Cell Guiding Multicomponent Nanoyarn Tendon Scaffolds with Tunable Morphology and Flexibility.

Nanofibrous scaffolds are widely investigated for tendon tissue engineering due to their porous structure, high flexibility, and the ability to guide cells in a preferred direction. Previous research has shown that providing a microenvironment similar to in vivo settings improves tissue regeneration. Therefore, in this work, ingenious multicomponent nanoyarn scaffolds that mimic the fibrillar and tubular structures of tendons are developed for the first time through electrospinning and bundling nanoyarns followed by electrospinning of a nanofibrous shell around the bundle. Multicomponent nanoyarn scaffolds out of poly(ε-caprolactone) with varying porosity, density, and diameter were successfully produced by coelectrospinning with water-soluble poly(2-ethyl-2-oxazoline) as a sacrificial component. The diameter and fiber orientation of the nanoyarns were successfully tuned based on parameter-morphology models obtained by the design of experiments. Cyclic bending tests were performed, indicating that the flexibility of the multicomponent nanoyarn scaffolds depends on the morphology and can be tuned through controlling the number of nanoyarns in the bundle and the porosity. Indirect and direct cell culture tests using mouse and equine tendon cells revealed excellent cytocompatibility of the nanofibrous products and demonstrated the potential of the nanoyarns to guide the growing cells along the nanofiber direction, which is crucial for tendon tissue engineering.

Transformative Materials to Create 3D Functional Human Tissue Models In Vitro in a Reproducible Manner.

Recreating human tissues and organs in the petri dish to establish models as tools in biomedical sciences has gained momentum. These models can provide insight into mechanisms of human physiology, disease onset, and progression, and improve drug target validation, as well as the development of new medical therapeutics. Transformative materials play an important role in this evolution, as they can be programmed to direct cell behavior and fate by controlling the activity of bioactive molecules and material properties. Using nature as an inspiration, scientists are creating materials that incorporate specific biological processes observed during human organogenesis and tissue regeneration. This article presents the reader with state-of-the-art developments in the field of in vitro tissue engineering and the challenges related to the design, production, and translation of these transformative materials. Advances regarding (stem) cell sources, expansion, and differentiation, and how novel responsive materials, automated and large-scale fabrication processes, culture conditions, in situ monitoring systems, and computer simulations are required to create functional human tissue models that are relevant and efficient for drug discovery, are described. This paper illustrates how these different technologies need to converge to generate in vitro life-like human tissue models that provide a platform to answer health-based scientific questions.

Phylogenetics and the evolution of terrestriality in mudskippers (Gobiidae: Oxudercinae).

The initial vertebrate conquest of land by stegocephalians (Sarcopterygia) allowed access to new resources and exploitation of untapped niches precipitating a major phylogenetic diversification. However, a paucity of fossils has left considerable uncertainties about phylogenetic relationships and the eco-morphological stages in this key transition in Earth history. Among extant actinopterygians, three genera of mudskippers (Gobiidae: Oxudercinae), Boleophthalmus, Periophthalmus and Periophthalmodon are the most terrestrialized, with vertebral, appendicular, locomotory, respiratory, and epithelial specializations enabling overland excursions up to 14 h. Unlike early stegocephalians, the ecologies and morphologies of the 45 species of oxudercines are well known, making them viable analogs for the initial vertebrate conquest of land. Nevertheless, they have received little phylogenetic attention. We compiled the largest molecular dataset to date, with 29 oxudercine species, and 5 nuclear and mitochondrial loci. Phylogenetic and comparative analyses revealed strong support for two independent terrestrial transitions, and a complex suit of ecomorphological forms in estuarine environments. Furthermore, neither Oxudercinae nor their presumed sister-group the eel gobies (Amblyopinae, a group of elongated gobies) were monophyletic with respect to each other, requiring a merging of these two subfamilies and revealing an expansion of phenotypic variation within the "mudskipper" clade. We did not find support for the expected linear model of ecomorphological and locomotory transition from fully aquatic, to mudswimming, to pectoral-aided mudswimming, to lobe-finned terrestrial locomotion proposed by earlier morphological studies. This high degree of convergent or parallel transitions to terrestriality, and apparent divergent directions of estuarine adaptation, promises even greater potential for this clade to illuminate the conquest of land. Future work should focus on these less-studied species with "transitional" and other mud-habitat specializations to fully resolve the dynamics of this diversification.

Is the Microgel Collapse a Two-Step Process? Exploiting Cononsolvency to Probe the Collapse Dynamics of Poly-N-isopropylacrylamide (pNIPAM).

Many applications of responsive microgels rely on the fast adaptation of the polymer network. However, the underlying dynamics of the de-/swelling process of the gels have not been fully understood. In the present work, we focus on the collapse kinetics of poly-N-isopropylacrylamide (pNIPAM) microgels due to cononsolvency. Cononsolvency means that either of the pure solvents, e.g., pure water or pure methanol, act as a so-called good solvent, leading to a swollen state of the polymer network. However, in mixtures of water and methanol, the previously swollen network undergoes a drastic volume loss. To further elucidate the cononsolvency transition, pNIPAM microgels with diameters between 20 and 110 µm were synthesized by microfluidics. To follow the dynamics, pure water was suddenly exchanged with an unfavorable mixture of 20 mol% methanol (solvent-jump) within a microfluidic channel. The dynamic response of the microgels was investigated by optical and fluorescence microscopy and Raman microspectroscopy. The experimental data provide unique and detailed insight into the size-dependent kinetics of the volume phase transition due to cononsolvency. The change in the microgel's diameter over time points to a two-step process of the microgel collapse with a biexponential behavior. Furthermore, the dependence between the two time constants from this biexponential behavior and the microgel's diameter in the collapsed state deviates from the square-power law proposed by Tanaka and Fillmore [ J. Chem. Phys. 1979, 70, 1214-1218]. The deviation is discussed considering the adhesion-induced deformation of the gels and the physical processes underlying the collapse.