Cells‐Micropatterning Biomaterials for Immune Activation and Bone Regeneration

Abstract

Natural tissues are composed of ordered architectural organizations of multiple tissue cells. The spatial distribution of cells is crucial for directing cellular behavior and maintaining tissue homeostasis and function. Herein, an artificial bone bioceramic scaffold with star-, Tai Chi-, or interlacing-shaped multicellular patterns is constructed. The "cross-talk" between mesenchymal stem cells (MSCs) and macrophages can be effectively manipulated by altering the spatial distribution of two kinds of cells in the scaffolds, thus achieving controllable modulation of the scaffold-mediated osteo-immune responses. Compared with other multicellular patterns, the Tai Chi pattern with a 2:1 ratio of MSCs to macrophages is more effective in activating anti-inflammatory M2 macrophages, improving MSCs osteogenic differentiation, and accelerating new bone formation in vivo. In brief, the Tai Chi pattern generates a more favorable osteo-immune environment for bone regeneration, exhibiting enhanced immunomodulation and osteogenesis, which may be associated with the activation of BMP-Smad, Oncostatin M (OSM), and Wnt/𝜷-catenin signaling pathways in MSCs mediated by macrophage-derived paracrine signaling mediators. The study suggests that the manipulation of cell distribution to improve tissue formation is a feasible approach that can offer new insights for the design of tissue-engineered bone substitutes with multicellular interactions.

Liquefied Microcapsules Compartmentalizing Macrophages and Umbilical Cord‐Derived Cells for Bone Tissue Engineering

“…[17,18] The amount of encapsulated macrophages was inspired by studies that show that the 2:1 ratio of MSCs cocultured with macrophages was more favorable to osteogenic differentiation of MSCs. [57][58][59] In most conditions, the ALP activity was significantly higher in TRI microcapsules (Figure 2c). ALP is considered an early marker of osteoblastic differentiation.…”

Selenium-Doped Mesoporous Bioactive Glass Regulates Macrophage Metabolism and Polarization by Scavenging ROS and Promotes Bone Regeneration In Vivo

“…Macrophage polarization (decisive for maintaining bone homeostasis) helps regulate the dynamic balance between bone tissue destruction and formation . Macrophage polarization manipulation toward M2 significantly promotes bone tissue regeneration, which is dominant among many factors . Therefore, for bone regeneration, biomaterials should shift from relative inertness to those with osteoimmunomodulatory properties, emphasizing efficient regulation of macrophage polarization toward M2.…”

Hydrophilic surface-modified 3D printed flexible scaffolds with high ceramic particle concentrations for immunopolarization-regulation and bone regeneration

“…54,55 Zhang et al found that activating the Wnt/β-catenin signalling pathway mediated via the macrophage-derived paracrine signalling mediator (Wnt10b) could improve the osteogenic properties of mesenchymal stem cells. 56 This meant that alkalitreated scaffolds might directly activate the Wnt/β-catenin pathway of osteoblasts to enhance osteogenic differentiation, regulate macrophage polarization to act on osteoblasts via triggering the Wnt/β-catenin pathway of macrophages, or both. In general, the Wnt/β-catenin signalling pathway might participate in the signal transduction involved in hydrophilic surfacemodified PCL/HA scaffold-regulated osteogenesis.…”