Linking the Transcriptional Landscape of Bone Induction to Biomaterial Design Parameters

Abstract

New engineering possibilities allow biomaterials to serve as active orchestrators of the molecular and cellular events of tissue regeneration. Here, the molecular control of tissue regeneration for calcium phosphate (CaP)-based materials is established by defining the parameters critical for tissue induction and those are linked to the molecular circuitry controlling cell physiology. The material properties (microporosity, ion composition, protein adsorption) of a set of synthesized osteoinductive and noninductive CaP ceramics are parameterized and these properties are correlated to a transcriptomics profile of osteogenic cells grown on the materials in vitro. Using these data, a genetic network controlling biomaterial-induced bone formation is built. By isolating the complex material properties into single-parameter test conditions, it is verified that a subset of these genes is indeed controlled by surface topography and ions released from the ceramics, respectively. The gene network points to a decisive role for extracellular matrix deposition in osteoinduction by genes such as tenascin C and hyaluronic acid synthase 2, which are controlled by calcium and phosphate ions as well as surface topography. This work provides insight into the biomaterial composition and material engineering aspects of bone void filling and can be used as a strategy to explore the interface between biomaterials and tissue regeneration.

The Components of Bone and What They Can Teach Us about Regeneration

“…Although it is not clear exactly how this works, the bone-inducing mechanism of such ceramics has started to be elucidated. Factors, such as chemistry and topography, are being isolated and systematically studied [ 108 , 109 , 110 , 111 ]. Undoubtedly, calcium phosphate materials have been, and will be, used extensively in many bone regeneration strategies.…”

Effect of the nano/microscale structure of biomaterial scaffolds on bone regeneration

“…22 Biomaterial fabrication methods include salt leaching, gas foaming, lyophilization technique, electrospinning, additive manufacturing (AM) technologies, and self-assembly. 7,22,23 Thereinto, salt leaching, gas foaming and lyophilization techniques have been applied to produce porous scaffolds and change pore parameters while designing scaffolds. In the salt leaching method, pore sizes are controlled through using some porogens, such as wax, salt, and sugars; in the gas foaming technique, a porous structure is produced by using high-pressure carbon dioxide and controlling gas amount; while in the lyophilization technique, scaffolds are designed via the sublimation of the desired concentration of a solution.…”

How Not To Drown in Data: A Guide for Biomaterial Engineers

“…Gene expression analysis has been used to identify hub genes which, upon activation, trigger ectopic bone formation on calcium scaffolds in vivo [15]. In another study, MG63 cells were cultured on a variety of osteoinductive and non-osteoinductive biomaterials, and gene pathway and network exploration tools were employed to construct a signaling map of osteogenesis on biomaterials [16].…”