Sulfated and Phosphorylated Agarose as Biomaterials for a Biomimetic Paradigm for FGF-2 Release.

Cardiovascular diseases such as myocardial infarction or limb ischemia are characterized by regression of blood vessels. Local delivery of growth factors (GFs) involved in angiogenesis such as fibroblast blast growth factor-2 (FGF-2) has been shown to trigger collateral neovasculature and might lead to a therapeutic strategy. In vivo, heparin, a sulfated polysaccharide present in abundance in the extracellular matrix (ECM), has been shown to function as a local reservoir for FGF-2 by binding FGF-2 and other morphogens and it plays a role in the evolution of GF gradients.

Towards a 3D-Printed Millifluidic Device for Investigating Cellular Processes.

Microfluidic devices (µFDs) have been explored extensively in drug screening and studying cellular processes such as migration and metastasis. However, the fabrication and implementation of microfluidic devices pose cost and logistical challenges that limit wider-spread adoption. Despite these challenges, light-based 3D printing offers a potential alternative to device fabrication.

Modulation of Short-Term Delivery of Proteins from Hydrogels.

For modulation of cellular behavior, systems that can provide controlled delivery of proteins (soluble signals) over a few hours to a few days are highly desirable. Conventional erosion-controlled systems are inadequate as their degradation spans days to months. Conversely, hydrogels offer quicker release but are limited by a high burst release that can lead to cytotoxicity and rapid depletion of the permeant.

Toward 3D Bioprinting of Osseous Tissue of Predefined Shape Using Single-Matrix Cell-Bioink Constructs.

Engineering living bone tissue of defined shape on-demand has remained a challenge. 3D bioprinting (3DBP), a biofabrication process capable of yielding cell constructs of defined shape, when combined with developmental engineering can provide a possible path forward. Through the development of a bioink possessing appropriate rheological properties to carry a high cell load and concurrently yield physically stable structures, printing of stable, cell-laden, single-matrix constructs of anatomical shapes is realized without the need for fugitive or support phases.

Mesenchymal-endothelial nexus in breast cancer spheroids induces vasculogenesis and local invasion in a CAM model.

Interplay between non-cancerous cells (immune, fibroblasts, mesenchymal stromal cells (MSC), and endothelial cells (EC)) has been identified as vital in driving tumor progression. As studying such interactions in vivo is challenging, ex vivo systems that can recapitulate in vivo scenarios can aid in unraveling the factors impacting tumorigenesis and metastasis. Using the synthetic tumor microenvironment mimics (STEMs)-a spheroid system composed of breast cancer cells (BCC) with defined human MSC and EC fractions, here we show that EC organization into vascular structures is BC phenotype dependent, and independent of ERα expression in epithelial cancer cells, and involves MSC-mediated Notch1 signaling.

Double-interpenetrating nanostructured networks of marine polysaccharides possessing properties comparable to synthetic polymers.

Sustainable circular economy requires materials that possess a property profile comparable to synthetic polymers and, additionally, processing and sourcing of raw materials that have a small environmental footprint. Here, we present a paradigm for processing marine biopolymers into materials that possess both elastic and plastic behavior within a single system involving a double-interpenetrating polymer network comprising the elastic phase of dynamic physical cross-links and stress-dissipating ionically cross-linked domains. As a proof of principle, films possessing more than twofold higher elastic modulus, ultimate tensile strength, and yield stress than those of polylactic acid were realized by blending two water-soluble marine polysaccharides, namely alginic acid (Alg) with physically cross-linkable carboxylated agarose (CA) followed by ionic cross-linking with a divalent cation.

3D Printed Solutions for Spheroid Engineering and Cancer Research.

In multicellular organisms, cells are organized in a 3-dimensional framework and this is essential for organogenesis and tissue morphogenesis. Systems to recapitulate 3D cell growth are therefore vital for understanding development and cancer biology. Cells organized in 3D environments can evolve certain phenotypic traits valuable to physiologically relevant models that cannot be accessed in 2D culture.

Reversible, β-sheet-dependent self-assembly of the phosphoprotein phosvitin is controlled by the concentration and valency of cations.

The hyperphosphorylated protein phosvitin (PV) undergoes a pH-dependent transition between P and β-sheet secondary structures, a process deemed crucial for its role in the promotion of biogenic apatite formation. The transition occurs surprisingly slowly (minutes to hours). This is consistent with a slow aggregation process involving ionic interactions of charged groups on the protein surface.

Biobridge: An Outlook on Translational Bioinks for 3D Bioprinting.

3D-bioprinting (3DBP) possesses several elements necessary to overcome the deficiencies of conventional tissue engineering, such as defining tissue shape a priori, and serves as a bridge to clinical translation. This transformative potential of 3DBP hinges on the development of the next generation of bioinks that possess attributes for clinical use. Toward this end, in addition to physicochemical characteristics essential for printing, bioinks need to possess proregenerative attributes, while enabling printing of stable structures with a defined biological function that survives implantation and evolves in vivo into functional tissue.

Extrusion-Based 3D Bioprinting of Gradients of Stiffness, Cell Density, and Immobilized Peptide Using Thermogelling Hydrogels.

To study biological processes , biomaterials-based engineering solutions to reproduce the gradients observed in tissues are necessary. We present a platform for the 3D bioprinting of functionally graded biomaterials based on carboxylated agarose, a bioink amendable by extrusion bioprinting. Using this bioink, objects with a gradient of stiffness and gradient of cell concentration were printed.

Hydrogel-Forming Algae Polysaccharides: From Seaweed to Biomedical Applications.

With the increasing growth of the algae industry and the development of algae biorefinery, there is a growing need for high-value applications of algae-extracted biopolymers. The utilization of such biopolymers in the biomedical field can be considered as one of the most attractive applications but is challenging to implement. Historically, polysaccharides extracted from seaweed have been used for a long time in biomedical research, for example, agarose gels for electrophoresis and bacterial culture.

Advanced Bioink for 3D Bioprinting of Complex Free-Standing Structures with High Stiffness.

One of the challenges in 3D-bioprinting is the realization of complex, volumetrically defined structures, that are also anatomically accurate and relevant. Towards this end, in this study we report the development and validation of a carboxylated agarose (CA)-based bioink that is amenable to 3D printing of free-standing structures with high stiffness at physiological temperature using microextrusion printing without the need for a fugitive phase or post-processing or support material (FRESH). By blending CA with negligible amounts of native agarose (NA) a bioink formulation (CANA) which is suitable for printing with nozzles of varying internal diameters under ideal pneumatic pressure was developed.

Unraveling the role of β1 integrin isoforms in cRGD-mediated uptake of nanoparticles bearing hydrophilized alkyne moieties in epithelial and endothelial cells.

The uptake and trafficking of NPs is impacted by several attributes such as size, shape, surface charge and importantly by surface ligands that can interact with the cell plasma membrane. We envision that NPs which can be readily modified in aqueous environments will be key to engineering patient-specific nanotherapeutics. Towards such systems that can be functionalized "on demand" in aqueous environments, an α-ω epoxy ester monomer that bears an alkyne group at the end of an oligoethylene glycol moiety was designed and synthesized.

Renal clearance of polymeric nanoparticles by mimicry of glycan surface of viruses.

It has been shown that viral particles such as herpes simplex virus-1 and cytomegalovirus show renal clearance despite their large size (155-240 nm). Interestingly, one of the common characteristics of these viruses is their glycoprotein rich viral envelope. Since, glycosaminoglycans (GAGs) share similarities with oligosaccharide chains in the glycoproteins, we hypothesize that modification of nanoparticles (NPs) surface with naturally found GAGs could alter NP clearance characteristics by mimicking physicochemical aspects of viral glycoprotein envelope.

Autophagy inhibition enhances Matrine derivative MASM induced apoptosis in cancer cells via a mechanism involving reactive oxygen species-mediated PI3K/Akt/mTOR and Erk/p38 signaling.

Background: In the quest for new anti-cancer drugs, the drug discovery process has shifted to screening of active ingredients in traditional eastern medicine. Matrine is an active alkaloid isolated from plants of the Sophora genus used in traditional Chinese herbal medicine that exhibits a wide spectrum of biological properties and has a potential as an anti-proliferative agent. In this study, we investigated the anticancer property of MASM, ([(6aS, 10S, 11aR, 11bR, 11cS)210-Methylamino-dodecahydro-3a, 7a-diaza-benzo (de)anthracene-8-thione]), a potent derivative of matrine.

Silencing of GFP expression in human mesenchymal stem cells using quaternary polyplexes of siRNA-PEI with glycosaminoglycans and albumin.

In recent years evidence has been mounting for a role for mesenchymal stem cells (MSCs) in immunomodulation, anti-inflammatory processes, and paracrine signaling via secreted extracellular vesicles. In order to exploit these biological functions, systems to efficiently deliver genetic material into MSCs would therefore be highly desirable. In this study, efficient silencing of GFP expression by combining high N/P ratio siRNA and branched PEI (bPEI) polyplexes (siRNA-bPEI) polyplexes with glycosaminoglycans (GAGs), namely hyaluronic acid (HA), chondroitin sulfate (CS) and heparin sulfate (HS), and human serum albumin (HSA) is reported.

Biotin-Avidin-Mediated Capture of Microspheres on Polymer Fibers.

Systems for efficient and selective capture of micro-scale objects and structures have application in many areas and are of particular relevance for selective isolation of mammalian cells. Systems for the latter should also not interfere with the biology of the cells. This study demonstrates the capture of microspheres through orthogonal coupling using biotin (ligand) and (strept)avidin (receptor).

Corrigendum to "Impact and Challenges of Mesenchymal Stem Cells in Medicine: An Overview of the Current Knowledge".

[This corrects the article DOI: 10.1155/2018/5023925.].

Mechanically Defined Microenvironment Promotes Stabilization of Microvasculature, Which Correlates with the Enrichment of a Novel Piezo-1 Population of Circulating CD11b /CD115 Monocytes.

Vascularization is a critical step in the restoration of cellular homeostasis. Several strategies including localized growth factor delivery, endothelial progenitor cells, genetically engineered cells, gene therapy, and prevascularized implants have been explored to promote revascularization. But, long-term stabilization of newly induced vessels remains a challenge.

RGDSP functionalized carboxylated agarose as extrudable carriers for chondrocyte delivery.

The limited potential of cartilage to regenerate itself has led to development of new strategies and biomaterials for cartilage tissue engineering and regenerative medicine. Although de novo strategies for cartilage repair have been realized, extrudable hydrogels that can be administered in minimally invasive manner while simultaneously supporting chondrogenic differentiation could lead to development of new systems to deliver cells to cartilage lesions. In this work, we explored the suitability of thermo-reversible, extrudable gels derived from carboxylated agarose for maintaining human articular chondrocyte (HAC) phenotype.

Cell number in mesenchymal stem cell aggregates dictates cell stiffness and chondrogenesis.

Background: Although mesenchymal stem/stromal cell (MSC) chondrogenic differentiation has been thoroughly investigated, the rudiments for enhancing chondrogenesis have remained largely dependent on external cues. Focus to date has been on extrinsic variables such as soluble signals, culture conditions (bioreactors), and mechanical stimulation. However, the role of intrinsic mechanisms of MSC programming-based mechanobiology remains to be explored.

Generation of 3D Soluble Signal Gradients in Cell-Laden Hydrogels Using Passive Diffusion.

Soluble signal gradients play an important role in organ patterning, cell migration, and differentiation. Currently, signal gradients in 2D cell culture are realized using microfluidics and here cells are exposed to high and nonphysiological shear stress. Tissue morphogenesis (organogenesis) however occurs in 3D and therefore there is a need for simple and practical systems to impose gradients to cells dispersed in 3D matrix.

Hyperstimulation of CaSR in human MSCs by biomimetic apatite inhibits endochondral ossification via temporal down-regulation of PTH1R.

In adult bone injuries, periosteum-derived mesenchymal stem/stromal cells (MSCs) form bone via endochondral ossification (EO), whereas those from bone marrow (BM)/endosteum form bone primarily through intramembranous ossification (IMO). We hypothesized that this phenomenon is influenced by the proximity of MSCs residing in the BM to the trabecular bone microenvironment. Herein, we investigated the impact of the bone mineral phase on human BM-derived MSCs' choice of ossification pathway, using a biomimetic bone-like hydroxyapatite (BBHAp) interface.

A long-lasting oral preformulation of the angiotensin II AT1 receptor antagonist losartan.

Losartan (Los), a non-peptidic orally active agent, reduces arterial pressure through specific and selective blockade of angiotensin II receptor AT1. However, this widely used AT1 antagonist presents low bioavailability and needs once or twice a day dosage. In order to improve its bioavailability, we used the host: guest strategy based on β-cyclodextrin (βCD).