The Effect of Biomolecular Gradients on Mesenchymal Stem Cell Chondrogenesis under Shear Stress

Tissue engineering is viewed as a promising option for long-term repair of cartilage lesions, but current engineered cartilage constructs fail to match the mechanical properties of native tissue. The extracellular matrix of adult human articular cartilage contains highly organized collagen fibrils that enhance the mechanical properties of the tissue. Unlike articular cartilage, mesenchymal stem cell (MSC) based tissue engineered cartilage constructs lack this oriented microstructure and therefore display much lower mechanical strength. The goal of this study was to investigate the effect of biomolecular gradients and shear stress on MSCs undergoing chondrogenesis within a microfluidic device. Via poly(dimethyl siloxane) soft-lithography, microfluidic devices containing a gradient generator were created. Human MSCs were seeded within these chambers and exposed to flow-based transforming growth factor β1 (TGF-β1) gradients. When the MSCs were both confluent and exposed to shear stress, the cells aligned along the flow direction. Exposure to TGF-β1 gradients led to chondrogenesis of MSCs, indicated by positive type II collagen staining. These results, together with a previous study that showed that aligned MSCs produce aligned collagen, suggest that oriented cartilage tissue structures with superior mechanical properties can be obtained by aligning MSCs along the flow direction and exposing MSCs to chondrogenic gradients

Soil mobility of synthetic and virus-based model nanopesticides

Large doses of chemical pesticides are required to achieve effective concentrations in the rhizosphere, which results in the accumulation of harmful residues. Precision farming is needed to improve the efficacy of pesticides, but also to avoid environmental pollution, and slow-release formulations based on nanoparticles offer one solution. Here, we tested the mobility of synthetic and virus-based model nanopesticides by combining soil column experiments with computational modelling. We found that the tobacco mild green mosaic virus and cowpea mosaic virus penetrate soil to a depth of at least 30 cm, and could therefore deliver nematicides to the rhizosphere, whereas the Physalis mosaic virus remains in the first 4 cm of soil and would be more useful for the delivery of herbicides. Our experiments confirm that plant viruses are superior to synthetic mesoporous silica nanoparticles and poly(lactic-co-glycolic acid) for the delivery and controlled release of pesticides, and could be developed as the next generation of pesticide delivery systems

Conversion of Mechanical Force into TGF-beta-Mediated Biochemical Signals

SummaryMechanical forces influence homeostasis in virtually every tissue [1, 2]. Tendon, constantly exposed to variable mechanical force, is an excellent model in which to study the conversion of mechanical stimuli into a biochemical response [3–5]. Here we show in a mouse model of acute tendon injury and in vitro that physical forces regulate the release of active transforming growth factor (TGF)-β from the extracellular matrix (ECM). The quantity of active TGF-β detected in tissue exposed to various levels of tensile loading correlates directly with the extent of physical forces. At physiological levels, mechanical forces maintain, through TGF-β/Smad2/3-mediated signaling, the expression of Scleraxis (Scx), a transcription factor specific for tenocytes and their progenitors. The gradual and temporary loss of tensile loading causes reversible loss of Scx expression, whereas sudden interruption, such as in transection tendon injury, destabilizes the structural organization of the ECM and leads to excessive release of active TGF-β and massive tenocyte death, which can be prevented by the TGF-β type I receptor inhibitor SD208. Our findings demonstrate a critical role for mechanical force in adult tendon homeostasis. Furthermore, this mechanism could translate physical force into biochemical signals in a much broader variety of tissues or systems in the body

Coating bioactive microcapsules with tannic acid enhances the phenotype of the encapsulated pluripotent stem cells

El títol alternatiu correspon al preprint de l'article publicat.Human pluripotent stem cells (hPSCs) may be differentiated into any adult cell type and therefore hold incredible promise for cell therapeutics and disease modeling. There is increasing interest in three-dimensional (3D) hPSC culture because of improved differentiation outcomes and potential for scale up. Our team has recently described bioactive heparin (Hep)-containing core-shell microcapsules that promote rapid aggregation of stem cells into spheroids and may also be loaded with growth factors for the local and sustained delivery to the encapsulated cells. In this study, we explored the possibility of further modulating bioactivity of microcapsules through the use of an ultrathin coating composed of tannic acid (TA). Deposition of the TA film onto model substrates functionalized with Hep and poly(ethylene glycol) was characterized by ellipsometry and atomic force microscopy. Furthermore, the presence of the TA coating was observed to increase the amount of basic fibroblast growth factor (bFGF) incorporation by up to twofold and to extend its release from 5 to 7 days. Most significantly, TA-microcapsules loaded with bFGF induced higher levels of pluripotency expression compared to uncoated microcapsules containing bFGF. Engineered microcapsules described here represent a new stem cell culture approach that enables 3D cultivation and relies on local delivery of inductive cues