Control of microenvironmental cues with a smart biomaterial composite promotes endothelial progenitor cell angiogenesis

Abstract

Smart biomaterials play a key role when aiming at successful tissue repair by means of regenerative medicine approaches, and are expected to contain chemical as well as mechanical cues that will guide the regenerative process. Recent advances in the understanding of stem cell biology and mechanosensing have shed new light onto the importance of the local microenvironment in determining cell fate. Herein we report the biological properties of a bioactive, biodegradable calcium phosphate glass/polylactic acid composite biomaterial that promotes bone marrowderived endothelial progenitor cell (EPC) mobilisation, differentiation and angiogenesis through the creation of a controlled bone healing-like microenvironment. The angiogenic response is triggered by biochemical and mechanical cues provided by the composite, which activate two synergistic cell signalling pathways: a biochemical one mediated by the calcium-sensing receptor and a mechanosensitive one regulated by non-muscle myosin II contraction. Together, these signals promote a synergistic response by activating EPCs-mediated VEGF and VEGFR-2 synthesis, which in turn promote progenitor cell homing, differentiation and tubulogenesis. These findings highlight the importance of controlling microenvironmental cues for stem/progenitor cell tissue engineering and offer exciting new therapeutical opportunities for biomaterialbased vascularisation approaches and clinical applications.

The proangiogenic potential of a novel calcium releasing biomaterial: Impact on cell recruitment

“…We have recently demonstrated that the release of calcium ions induces the migration, maturation and organization of endothelial progenitors in vitro [10,11,20]. In this line, here we developed a electrospun composite membrane, based on poly(lactic acid), approved for clinical use in a wide range of applications, and calcium phosphate ormoglass nanoparticles, able to provide chemical bioactive cues.…”

“…Indeed, in another approach and using different material conformation (i.e. solvent casting) we could show that this composite could elicit proangiogenic and chemotactic properties on endothelial precursor cells, in vitro [11].…”

3D printed PLA-based scaffolds

“…19 It has been demonstrated that the presence of G5 glass particles not only increases cell attachment and spreading but also triggers angiogenesis and bone formation owing the Ca 2+ release and stiffness of the glass. 22,23 Indeed, several studies have demonstrated the relevant role of ions on tissue regeneration. 24,25 Given that the glass particles incorporated into the polymer scaffold are partially exposed in the surface, as demonstrated by an alizarin red assay (where only the calcified inorganic phase is stained in red color, Fig.…”

Angiogenic effects of ionic dissolution products released from a boron-doped 45S5 bioactive glass

“…[1][2][3][4] Biomaterials have been categorized as rst-, second-and third-generation biomaterials, according to the biological behavior they are able to trigger. First-generation materials show inert (non-bioactive) behavior, whereas second-and third-generation materials show bioactive properties.…”