Bioengineered Tumor-Stroma Prostate Cancer In Vitro Models for Screening Therapeutics.

Cancer-associated fibroblasts are increasingly recognized to have a high impact on prostate tumor growth and drug resistance. Here, we bioengineered organotypic prostate cancer 3D in vitro models to better understand tumor-stroma interplay, the metabolomic profile underlying such interactions, and their impact on standard-of-care therapeutics performance. The assembly of robust and uniform spheroids was evaluated and compared in monotypic PC-3 and heterotypic microtumors comprised of either a healthy or malignant stroma and prostate cancer cells.

Flow-on-repellent biofabrication of fibrous decellularized breast tumor-stroma models.

On-the-fly biofabrication of reproducible 3D tumor models at a pre-clinical level is highly desirable to level-up their applicability and predictive potential. Incorporating ECM biomolecular cues and its complex 3D bioarchitecture in the design stages of such in vitro platforms is essential to better recapitulate the native tumor microenvironment. To materialize these needs, herein we describe an innovative flow-on-repellent (FLORE) 3D extrusion bioprinting technique that leverages expedited and automatized bioink deposition onto a customized superhydrophobic printing bed.

Photoacoustic processing of decellularized extracellular matrix for biofabricating living constructs.

The diverse biomolecular landscape of tissue-specific decellularized extracellular matrix (dECM) biomaterials provides a multiplicity of bioinstructive cues to target cells, rendering them highly valuable for various biomedical applications. However, the isolation of dECM biomaterials entails cumbersome xenogeneic enzymatic digestions and also additional inactivation procedures. Such, increases processing time, increments costs and introduces residues of non-naturally present proteins in dECM formulations that remain present even after inactivation.

Brewer's Spent Yeast Cell Wall Polysaccharides as Vegan and Clean Label Additives for Mayonnaise Formulation.

Brewer's spent yeast (BSY) mannoproteins have been reported to possess thickening and emulsifying properties. The commercial interest in yeast mannoproteins might be boosted considering the consolidation of their properties supported by structure/function relationships. This work aimed to attest the use of extracted BSY mannoproteins as a clean label and vegan source of ingredients for the replacement of food additives and protein from animal sources.

Advances in bioengineering pancreatic tumor-stroma physiomimetic Biomodels.

Pancreatic cancer exhibits a unique bioarchitecture and desmoplastic cancer-stoma interplay that governs disease progression, multi-resistance, and metastasis. Emulating the biological features and microenvironment heterogeneity of pancreatic cancer stroma in vitro is remarkably complex, yet highly desirable for advancing the discovery of innovative therapeutics. Diverse bioengineering approaches exploiting patient-derived organoids, cancer-on-a-chip platforms, and 3D bioprinted living constructs have been rapidly emerging in an endeavor to seamlessly recapitulate major tumor-stroma biodynamic interactions in a preclinical setting.

Organotypic 3D decellularized matrix tumor spheroids for high-throughput drug screening.

Decellularized extracellular matrix (dECM) is emerging as a valuable tool for generating 3D in vitro tumor models that better recapitulate tumor-stroma interactions. However, the development of dECM-3D heterotypic microtumors exhibiting a controlled morphology is yet to be materialized. Precisely controlling microtumors morphologic features is key to avoid an inaccurate evaluation of therapeutics performance during preclinical screening.

Bioimaging of Mesenchymal Stem Cells Spatial Distribution and Interactions with 3D In Vitro Tumor Spheroids.

In solid tumors, mesenchymal stem cells (MSCs) are recognized to establish complex intercommunication networks with cancer cells and to significantly influence their invasion and metastasis potential. Such bidirectional interplay occurs between both tissue resident/tumor-associated MSCs (TA-MSCs) and also tumor infiltrating MSCs (TM-MSCs) that migrate from distant sites such as the bone marrow. Interestingly, malignant cells interactions with MSCs in the tumor microenvironment extends beyond conventional exchanges of signaling factors and extracellular vesicles, including unconventional direct exchanges of intracellular components, or cancer cells cannibalism of MSCs.

Consistent Inclusion of Mesenchymal Stem Cells into In Vitro Tumor Models.

Over recent years, the role of distinct mesenchymal stem cell populations in cancer progression has become increasingly evident. In this regard, developing in vitro preclinical tumor models capable of portraying tumor-associated mesenchymal stem cells (TA-MSCs) interactions with the tumor microenvironment (TME), cellular and extracellular components, would allow to improve the predictive potential of these platforms and expedite preclinical drug screening. Although recent studies successfully developed in vitro tumor models in which the biomolecular and cellular behaviors of TA-MSCs were recapitulated in the context of their interactions with specific TME components, no consensus has yet been reached regarding distinct TA-MSCs influence in the evolution of solid tumors.

Screening of dual chemo-photothermal cellular nanotherapies in organotypic breast cancer 3D spheroids.

Living therapeutics approaches that exploit mesenchymal stem cells (MSCs) as nanomedicine carriers are highly attractive due to MSCs native tropism toward the 3D tumor microenvironment. However, a streamlined pre-clinical evaluation of nano-in-cell anti-cancer therapies remains limited by the lack of in vitro testing platforms for screening MSCs-3D microtumor interactions. Herein we generated dense breast cancer mono and heterotypic 3D micro-spheroids for evaluating MSCs-solid tumors interactions and screen advanced nano-in-MSCs therapies.

Cutting Forces Assessment in CNC Machining Processes: A Critical Review.

Machining processes remain an unavoidable technique in the production of high-precision parts. Tool behavior is of the utmost importance in machining productivity and costs. Tool performance can be assessed by the roughness left on the machined surfaces, as well as of the forces developed during the process.

Decellularized Extracellular Matrix for Bioengineering Physiomimetic 3D in Vitro Tumor Models.

Recent advances in the extraction and purification of decellularized extracellular matrix (dECM) obtained from healthy or malignant tissues open new avenues for engineering physiomimetic 3D in vitro tumor models, which closely recapitulate key biomolecular hallmarks and the dynamic cancer cell-ECM interactions in the tumor microenvironment. We review current and upcoming methodologies for chemical modification of dECM-based biomaterials and advanced bioprocessing into organotypic 3D solid tumor models. A comprehensive review of disruptive advances and shortcomings of exploring dECM-based biomaterials for recapitulating the native tumor-supporting matrix is also provided.

Hydrogel 3D in vitro tumor models for screening cell aggregation mediated drug response.

Hydrogel-based 3D in vitro models comprising tumor ECM-mimetic biomaterials exhibit superlative potential as preclinical testing platforms for drug discovery and bioperformance screening. However, during hydrogel design and testing stages, the ideal selection between cancer cell laden 3D models or spheroid embedded hydrogel platforms remains to be elucidated. Selecting a disease-mimicking cellular arrangement within ECM hydrogels is paramount for anti-cancer therapeutics performance evaluation and may lead to differential outcomes.

Mesenchymal Stem Cells Relevance in Multicellular Bioengineered 3D In Vitro Tumor Models.

In vitro 3D tumor microenvironment mimicking models are gathering momentum as alternatives to traditional 2D flat monolayer cultures due to their potential for recapitulating major cancer hallmarks. To fulfill such potential, it is crucial that 3D tumor testing platforms completely emulate in vitro the complex in vivo tumor niche and its cellular constituents. Mesenchymal stem cells (MSCs) are recognized to play a pivotal multi-modulatory role in cancer, generating interest as biological targets and as key tumor suppressing, or tumor promoting effectors.