Abstract
Bone damage leading to bone loss can arise from a wide range of causes, including those intrinsic to individuals such as infections or diseases with metabolic (diabetes), genetic (osteogenesis imperfecta), and/or age-related (osteoporosis) etiology, or extrinsic ones coming from external insults such as trauma or surgery. Although bone tissue has an intrinsic capacity of self-repair, large bone defects often require anabolic treatments targeting bone formation process and/or bone grafts, aiming to restore bone loss. The current bone surrogates used for clinical purposes are autologous, allogeneic, or xenogeneic bone grafts, which although effective imply a number of limitations: the need to remove bone from another location in the case of autologous transplants and the possibility of an immune rejection when using allogeneic or xenogeneic grafts. To overcome these limitations, cutting edge therapies for skeletal regeneration of bone defects are currently under extensive research with promising results; such as those boosting endogenous bone regeneration, by the stimulation of host cells, or the ones driven exogenously with scaffolds, biomolecules, and mesenchymal stem cells as key players of bone healing process.
Highlights
Bone, a dynamic natural composite, is constantly remodeled by fine-tuned bone formation and bone resorption processes, carried out by osteoblasts and osteoclasts, respectively, throughout an individual’s lifespan [1]
Bone fracture healing relying on mesenchymal stem cells (MSCs) derived osteoblasts performance, can occur through two different mechanisms: intramembranous and endochondral bone formation
Osteoblasts begin the mineralization process with the secretion of vesicles filled with amorphous calcium phosphate (ACP), a calcium phosphate (CaP) precipitate of variable composition that acts as a precursor of mineralized bone matrix
Summary
A dynamic natural composite, is constantly remodeled by fine-tuned bone formation and bone resorption processes, carried out by osteoblasts and osteoclasts, respectively, throughout an individual’s lifespan [1]. While the intramembranous ossification directly forms the bone from MSCs that are differentiated into osteoblasts, for endochondral bone formation, there are two key players required; the presence of cartilage, and the vascularization process [2,3]. An ideal scaffold with bone regeneration purposes should mimic the extracellular matrix (ECM) of natural bone tissue, providing the cells an adequate substrate for adhesion, proliferation, migration, and differentiation [13]. This ECM-cell interaction (including osteoblasts, endothelial cells (EC) and immune cells) will direct the cells fate and control bone repair and regeneration [14]. The current review will summarize recent approaches addressing this aim, either by promoting the mobilization and differentiation of endogenous bone progenitor cells or by treating bone defects with the exogenous addition of different agents (scaffolds, biomolecules, MSCs)
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