Abstract
Large bone defects are a major health concern worldwide. The conventional bone repair techniques (e.g., bone-grafting and Masquelet techniques) have numerous drawbacks, which negatively impact their therapeutic outcomes. Therefore, there is a demand to develop an alternative bone repair approach that can address the existing drawbacks. Bone tissue engineering involving the utilization of human mesenchymal stem cells (hMSCs) has recently emerged as a key strategy for the regeneration of damaged bone tissues. However, the use of tissue-engineered bone graft for the clinical treatment of bone defects remains challenging. While the role of mechanical loading in creating a bone graft has been well explored, the effects of mechanical loading factors (e.g., loading types and regime) on clinical outcomes are poorly understood. This review summarizes the effects of mechanical loading on hMSCs for bone tissue engineering applications. First, we discuss the key assays for assessing the quality of tissue-engineered bone grafts, including specific staining, as well as gene and protein expression of osteogenic markers. Recent studies of the impact of mechanical loading on hMSCs, including compression, perfusion, vibration and stretching, along with the potential mechanotransduction signalling pathways, are subsequently reviewed. Lastly, we discuss the challenges and prospects of bone tissue engineering applications.
Highlights
Bone is a specialized hard tissue composed of bone cells embedded in a mineralized organic matrix, consisting mainly of calcium phosphate, collagen and water [1]
This study suggests that the extension of loading duration might lead to further activation of many genes involved in the osteogenic differentiation of human mesenchymal stem cells (hMSCs)
Fluid shear stress is predominantly imposed on osteocytes and MSCs [82,83]. hMSCs in 2D planar culture have been subjected to fluid shear stress (0.12–12 dyn/cm2) through perfusion to assess their osteogenic potential [47,63,64]
Summary
Bone is a specialized hard tissue composed of bone cells (e.g., osteoblasts, osteocytes and osteoclasts) embedded in a mineralized organic matrix, consisting mainly of calcium phosphate, collagen and water [1]. Six months after the implantation in the large-animal bone defect models, it was found that the bioreactor-generated bone grafts induced more new bone formation compared static-culture-generated bone grafts or cell-free scaffolds [21,23,24]. This evidence suggests that mechanical loading is a key component in bone tissue engineering, given that native bone is constantly subjected to mechanical loading in daily activities [25]. The challenges associated with the future translation of hMSC-derived bone grafts to large bone defect therapy are discussed
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