No abstract

Functional wound dressing with tailored physicochemical and biological properties is vital for diabetic foot ulcer (DFU) treatment. Our main objective in the current study was to fabricate Cellulose Acetate/ Gelatin (CA/Gel) electrospun mat loaded with berberine (Beri) as the DFU-specific wound dressing. The wound healing efficacy of the fabricated dressings was evaluated in streptozotocin-induced diabetic rats. The results demonstrated an average nanofiber diameter of 502 ± 150 nm, and the tensile strength, contact angle, porosity, water vapor permeability and water uptake ratio of CA/Gel nanofibers were around 2.83 ± 0.08 MPa, 58.07 ± 2.35°, 78.17 ± 1.04%, 11.23 ± 1.05 mg/cm 2 /hr, and 12.78 ± 0.32%, respectively, while these values for CA/Gel/Beri nanofibers were 2.69 ± 0.05 MPa, 56.93 ± 1°, 76.17 ± 0.76%, 10.17 ± 0.21 mg/cm 2 /hr, and 14.37 ± 0.42%, respectively. The antibacterial evaluations demonstrated that the dressings exhibited potent antibacterial activity. The collagen density of 88.8 ± 6.7% and the angiogenesis score of 19.8 ± 3.8 obtained in the animal studies indicate a proper wound healing. These findings implied that the incorporation of berberine did not compromise the physical properties of dressing, while improving the biological activities. In conclusion, our results indicated that the prepared mat is a proper wound dressing for DFU management and treatment. Diabetes mellitus is classified as a metabolic disease that has various complications such as chronic wounds, arterial damage, and neuropathy resulting from uncontrolled blood sugar. The wound healing process is a complex and multiphase process that is delayed in diabetic patients because of various complexities 1,2. In these patients, the angiogenesis and re-epithelialization are inadequate because of low interaction between growth factors and their target site. Severe inflammation is an additional deleterious factor resulting from neutrophil infiltration. Moreover, diabetic foot ulcer (DFU) is another complication that is the consequence of intense inflammation,

No abstract

Porous membranes are ubiquitous in cell co-culture and tissue-on-a-chip studies. These materials are predominantly chosen for their semi-permeable and size exclusion properties to restrict or permit transmigration and cell-cell communication. However, previous studies have shown pore size, spacing and orientation affect cell behavior including extracellular matrix production and migration. The mechanism behind this behavior is not fully understood. In this study, we fabricated micropatterned non-fouling polyethylene glycol (PEG) islands to mimic pore openings in order to decouple the effect of surface discontinuity from potential grip on the vertical contact area provided by pore wall edges. Similar to previous findings on porous membranes, we found that the PEG islands hindered fibronectin fibrillogenesis with cells on patterned substrates producing shorter fibrils. Additionally, cell migration speed over micropatterned PEG islands was greater than unpatterned controls, suggesting that disruption of cell-substrate interactions by PEG islands promoted a more dynamic and migratory behavior, similarly to enhanced cell migration on microporous membranes. Preferred cellular directionality during migration was nearly indistinguishable between substrates with identically patterned PEG islands and previously reported behavior over micropores of the same geometry, further confirming disruption of cellsubstrate interactions as a common mechanism behind the cellular responses on these substrates. Interestingly, compared to respective controls, there were differences in cell spreading and a lower increase in migration speed over PEG islands compared prior results on micropores with identical feature size and spacing. This suggests that membrane pores not only disrupt cell-substrate interactions, but also provide additional physical factors that affect cellular response.

No abstract

Porous membranes are fundamental elements for tissue‐chip barrier and co‐culture models. However, the exaggerated thickness of commonly available membranes may represent a stumbling block impeding a more accurate in vitro modeling. Existing techniques to fabricate membranes such as solvent cast, spin‐coating, sputtering, and plasma‐enhanced chemical vapor deposition (PE‐CVD) result in uniform thickness films. Here, a robust method to generate ultrathin porous parylene C (UPP) membranes is developed not just with precise thicknesses down to 300 nm, but with variable gradients in thicknesses, while at the same time having porosities up to 25%. Surface etching and increased roughness which lead to improved cell attachment is also shown. Next, the mechanical properties of UPP membranes with varying porosity and thickness is examined and the data is fitted to previously published models, which can help determine the practical upper limits of porosity and lower limits of thickness. Lastly, a straightforward approach allowing the successful integration of the UPP membranes into a prototyped 3D‐printed scaffold is validated, demonstrating mechanical robustness and allowing cell adhesion under varying flow conditions. Collectively, the results support the integration and the use of UPP membranes to examine cell–cell interaction in vitro.

Inflammatory diseases and cancer metastases lack concrete pharmaceuticals for their effective treatment despite great strides in advancing our understanding of disease progression. One feature of these disease pathogeneses that remains to be fully explored, both biologically and pharmaceutically, is the passage of cancer and immune cells from the blood to the underlying tissue in the process of extravasation. Regardless of migratory cell type, all steps in extravasation involve molecular interactions that serve as a rich landscape of targets for pharmaceutical inhibition or promotion. Transendothelial migration (TEM), or the migration of the cell through the vascular endothelium, is a particularly promising area of interest as it constitutes the final and most involved step in the extravasation cascade. While in vivo models of cancer metastasis and inflammatory diseases have contributed to our current understanding of TEM, the knowledge surrounding this phenomenon would be significantly lacking without the use of in vitro platforms. In addition to the ease of use, low cost, and high controllability, in vitro platforms permit the use of human cell lines to represent certain features of disease pathology better, as seen in the clinic. These benefits over traditional pre-clinical models for efficacy and toxicity testing are especially important in the modern pursuit of novel drug candidates. Here, we review the cellular and molecular events involved in leukocyte and cancer cell extravasation, with a keen focus on TEM, as discovered by seminal and progressive in vitro platforms. In vitro studies of TEM, specifically, showcase the great experimental progress at the lab bench and highlight the historical success of in vitro platforms for biological discovery. This success shows the potential for applying these platforms for pharmaceutical compound screening. In addition to immune and cancer cell TEM, we discuss the promise of hepatocyte transplantation, a process in which systemically delivered hepatocytes must transmigrate across the liver sinusoidal endothelium to successfully engraft and restore liver function. Lastly, we concisely summarize the evolving field of porous membranes for the study of TEM.

Cellular processes are linked to the alignment (anisotropy) and orientation (directionality) of collagen fibers (i.e., landscape) in the native extracellular matrix (ECM). Given the vital role that cell‐matrix interactions play in regulating biological functions, several microfluidic methods have successfully established anisotropic 3D collagen gels to develop quantitative relationships between structural cues and cellular responses. However, independently tailoring the fiber anisotropy and fiber directionality within a landscape remains a challenge. Here, a user‐friendly microfluidic platform with a non‐uniform channel geometry is used to control the degree of fiber anisotropy and directionality as a function of extensional strain rate and a defined flow path, respectively. New experimental capabilities, including independent control over the degree of fiber anisotropy and directionality, spatial gradients in anisotropy, and multi‐material interfaces, are demonstrated. A channel peel‐off technique provides direct access to the microengineered collagen landscapes, and the alignment of single MD‐MB‐231 cancer cells and monolayers of human umbilical vein endothelial cells (HUVEC) is shown. Finally, the platform's modular capability is highlighted by integrating an ultrathin porous Parylene (UPP) membrane onto the microengineered collagen landscape as a method to control the degree of cell‐matrix interaction.