Abstract
Treatment of bone defects remains a challenge in the clinic. Artificial bone grafts are the most promising alternative to autologous bone grafting. However, one of the limiting factors of artificial bone grafts is the limited means of regulating stem cell differentiation during bone regeneration. As a weight-bearing organ, bone is in a continuous mechanical environment. External mechanical force, a type of biophysical stimulation, plays an essential role in bone regeneration. It is generally accepted that osteocytes are mechanosensitive cells in bone. However, recent studies have shown that mesenchymal stem cells (MSCs) can also respond to mechanical signals. This article reviews the mechanotransduction mechanisms of MSCs, the regulation of mechanical stimulation on microenvironments surrounding MSCs by modulating the immune response, angiogenesis and osteogenesis, and the application of mechanical stimulation of MSCs in bone regeneration. The review provides a deep and extensive understanding of mechanical stimulation mechanisms, and prospects feasible designs of biomaterials for bone regeneration and the potential clinical applications of mechanical stimulation.
Highlights
The bone defect first triggers an inflammatory process, which leads to the recruitment of mesenchymal stem cells (MSCs) to the bone defect by inflammatory factors
The results showed that oscillatory fluid flow (OFF) promoted the proliferation of human MSCs (hMSCs), increased the expression of osteogenic genes, and demonstrated that primary cilia mediated the response of hMSCs to fluid shear stress stimulation (Hoey et al, 2012)
Wang et al found that DNA methyltransferase 3b (Dnmt3b) inhibited the expression of Hedgehog signaling by binding to the Shh gene promoter to downregulate the sensitivity of MSCs to stretch stimulation (Wang et al, 2017)
Summary
The bone defect first triggers an inflammatory process, which leads to the recruitment of mesenchymal stem cells (MSCs) to the bone defect by inflammatory factors These MSCs differentiate into cartilage that gradually ossifies with the growth of blood vessels into the cartilage model. MSCs regulate the immuno-microenvironment by interacting with macrophages and regulating blood vessel formation by secreting angiogenic growth factors This process involves interacting cells, including MSCs, macrophages, and vascular endothelial cells, as well as extracellular matrix molecules and cytokines, all of which constitute the MSC niche that is of great significance in regulating bone regeneration (Moore and Lemischka, 2006; Kuhn and Tuan, 2010; Vafaei et al, 2017). Several types of bone cells can sense mechanical stimulation, including bone marrow MSCs and osteocytes These cells function in different physiological processes and respond to external mechanical stimuli
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