Hydrogel–mesh composite for wound closure

During operations, surgical mesh is commonly fixed on tissues through fasteners such as sutures and staples. Attributes of surgical mesh include biocompatibility, flexibility, strength, and permeability, but sutures and staples may cause stress concentration and tissue damage. Here, we show that the functions of surgical mesh can be significantly broadened by developing a family of materials called hydrogel–mesh composites (HMCs). The HMCs retain all the attributes of surgical mesh and add one more: adhesion to tissues. We fabricate an HMC by soaking a surgical mesh with a precursor, and upon cure, the precursor forms a polymer network of a hydrogel, in macrotopological entanglement with the fibers of the surgical mesh. In a surgery, the HMC is pressed onto a tissue, and the polymers in the hydrogel form covalent bonds with the tissue. To demonstrate the concept, we use a poly(N-isopropylacrylamide) (PNIPAAm)/chitosan hydrogel and a polyethylene terephthalate (PET) surgical mesh. In the presence a bioconjugation agent, the chitosan and the tissue form covalent bonds, and the adhesion energy reaches above 100 J⋅m−2. At body temperature, PNIPAAm becomes hydrophobic, so that the hydrogel does not swell and the adhesion is stable. Compared with sutured surgical mesh, the HMC distributes force over a large area. In vitro experiments are conducted to study the application of HMCs to wound closure, especially on tissues under high mechanical stress. The performance of HMCs on dynamic living tissues is further investigated in the surgery of a sheep.

Preventing Engrailed-1 activation in fibroblasts yields wound regeneration without scarring

Skin scarring, the end result of adult wound healing, is detrimental to tissue form and function. Engrailed-1 lineage–positive fibroblasts (EPFs) are known to function in scarring, but Engrailed-1 lineage–negative fibroblasts (ENFs) remain poorly characterized. Using cell transplantation and transgenic mouse models, we identified a dermal ENF subpopulation that gives rise to postnatally derived EPFs by activating Engrailed-1 expression during adult wound healing. By studying ENF responses to substrate mechanics, we found that mechanical tension drives Engrailed-1 activation via canonical mechanotransduction signaling. Finally, we showed that blocking mechanotransduction signaling with either verteporfin, an inhibitor of Yes-associated protein (YAP), or fibroblast-specific transgenic YAP knockout prevents Engrailed-1 activation and promotes wound regeneration by ENFs, with recovery of skin appendages, ultrastructure, and mechanical strength. This finding suggests that there are two possible outcomes to postnatal wound healing: a fibrotic response (EPF-mediated) and a regenerative response (ENF-mediated).

To form and function: on the role of basement membrane mechanics in tissue development, homeostasis and disease

The basement membrane (BM) is a special type of extracellular matrix that lines the basal side of epithelial and endothelial tissues. Functionally, the BM is important for providing physical and biochemical cues to the overlying cells, sculpting the tissue into its correct size and shape. In this review, we focus on recent studies that have unveiled the complex mechanical properties of the BM. We discuss how these properties can change during development, homeostasis and disease via different molecular mechanisms, and the subsequent impact on tissue form and function in a variety of organisms. We also explore how better characterization of BM mechanics can contribute to disease diagnosis and treatment, as well as development of better in silico and in vitro models that not only impact the fields of tissue engineering and regenerative medicine, but can also reduce the use of animals in research.

The neuroscience of diabetic retinopathy

Diabetic retinopathy remains a leading cause of blindness despite recent advance in therapies. Traditionally, this complication of diabetes was viewed predominantly as a microvascular disease but research has pointed to alterations in ganglion cells, glia, microglia, and photoreceptors as well, often occurring without obvious vascular damage. In neural tissue, the microvasculature and neural tissue form an intimate relationship with the neural tissue providing signaling cues for the vessels to form a distinct barrier that helps to maintain the proper neuronal environment for synaptic signaling. This relationship has been termed the neurovascular unit (NVU). Research is now focused on understanding the cellular and molecular basis of the neurovascular unit and how diabetes alters the normal cellular communications and disrupts the cellular environment contributing to loss of vision in diabetes.

Actual problems of mycoses caused by dimorphic pathogens

The literature review focuses on actual problems of the particularly dangerous mycoses – coccidioidomycosis, histoplasmosis, blastomycosis, paracoccidioidomycosis. The review presents modern data on the global spread of these fungal infections. Planetary climate changes widen the endemic areas of particularly dangerous mycoses by increase of the inhalational exposure of soil after dust storms, earthquakes and floodings. The prevaling view on the life cycle of agents of coccidioidomycosis (Coccidioides immitis, C.posadasii) is that these fungi dwell in soil (are saprobes) and so for them human and small-mammal fauna are only accidental hosts. The new alternative hypothesis implies that tissue form (spherule) of Coccidioides spp. lives in host granulomas of small mammals and transforms into spore producing hyphae when the animal host dies. It is demonstrated that Histoplasma capsulatum contains at least four different cryptic species, that differ genetically and express different virulence. Recently, discoveries of novel dimorphic systemic fungal pathogens have challenged the current taxonomy of family Ajellomycetacae. The new genus Emergomyces including five species is described. Another dimorphic pathogen is discovered and named Blastomyces percursus. These fungi cause disseminated mycoses globally, primarily in HIVinfected patients.

Wnt/β-catenin Signaling in Tissue Self-Organization

Across metazoans, animal body structures and tissues exist in robust patterns that arise seemingly out of stochasticity of a few early cells in the embryo. These patterns ensure proper tissue form and function during early embryogenesis, development, homeostasis, and regeneration. Fundamental questions are how these patterns are generated and maintained during tissue homeostasis and regeneration. Though fascinating scientists for generations, these ideas remain poorly understood. Today, it is apparent that the Wnt/β-catenin pathway plays a central role in tissue patterning. Wnt proteins are small diffusible morphogens which are essential for cell type specification and patterning of tissues. In this review, we highlight several mechanisms described where the spatial properties of Wnt/β-catenin signaling are controlled, allowing them to work in combination with other diffusible molecules to control tissue patterning. We discuss examples of this self-patterning behavior during development and adult tissues’ maintenance. The combination of new physiological culture systems, mathematical approaches, and synthetic biology will continue to fuel discoveries about how tissues are patterned. These insights are critical for understanding the intricate interplay of core patterning signals and how they become disrupted in disease.

ALARIOSIS OF CARNIVOROUS ANIMALS IN CENTRAL RUSSIA

The spread of alariosis of fishing animals of Central Russia was clarified and a circle of host agents among mammals was identified. The material for the study was the arcasses of trade animals. The period of work was 2018–2020. Animals were studied according to the method of complete helminthological study on K.I. Skryabin (1928). The tissue form of alariosis was examined by trichinelloscopic methods. During the reporting period, 107 heads of carnivorous animals (of which 27 heads (25.2%) are considered stray domestic) extracted in the territory of the Ryazan, Vladimir and Moscow regions. Of the Canidae family, 54 heads have undergone helminthological examination (29 foxes, 17 domestic dogs, 7 raccoon dogs, and 1 wolf). Of the cat (Felidae), 11 heads have been studied (domestic cats – 10, lynx – 1). Martens animals (Mustelinae) have been studied 42 heads (forest мartens – 19, stone мartens – 6, river otter – 4, ermines – 7, badgers – 2, аmerican mink – 4). Adult trematodes have been identified in 37 carnivorous animals (34.6%) in the thin part of the intestine. Canidae animals representing trade species (fox, raccoon dog, wolf) are 100% infected with the agent of alariosis. The intensity invasion of fox was 4–250 copies per head, raccoon dogs – 11–284, wolf – 84. The larval form of the agent was recorded in one fox (3.5%), 2 forest мartens (10.5%) and one аmerican mink (25.0%). Mesocercaries of trematodes were localized in a transparent capsule in lung parenchyma, in diaphragm muscle tissue, in esophageal muscle tissue.