Bone Cell Exosomes and Emerging Strategies in Bone Engineering

Abstract

Bone tissue remodeling is a highly regulated process balancing bone formation and resorption through complex cellular crosstalk between resident bone and microenvironment cells. This cellular communication is mediated by direct cell and cell–matrix contact, autocrine, endocrine, and paracrine receptor mediated mechanisms such as local soluble signaling molecules and extracellular vesicles including nanometer sized exosomes. An impairment in this balanced process leads to development of pathological conditions. Bone tissue engineering is an emerging interdisciplinary field with potential to address bone defects and disorders by synthesizing three-dimensional bone substitutes embedded with cells for clinical implantation. However, current cell-based therapeutic approaches have faced hurdles due to safety and ethical concerns, challenging their clinical translation. Recent studies on exosome-regulated bone homeostasis and regeneration have gained interest as prospective cell free therapy in conjugation with tissue engineered bone grafts. However, exosome research is still in its nascent stages of bone tissue engineering. In this review, we specifically describe the role of exosomes secreted by cells within bone microenvironment such as osteoblasts, osteocytes, osteoclasts, mesenchymal stem cell cells, immune cells, endothelial cells, and even tumor cells during bone homeostasis and crosstalk. We also review exosome-based osteoinductive functionalization strategies for various bone-based biomaterials such as ceramics, polymers, and metals in bone tissue engineering. We further highlight biomaterials as carrier agents for exosome delivery to bone defect sites and, finally, the influence of various biomaterials in modulation of cell exosome secretome.

Doped Electrospinned Material-Guides High Efficiency Regional Bone Regeneration

“…Osteoblasts, more abundant at the top regions of the defect in samples treated with Zn-Si-M and Si-M ( Figure 2 and Figure 3 ) secrete VEGFs, and endothelial cells secrete bone morphogenetic protein (BMP)2 to combine osteogenesis and angiogenesis [ 38 ]. Bone generation initiates with osteogenic differentiation of mesenchymal stem cells into osteoblasts [ 14 ]. Osteoblasts produce mineralization of bones, apart from expressing osteogenic and osteoclastogenic factors [ 27 , 39 ].…”

“…Zn-Si-M caused a major presence of osteocytes, osteoblasts and vascular vessels in the top regions of the bone defect ( Figure 2 and Figure 3 ), mostly concentrated in the trabecular woven bone that emerge in the vicinity of the membrane ( Figure S6 ). A subpopulation of osteoblasts is terminally differentiated into osteocytes in the process of bone generation [ 14 ]. Osteocytes reside in lacuna-canalicular porosities within the mineralized bone matrix ( Figure 5 , Figures S4B and S5B ), forming an organized intercellular network interconnected by dendritic cell processes [ 45 ].…”

“…Macrophages aggregate, produce adenosine triphosphate (ATP) and gradually polarize to the M2 phenotype, secreting vascular endothelial grow factor (VEGF) which stimulates the generation and chemotaxis of endothelial cell precursor cells [ 17 ] and also promote osteoblasts differentiation [ 48 ]. There is a synergistic crosstalk between the osteoblast precursors and endothelial cells [ 14 ], which can be appreciated in our histological analysis, due to their interconnected contact ( Figure S8 ). M1 initiates angiogenesis by secreting VEGF.…”

“…Bone cells, such as osteoblasts, osteoclasts, osteocytes and immune cells like macrophages share the same micro-environment and a variety of molecules, working together within the concept of osteoimmunology [ 13 ]. Bone homeostasis is highly regulated with coordinated crosstalk among these cells [ 14 ]. Osteoblasts are bone-forming cells derived from multipotent mesenchymal precursors.…”

Effects of E’Jiao on Skeletal Mineralisation, Osteocyte and WNT Signalling Inhibitors in Ovariectomised Rats

“…Bone remodelling is important in maintaining the integrity and functions of bone tissues, whereby osteoblasts, osteoclasts and osteocytes work sequentially in governing this biological process throughout life [ 7 ]. Osteocytes are the master regulator of bone remodelling and the most populous cells in the bone [ 8 , 9 ]. They could sense mechanical loading and mediate bone formation by osteoblasts and bone resorption by osteoclasts [ 10 ].…”