Recent Advances in Mechanically Loaded Human Mesenchymal Stem Cells for Bone Tissue Engineering

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.

Biomimetic Mineralization Promotes Viability and Differentiation of Human Mesenchymal Stem Cells in a Perfusion Bioreactor

“…This mechanical stimulus has been pointed out as a potent promoter of hMSC osteodifferentiation [ 27 , 37 ]. A recent review suggests that the cultivation of hMSC under oscillatory or pulsative flow in 3D scaffolds (100–800 μm) and in the presence of osteoinductive supplements provides optimal effect on hMSC osteogenesis [ 23 ]. In this line, we obtained 3D scaffolds with pore size distribution (50–700 μm) inside the range previously commented.…”

“…In spite of these good results, even after 14 days of cell culture, few cells arrived to the bottom inner part of the scaffolds [ 22 ]. This is likely due to the fact that in vitro static cell culture on tridimensional scaffolds presents scarce mass transport prompting to limited cell colonization through few hundred microns and apoptosis or necrosis of cells at the central core of the scaffold [ 23 ].…”

“…Over the last decade, bioreactor systems have been engineered to improve the transport of gases and nutrients and enhance cell distribution, overcoming the main limitations of static cell culture [ 7 , 23 , 24 , 25 ]. Perfusion bioreactors also generate dynamic biophysical stimuli such as shear stress and mechanical loading [ 7 , 23 , 24 , 25 ]. Cells in bone tissues (i.e., osteoclast, osteoblast, osteocytes and MSCs) are mechanosensitive and respond to biophysical factors in the environment [ 23 ].…”

“…Perfusion bioreactors also generate dynamic biophysical stimuli such as shear stress and mechanical loading [ 7 , 23 , 24 , 25 ]. Cells in bone tissues (i.e., osteoclast, osteoblast, osteocytes and MSCs) are mechanosensitive and respond to biophysical factors in the environment [ 23 ]. It has been widely demonstrated that dynamic cell culture in different type of scaffolds such as ceramic scaffolds, metallic scaffolds, decellularized bone matrix from animal sources, synthetic polymer scaffolds, e.g., poly (l-latic acid), or hybrid scaffolds made of HA and chitosan, enhanced cell proliferation and osteogenic differentiation [ 26 , 27 ].…”

“…It has been widely demonstrated that dynamic cell culture in different type of scaffolds such as ceramic scaffolds, metallic scaffolds, decellularized bone matrix from animal sources, synthetic polymer scaffolds, e.g., poly (l-latic acid), or hybrid scaffolds made of HA and chitosan, enhanced cell proliferation and osteogenic differentiation [ 26 , 27 ]. Several in vivo studies also demonstrated that MSC preconditioning in bioreactor prior to implantation enhanced in vivo results as quantity and quality of new bone [ 23 , 28 , 29 ]. A more recent work demonstrated that bioreactor-based preconditioning augments the bone-forming potential of human bone marrow aspirates [ 30 ].…”