Cell volume regulation modulates macrophage-related inflammatory responses via JAK/STAT signaling pathways.

Cell volume as a characteristic of changes in response to external environmental cues has been shown to control the fate of stem cells. However, its influence on macrophage behavior and macrophage-mediated inflammatory responses have rarely been explored. Herein, through mediating the volume of macrophages by adding polyethylene glycol (PEG), we demonstrated the feasibility of fine-tuning cell volume to regulate macrophage polarization towards anti-inflammatory phenotypes, thereby enabling to reverse macrophage-mediated inflammation response.

Matrix stiffness regulates the immunomodulatory effects of mesenchymal stem cells on macrophages via AP1/TSG-6 signaling pathways.

It is well-recognized that the matrix stiffness as an important stem cell niche can mediate stem cell behavior such as attachment, proliferation and differentiation, but how matrix stiffness affects the immunomodulatory efficacy of stem cells has been little explored, which, however, is of significant importance in determining the outcomes of stem cell-based therapies and engineered tissue mimics. We herein studied the immunomodulatory efficacy of mesenchymal stem cells (MSCs) in response to matrix stiffness by the evaluation of macrophage polarization in vitro and inflammatory response in vivo by subcutaneous implantation of MSC-laden hydrogels. Remarkably, we found that soft matrix enabled MSCs to produce significantly higher levels of immunomodulatory factors compared to stiff matrix, and induced the presence of more anti-inflammatory macrophages in vitro and attenuated macrophages-mediated inflammatory response in vivo.

Gelatin-Based Colloidal Versus Monolithic Gels to Regulate Macrophage-Mediated Inflammatory Response.

Unlike conventional monolithic hydrogels with covalent cross-linkage that are typically elastic, colloidal gels assembled by reversibly assembled particles as building blocks have shown fascinating viscoelastic properties. They follow a gel-sol transition upon yielding and recover to the initial state upon the release of the shear force (so-called shear-thinning and self-healing behavior); this makes them an ideal candidate as injectable and moldable biomaterials for tissue regeneration. The immune response provoked by the implantation of the colloidal gels with special viscoelastic and structural features is critical for the successful integration of the implants with the host tissues, which, however, remains little explored.

Species-independent stimulation of osteogenic differentiation induced by osteoclasts.

The coupling of bone resorption and bone formation is well-recognized in the bone remodeling process, in which osteoblasts and osteoclasts are key players. However, the anabolic effect of human primary osteoclasts has rarely been reported as mouse and cell line derived osteoclasts were mostly used in previous reports. Therefore, a comprehensive comparison of mouse and human osteoclasts and their corresponding functions is needed to study cell-cell interactions between osteoclasts and osteoblasts.

An All-in-One Tannic Acid-Containing Hydrogel Adhesive with High Toughness, Notch Insensitivity, Self-Healability, Tailorable Topography, and Strong, Instant, and On-Demand Underwater Adhesion.

Hydrogels that are mechanically tough and capable of strong underwater adhesion can lead to a paradigm shift in the design of adhesives for a variety of biomedical applications. We hereby innovatively develop a facile but efficient strategy to prepare hydrogel adhesives with strong and instant underwater adhesion, on-demand detachment, high toughness, notch-insensitivity, self-healability, low swelling index, and tailorable surface topography. Specifically, a polymerization lyophilization conjugation fabrication method was proposed to introduce tannic acid (TA) into the covalent network consisting of polyethylene glycol diacrylate (PEGDA) of substantially high molecular weight.

Control of Matrix Stiffness Using Methacrylate-Gelatin Hydrogels for a Macrophage-Mediated Inflammatory Response.

The successful tissue integration of a biomedical material is mainly determined by the inflammatory response after implantation. Macrophage behavior toward implanted materials is pivotal to determine the extent of the inflammatory response. Hydrogels with different properties have been developed for various biomedical applications such as wound dressings or cell-loaded scaffolds.

Entanglement-Driven Adhesion, Self-Healing, and High Stretchability of Double-Network PEG-Based Hydrogels.

Hydrogels that are capable of wet adhesion and self-healing can enable major advances in a variety of biomedical applications such as tissue regeneration, wound dressings, wearable/implantable devices, and drug delivery. We hereby developed an innovative but simple strategy to achieve adhesive, self-healing, and highly stretchable double-network hydrogels, which were composed of a primary covalent polyethylene glycol diacrylate (PEGDA) network in combination with a noncovalent network of highly diffusive, giant PEG chains. The adhesion to substrates including tissue matrices was instant and repeatable due to the diffusive PEG chains that can spontaneously penetrate and entangle with the substrate network.

Gab2 Ablation Reverses the Stemness of HER2-Overexpressing Breast Cancer Cells.

Background/aims: HER2 has been implicated in mammary tumorigenesis as well as aggressive tumor growth and metastasis. Its overexpression is related to a poor prognosis and chemoresistance in breast cancer patients. Although Grb2-associated binding protein 2 (Gab2) is important in the development and progression of human cancer, its effects and mechanisms in HER2-overexpressing breast cancer are unclear.

Effect of arenobufagin on human pancreatic carcinoma cells.

Pancreatic carcinoma (PC) is a deadly form of cancer with poor overall survival. Currently, chemotherapy such as gemcitabine and 5-fluorouracil (5-FU) are the most popular medications that can improve survival, but rapid drug-resistance makes the search for more effective drugs urgent. Upon looking for natural components to treat PC, it was found that arenobufagin, a cardiac glycosides-like compound, showed significant effects on the gemcitabine-resistant pancreatic carcinoma cell line Panc-1 and the gemcitabine-sensitive cell line ASPC-1 at nanomolar concentrations.