Regenerative Medicine: A New Paradigm in Bone Regeneration

Abstract

Bone defects are the cause of functional disability and the restoration of skeletal function remains an important challenge on orthopedics, neurosurgery and oral and maxillofacial surgery. Because of the limitations of the currently used techniques for the reconstruction of bone defects and the difficulties for the implementation of new therapeutic strategies, a new paradigm in the field of reconstructive surgery has arisen, leading to tissue engineering and regenerative medicine. Mesenchymal stem cells (MSC) have emerged as a promising alternative for the treatment of bone lesions. It was postulated that the therapeutic action was the result of proliferation and differentiation of MSCs, replacing injured tissue. However, recent studies have shown that MSCs secrete a number of trophic factors that have a strong effect during repair and tissue regeneration. This represents a shift from a paradigm centered on MSC proliferation and differentiation to a new paradigm in which the MSCs exert their beneficial effect by the secretion of paracrine factors that induce endogenous repair mechanisms. This chapter will bring together basic and clinical aspects, focused on novel findings on MSC paracrine effect and the development of new therapeutic strategies based on growth factors, cytokines and signaling molecules involved in bone regeneration.

Prospect of Stem Cell Therapy and Regenerative Medicine in Osteoporosis

“…Cell-based regenerative medicine can be invaluable in osteoporosis treatment through bone resorption modulation, fractures susceptibility reduction, and lost mineral density enhancement. These are possible by increasing the number of progenitor stem cells and improve the function of stem cells (proliferation and differentiation into bone-forming cells) (20,102,105,106). Since the bone tissue repair cascade can be controlled by local signals from various cytokines and growth factors through the inducing osteoprogenitor cells migration, differentiation, proliferation, revascularization, and extracellular matrix production (56,107,108), stem cells (especially MSCs) can support bone regeneration by secreting bioactive molecules such as IGF-1, TGF-β, vascular endothelial growth factor (VEGF), angiogenin, hepatocyte growth factor (HGF), IL-6, and etc.…”

Adjuvant Drug-Assisted Bone Healing: Advances and Challenges in Drug Delivery Approaches

“…Estrogen deficiency reduces bone mineral density, making the bone more fragile. If bone defects are of critical size or patients have an impaired bone healing due to metabolic or inflammatory diseases such as diabetes mellitus and osteoporosis, the defects will not heal completely without additional surgical intervention [1][2][3][4][5][6].…”

“…Bone, as a complex structured tissue, requires a well-orchestrated healing process regarding timeframe and localization. In the literature, the bone healing process and defining molecular pathways are already described extensively [2,3,[6][7][8][9][10][11][12][13]. Briefly, bone regeneration can be sectioned into an inflammatory, reparative, and remodeling phase.…”

“…Although intensive research has been carried out on these concepts, the gap towards translation into clinical application has yet to be closed. Thus, there is an urgent clinical need for smart adjuvant therapy approaches with bone scaffolds being biocompatible, well implantable in host tissue, and suitable as drug delivery platforms [1][2][3][7][8][9][15][16][17].…”

Advanced gelatin-based vascularization bioinks for extrusion-based bioprinting of vascularized bone equivalents

“…In bone tissue engineering (BTE), osteogenic cells, extracellular matrix (ECM) components and various stimuli are combined to build constructs that resemble native bone tissue (BT) in structure and function 1 . Such constructs could be applied to treat in vivo bone defects 2 .…”