Physical confinement in alginate cryogels determines macrophage polarization to a M2 phenotype by regulating a STAT-related mRNA transcription pathway

Abstract

The immunologic response is considered to play a pivotal role in the application of biomaterial implants, and intrinsic properties of biomaterials can significantly modulate the anti-inflammatory effects. However, how physical...

Fabrication of a Coculture Organoid Model in the Biomimetic Matrix of Alginate to Investigate Breast Cancer Progression in a TAMs-Leading Immune Microenvironment

“…The alginate cryogels showed a highly interconnected pore structure (Figure B). The average pore size was 204.9 ± 51.8 μm, and the porosity was 64.9 ± 5.6%, in accordance with our previous study . Compression tests were performed to investigate their mechanical properties.…”

“…Thus, it is still a challenge to examine the influence of the direct cell-to-cell interplays between cancer cells and macrophages without disturbance from ECM components. Therefore, in this study, leveraging our experience in culturing cancer cells and TAMs in vitro using biomaterials, , we established a sequential culture method for the direct BCCs–TAMs coculture by using a 3D alginate cryogel matrix without introducing growth factors to retain M2-type TAM identity. This approach resulted in the recapitulation of direct crosstalk between two cell populations and enabled the elucidation of phenotype changes in proliferation (Figure ), stemness (Figure ), migration (Figure ), and ECM remodeling (Figure ) that occur within breast cancer progression.…”

“…Alginates with a viscosity of 5− 40 mPa s was purchased from Aladdin (China), which was used to fabricate hydrated cryogels with large pore sizes beneficial to induce M2 polarization according to our previous study. 20 In the live/dead staining experiment, calcein AM and propidium iodide (PI) were purchased from Solarbio (China). In the immunostaining experiment, Ki67 and anti-CD163 were purchased from Abcam, and anti-CD133 was procured from Cell Signaling Technology.…”

“…The 3D culture cryogels were prepared based on previous research. 20 First, 2% alginate solution (w/v) in ddH 2 O was prepared and added to multiwell cell culture plates, followed by freezing at −80 °C for 4 h and subsequent freeze-drying for 12 h. Then, the cryogels were rapidly immersed in a 2% CaCl 2 solution for 1 h to form ionic cross-linking by calcium ions and washed with deionized water under gentle stirring to remove extra ions. Cell-adhesive cryogels were further prepared by adding 100 μg mL −1 Arg−Gly−Asp peptide solution and incubating for 1 h before use.…”

Extracellular Matrix‐Mimetic Immunomodulatory Hydrogel for Accelerating Wound Healing

“…[21] In addition, the ECM's loose structure with low physical confinement has been demonstrated to promote macrophage M2 polarization and foster a pro-regenerative environment by regulating a STAT-related mRNA transcription pathway. [22] Furthermore, ECM components, including collagen, laminin, and proteoglycan, can specifically recognize immune cell surface receptors, such as integrins, to mediate their adhesion and trafficking. [15,19,23] Numerous studies have indicated that cell adhesion behaviors play a critical role in regulating macrophage M2 polarization.…”