Joshi, Arundhati
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Item type:Publication, Structure, Properties and Degradation of Self-Assembled Fibrinogen Nanofiber Scaffolds(American chemical society, 2024-09-16); ; ; ; Self-assembled fibrinogen nanofibers are promising candidates for skin tissue engineering due to their biocompatibility and ability to mimic the native blood clot architecture. Here, we studied the structure-property relationship and degradation of rehydrated fibrinogen nanofibers prepared by salt-induced self-assembly, focusing on the effect of scaffold layering, cross-linking time and freeze-drying. Optimal fiber stability was achieved with cross-linking by formaldehyde (FA) vapor, while treatment with liquid aldehydes, genipin, EDC, and transglutaminase failed to preserve the nanofibrous architecture upon rehydration. Scaffold layering did not significantly influence the mechanical properties but changed the scaffold architecture, with bulk fiber scaffolds being more compact than layered scaffolds. Freeze-drying maintained the mechanical properties and interconnected pore network with average pore diameters around 20 μm, which will enhance the storage stability of self-assembled fibrinogen scaffolds. Varying cross-linking times altered the scaffold mechanics without affecting the swelling behavior, indicating that scaffold hydration can be controlled independently of the mechanical characteristics. Cross-linking times of 240 min increased scaffold stiffness and decreased elongation, while 30 min resulted in mechanical properties similar to native skin. Cross-linking for 120 min was found to reduce scaffold degradation by various enzymes in comparison to 60 min. Overall, after 35 days of incubation, plasmin and a combination of urokinase and plasminogen exhibited the strongest degradative effect, with nanofibers being more susceptible to enzymatic degradation than planar fibrinogen due to their higher specific surface area. Based on these results, self-assembled fibrinogen fiber scaffolds show great potential for future applications in soft tissue engineering that require controlled structure-function relationships and degradation characteristics.journal articleBand:7Heft:987 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Biomimetic Fibrinogen Nanofiber Scaffolds for Vascular Hematopoietic Stem Cell Niche Engineering.(Wiley-VCH, 2025-10); ; Lee-Thedieck, CorneliaHematopoietic stem cells (HSCs) can reconstitute the human blood system. In vivo, HSCs are localized in and regulated by distinct bone marrow (BM) microenvironments, or niches, like the vascular HSC niches near fenestrated sinusoidal blood vessels. These delicate structures, comprising a single-layered endothelium and a discontinuous basement membrane, pose challenges in soft tissue engineering. In this study, the basement membrane in vascular niches is mimicked using nanofibrous fibrinogen scaffolds. A novel clamping system enables handling the scaffold as a membrane and seeding both sides-one with microvascular endothelial cells (HMEC-1) and the other with mesenchymal stem and stroma cells (iMSC#3). Subsequently, HSCs and their progenitors (HSPCs) are introduced from both sides to emulate their niche dynamics (residency, exit, and homing). The study reveals that the fibrinogen scaffolds are highly cytocompatible and show good cell-adhesive properties. In addition, HSPCs are able to migrate through the scaffolds, validating them as fenestrated basement membrane mimetics. This in vitro model offers insights into HSPC behavior in the vascular niche and can serve as a drug testing platform in future studies. Moreover, beyond HSCs, the presented scaffold-based mimetic of the basement membrane offers new opportunities for mimicking and studying vasculature in tissue engineering approaches.journal article37 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Self-Assembled Fibrinogen Scaffolds Support Cocultivation of Human Dermal Fibroblasts and HaCaT Keratinocytes(American Chemical Society, 2023-03-07); ; Self-assembled fibrinogen scaffolds are highly attractive biomaterials to mimic native blood clots. To explore their potential for wound healing, we studied the interaction of cocultures of human dermal fibroblasts (HDFs) and HaCaT keratinocytes with nanofibrous, planar, and physisorbed fibrinogen. Cell viability analysis indicated that the growth of HDFs and HaCaTs was supported by all fibrinogen topographies until 14 days, either in mono- or coculture. Using scanning electron microscopy and cytoskeletal staining, we observed that the native morphology of both cell types was preserved on all topographies. Expression of the marker proteins vimentin and cytokeratin-14 showed that the native phenotype of fibroblasts and undifferentiated keratinocytes, respectively, was maintained. HDFs displayed their characteristic wound healing phenotype, characterized by expression of fibronectin. Finally, to mimic the multilayered microenvironment of skin, we established successive cocultures of both cells, for which we found consistently high metabolic activities. SEM analysis revealed that HaCaTs arranged into a confluent top layer after 14 days, while fluorescent labeling confirmed the presence of both cells in the layered structure after 6 days. In conclusion, all fibrinogen topographies successfully supported the cocultivation of fibroblasts and keratinocytes, with fibrinogen nanofibers being particularly attractive for skin regeneration due to their biomimetic porous architecture and the technical possibility to be detached from an underlying substrate.journal articleBand:8Heft:9103 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Self-assembled fibrinogen nanofibers support fibroblast adhesion and prevent E. coli infiltration(Elsevier Science, 2021-07); ; ; ; Fibrinogen nanofibers hold great potential for wound healing applications since they mimic the native blood clot architecture and offer important binding sites to support fibroblast adhesion and migration. Recently, we introduced a new method of saltinduced self-assembly to prepare nanofibrous fibrinogen scaffolds. Here, we present our results on the mechanical properties of these scaffolds and their interaction with 3T3 fibroblasts and E. coli bacteria, which we used as model systems for wound healing. Hydrated, nanofibrous fibrinogen scaffolds showed a Young's modulus of 1.3 MPa, which is close to the range of native fibrin. 3T3 fibroblasts adhered and proliferated well on nanofibrous and planar fibrinogen up to 72 h with a less pronounced actin cytoskeleton on nanofibers in comparison to planar fibrinogen. Fibroblasts on nanofibers were smaller with many short filopodia while larger cells with few long filopodia were found on planar fibrinogen. Live cell tracking revealed higher migration velocities on nanofibers in comparison to planar fibrinogen. The growth of E. coli bacteria on nanofibrous fibrinogen was significantly reduced as compared to agar controls with no bacteria migrating through the nanofibers. In summary, we conclude that self-assembled fibrinogen nanofibers could become highly attractive as future scaffolds for wound healing applications.journal articleHeft:126356 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Self-assembled fibrinogen nanofibers support fibroblast adhesion and prevent E. coli infiltration(Elsevier Science, 2021-07); ; ; ; Fibrinogen nanofibers hold great potential for wound healing applications since they mimic the native blood clot architecture and offer important binding sites to support fibroblast adhesion and migration. Recently, we introduced a new method of salt-induced self-assembly to prepare nanofibrous fibrinogen scaffolds. Here, we present our results on the mechanical properties of these scaffolds and their interaction with 3T3 fibroblasts and E. coli bacteria, which we used as model systems for wound healing. Hydrated, nanofibrous fibrinogen scaffolds showed a Young's modulus of 1.3 MPa, which is close to the range of native fibrin. 3T3 fibroblasts adhered and proliferated well on nanofibrous and planar fibrinogen up to 72 h with a less pronounced actin cytoskeleton on nanofibers in comparison to planar fibrinogen. Fibroblasts on nanofibers were smaller with many short filopodia while larger cells with few long filopodia were found on planar fibrinogen. Live cell tracking revealed higher migration velocities on nanofibers in comparison to planar fibrinogen. The growth of E. coli bacteria on nanofibrous fibrinogen was significantly reduced as compared to agar controls with no bacteria migrating through the nanofibers. In summary, we conclude that self-assembled fibrinogen nanofibers could become highly attractive as future scaffolds for wound healing applications.journal articleBand:12687 100