Regulation of Macrophage Polarization by Mineralized Collagen Coating to Accelerate the Osteogenic Differentiation of Mesenchymal Stem Cells

Abstract

Osteogenesis on the interface between the implant and host bone is a synergistic processing of multiple systems involved in immune response, angiogenesis, osteogenesis, etc. However, regulation of the osteoimmune microenvironment on the implant surface to accelerate the osteogenesis through manipulating the polarization of macrophage phenotype is still beginning to be explored. We here demonstrate that macrophage phenotype is able to be regulated by decoration of mineralized collagen (MC) coating on the titanium implant surface via triggering the integrin-related cascade pathway of macrophages. Furthermore, regulation of the macrophage polarization and construction of the osteoimmune microenvironment by MC coating would subsequently accelerate the osteogenic differentiation of the mesenchymal stem cells. This work therefore emphasizes the importance of the osteoimmune microenvironment on osteogenesis and provides a promising strategy to improve the osteointegration of implants.

ROS-scavenging hydrogel as protective carrier to regulate stem cells activity and promote osteointegration of 3D printed porous titanium prosthesis in osteoporosis

“…In this study, our prepared EGCG-based hydrogel alleviated ROS accumulation in osteoporotic microenvironment, thus reducing the number of pro-inflammatory M1 macrophages and increasing the number of M2 regenerative macrophages. It is worth mentioning that the effect of Ti-BMSCs@HG group on inducing macrophages to polarize from M1 to M2 is more obvious than that of Ti-HG group, which may be attributed to the immune regulation of loaded rBMSCs in a relieved osteoporosis microenvironment (Liu C. et al, 2022;Shao et al, 2022).…”

Biomaterial Integration in the Joint: Pathological Considerations, Immunomodulation, and the Extracellular Matrix

“…[64,65] The changes in bone turnover rates and activated signaling pathways may influence the hyaline construct mimicry of a biomaterial and may affect long-term tissue integration, since mineralized collagens can induce osteoformation. [66] The synovial cavity is protected by a barrier of fibroblastlike synoviocytes (FLS) and locally resident synovial macrophages. [67,68] FLS are the main cells producing HA and joint lubricants such as proteoglycan 4 (lubricin), as well as matrix components for the synovial ECM such as fibronectin and collagens.…”

“…[ 64,65 ] The changes in bone turnover rates and activated signaling pathways may influence the hyaline construct mimicry of a biomaterial and may affect long‐term tissue integration, since mineralized collagens can induce osteoformation. [ 66 ]…”

Remote Activation of M2 Macrophage Polarization via Magneto-Mechanical Stimulation To Promote Osteointegration

“…Traditional bone tissue engineering approaches, such as incorporating anti-inflammatory cytokines and constructing bioactive coatings, focus on altering the biochemical property of biomaterials to modulate macrophage polarization toward M2 phenotype. − Nevertheless, limited half-lives, introduction of exogenous microorganisms, and lack of active response property restrict their use in clinical practice. , Actually, macrophages are highly sensitive not only to biochemical cues but also to mechanical and topographical cues from the microenvironment. − Once perceived by macrophages through the receptors on the cell membrane, mechanical stimulations can be transmitted to the nucleus along the cytoskeleton and converted into biosignals to activate gene transcription and drive specific phenotypic transformation. − Recently, a study has observed that stretch-activated macrophages polarize into M2 phenotype and remarkably upregulate the expression of bone morphogenetic protein-2 (BMP-2), thereby inducing osteogenesis of mesenchymal stem cells (MSCs) . However, exerting mechanical stimulation on macrophages in vivo with a spatiotemporal controllable way still remains a challenge.…”