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OBJECTIVE Currently used patch materials in congenital cardiac surgery do not grow, renew, or remodel. Patch calcification occurs more rapidly in pediatric patients eventually leading to reoperations. Bacterial cellulose (BC) as a biogenic polymer offers high tensile strength, biocompatibility, and hemocompatibility. Thus, we further investigated the biomechanical properties of BC for use as patch material. METHODS The BC-producing bacteria Acetobacter xylinum were cultured in different environments to investigate optimal culturing conditions. For mechanical characterization, an established method of inflation for biaxial testing was used. The applied static pressure and deflection height of the BC patch were measured. Furthermore, a displacement and strain distribution analysis was performed and compared to a standard xenograft pericardial patch. RESULTS The examination of the culturing conditions revealed that the BC became homogenous and stable when cultivated at 29°C, 60% oxygen concentration, and culturing medium exchange every third day for a total culturing period of 12 days. The estimated elastic modulus of the BC patches ranged from 200 to 530 MPa compared to 230 MPa for the pericardial patch. The strain distributions, calculated from preloaded (2 mmHg) to 80 mmHg inflation, show BC patch strains ranging between 0.6% and 4%, which was comparable to the pericardial patch. However, the pressure at rupture and peak deflection height varied greatly, ranging from 67 to around 200 mmHg and 0.96 to 5.28 mm, respectively. The same patch thickness does not automatically result in the same material properties indicating that the manufacturing conditions have a significant impact on durability. CONCLUSIONS BC patches can achieve comparable results to pericardial patches in terms of strain behavior as well as in the maximum applied pressure that can be withstood without rupture. Bacterial cellulose patches could be a promising material worth further research.

Vertebrate lonesome kinase (VLK) is the only known secreted tyrosine kinase and responsible for the phosphorylation of a broad range of secretory pathway-resident and extracellular matrix proteins. However, its cell-type specific functions in vivo are still largely unknown. Therefore, we generated mice lacking the VLK gene (protein kinase domain containing, cytoplasmic (Pkdcc)) in mesenchymal cells. Most of the homozygous mice died shortly after birth, most likely as a consequence of their lung abnormalities and consequent respiratory failure. E18.5 embryonic lungs showed a reduction of alveolar type II cells, smaller bronchi, and an increased lung tissue density. Global mass spectrometry-based quantitative proteomics identified 97 proteins with significantly and at least 1.5-fold differential abundance between genotypes. Twenty-five of these had been assigned to the extracellular region and 15 to the mouse matrisome. Specifically, fibromodulin and matrilin-4, which are involved in extracellular matrix organization, were significantly more abundant in lungs from Pkdcc knockout embryos. These results support a role for mesenchyme-derived VLK in lung development through regulation of matrix dynamics and the resulting modulation of alveolar epithelial cell differentiation., Cellular and Molecular Life Sciences, 80 (4), ISSN:1420-682X, ISSN:1420-9071

Frontiers in Bioengineering and Biotechnology 10, 1-12 (2022). doi:10.3389/fbioe.2022.844119, Published by Frontiers Media, Lausanne

Idiopathic pulmonary fibrosis (IPF) is characterized by permanent scarring of lung tissue and declining lung function, and is an incurable disease with increase in prevalence over the past decade. The current consensus is that aberrant wound healing following repeated injuries to the pulmonary epithelium is the most probable cause of IPF, with various immune inflammatory pathways having been reported to impact disease pathogenesis. While the role of immune cells, specifically T lymphocytes and regulatory T cells (Treg), in IPF pathogenesis has been reported and discussed recently, the pathogenic or beneficial roles of these cells in inducing or preventing lung fibrosis is still debated. This lack of understanding could be due in part to the difficulty in obtaining diseased human lung tissue for research purposes. For this reason, many animal models have been developed over the years to attempt to mimic the main clinical hallmarks of IPF: among these, inducing lung injury in rodents with the anti-cancer agent bleomycin has now become the most commonly studied animal model of IPF. Pulmonary fibrosis is the major side effect when bleomycin is administered for cancer treatment in human patients, and a similar effect can be observed after intra-tracheal administration of bleomycin to rodents. Despite many pathophysiological pathways of lung fibrosis having been investigated in bleomycin-injured animal models, one central facet still remains controversial, namely the involvement of specific T lymphocyte subsets, and in particular Treg, in disease pathogenesis. This review aims to summarize the major findings and conclusions regarding the involvement of immune cells and their receptors in the pathogenesis of IPF, and to elaborate on important parallels between animal models and the human disease. A more detailed understanding of the role of Treg and other immune cell subsets in lung injury and fibrosis derived from animal models is a critical basis for translating this knowledge to the development of new immune-based therapies for the treatment of human IPF.

In idiopathic pulmonary fibrosis (IPF), basal-like cells are atypically present in the alveolar region, where they may affect adjacent stromal cells by paracrine mechanisms. We here aimed to confirm the presence of basal-like cells in peripheral IPF lung tissue