Synergistic Treatment of Breast Cancer by Combining the Antimicrobial Peptide Piscidin with a Modified Glycolipid.

Piscidin 3 (P3), a peptide produced by fish, and a hexyl ester-modified sophorolipid (SL-HE), have individually shown promise as antimicrobial and anticancer drugs. A recent report by our team revealed that combining P3 with SL-HE in a 1:8 molar ratio resulted in an 8-fold enhancement in peptide activity, while SL-HE improved by 25-fold its antimicrobial activity against the Gram-positive microorganism . Extending these findings, the same P3/SL-HE combination was assessed on two breast cancer cell lines: BT-474, a hormonally positive cell line, and MDA-MB-231, an aggressive triple-negative cell line.

Characterization of TGFβ1-induced tendon-like structure in the scaffold-free three-dimensional tendon cell culture system.

The biological mechanisms regulating tenocyte differentiation and morphological maturation have not been well-established, partly due to the lack of reliable in vitro systems that produce highly aligned collagenous tissues. In this study, we developed a scaffold-free, three-dimensional (3D) tendon culture system using mouse tendon cells in a differentially adherent growth channel. Transforming Growth Factor-β (TGFβ) signaling is involved in various biological processes in the tendon, regulating tendon cell fate, recruitment and maintenance of tenocytes, and matrix organization.

A Systems Approach to Biomechanics, Mechanobiology, and Biotransport.

The human body represents a collection of interacting systems that range in scale from nanometers to meters. Investigations from a systems perspective focus on how the parts work together to enact changes across spatial scales, and further our understanding of how systems function and fail. Here, we highlight systems approaches presented at the 2022 Summer Biomechanics, Bio-engineering, and Biotransport Conference in the areas of solid mechanics; fluid mechanics; tissue and cellular engineering; biotransport; and design, dynamics, and rehabilitation; and biomechanics education.

DMT1-dependent endosome-mitochondria interactions regulate mitochondrial iron translocation and metastatic outgrowth.

Transient early endosome (EE)-mitochondria interactions can mediate mitochondrial iron translocation, but the associated mechanisms are still elusive. We showed that Divalent Metal Transporter 1 (DMT1) sustains mitochondrial iron translocation via EE-mitochondria interactions in triple-negative MDA-MB-231, but not in luminal A T47D breast cancer cells. DMT1 silencing increases labile iron pool (LIP) levels and activates PINK1/Parkin-dependent mitophagy in MDA-MB-231 cells.

Molecularly Engineered Surfactin Analogues Induce Nonapoptotic-Like Cell Death and Increased Selectivity in Multiple Breast Cancer Cell Types.

Surfactin, a negatively charged amphiphilic lipopeptide biosurfactant, is synthesized by the bacterium . It consists of a cyclic heptapeptide and an 11-15C β-hydroxy fatty acid. To probe how the modification of the molecular skeleton of surfactin influences its selectivity and activity against breast cancer, six synthetic surfactins were generated.

Sophorolipid Candidates Demonstrate Cytotoxic Efficacy against 2D and 3D Breast Cancer Models.

Sophorolipids are biosurfactants derived from the nonpathogenic yeasts such as with potential efficacy in anticancer applications. Simple and cost-effective synthesis of these drugs makes them a promising alternative to traditional chemotherapeutics, pending their success in preliminary drug-screening. Drug-screening typically utilizes 2D cell monolayers due to their simplicity and ease of high-throughput assessment.

Tendon cell and tissue culture: Perspectives and recommendations.

The wide variety of cell and tissue culture systems used to study and engineer tendons can make it difficult to choose the best approach and "optimal" culture conditions to test a given hypothesis. Therefore, a breakout session was organized at the 2022 ORS Tendon Section Meeting that focused on establishing a set of guidelines for conducting cell and tissue culture studies of tendon. This paper summarizes the outcomes of that discussion and presents recommendations for future studies.

Can biomechanics turn youth sports into a venue for informal STEM engagement?

A common pitfall of existing Science, Technology, Engineering, and Math (STEM) outreach programs is that they preferentially engage youth with a preexisting interest in STEM. Biomechanics has the unique potential to broaden access to STEM enrichment due to its direct applicability to sports and human performance. In this study we examine whether biomechanics within youth sports can be used as a venue for STEM outreach, and whether recruiting participants through youth sports programs could broaden access to the STEM pipeline.

Viscoelastic Properties of Bioprinted Alginate Microbeads Compared to Their Bulk Hydrogel Analogs.

Hydrogel microbeads are engineered spherical microgels widely used for biomedical applications in cell cultures, tissue engineering, and drug delivery. Their mechanical and physical properties (i.e.

Non-Destructive Evaluation of Regional Cell Density Within Tumor Aggregates Following Drug Treatment.

Multicellular tumor spheroid (MCTSs) models have demonstrated increasing utility for in vitro study of cancer progression and drug discovery. These relatively simple avascular constructs mimic key aspects of in vivo tumors, such as 3D structure and pathophysiological gradients. MCTSs models can provide insights into cancer cell behavior during spheroid development and in response to drugs; however, their requisite size drastically limits the tools used for non-destructive assessment.

Sophorolipids: Anti-cancer activities and mechanisms.

Sophorolipids (SLs) are biosurfactants synthesized as secondary metabolites by non-pathogenic yeasts and other microorganisms. They are members of glycolipid microbial surfactant family that consists of a sophorose polar head group and, most often, an ω-1 hydroxylated fatty acid glycosidically linked to the sophorose moiety. Since the fermentative production of SLs is high (>200 g/L), SLs have the potential to provide low-cost therapeutics.

Lipase-Catalyzed Poly(glycerol-1,8-octanediol-sebacate): Biomaterial Engineering by Combining Compositional and Crosslinking Variables.

This study examined poly(glycerol-1,8-octanediol-sebacate) (PGOS) copolymers with low-level substitution of O (1,8-octanediol) for G (glycerol) units (G/O ratios 0.5:0.5, 0.

A Bioreactor for Controlled Electrical and Mechanical Stimulation of Developing Scaffold-Free Constructs.

Bioreactors are commonly used to apply biophysically relevant stimulations to tissue-engineered constructs in order to explore how these stimuli influence tissue development, healing, and homeostasis, and they offer great flexibility because key features of the stimuli (e.g., duty cycle, frequency, amplitude, and duration) can be controlled to elicit a desired cellular response.

Mechanobiology in Tendon, Ligament, and Skeletal Muscle Tissue Engineering.

Tendon, ligament, and skeletal muscle are highly organized tissues that largely rely on a hierarchical collagenous matrix to withstand high tensile loads experienced in activities of daily life. This critical biomechanical role predisposes these tissues to injury, and current treatments fail to recapitulate the biomechanical function of native tissue. This has prompted researchers to pursue engineering functional tissue replacements, or dysfunction/disease/development models, by emulating in vivo stimuli within in vitro tissue engineering platforms-specifically mechanical stimulation, as well as active contraction in skeletal muscle.

Non-Destructive Tumor Aggregate Morphology and Viability Quantification at Cellular Resolution, During Development and in Response to Drug.

Three-dimensional (3D) tissue-engineered in vitro models, particularly multicellular spheroids and organoids, have become important tools to explore disease progression and guide the development of novel therapeutic strategies. These avascular constructs are particularly powerful in oncological research due to their ability to mimic several key aspects of in vivo tumors, such as 3D structure and pathophysiologic gradients. Advancement of spheroid models requires characterization of critical features (i.

Enzymatic Polymerization of Poly(glycerol-1,8-octanediol-sebacate): Versatile Poly(glycerol sebacate) Analogues that Form Monocomponent Biodegradable Fiber Scaffolds.

A family of poly(glycerol sebacate) (PGS) analogues were synthesized by lipase B (CALB) catalysis to tailor biomaterial properties. Different fractions of glycerol (G) units in PGS were replaced by 1,8-octanediol (O) units. Poly(glycerol-1,8-octanediol-sebacate), PGOS, synthesized by CALB catalysis with a 1:3 molar ratio of G to O units has and values of 9500 and 92,000, respectively.

Characterization of Spatially Graded Biomechanical Scaffolds.

Advances in fabrication have allowed tissue engineers to better mimic complex structures and tissue interfaces by designing nanofibrous scaffolds with spatially graded material properties. However, the nonuniform properties that grant the desired biomechanical function also make these constructs difficult to characterize. In light of this, we developed a novel procedure to create graded nanofibrous scaffolds and determine the spatial distribution of their material properties.

On-Demand Radial Electrodeposition of Alginate Tubular Structures.

We present an electrodeposition technique for fabricating tubular alginate structures. In this technique, two electrodes (anode and cathode) are suspended in a solution of alginate and insoluble calcium carbonate particles, and the application of an electrical potential produces a localized pH change at the anode surface causing suspended divalent cations to become soluble and cross-link the alginate. We robustly characterize how the fabrication parameters influence the rate of radial deposition on the anode, including deposition time, applied voltage, alginate concentration, type of divalent cation and concentration, and anode diameter.

Laser-based 3D bioprinting for spatial and size control of tumor spheroids and embryoid bodies.

3D multicellular aggregates, and more advanced organotypic systems, have become central tools in recent years to study a wide variety of complex biological processes. Most notably, these model systems have become mainstream within oncology (multicellular tumor spheroids) and regenerative medicine (embryoid bodies) research. However, the biological behavior of these in vitro tissue surrogates is extremely sensitive to their aggregate size and geometry.

Multi-modal characterization of polymeric gels to determine the influence of testing method on observed elastic modulus.

Demand for materials that mechanically replicate native tissue has driven development and characterization of various new biomaterials. However, a consequence of materials and characterization technique diversity is a lack of consensus within the field, with no clear way to compare values measured via different modalities. This likely contributes to the difficulty in replicating findings across the research community; recent evidence suggests that different modalities do not yield the same mechanical measurements within a material, and direct comparisons cannot be made across different testing platforms.

Cyclic Uniaxial Tensile Strain Enhances the Mechanical Properties of Engineered, Scaffold-Free Tendon Fibers.

The treatment of injured tendon is an ever-increasing clinical and financial burden, for which tissue-engineered replacements have shown great promise. Recently, there has been growing interest in a more regenerative approach to tissue engineering, in which the cells' abilities to self-assemble and create matrix are harnessed to create tissue constructs without the use of a scaffold. Herein, utilizing our scaffold-free technique to engineer tendon at the single fiber level, we study how applied mechanical loading, namely cyclic uniaxial strain, influences the mechanical properties and nuclear alignment of developing tendon fiber constructs.

Poly-l-lactic acid--poly(pentadecalactone) Electrospun Fibers Result in Greater Neurite Outgrowth of Chick Dorsal Root Ganglia in Vitro Compared to Poly-l-lactic Acid Fibers.

Electrospun poly-l-lactic acid (PLLA) fiber scaffolds are used to direct axonal extension in neural engineering models. We aimed to improve the efficacy of these fibers in promoting neurite outgrowth by altering surface topography and reducing fiber elastic modulus through the incorporation of a compatibilized blend, poly-l-lactic acid-poly(pentadecalactone) (PLLA-PPDL) into the solution prior to electrospinning. PLLA+PLLA-PPDL fibers had a larger diameter, increased surface nanotopography, and lower glass transition temperature than PLLA fibers but had similar mechanical properties.

Solvent retention in electrospun fibers affects scaffold mechanical properties.

Electrospinning is a robust material fabrication method allowing for fine control of mechanical, chemical, and functional properties in scaffold manufacturing. Electrospun fiber scaffolds have gained prominence for their potential in a variety of applications such as tissue engineering and textile manufacturing, yet none have assessed the impact of solvent retention in fibers on the scaffold's mechanical properties. In this study, we hypothesized that retained electrospinning solvent acts as a plasticizer, and gradual solvent evaporation, by storing fibers in ambient air, will cause significant increases in electrospun fiber scaffold brittleness and stiffness, and a significant decrease in scaffold toughness.

The effect of engineered nanotopography of electrospun microfibers on fiber rigidity and macrophage cytokine production.

Currently, it is unknown how the mechanical properties of electrospun fibers, and the presentation of surface nanotopography influence macrophage gene expression and protein production. By further elucidating how specific fiber properties (mechanical properties or surface properties) alter macrophage behavior, it may be possible to create electrospun fiber scaffolds capable of initiating unique cellular and tissue responses. In this study, we determined the elastic modulus and rigidity of fibers with varying topographies created by finely controlling humidity and including a non-solvent during electrospinning.