Abstract
Critical bone defects and related delayed union and nonunion are still worldwide problems to be solved. Bone tissue engineering is mainly aimed at achieving satisfactory bone reconstruction. Mesenchymal stem cells (MSCs) are a kind of pluripotent stem cells that can differentiate into bone cells and can be used as one of the key pillars of bone tissue engineering. In recent decades, immune responses play an important role in bone regeneration. Innate immune responses provide a suitable inflammatory microenvironment for bone regeneration and initiate bone regeneration in the early stage of fracture repair. Adaptive immune responses maintain bone regeneration and bone remodeling. MSCs and immune cells regulate each other. All kinds of immune cells and secreted cytokines can regulate the migration, proliferation, and osteogenic differentiation of MSCs, which have a strong immunomodulatory ability to these immune cells. This review mainly introduces the interaction between MSCs and immune cells on bone regeneration and its potential mechanism, and discusses the practical application in bone tissue engineering by modulating this kind of cell-to-cell crosstalk. Thus, an in-depth understanding of these principles of bone immunology can provide a new way for bone tissue engineering.
Highlights
Bone tissue can undergo self-healing during bone repair, critical bone defects caused by severe fracture, tumor excision, congenital defects, arthritis, and osteoporosis remain a global concern because regenerative requirement exceeds the bone’s capacity to heal itself [1, 2]
Most current studies have mainly focused on osteogenesis and angiogenesis during bone healing because osteogenesis stimulates the deposition of collagen and hydroxyapatite; angiogenesis promotes the delivery of oxygen and nutrients for bone cells to exert their functions [8, 9]
Such a biphasic effect indicates the plasticity of immune regulation in Mesenchymal stem cells (MSCs), and we speculate whether MSCs can trigger the necessary inflammatory response while suppressing excessive immune responses and maintaining a local microenvironment conducive to tissue repair
Summary
Bone tissue can undergo self-healing during bone repair, critical bone defects caused by severe fracture, tumor excision, congenital defects, arthritis, and osteoporosis remain a global concern because regenerative requirement exceeds the bone’s capacity to heal itself [1, 2]. Allogenic bone grafting and xenogenic bone grafting are alternative approaches for critical bone defects, but they show predominant disadvantages, including high costs and risks of disease transmission and immune rejection [5, 6]. These bone grafts have limitations, so novel bone regeneration strategies for critical bone defects should be developed. Bone tissue engineering is a potential strategy for critical bone defects, which are composed of four pillars, namely, biomaterial scaffolds, stem cells, bioactive factors, and biophysical stimuli [7]. Potential modulations are reviewed in detail to be used in bone tissue engineering by targeting the interaction between MSCs and immune cells. This review can be used as a basis for conducting future studies on bone tissue engineering that consider immunomodulation into bone regeneration
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