Sex-specific cardiovascular adaptations to simulated microgravity in Sprague-Dawley rats.

Men and women have different cardiovascular responses to spaceflight; however, few studies have focused on direct comparisons between sexes. We investigated the mechanisms of aortic stiffening in socially and sexually mature 20-week-old male and female Sprague Dawley (SD) rats exposed to hindlimb unloading (HLU) for 14 days. Pulse wave velocity (PWV) was greater in the aortic arch of females after HLU versus control females (n = 6-8).

Enhancing the Efficacy of HIPEC Through Bromelain: A Preclinical Investigation in Appendiceal Cancer.

Introduction: Appendiceal cancer (AC) excessive mucin production is a barrier to heated intraperitoneal chemotherapy (HIPEC) drug delivery. Bromelain is a pineapple stem extract with mucolytic properties. We explored bromelain treatment effects against mucinous AC in a patient-derived tumor organoid (PTO) model and an AC cell line.

In Vitro Three-Dimensional (3D) Models for Melanoma Immunotherapy.

Melanoma is responsible for the majority of skin cancer-related fatalities. Immune checkpoint inhibitor (ICI) treatments have revolutionized the management of the disease by significantly increasing patient survival rates. However, a considerable number of tumors treated with these drugs fail to respond or may develop resistance over time.

3D Bioprinted Liver-on-a-Chip for Drug Cytotoxicity Screening.

Tissues on a chip are sophisticated three-dimensional (3D) microphysiological systems designed to replicate human tissue conditions within dynamic physicochemical environments. However, the current fabrication methods for tissue spheroids on a chip require multiple parts and manual processing steps, including the deposition of spheroids onto prefabricated "chips." These challenges also lead to limitations regarding scalability and reproducibility.

Multicellular bioprinted skin facilitates human-like skin architecture in vivo.

Bioprinting is a promising alternative method to generate skin substitutes because it can replicate the structural organization of the skin into biomimetic layers in vitro. In this study, six primary human skin cell types were used to bioprint a trilayer skin construct consisting of epidermis, dermis, and hypodermis. Transplantation of the bioprinted skin with human cells onto full-thickness wounds of nu/nu mice promoted rapid vascularization and formation of epidermal rete ridges analogous to the native human epidermis, with a normal-looking extracellular matrix.

Cisplatin exhibits superiority over MMC as a perfusion agent in a peritoneal mesothelioma patient specific organoid HIPEC platform.

Peritoneal mesothelioma (PM) is a rare malignancy with poor prognosis, representing about 10-15% of all mesothelioma cases. Herein we apply PM patient-derived tumor organoids (PTOs) in elucidating personalized HIPEC responses to bypass rarity of disease in generating preclinical data. Specimens were obtained from PM patients undergoing cytoreductive surgery with HIPEC.

Protective effectiveness of anise against testicular ischemia and reperfusion injury: An experimental study in rats.

Testicular torsion is a frequently encountered clinical condition that requires urgent treatment. The aim of this study is to investigate the efficacy of Anise (Pimpinella anisum L.) in treating the pathological condition due to ischemia and reperfusion injury by using biochemical, histopathological and immunohistochemical methods.

Cell Viability Assays for 3D Cellular Constructs.

In vitro models fall short of replicating the complex in vivo processes including cell growth and differentiation. For many years, molecular biology research and drug development have relied on the use of cells grown within tissue culture dishes. These traditional in vitro two-dimensional (2D) cultures fail to recapitulate the 3D microenvironment of in vivo tissues.

Application of immune enhanced organoids in modeling personalized Merkel cell carcinoma research.

Merkel cell carcinoma (MCC) is a rare neuroendocrine cutaneous cancer, with incidence of less than 1/100,000, low survival rates and variable response to chemotherapy or immunotherapy. Herein we explore the application of patient tumor organoids (PTOs) in modeling personalized research in this rare malignancy. Unsorted and non-expanded MCC tumor cells were isolated from surgical specimens and suspended in an ECM based hydrogel, along with patient matched blood and lymph node tissue to generate immune enhanced organoids (iPTOs).

Immuno-reactive cancer organoid model to assess effects of the microbiome on cancer immunotherapy.

Immune checkpoint blockade (ICB) therapy has demonstrated good efficacy in many cancer types. In cancers such as non-resectable advanced or metastatic triple-negative breast cancer (TNBC), it has recently been approved as a promising treatment. However, clinical data shows overall response rates (ORRs) from ~ 3-40% in breast cancer patients, depending on subtype, previous treatments, and mutation status.

Bioreactor design and validation for manufacturing strategies in tissue engineering.

The fields of regenerative medicine and tissue engineering offer new therapeutic options to restore, maintain or improve tissue function following disease or injury. To maximize the biological function of a tissue-engineered clinical product, specific conditions must be maintained within a bioreactor to allow the maturation of the product in preparation for implantation. Specifically, the bioreactor should be designed to mimic the mechanical, electrochemical and biochemical environment that the product will be exposed to in vivo.

Development of a Rat Model of Fasciotomy Treatment for Compartment Syndrome.

Skeletal muscle injuries are a major cause of disability for military and civilian populations. Compartment syndrome (CS) in skeletal muscle results from an edema-induced increase in intracompartmental pressure (ICP) after primary injury. Untreated ICP will occlude the tissue vasculature, tissue necrosis, and potential loss of limb.

Pleural Effusion Aspirate for Use in 3D Lung Cancer Modeling and Chemotherapy Screening.

Lung cancer is the leading cause of cancer-related deaths worldwide, yet most currently used in vitro cancer models are confined to traditional 2D cell culture conditions. Recently; however, innovative 3D models such as tumor tissue equivalents (organoids) have been adopted by researchers to recapitulate tissue architecture and physiology in order to improve disease modeling and drug testing. We have hypothesized that 3D lung organoids, incorporating cells directly from patients, will enable personalized disease modeling and tumor cell characterization compared to traditional 2D cultures.

Exploiting maleimide-functionalized hyaluronan hydrogels to test cellular responses to physical and biochemical stimuli.

Currentthree-dimensional (3D) models of liver tissue have been limited by the inability to study the effects of specific extracellular matrix (ECM) components on cell phenotypes. This is in part due to limitations in the availability of chemical modifications appropriate for this purpose. For example, hyaluronic acid (HA), which is a natural ECM component within the liver, lacks key ECM motifs (e.

Intrapleural nano-immunotherapy promotes innate and adaptive immune responses to enhance anti-PD-L1 therapy for malignant pleural effusion.

Malignant pleural effusion (MPE) is indicative of terminal malignancy with a uniformly fatal prognosis. Often, two distinct compartments of tumour microenvironment, the effusion and disseminated pleural tumours, co-exist in the pleural cavity, presenting a major challenge for therapeutic interventions and drug delivery. Clinical evidence suggests that MPE comprises abundant tumour-associated myeloid cells with the tumour-promoting phenotype, impairing antitumour immunity.

T Cells Promote Metastasis by Regulating Extracellular Matrix Remodeling following Chemotherapy.

Metastasis is the main cause of cancer-related mortality. Despite intense efforts to understand the mechanisms underlying the metastatic process, treatment of metastatic cancer is still challenging. Here we describe a chemotherapy-induced, host-mediated mechanism that promotes remodeling of the extracellular matrix (ECM), ultimately facilitating cancer cell seeding and metastasis.

Biofabricated 3D in vitro model of fibrosis-induced abnormal hepatoblast/biliary progenitors' expansion of the developing liver.

Congenital disorders of the biliary tract are the primary reason for pediatric liver failure and ultimately for pediatric liver transplant needs. Not all causes of these disorders are well understood, but it is known that liver fibrosis occurs in many of those afflicted. The goal of this study is to develop a simple yet robust model that recapitulates physico-mechanical and cellular aspects of fibrosis mediated via hepatic stellate cells (HSCs) and their effects on biliary progenitor cells.

Organoid Platform in Preclinical Investigation of Personalized Immunotherapy Efficacy in Appendiceal Cancer: Feasibility Study.

Purpose: Immunotherapy efficacy data on appendiceal cancer from clinical trials does not exist, due to appendiceal cancer incidence of 0.97 per 100,000. The goal of this study was to preclinically explore the application of immunotherapy in treating appendiceal cancer in a personalized organoid model.

Bio-instructive hydrogel expands the paracrine potency of mesenchymal stem cells.

The therapeutic efficacy of clinically applied mesenchymal stromal cells (MSCs) is limited due to their injection into harshenvironments, resulting in the significant loss of their secretory function upon transplantation. A potential strategy for preserving their full therapeutic potential is encapsulation of MSCs in a specialized protective microenvironment, for example hydrogels. However, commonly used injectable hydrogels for cell delivery fail to provide the bio-instructive cues needed to sustain and stimulate cellular therapeutic functions.

Cell Viability Assays in Three-Dimensional Hydrogels: A Comparative Study of Accuracy.

Three-dimensional (3D) cell culture systems, such as tumor organoids and multicellular tumor spheroids, have been developed in part as a result of major advances in tissue engineering and biofabrication techniques. 3D cell culture offers great capabilities in drug development, screening, testing, and precision medicine owing to its physiological accuracy. However, since the inception of 3D systems, few methods have been reported to successfully analyze cell viability quantitatively within hydrogel constructs.

High-throughput microscopy reveals the impact of multifactorial environmental perturbations on colorectal cancer cell growth.

Background: Colorectal cancer (CRC) mortality is principally due to metastatic disease, with the most frequent organ of metastasis being the liver. Biochemical and mechanical factors residing in the tumor microenvironment are considered to play a pivotal role in metastatic growth and response to therapy. However, it is difficult to study the tumor microenvironment systematically owing to a lack of fully controlled model systems that can be investigated in rigorous detail.

Comprehensive characterization of the human pancreatic proteome for bioengineering applications.

Interactions between the pancreatic extracellular matrix (ECM) and islet cells are known to regulate multiple aspects of islet physiology, including survival, proliferation, and glucose-stimulated insulin secretion. Recognizing the essential role of ECM in islet survival and function, various engineering approaches have been developed that aim to utilize ECM-based materials to recreate a native-like microenvironment. However, a major impediment to the success of these approaches has been the lack of a robust and comprehensive characterization of the human pancreatic proteome.

Semiconducting polymer nanoparticles for photothermal ablation of colorectal cancer organoids.

Colorectal cancer (CRC) treatment is currently hindered by micrometastatic relapse that cannot be removed completely during surgery and is often chemotherapy resistant. Targeted theranostic nanoparticles (NPs) that can produce heat for ablation and enable tumor visualization via their fluorescence offer advantages for detection and treatment of disseminated small nodules. A major hurdle in clinical translation of nanoparticles is their interaction with the 3D tumor microenvironment.