title: The tissue engineeting puzzle: a molecular perspective.
abstract: The inability of biomaterial scaffolds to functionally integrate into surrounding tissue is one of the major roadblocks to developing new biomaterials and tissue-engineering scaffolds. Despite considerable advances, current approaches to engineering cell-surface interactions fall short in mimicking the complexity of signals through which surrounding tissue regulates cell behavior. Cells adhere and interact with their extracellular environment via integrins, and their ability to activate associated downstream signaling pathways depends on the character of adhesion complexes formed between cells and their extracellular matrix. In particular, alpha5beta1 and alphavbeta3 integrins are central to regulating downstream events, including cell survival and cell-cycle progression. In contrast to previous findings that alphavbeta3 integrins promote angiogenesis, recent evidence argues that alphavbeta3 integrins may act as negative regulators of proangiogenic integrins such as alpha5beta1. This suggests that fibronectin is critical for scaffold vascularization because it is the only mammalian adhesion protein that binds and activates alpha5beta1 integrins. Cells are furthermore capable of stretching fibronectin matrices such that the protein partially unfolds, and recent computational simulations provide structural models of how mechanical stretching affects fibronectin function. We propose a model whereby excessive tension generated by cells in contact to biomaterials may in fact render fibronectin fibrils nonangiogenic and potentially inhibit vascularization. The model could explain why current biomaterials independent of their surface chemistries and textures fail to vascularize.
authors.affiliation: Department of Bioengineering and Center for Nanotechnology, University of Washington, Seattle, Washington 98195, USA. vvogel@u.washington.edu
authors.forename: Viola
authors.initials: V
authors.lastname: Vogel
authors.forename: Gretchen
authors.initials: G
authors.lastname: Baneyx
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D002448:Cell Adhesion / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology*; D005353:Fibronectins / Q000502:physiology*; D006801:Humans; D016023:Integrins / Q000502:physiology*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D019736:Prostheses and Implants; D011475:Prosthesis Failure; D013314:Stress, Mechanical; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D001672:Biocompatible Materials; D005353:Fibronectins; D016023:Integrins