5 research outputs found
Higher Chain Length Distribution in Debranched Type-3 Resistant Starches (RS3) Increases TLR Signaling and Supports Dendritic Cell Cytokine Production
Scope: Resistant starches (RSs) are classically considered to elicit health benefits through fermentation. However, it is recently shown that RSs can also support health by direct immune interactions. Therefore, it has been hypothesized that the structural traits of RSs might impact the health benefits associated with their consumption. Methods and results: Effects of crystallinity, molecular weight, and chain length distribution of RSs are determined on immune Toll-like receptors (TLRs), dendritic cells (DCs), and T-cell cytokines production. To this end, four type-3 RSs (RS3) are compared, namely Paselli WFR, JD150, debranched Etenia, and Amylose fraction V, which are extracted from potatoes and enzymatically modified. Dextrose equivalent seems to be the most important feature influencing immune signaling via activation of TLRs. TLR2 and TLR4 are most strongly stimulated. Especially Paselli WFR is a potent activator of multiple receptors. Moreover, the presence of amylose, even to residual levels, enhances DC and T-cell cytokine responses. Paselli WFR and Amylose fraction V influence T-cell polarization. Conclusions: It has been shown here that chain length and particularly dextrose equivalent are critical features for immune activation. This knowledge might lead to tailoring and design of immune-active RS formulations.</p
Modulation of Biomaterial-Associated Fibrosis by Means of Combined Physicochemical Material Properties
Biomaterial-associated fibrosis remains a significant challenge in medical implants. To optimize implant design, understanding the interplay between biomaterials and host cells during the foreign body response (FBR) is crucial. Material properties are known to influence cellular behavior and can be used to manipulate cell responses, but predicting the right combination for the desired outcomes is challenging. This study explores how combined physicochemical material properties impact early myofibroblast differentiation using the Biomaterial Advanced Cell Screening (BiomACS) technology, which assesses hundreds of combinations of surface topography, stiffness, and wettability in a single experiment. Normal human dermal fibroblasts (NHDFs) are screened for cell density, area, and myofibroblast markers α-smooth muscle actin (α-SMA) and Collagen type I (COL1) after 24 h and 7 days of culture, with or without transforming growth factor-beta (TGF-β). Results demonstrated that material properties influence fibroblast behavior after 7 days with TGF-β stimulation, with wettability emerging as the predominant factor, followed by stiffness. The study identified regions with increased cell adhesion while minimizing myofibroblast differentiation, offering the potential for implant surface optimization to prevent fibrosis. This research provides a powerful tool for cell-material studies and represents a critical step toward enhancing implant properties and reducing complications, ultimately improving patient outcomes.</p
Three dimensional lung models - Three dimensional extracellular matrix models
In vitro models for investigating mechanisms underlying repair and regeneration in lung disease have advanced greatly in the last decades. Of these models, three-dimensional (3D) models are particularly interesting, owing to their enhanced resemblance of the physiological conditions in vivo. Three-dimensional in vitro models can be created using natural or synthetic biomaterials; where utilizing the extracellular matrix (ECM) from the lung itself or ECM-derived biomaterials have improved our understanding of lung disease and repair mechanisms. Homeostasis of lung ECM is critically important for the function of the lungs for gas exchange, and disruption of the ECM occurs in most chronic lung diseases. Reflecting the complexity of the architecture of lung tissue, several different types of in vitro models based on ECM have been developed. Materials derived from collagen, gelatin, hyaluronic acid, and their derivatives are among the most used single ECM protein-based models. Although these models lack the 3D architecture and organization of the native ECM, they facilitate the collection of extensive information via mimicking the lung microenvironment in health and disease. Decellularized lung matrices have been used as scaffolds for in vitro models, enabling the preservation of native architecture and composition within the ECM. However, reintroducing and imaging to localize cells pose some novel challenges in working within these 3D models. Hydrogels that are prepared using these decellularized lung matrices are emerging as a new opportunity, bringing the native lung ECM composition and the ability to control the model shape together. In this chapter we discuss the ECM-based 3D in vitro models for lung disease, repair, and regeneration. First, we briefly outline the lung ECM and the changes associated with chronic lung diseases. Then we summarize the progress and state-of-the-art research performed using these models, discussing the advantages and challenges related to these models and summarizing the properties of an ideal 3D model
