Abstract

RIPAMONTI, Ugo  and  DUARTE, Raquel. Inductive surface geometries: Beyond morphogens and stem cells. S. Afr. dent. j. [online]. 2019, vol.74, n.8, pp.421-444. ISSN 0375-1562.  http://dx.doi.org/10.17159/2519-0105/2019/v74no8a1.

The requirement of biomimetic matrices for bone tissue engineering is now to construct functionalized surfaces with bioactive nanotopographical geometric cues. Functionalized surfaces prime stem cells to set into motion gene expression, synthesis and embedding of gene products within the functionalized surfaces. Embedded proteins initiate the spontaneous induction of bone formation without the exogenous application of the soluble osteogenic molecular signals of the transforming growth factor-β (TGF-β) supergene family. Concavities cut by osteoclastogenesis along the surfaces of calcium phosphate-based biomimetic matrices are the driving morphogenetic cues that initiate the induction of bone formation biomimetizing the remodelling cycle of the cortico-cancellous bone. Geometric recognition activates mechano-transducer(s) that generate cytoskeletal motors that deforms the nuclear geometry, ultimately regulating stem cell differentiation. Osteoclastogenesis drives nano-patterned geometric topographies releasing Ca⁺⁺ that induce angiogenesis and cellular differentiation. Expressed and secreted bone morphogenetic proteins (BMPs) are embedded into the implanted substrata initiating the induction of bone formation as a secondary response. Cell attachment to geometrically modified titania' surfaces is controlled by Rho-associated kinase (ROCK) and focal adhesion kinase (FAK) up regulating the transcription factor RUNX2 controlling osteoblasts differentiation and BMPs expression. Geometry is the unifying biological theme of "finding meaning in complexity", a theme that sets morphogenetic inductive cues via nanotopographical surface modifications.

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