Porous Matrix Stiffness Modulates Response to Targeted Therapy in Breast Carcinoma.

Porous matrix stiffness modulates response to targeted therapy. Poroelastic behavior within porous matrix may modulate the molecule events in cell-matrix and cell-cell interaction like the complex formation of human epidermal growth factor receptor-2 (HER2)-Src-α6ß4 integrin, influencing the targeted therapy with lapatinib.

In Situ Self-Organizing Materials for Local Stress-Responsive Reconstruction of Skin Interstitium.

Remodeling of the fibrous network in the skin interstitium is a crucial step in the process of skin wound healing. In the present study, a hierarchically structured xanthan gum-chitosan (XG-CS) composite hydrogel is developed as a skin wound healing material that responds to stress at wound sites by in situ self-organizing and self-repairing the interstitial fibrous network. The composite gel adheres tightly to the injured fibers forming an intact interstitial pathway, and thereby promotes the physiological function of fibroblasts. A software-based quantitative assessment is performed to evaluate the stress state at wound sites, which confirms that the composite gel adapted in vivo to wound stress and ultimately promotes fast wound healing. The results highlight the importance of interstitial reconstruction in tissue recovery, and will inspire novel strategies in regenerative medicine.

Fluid in the tissue channels of vascular adventitia investigated by AFM and TEM.

BACKGROUND: Tissue channels as a part of microcirculation system have been proposed over three decades, playing an important role in fluid transportation as reported. Adventitia of inferior vena cava (IVC) is a typical hierarchical porous media with abundant tissue channels. Its fluid transportation behaviors attract massive research interest. However, the mechanism of the driving force and microstructure was lack of deep research. OBJECTIVE: This study was to investigate the microstructural basis of fluid transportation within inferior vena cava (IVC). METHODS: Rat IVC samples were extracted and fixed on a gelatin substrate. Four samples were randomly used as 4 cases: Case 1 with AFM loading and the fluorescent tracer adding; Case 2 with fluorescent tracer adding only; Case 3 with AFM loading only as the control group; Case 4 with no treatment. The movement of fluorescent tracer was observed by two-photon fluorescent microscope and analyzed by self-made Matlab program. The microscopic structure was characterized by high resolution TEM. RESULTS: The fluorescent tracer in Case 1 exhibited faster and longer transportation comparing to other cases, while in Case 2 diffused normally following Fick's law. Case 3 with only AFM loading demonstrated that collagen bundles twisting along the fluid orientation, while the bundles in Case 4 with no treatment were straggling. The brush-like macromolecule structure of collagen microfibril was found on the bundle surfaces under TEM. CONCLUSIONS: Transportation within loose connective tissues is observed ex vivo. AFM loading, as the mechanical stimulation resemblance to muscle constrictions and blood pulsations, can facilitate the transportation as the driving force. The brush-like glycosaminoglycan macromolecules on the surfaces of the collagen bundles can be considered as a type of hierarchical porous media, which might form the transport pathway for fluids. The possible mechanism was conducted regarding the conformation of the superficial macromolecule brushes.

AuNP-Collagen Matrix with Localized Stiffness for Cardiac-Tissue Engineering: Enhancing the Assembly of Intercalated Discs by ß1-Integrin-Mediated Signaling.

A schematic for the mechanism of accelerating the assembly of intercalated discs (IDs) in cardiac myocytes regulated by gold nanoparticles (AuNPs) is presented. AuNPs with local nanoscale stiffness in the substrate activate ß1-integrin signaling, which mediates the activation of integrin-linked kinase (ILK) and its downstream signal kinase by stimulating expression of the transcription factors GATA4 and MEF-2c.