Spatiotemporal Control Strategies for Bone Formation through Tissue Engineering and Regenerative Medicine Approaches

Abstract

Global increases in life expectancy drive increasing demands for bone regeneration. The gold standard for surgical bone repair is autografting, which enjoys excellent clinical outcomes; however, it possesses significant drawbacks including donor site morbidity and limited availability. Although collagen sponges delivered with bone morphogenetic protein, type 2 (BMP2) are a common alternative or supplement, they do not efficiently retain BMP2, necessitating extremely high doses to elicit bone formation. Hence, reports of BMP2 complications are rising, including cancer promotion and ectopic bone formation, the latter inducing complications such as breathing difficulties and neurologic impairments. Thus, efforts to exert spatial control over bone formation are increasing. Several tissue engineering approaches have demonstrated the potential for targeted and controlled bone formation. These approaches include biomaterial scaffolds derived from synthetic sources, e.g., calcium phosphates or polymers; natural sources, e.g., bone or seashell; and immobilized biofactors, e.g., BMP2. Although BMP2 is the only protein clinically approved for use in a surgical device, there are several proteins, small molecules, and growth factors that show promise in tissue engineering applications. This review profiles the tissue engineering advances in achieving control over the location and onset of bone formation (spatiotemporal control) toward avoiding the complications associated with BMP2.

Engineered Extracellular Vesicles From Human Periodontal-Ligament Stem Cells Increase VEGF/VEGFR2 Expression During Bone Regeneration

“…Moreover, also the age may be important, for example patients less than 2 years old may regenerate calvarial defects, on the contrary, elderly patients possess minor regenerative capacity (Szpalski et al, 2010). Autologous bone grafts represent a gold-standard but show many limitations and for this reason the development of new approaches based on the use of scaffolds and/ or stem cells is under research (Dimitriou et al, 2011; Jin and Lee, 2018; White and Olabisi, 2019). In particular, mesenchymal stem cells (MSCs) and their derivatives, such as conditioned medium (CM) and extracellular vesicles (EVs), in association with biomaterials have shown to be able to regenerate bone tissues, including calvaria defects (Diomede et al, 2018a,b,c,d).…”

Micropatterning biomineralization with immobilized mother of pearl proteins

“…Despite a need to prevent such ectopic bone growth, spatiotemporal control over bone tissue formation as we report herein (Fig. 1 ) is relatively unreported in literature, particularly microspatial control 10 .

Figure 1 Patterned acellular ( A – C ) and osteoblast-directed mineralization ( D – F ) in response to PEG-WSM patterned substrates.

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“…In essence, some nacre proteins could either nucleate calcium or initiate osteogenesis, yet any link between these two processes had not been elucidated. Likewise, in bone biomineralization, although headway has been made in determining which bone-derived proteins are “osteonucleators” and which are osteoinductors, little data exists to elucidate any relationship between acellular mineralization and osteogenic activity, and few studies have directly compared the two processes 10 . This relationship between cell- and protein-mediated processes may further the understanding of microspatial control of bone tissue formation.…”

Ckip‑1 regulates C3H10T1/2 mesenchymal cell proliferation and osteogenic differentiation via Lrp5

“…Bone defects, which can be caused by trauma, infection, tumors or congenital deformation, have been accepted as difficult-to-treat conditions in medicine (1). To date, autologous bone grafting has been regarded as the most common strategy for the treatment of bone defects (2)(3)(4); however, it is considered as a 'wound-repairing-wound' method with disadvantages, such as donor site pain, infection, haemorrhage, nerve damage and limited blood supply (5). The development of cell and molecular biology as well as biomaterial science has enabled the introduction of bone tissue engineering (BTE) as a promising strategy for bone repair (6).…”