Overview of Dynamic Bond Based Hydrogels for Reversible Adhesion Processes.

Polymeric hydrogels are soft materials with a three-dimensional (3D) hydrophilic network capable of retaining and absorbing large amounts of water or biological fluids. Due to their customizable properties, these materials are extensively studied for developing matrices for 3D cell culture scaffolds, drug delivery systems, and tissue engineering. However, conventional hydrogels still exhibit many drawbacks; thus, significant efforts have been directed towards developing dynamic hydrogels that draw inspiration from organisms' natural self-repair abilities after injury.

The β-arrestin1/endothelin axis bolsters ovarian fibroblast-dependent invadosome activity and cancer cell metastatic potential.

Recruitment of fibroblasts to tumors and their activation into cancer-associated fibroblasts (CAFs) is a strategy used by tumor cells to direct extracellular matrix (ECM) remodeling, invasion, and metastasis, highlighting the need to investigate the molecular mechanisms driving CAF function. Endothelin-1 (ET-1) regulates the communication between cancer and stroma and facilitates the progression of serous ovarian cancer (SOC). By binding to Endothelin A (ET) and B (ET) receptors, ET-1 enables the recruitment of β-arrestin1 (β-arr1) and the formation of signaling complexes that coordinate tumor progression.

Kinetic Detection of Apoptosis Events Via Caspase 3/7 Activation in a Tumor-Immune Microenvironment on a Chip.

The development of advanced biological models like microphysiological systems, able to rebuild the complexity of the physiological and/or pathological environments at a single-cell detail level in an in-vivo-like approach, is proving to be a promising tool to understand the mechanisms of interactions between different cell populations and main features of several diseases. In this frame, the tumor-immune microenvironment on a chip represents a powerful tool to profile key aspects of cancer progression, immune activation, and response to therapy in several immuno-oncology applications. In the present chapter, we provide a protocol to identify and characterize the time evolution of apoptosis by time-lapse fluorescence and confocal imaging in a 3D microfluidic coculture murine model including cancer and spleen cells.

Modulation of Methacrylated Hyaluronic Acid Hydrogels Enables Their Use as 3D Cultured Model.

Bioengineered hydrogels represent physiologically relevant platforms for cell behaviour studies in the tissue engineering and regenerative medicine fields, as well as in in vitro disease models. Hyaluronic acid (HA) is an ideal platform since it is a natural biocompatible polymer that is widely used to study cellular crosstalk, cell adhesion and cell proliferation, and is one of the major components of the extracellular matrix (ECM). We synthesised chemically modified HA with photo-crosslinkable methacrylated groups (HA-MA) in aqueous solutions and in strictly monitored pH and temperature conditions to obtain hydrogels with controlled bulk properties.

The interaction of β-arrestin1 with talin1 driven by endothelin A receptor as a feature of α5β1 integrin activation in high-grade serous ovarian cancer.

Dissemination of high-grade serous ovarian cancer (HG-SOC) in the omentum and intercalation into a mesothelial cell (MC) monolayer depends on functional α5β1 integrin (Intα5β1) activity. Although the binding of Intα5β1 to fibronectin drives these processes, other molecular mechanisms linked to integrin inside-out signaling might support metastatic dissemination. Here, we report a novel interactive signaling that contributes to Intα5β1 activation and accelerates tumor cells toward invasive disease, involving the protein β-arrestin1 (β-arr1) and the activation of the endothelin A receptor (ETR) by endothelin-1 (ET-1).

Droplet-based microfluidic synthesis of nanogels for controlled drug delivery: tailoring nanomaterial properties pneumatically actuated flow-focusing junction.

Conventional batch syntheses of polymer-based nanoparticles show considerable shortcomings in terms of scarce control over nanomaterials morphology and limited lot-to-lot reproducibility. Droplet-based microfluidics represents a valuable strategy to overcome these constraints, exploiting the formation of nanoparticles within discrete microdroplets. In this work, we synthesized nanogels (NGs) composed of hyaluronic acid and polyethyleneimine using a microfluidic flow-focusing device endowed with a pressure-driven micro-actuator.

A Soft Zwitterionic Hydrogel as Potential Coating on a Polyimide Surface to Reduce Foreign Body Reaction to Intraneural Electrodes.

Invasive intraneural electrodes can control advanced neural-interfaced prostheses in human amputees. Nevertheless, in chronic implants, the progressive formation of a fibrotic capsule can gradually isolate the electrode surface from the surrounding tissue leading to loss of functionality. This is due to a nonspecific inflammatory response called foreign-body reaction (FBR).

Biomedical and Tissue Engineering Strategies to Control Foreign Body Reaction to Invasive Neural Electrodes.

Neural-interfaced prostheses aim to restore sensorimotor limb functions in amputees. They rely on bidirectional neural interfaces, which represent the communication bridge between nervous system and neuroprosthetic device by controlling its movements and evoking sensory feedback. Compared to extraneural electrodes (i.

Nano-encapsulation of hydroxytyrosol into formulated nanogels improves therapeutic effects against hepatic steatosis: An in vitro study.

Nanomaterials hold promise as a straightforward approach for enhancing the performance of bioactive compounds in several healthcare scenarios. Indeed, nanoencapsulation represents a valuable strategy to preserve the bioactives, maximizing their bioavailability. Here, a nanoencapsulation strategy for the treatment of nonalcoholic fatty liver disease (NAFLD) is presented.

Synthesis of Nanogels: Current Trends and Future Outlook.

Nanogels represent an innovative platform for tunable drug release and targeted therapy in several biomedical applications, ranging from cancer to neurological disorders. The design of these nanocarriers is a pivotal topic investigated by the researchers over the years, with the aim to optimize the procedures and provide advanced nanomaterials. Chemical reactions, physical interactions and the developments of engineered devices are the three main areas explored to overcome the shortcomings of the traditional nanofabrication approaches.

Biofabrication of Hepatic Constructs by 3D Bioprinting of a Cell-Laden Thermogel: An Effective Tool to Assess Drug-Induced Hepatotoxic Response.

A thermoresponsive Pluronic/alginate semisynthetic hydrogel is used to bioprint 3D hepatic constructs, with the aim to investigate liver-specific metabolic activity of the 3D constructs compared to traditional 2D adherent cultures. The bioprinting method relies on a bioinert hydrogel and is characterized by high-shape fidelity, mild depositing conditions and easily controllable gelation mechanism. Furthermore, the dissolution of the sacrificial Pluronic templating agent significantly ameliorates the diffusive properties of the printed hydrogel.

Quercetin and hydroxytyrosol as modulators of hepatic steatosis: A NAFLD-on-a-chip study.

Organs-on-chip (OoCs) are catching on as a promising and valuable alternative to animal models, in line with the 3Rs initiative. OoCs enable the creation of three-dimensional (3D) tissue microenvironments with physiological and pathological relevance at unparalleled precision and complexity, offering new opportunities to model human diseases and to test the potential therapeutic effect of drugs, while overcoming the limited predictive accuracy of conventional 2D culture systems. Here, we present a liver-on-a-chip model to investigate the effects of two naturally occurring polyphenols, namely quercetin and hydroxytyrosol, on nonalcoholic fatty liver disease (NAFLD) using a high-content analysis readout methodology.

Direct-Write Deposition of Thermogels.

The use of biocompatible hydrogels has widely extended the potential of additive manufacturing (AM) in the biomedical field leading to the production of 3D tissue and organ analogs for in vitro and in vivo studies.In this work, the direct-write deposition of thermosensitive hydrogels is described as a facile route to obtain 3D cell-laden constructs with controlled 3D structure and stable behavior under physiological conditions.

Biomechanical Characterization at the Cell Scale: Present and Prospects.

The rapidly growing field of mechanobiology demands for robust and reproducible characterization of cell mechanical properties. Recent achievements in understanding the mechanical regulation of cell fate largely rely on technological platforms capable of probing the mechanical response of living cells and their physico-chemical interaction with the microenvironment. Besides the established family of atomic force microscopy (AFM) based methods, other approaches include optical, magnetic, and acoustic tweezers, as well as sensing substrates that take advantage of biomaterials chemistry and microfabrication techniques.

Surface functionalization of polyurethane scaffolds mimicking the myocardial microenvironment to support cardiac primitive cells.

Scaffolds populated with human cardiac progenitor cells (CPCs) represent a therapeutic opportunity for heart regeneration after myocardial infarction. In this work, square-grid scaffolds are prepared by melt-extrusion additive manufacturing from a polyurethane (PU), further subjected to plasma treatment for acrylic acid surface grafting/polymerization and finally grafted with laminin-1 (PU-LN1) or gelatin (PU-G) by carbodiimide chemistry. LN1 is a cardiac niche extracellular matrix component and plays a key role in heart formation during embryogenesis, while G is a low-cost cell-adhesion protein, here used as a control functionalizing molecule.

Postbariatric Brachioplasty with Posteromedial Scar: Physical Model, Technical Refinements, and Clinical Outcomes.

Background: Brachioplasty is an increasingly performed procedure following massive weight loss. A visible scar is the main hindrance to this surgery. The aims of the study were to develop a physical model to investigate the ideal location of the surgical incision and to present the authors' technical refinements with the posteromedial scar approach.

Computationally Informed Design of a Multi-Axial Actuated Microfluidic Chip Device.

This paper describes the computationally informed design and experimental validation of a microfluidic chip device with multi-axial stretching capabilities. The device, based on PDMS soft-lithography, consisted of a thin porous membrane, mounted between two fluidic compartments, and tensioned via a set of vacuum-driven actuators. A finite element analysis solver implementing a set of different nonlinear elastic and hyperelastic material models was used to drive the design and optimization of chip geometry and to investigate the resulting deformation patterns under multi-axial loading.

Engineering muscle cell alignment through 3D bioprinting.

Processing of hydrogels represents a main challenge for the prospective application of additive manufacturing (AM) to soft tissue engineering. Furthermore, direct manufacturing of tissue precursors with a cell density similar to native tissues has the potential to overcome the extensive in vitro culture required for conventional cell-seeded scaffolds seeking to fabricate constructs with tailored structural and functional properties. In this work, we present a simple AM methodology that exploits the thermoresponsive behavior of a block copolymer (Pluronic ) as a means to obtain good shape retention at physiological conditions and to induce cellular alignment.

Investigating Nonalcoholic Fatty Liver Disease in a Liver-on-a-Chip Microfluidic Device.

Background And Aim: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease worldwide, ranging from simple steatosis to nonalcoholic steatohepatitis, which may progress to cirrhosis, eventually leading to hepatocellular carcinoma (HCC). HCC ranks as the third highest cause of cancer-related death globally, requiring an early diagnosis of NAFLD as a potential risk factor. However, the molecular mechanisms underlying NAFLD are still under investigation.

Functionalization of poly(ε-caprolactone) surface with lactose-modified chitosan via alkaline hydrolysis: ToF-SIMS characterization.

Functionalization of poly(ε-caprolactone) (PCL) was performed via hydrolysis and subsequent grafting of lactose-modified chitosan (chitlac) at two different degrees of derivatization (9% and 64%). Time of flight secondary ion mass spectrometry (ToF-SIMS) and multivariate analysis (principal component analysis) were successfully applied to the characterization of PCL surface chemistry, evidencing changes in the biopolymer surface following base-catalyzed hydrolysis treatment. ToF-SIMS analysis also confirmed positive EDC/NHS-catalyzed (EDC: N-ethyl-N'-(3-(dimethylamino)propyl)carbodiimide; NHS: N-hydroxysuccinimide) immobilization of chitlac onto activated PCL surface, with formation of amide bonds between PCL surface carboxyl groups and amine residues of chitlac.

The effect of post-mastectomy radiation therapy on breast implants: Unveiling biomaterial alterations with potential implications on capsular contracture.

Post-mastectomy breast reconstruction with expanders and implants is recognized as an integral part of breast cancer treatment. Its main complication is represented by capsular contracture, which leads to poor expansion, breast deformation, and pain, often requiring additional surgery. In such a scenario, the debate continues as to whether the second stage of breast reconstruction should be performed before or after post-mastectomy radiation therapy, in light of potential alterations induced by irradiation to silicone biomaterial.

A primer of statistical methods for correlating parameters and properties of electrospun poly(L-lactide) scaffolds for tissue engineering--PART 2: regression.

This two-articles series presents an in-depth discussion of electrospun poly-L-lactide scaffolds for tissue engineering by means of statistical methodologies that can be used, in general, to gain a quantitative and systematic insight about effects and interactions between a handful of key scaffold properties (Ys) and a set of process parameters (Xs) in electrospinning. While Part-1 dealt with the DOE methods to unveil the interactions between Xs in determining the morphomechanical properties (ref. Y₁₋₄), this Part-2 article continues and refocuses the discussion on the interdependence of scaffold properties investigated by standard regression methods.

Polyurethane-based scaffolds for myocardial tissue engineering.

Bi-layered scaffolds with a 0°/90° lay-down pattern were prepared by melt-extrusion additive manufacturing (AM) using a poly(ester urethane) (PU) synthesized from poly(ε-caprolactone) diol, 1,4-butandiisocyanate and l-lysine ethyl ester dihydrochloride chain extender. Rheological analysis and differential scanning calorimetry of the starting material showed that compression moulded PU films were in the molten state at a higher temperature than 155°C. The AM processing temperature was set at 155°C after verifying the absence of PU thermal degradation phenomena by isothermal thermogravimetry analysis and rheological characterization performed at 165°C.