Bone joint pathologies caused by several diseases, congenital defects, infections and trauma significantly decrease the quality of human's life, may be life-limiting and are recognized to be among the major health and social challenges of our time.1,2 Bone has a remarkable regenerative potential -fracture healing is a complex process that follows specific regenerative patterns involving several molecular, genetic, biochemical and cellular mechanisms. When the size of the lost bone is greater than the healing capacity of osteogenic tissues there is a need of bone implants. Nowadays, autologous (the gold standard for repairing bone defects) and allogeneic bone grafts are still widely used in clinical practice for repairing bone defects but their application has been connected with various challenges including limited availability, additional surgical trauma and postoperative complications (in the case of autografts), foreign body immune reactions, risk of infections (for example transmission of Hepatitis C virus, Human immunodeficiency virus), poor degree of cellularity, less revascularization and a higher resorption rate (in the case of allografts). 3,4 That is why there is an urgent need for design of suitable substitute with improved incorporation, osteogenicity, osteoconductivity, and osteoinductivity that can mimic to the highest degree the biological, physical and mechanical characteristics of the normal autogenous bone.
Bone tissue engineeringBone tissue engineering (BTE) is a strategy combining the knowledge and principles of orthopedics, bioengineering, molecular/ cellular biology, cell transplantation, and materials' science to construct substitutes that can restore and maintain normal functions of injured and diseased bone. This innovative approach involves the use of stem cells that are seeded into 3D biocompatible scaffolds and induced by appropriate stimulation (growth factors, cytokines, etc) to generate genuine new bone.
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Stem cellsStem cells (SCs) are unspecialized types of cells with the ability to proliferate, self-renew and differentiate under certain physiologic conditions and signaling. The initial concept of stem cells appeared more than one century ago. Although the major advances in clarifying the biology / behavior of SCs that occurred over the last three decades, our knowledge about their nature and ability to explore therapeutic potential are still insufficient.6,7 As compared to embryonic stem cells (ESCs) the adult (or somatic) stem cells are rare, quiescent cells with a more limited self-renewal and differentiation. At the same time, adult stem cells have two very important advantages: they circumvent ethical issues and show less tumorigenicity. Thousands of clinical trials using stem cells are currently in progress.
Mesenchymal stem cellsMesenchymal stem cells (MSCs -multipotent stem cells with fibroblast-like morphology) are of mesodermal origin, except for the facial bones, which arise from neural crest.9 MSCs can be isolated from several adult tissues (bone marrow, adipose ...