Abstract
Bone extracellular matrix (ECM) is a natural composite made of collagen and mineral hydroxyapatite (HA). Dynamic cell-ECM interactions play a critical role in regulating cell differentiation and function. Understanding the principal ECM cues promoting osteogenic differentiation would be pivotal for both bone tissue engineering and regenerative medicine. Altering the mineral content generally modifies the stiffness as well as other physicochemical cues provided by composite materials, complicating the “cause-effect” analysis of resultant cell behaviour. To isolate the contribution of mechanical cues from other HA-derived signals, we developed and characterised composite HA/gelatin scaffolds with different mineral contents along with a set of stiffness-matched HA-free gelatin scaffolds. Samples were seeded with human periosteal derived progenitor cells (PDPCs) and cultured over 7 days, analysing their resultant morphology and gene expression. Our results show that both stiffness and HA contribute to directing PDPC osteogenic differentiation, highlighting the role of stiffness in triggering the expression of osteogenic genes and of HA in accelerating the process, particularly at high concentrations.
Highlights
Bone extracellular matrix (ECM) is a natural composite made of collagen and mineral hydroxyapatite (HA)
Cell morphology was analysed by scanning electron microscopy (SEM), while mRNA levels of genes expressed during the several phases of osteoblast differentiation were selectively assessed using quantitative real time PCR
The compressive modulus (E) of gelatin scaffolds (Gel) scaffolds follows a logarithmic-trend with GTA concentration: in a semi-log domain a linear relation was determined as E = 1 3.51∙log[GTA]
Summary
Bone extracellular matrix (ECM) is a natural composite made of collagen and mineral hydroxyapatite (HA). To isolate the contribution of mechanical cues from other HA-derived signals, we developed and characterised composite HA/gelatin scaffolds with different mineral contents along with a set of stiffness-matched HA-free gelatin scaffolds. To engineer novel biomaterials with an optimal stiffness and with mineral content and organic component capable of directing osteoregeneration, while limiting material-dependent senescent signals which may accelerate age-dependent processes, it would be useful to investigate the individual role of different environmental cues in modulating cell behaviour. To isolate the specific contribution of mechanical cues from the effects of other bulk and surface HA-related signals (e.g. roughness, mineral content) in modulating progenitor cell differentiation towards an osteogenic phenotype we designed composite hydroxyapatite/gelatin (HA/Gel) hydrogel scaffolds containing different amounts of inorganic phase and a parallel set of stiffness-matched HA-free gelatin scaffolds (Gel) crosslinked with various concentrations of glutaraldehyde (GTA)[32,33,34]. We show here that PDPC differentiation is modulated both by HA and substrate stiffness, but HA’s physicochemical signalling is a far more important trigger for osteogenic differentiation at high concentrations than substrate stiffness
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