This study reports that a methacrylic acid (MAA)‐based copolymer coating generates constructive remodeling of polypropylene (PP) surgical mesh in a subcutaneous model. This coating is non‐bioresorbable and follows the architecture of the mesh without impeding connective tissue integration. Following implantation, the tissue response is biased toward vascularization instead of fibrosis. The vessel density around the MAA mesh is double that of the uncoated mesh two weeks after implantation. This initial vasculature regresses after two weeks while mature vessels remain, suggesting an enhanced healing response. Concurrently, the MAA coating alters the foreign body response to the mesh. Fewer infiltrating cells, macrophages, and foreign body giant cells are found at the tissue–material interface three weeks after implantation. The coating also dampens inflammation, with lower expression levels of pro‐inflammatory and fibrogenic signals (e.g., Tgf‐β1, Tnf‐α, and Il1‐β) and similar expression levels of anti‐inflammatory cytokines (e.g., Il10 and Il6) compared to the uncoated mesh. Contrary to other coatings that aim to mitigate the foreign body response to PP mesh, a MAA coating does not require the addition of any biological agents to have an effect, making the coated mesh an attractive candidate for soft tissue repair.
There is a need to establish in vitro lung alveolar epithelial culture models to better understand the fundamental biological mechanisms that drive lung diseases. While primary alveolar epithelial cells (AEC) are a useful option to study mature lung biology, they have limited utility in vitro. Cells that survive demonstrate limited proliferative capacity and loss of phenotype over the first 3-5 days in traditional culture conditions. To address this limitation, we generated a novel physiologically relevant cell culture system for enhanced viability and maintenance of phenotype. Here we describe a method utilizing e-beam lithography, reactive ion etching, and replica molding to generate poly-dimethylsiloxane (PDMS) substrates containing hemispherical cavities that mimic the architecture and size of mouse and human alveoli. Primary AECs grown on these cavity-containing substrates form a monolayer that conforms to the substrate enabling precise control over cell sheet architecture. AECs grown in cavity culture conditions remain viable and maintain their phenotype over one week. Specifically, cells grown on substrates consisting of 50 μm diameter cavities remained 96 ± 4% viable and maintained expression of surfactant protein C (SPC), a marker of type 2 AEC over 7 days. While this report focuses on primary lung alveolar epithelial cells, our culture platform is potentially relevant and useful for growing primary cells from other tissues with similar cavity-like architecture and could be further adapted to other biomimetic shapes or contours.
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