Cutting Edge Endogenous Promoting and Exogenous Driven Strategies for Bone Regeneration

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.

Stem Cells and Their Derivatives—Implications for Alveolar Bone Regeneration: A Comprehensive Review

“…In the field of dentistry, the MSCs derived from oral tissue represent the most favorable cell type for exosome harvesting. Thanks to the high content of bioactive molecules, exosomes display similar activity to MSCs; moreover, they reduce the inherent safety risk, thus representing a cell-free alternative in bone tissue engineering and regeneration [103,104]. Furthermore, the therapeutic use of exosomes eliminates the risk of tumor formation because they do not mutate, do not duplicate, and cannot initiate metastasis.…”

Educating EVs to Improve Bone Regeneration: Getting Closer to the Clinic

“…On this basis, the field of bone tissue engineering has emerged, focused on developing "bone substitutes" that mimic the bone tissue features, usually formed by a 3D scaffold and bone-relevant cell types, which are able to promote osteogenic differentiation in host tissue without any adverse inflammatory response [8]. The features of mesenchymal stem cells (MSCs), such as their capacity to undergo osteogenic differentiation, immunomodulatory potential, and trophic effects, make them quite attractive components for these bone constructs [8,9].…”

“…On this basis, the field of bone tissue engineering has emerged, focused on developing "bone substitutes" that mimic the bone tissue features, usually formed by a 3D scaffold and bone-relevant cell types, which are able to promote osteogenic differentiation in host tissue without any adverse inflammatory response [8]. The features of mesenchymal stem cells (MSCs), such as their capacity to undergo osteogenic differentiation, immunomodulatory potential, and trophic effects, make them quite attractive components for these bone constructs [8,9]. In fact, the use of MSCs-based therapies in clinics is gaining interest in the field of bone regeneration due to the clinical improvements exhibited by patients affected by bone-related diseases, such as Osteogenesis Imperfecta (OI) after MSCs administrations [8,[10][11][12].…”

“…The features of mesenchymal stem cells (MSCs), such as their capacity to undergo osteogenic differentiation, immunomodulatory potential, and trophic effects, make them quite attractive components for these bone constructs [8,9]. In fact, the use of MSCs-based therapies in clinics is gaining interest in the field of bone regeneration due to the clinical improvements exhibited by patients affected by bone-related diseases, such as Osteogenesis Imperfecta (OI) after MSCs administrations [8,[10][11][12]. However, there are still some limitations to the clinical translation of MSCs, such as the large number of cells that are required as well as the high cellular heterogeneity, even within populations of MSCs from the same donor.…”

Gut Metabolite Urolithin A Inhibits Osteoclastogenesis and Senile Osteoporosis by Enhancing the Autophagy Capacity of Bone Marrow Macrophages

“…Osteoporosis is a systemic metabolic bone disease, and its etiology has been determined over the course of many years ( Macías et al, 2021 ). Senile osteoporosis (SOP) often occurs in people over 70 years old and is an inevitable degenerative disease with aging.…”