title: 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 marrow-derived 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 biomaterial-based vascularisation approaches and clinical applications.
authors: Institute for Bioengineering of Catalonia, Barcelona, Spain.
authors: Aitor
authors: A
authors: Aguirre
authors: Arlyng
authors: A
authors: González
authors: Melba
authors: M
authors: Navarro
authors: Óscar
authors: Ó
authors: Castaño
authors: Josep A
authors: JA
authors: Planell
authors: Elisabeth
authors: E
authors: Engel
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology*; D001853:Bone Marrow / Q000187:drug effects; D002130:Calcium Phosphates / Q000737:chemistry; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D060833:Cellular Microenvironment; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005898:Glass / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry; D040542:Mechanotransduction, Cellular / Q000187:drug effects* / Q000502:physiology; D024462:Myosin Type II / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011091:Polyesters; D011108:Polymers / Q000737:chemistry; D051381:Rats; D011917:Rats, Inbred Lew; D044169:Receptors, Calcium-Sensing / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D023822:Tissue Engineering; D054457:Tissue Scaffolds; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D002130:Calcium Phosphates; D011091:Polyesters; D011108:Polymers; D044169:Receptors, Calcium-Sensing; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D019344:Lactic Acid; C033616:poly(lactide); C020243:calcium phosphate; D040301:Vascular Endothelial Growth Factor Receptor-2; D024462:Myosin Type II