycin (ADM). Coupled with fluorescence microscopy, this system enabled on-chip drug response monitoring and cell viability assessment without the consumption of a large number of tumor cells. The organoids were divided into a resistant BCO group (RBCO) and a sensitive BCO group (SBCO) according to their half-inhibitory concentration (IC50). Different from cancer cell lines, BCOs demonstrated obvious heterogeneity in drug treatment. Ivermectin (IVM), a broad-spectrum antiparasitic agent approved by the Food and Drug Administration (FDA), was observed to synergistically augment ADM-induced cytotoxicity in organoids. The BCO chip provides a promising platform for investigation of drug resistance and preclinical drug screening based on clinical samples.

Thermoresponsive Brush Coatings for Cell Sheet Engineering with Low Protein Adsorption above the Polymers' Phase Transition Temperature.

Thermoresponsive polymer coatings on cell culture substrates enable noninvasive cell detachment and cell sheet fabrication for biomedical applications. Optimized coatings should support controlled culture and detachment of various cell types and allow chemical modifications, e.g., to introduce specific growth factors for enhanced gene expression. Furthermore, the sterilization and storage stability of the coatings must be assessed for translational attempts. Poly(glycidyl ether) (PGE) brush coatings with short alkoxy side chains provide a versatile platform for cell culture and detachment, but their polyether backbones are susceptible to oxidation and degradation. Thus, we rationally designed potential alternatives with thermoresponsive glycerol-based block copolymers comprising a stable polyacrylate or polymethacrylate backbone and an oligomeric benzophenone (BP)-based anchor. The resulting poly(ethoxy hydroxypropyl acrylate-b-benzophenone acrylate) (pEHPA-b-BP) and poly(ethoxy hydroxypropyl methacrylate-b-benzophenone methacrylate) (pEHPMA-b-BP) block copolymers preserve the short alkoxy-terminated side chains of the PGE derived structure on a stable, but hydrophobic, aliphatic backbone. The amphiphilicity balance is maintained through incorporated hydroxyl groups, which simultaneously can be used for chemical modification. The polymers were tailored into brush coatings on polystyrene surfaces via directed adsorption using the BP oligomer anchor. The resulting coatings with thickness values up to ∼3 nm supported efficient adhesion and proliferation of human fibroblasts despite minimal protein adsorption. The conditions for cell sheet fabrication on pEHPA-b-BP were gentler and more reliable than on pEHPMA-b-BP, which required additional cooling. Hence, the stability of pEHPA-b-BP and PGE coatings was evaluated post gamma and formaldehyde (FO) gas sterilization. Gamma sterilization partially degraded PGE coatings and hindered cell detachment on pEHPA-b-BP. In contrast, FO sterilization only slowed detachment on PGE coatings and had no adverse effects on pEHPA-b-BP, maintaining their efficient performance in cell sheet fabrication.

Exploring the Impact of Institutional Innovation in Free Trade Zones and Free Trade Ports on Cultural Exchange and Soft Power Construction

This paper explores how institutional innovations in Free Trade Zones (FTZ) and Free Trade Ports (FTP) promote cultural exchange and soft power construction. Through a systematic literature review and policy analysis, it is found that institutional innovations in FTZs and FTPs, including relaxed restrictions on foreign investment in the cultural industry, streamlined approval processes for cultural exchange activities, the establishment of diverse cultural exchange platforms, and optimization of cultural talent introduction policies, effectively enhance the depth and breadth of international cultural exchange. These efforts have significantly improved China’s cultural soft power. A case study of the Hainan Free Trade Port demonstrates how proactive cultural policy innovations have led China to achieve notable success in international cultural exchanges, offering new ideas for global soft power competition. This study provides reference recommendations for future policy formulation and academic research, especially in optimizing cultural policies in FTZs and FTPs to further enhance cultural soft power.

Research on Personalized Cultural Learning Platform Based on Collaborative Filtering and Popularity Recommendation

With the rapid progress of information technology, it has become the demand of the times to use the power of the Internet to inherit and develop Chinese traditional culture. Given the challenge of users searching for learning content in massive online resources, personalized recommendation systems have become the key to improving user experience. This paper focuses on building a personalized Chinese traditional culture learning platform based on collaborative filtering and popularity recommendation, aiming to stimulate users’ interest in learning traditional culture through intelligent algorithms. In terms of technical implementation, this study relies on the Django framework and MySQL database to build a feature-rich and user-friendly traditional cultural learning platform, supporting users’ diverse learning needs, and providing flexible learning paths and abundant learning resources. Experimental evaluation shows that the hybrid algorithm of collaborative filtering and popularity recommendation proposed in this paper has improved recommendation performance compared to existing methods, effectively enhancing user satisfaction and platform activity. This platform not only promotes the digital dissemination of traditional culture, but also provides users with a highly autonomous and personalized learning experience, meeting the contemporary society’s pursuit of diversified and personalized cultural learning.

Scalable production of uniform and mature organoids in a 3D geometrically-engineered permeable membrane

The application of organoids has been limited by the lack of methods for producing uniformly mature organoids at scale. This study introduces an organoid culture platform, called UniMat, which addresses the challenges of uniformity and maturity simultaneously. UniMat is designed to not only ensure consistent organoid growth but also facilitate an unrestricted supply of soluble factors by a 3D geometrically-engineered, permeable membrane-based platform. Using UniMat, we demonstrate the scalable generation of kidney organoids with enhanced uniformity in both structure and function compared to conventional methods. Notably, kidney organoids within UniMat show improved maturation, showing increased expression of nephron transcripts, more in vivo-like cell-type balance, enhanced vascularization, and better long-term stability. Moreover, UniMat’s design offers a more standardized organoid model for disease modeling and drug testing, as demonstrated by polycystic-kidney disease and acute kidney injury modeling. In essence, UniMat presents a valuable platform for organoid technology, with potential applications in organ development, disease modeling, and drug screening.

Bridging the Skills Gap Through Education Supply Chain to Meet Industry Requirements

In Bangladesh, a persistent mismatch exists between the skills fresh graduates possess and the competencies demanded by employers. This gap affects graduate employability and hampers economic growth. This article explores how key components— Program Curriculum Development (PCD), Instructor Portfolio Management (IPM), University Culture and Networking Platform (UCN), and University Facilities (UF)—can collectively address this issue. By integrating these elements into the educational supply chain, universities can produce skilled graduates who are better equipped to meet industry needs. The proposed framework offers a comprehensive approach to align academic outputs with labor market demands. The study highlights the importance of adapting curricula, engaging industry professionals in teaching, fostering strong university-industry connections, and investing in modern facilities to close the skills gap. This holistic approach ensures that graduates are employable, contributing to national development and societal betterment. The article concludes by emphasizing the need for further research on technological advancements and policy reforms to enhance higher education in Bangladesh.

Understanding Charitable Consumer Behavior on Digital Crowdfunding Platforms: Exploring the Influence of Cultural Values, Motivations, and Platform Attitudes

ABSTRACT Charitable crowdfunding on digital platforms has become a viable way for NGOs to raise funds. This study aims to investigate determinants of charitable behavior (CB) on digital crowdfunding platforms (DCPs), including national culture dimensions, motivations, crowdfunding platform attitude, and donors’ personal characteristics. Data were collected through a CAWI survey of 680 Amazon MTurk users from Europe, the Americas, and Southern Asia. Findings indicate that of the three national culture dimensions considered, CB on DCPs is positively associated with collectivism and negatively with uncertainty avoidance. The link between power distance and CB could be either positive, neutral or negative, due to the interactions with motivations for charity, uncertainty avoidance, and age. Extrinsic and intrinsic motivations do not show significant direct effects on CB but appear to exert their influence through interactions with other motivations, national culture dimensions and respondents’ attributes. People with higher incomes tend to donate more the better is their attitude toward the DCP. CB is stronger among donors more involved in voluntary activities and those living in the Americas as compared to Europe and Asia. The study addresses the knowledge gap concerning the antecedents of CB on DCPs and suggests how NGOs could improve their fundraising effectiveness.

Under the iceberg of “one-stop”: explore multi-actor engagement in one-stop digital cultural platforms through actor-network and commons theories

PurposeThis study investigates the roles and interactions of various actors of one-stop digital culture platforms (ODCPs) by applying actor-network theory (ANT).Design/methodology/approachData were collected from focus group interviews with 19 participants and over 20 policy texts related to the digitization of cultural services in China. Utilizing ANT as the analytical framework, we employed the grounded theory to analyze the dataset.FindingsThe empirical results indicate that: (1) governments, cultural institutions, enterprises and users each play dual roles, contributing to the functionality and development of ODCPs; (2) introduces the theory of commons to reconceptualize ODCPs as commons, highlighting the need for collective management and shared responsibility in the governance of ODCPs.Originality/valueThis study identifies and elaborates on the different roles of stakeholders and addresses conceptual ambiguities within ODCP projects. By introducing the theory of commons into the governance of ODCPs, this research provides new theoretical guidance for decision-makers and practitioners involved in ODCP projects.

An Innovative Perspective for Constructing Cultural and Creative e-Commerce Platforms: Integrating Insights from ICDT Theory and Brand Personality

Thriving in competitive business environments requires innovation, especially within cultural and creative-based e-commerce platforms. This study examines the application of two prominent theories, ICDT theory and brand personality, in assessing new business models. Focusing on 479 respondents from Taiwan, this research explores how the implementation of ICDT and brand personality in cultural and creative e-commerce influences customer behavior. Statistical analyses and the Smart PLS method are adopted to identify the significance of and relationships between the variables in the structural equation model. The profound influence of the ICDT model is evident in the emergence of virtual information space, virtual communication space, and virtual transaction space. Brand personality traits underscore the significance of intellectual excellence, M-type traits, seeking innovation and change, and stable reliability in shaping customer values. This research enriches the literature by emphasizing the essential role of innovative technologies and brand issues integrated with core product attributes for successful consumer acceptance in the fiercely competitive landscape of e-commerce platforms.

Data-driven optimization of the in silico design of ionic liquids as interfacial cell culture fluids

ABSTRACT As an alternative to conventional plastic dishes, the interface between water-immiscible hydrophobic fluids, such as perfluorocarbons and silicones, permits cell adhesion and growth. Thus, it is expected to replace the petroleum-derived products in a sustainable society. However, most hydrophobic fluids are cytotoxic, which limits the range of mechanical and chemical cues exposed to the cells. Using a data-driven approach, this study aimed to identify non-cytotoxic ionic liquids (ILs) as fluid culture platforms to take advantage of their ‘designer’ nature for broadening the possible physicochemical ranges exposed to cells and their repeated use owing to their high heat stability before their biological applications. The new candidates within the readily synthesize ammonium-type ILs were identified through the active cycle of regression and a limited number of cytotoxicity tests. Structure – cytotoxicity analysis indicated that the presence of multiple long alkyl branches was critical for low cytotoxicity. Particularly, we successfully cultured human mesenchymal stem cells (hMSCs) at the trihexylethylammonium trifluoromethylsulfonylimide interface and repeated their use after solvent extraction and heat sterilization. This study identified non-cytotoxic ILs that fulfill plastics’ 3 R ( R educe, R ecycle, and R eplace) requirements and opens new avenues for hMSC fate manipulation through mechanotransduction.

Dynamic reciprocal interactions between activated T cells and tumor associated macrophages drive macrophage reprogramming and proinflammatory T cell migration within prostate tumor models

Tumor-associated macrophages (TAMs) have been implicated as a tumor microenvironment (TME) cell population, which may be playing a vital role in the inhibition of effective T cell responses in the prostate TME. In this manuscript, we leverage a novel microscale cell culture platform, known as Stacks, to investigate mono-, co-, and tri-culture TME models comprised of prostate tumor cell lines, primary macrophages, and autologous T cells from patients with prostate cancer. Through multiplexed analysis of these multi-cellular prostate tumor models, we capture a dynamic interaction between primary TAMs and activated T cells that resulted in reciprocal proinflammatory activation of both cell populations upon interaction. These findings suggest that activated T cells are capable of reprogramming immunosuppressive TAMs in the context of prostate tumor models and that TAM reprogramming may play a key supportive role in restoring proinflammatory T cell tumor responses in the prostate TME.

How to Realize the Collaborative Supply of Cultural Resource Big Data with Government Participation: Experiences from China

To foster the sustainable development of culture, particularly focusing on the preservation of cultural heritage, encompassing relics, intangible cultural heritage, and historical sites, China has launched a strategy for the digitalization of culture, with the goal of establishing a holistic national big data framework for cultural resources. To improve the efficiency of collaborative supply of cultural resource big data among various parties and to further advance the sustainable development of culture, this research has created a cooperative model that includes cultural institutions, a cultural resource big data service platform, and government participation. Our research findings, based on prospect theory and evolutionary game theory combined with Chinese practice, are presented below. (1) Various factors, including the coefficient of digital infrastructure empowerment, access charges for digital infrastructure, government penalties, and the probability of data leakage, have varying effects on the system in different states. (2) Once the industry has developed, the government can increase the impact of digital infrastructure empowerment to create stronger incentives, rather than relying solely on rewards or penalties. (3) When the value level of cultural resource big data is high, the benefit distribution coefficient does not affect the system evolution results. Finally, we offer practical insights for the government, cultural organizations, and cultural resource big data service platforms based on our research results. Our research offers Chinese insights for global cultural sustainable development.

Temporal evolution of mechanical properties in PDMS: A comparative study of elastic modulus and relaxation time for storage in air and aqueous environment

Polydimethylsiloxane (PDMS) is a soft, biocompatible polymer extensively employed in biomedical research, notable for its tunable mechanical properties achieved through cross-linking. While many studies have assessed the mechanical properties of PDMS utilizing macroscopic and microscopic methods, these analyses are often limited to freshly prepared samples. However, the mechanical properties of PDMS can be expected to change during prolonged exposure to water or air, such as interface polymer chain loosening or surface hardening, which are critical considerations in applications like cell culture platforms or microfluidic devices. This paper presents a comprehensive 10-day investigation of the evolution of PDMS surface mechanical properties through AFM-based nano-indentation. We focused on the most commonly utilized crosslinker-to-base ratios of PDMS, 1:10 (r10) and 1:20 (r20), under conditions of air and deionized water storage. For r10 samples, a hardening process was detected, peaking at 2.12 ± 0.35 MPa within five days for those stored in air and 1.71 ± 0.16 MPa by the third day for those immersed in water. During indentation, the samples displayed multiple contact points, suggesting the formation of distinct regions with varying mechanical properties. In contrast, r20 samples exhibited better stability, with an observed elastic modulus averaging 0.62 ± 0.06 MPa for air-stored and 0.74 ± 0.06 MPa for water-stored samples. Relaxation experiments, interpreted via the General Maxwell Model featuring two distinct component responses, a relatively consistent fast response τ1 (on the order of 10−1 s), and a more variable, slower response τ2 (on the order of 10 s), throughout the study period. The identification of two distinct relaxation times suggests the involvement of two disparate material property regimes in the relaxation process, implying changes in the surface material composition at the interface with air/water. These variations in mechanical properties could significantly influence the long-term functionality of PDMS in various biomedical applications.

Combining human liver ECM with topographically featured electrospun scaffolds for engineering hepatic microenvironment

Liver disease cases are rapidly expanding worldwide, and transplantation remains the only effective cure for end-stage disease. There is an increasing demand for developing potential drug treatments, and regenerative therapies using in-vitro culture platforms. Human decellularized extracellular matrix (dECM) is an appealing alternative to conventional animal tissues as it contains human-specific proteins and can serve as scaffolding materials. Herein we exploit this with human donor tissue from discarded liver which was not suitable for transplant using a synergistic approach to combining biological and topographical cues in electrospun materials as an in-vitro culture platform. To realise this, we developed a methodology for incorporating human liver dECM into electrospun polycaprolactone (PCL) fibres with surface nanotopographies (230–580 nm). The hybrid scaffolds were fabricated using varying concentrations of dECM; their morphology, mechanical properties, hydrophilicity and stability were analysed. The scaffolds were validated using HepG2 and primary mouse hepatocytes, with subsequent results indicating that the modified scaffolds-maintained cell growth and influenced cell attachment, proliferation and hepatic-related gene expression. This work demonstrates a novel approach to harvesting the potential from decellularized human tissues in the form of innovative in-vitro culture platforms for liver.

Hydrogel Applications in the Diagnosis and Treatment of Glioblastoma.

Glioblastoma multiforme (GBM), a common malignant neurological tumor, has boundaries indistinguishable from those of normal tissue, making complete surgical removal ineffective. The blood-brain barrier (BBB) further impedes the efficacy of radiotherapy and chemotherapy, leading to suboptimal treatment outcomes and a heightened probability of recurrence. Hydrogels offer multiple advantages for GBM diagnosis and treatment, including overcoming the BBB for improved drug delivery, controlled drug release for long-term efficacy, and enhanced relaxation properties of magnetic resonance imaging (MRI) contrast agents. Hydrogels, with their excellent biocompatibility and customizability, can mimic the in vivo microenvironment, support tumor cell culture, enable drug screening, and facilitate the study of tumor invasion and metastasis. This paper reviews the classification of hydrogels and recent research for the diagnosis and treatment of GBM, including their applications as cell culture platforms and drugs including imaging contrast agents carriers. The mechanisms of drug release from hydrogels and methods to monitor the activity of hydrogel-loaded drugs are also discussed. This review is intended to facilitate a more comprehensive understanding of the current state of GBM research. It offers insights into the design of integrated hydrogel-based GBM diagnosis and treatment with the objective of achieving the desired therapeutic effect and improving the prognosis of GBM.

Convenient rapid prototyping microphysiological niche for mimicking liver native basement membrane: Liver sinusoid on a chip

Liver is responsible for the metabolization processes of up to 90 % of compounds and toxins in the body. Therefore liver-on-a-chip systems, as an in vitro promising cell culture platform, have great importance for fundamental science and drug development. In most of the liver-on-a-chip studies, seeding cells on both sides of a porous membrane, which represents the basement membrane, fail to resemble the native characteristics of biochemical, biophysical, and mechanical properties. In this study, polycarbonate (PC) and polyethylene terephthalate (PET) membranes were coated with gelatin to address this issue by accurately mimicking the native basement membrane present in the space of Disse. Various coating methods were used, including doctor blade, gel micro-injection, electrospinning, and spin coating. Spin coating was demonstrated to be the most effective technique owing to the ability to produce thin gel thickness with desirable surface roughness for cell interactions on both sides of the membrane. HepG2 and EA.HY926 cells were seeded on the upper and bottom sides of the gelatin-coated PET membrane and cultured on-chip for 7 days. Cell viability increased from 90 % to 95 %, while apoptotic index decreased. Albumin secretion notably rose between days 1–7 and 4–7, while GST-α secretion decreased from day 1 to day 7. In conclusion, the optimized spin coating process reported here can effectively modify the membranes to better mimic the native basement membrane niche characteristics.

Barrier-free, open-top microfluidic chip for generating two distinct, interconnected 3D microvascular networks

Developing microphysiological cell culture platforms with a three-dimensional (3D) microenvironment has been a significant advancement from traditional monolayer cultures. Still, most of the current microphysiological platforms are limited in closed designs, i.e. are not accessible after 3D cell culture loading. Here, we report an open-top microfluidic chip which enables the generation of two sequentially loaded 3D cell cultures without physical barriers restricting the nurture, gas exchange and cellular communication. As a proof-of-concept, we demonstrated the formation of two 3D vasculatures, one in the upper and the other in the lower compartment, under three distinct flow conditions: asymmetric side-to-center, symmetric side-to-center and symmetric center-to-side. We used computational modelling to characterize initial flow pressures in cell culture compartments. We showed prominent vessel formation and branched vasculatures in upper and lower cell culture compartments with interconnecting, lumenized vessels with in vivo-relevant diameter in all flow conditions. With advanced image processing, we quantified and compared the overall vascular network volume and the total length formed in asymmetric side-to-center, symmetric side-to-center and symmetric center-to-side flow conditions. Our results indicate that the developed chip can house two distinct 3D cell cultures with merging vessels between compartments and by providing asymmetric side-to-center or symmetric center-to-side flow vascular morphogenesis is enhanced in terms of overall network length. The developed open-top microfluidic chip may find various applications in generation of tissue-specific 3D-3D co-cultures for studying cellular interactions in vascularized tissues and organs.