Designer protein-based scaffolds for neural tissue engineering.
A key attribute missing from many current biomaterials is the ability to independently tune multiple biomaterial properties without simultaneously affecting other material parameters. Because cells are well known to respond to changes in the initial elastic modulus, degradation rate, and cell adhesivity of a biomaterial, it is critical to develop synthetic design strategies that allow decoupled tailoring of each individual parameter in order to systematically optimize cell-scaffold interactions. We present the development of a family of biomimetic scaffolds composed of chemically crosslinked, elastin-like proteins designed to support neural regeneration through a combination of cell adhesion and cell-induced degradation and remodeling. Through use of a modular protein-design strategy, a range of biomaterials is created that allows independent tuning over the initial elastic modulus, degradation rate, cell adhesivity, and neurite outgrowth. By combining these engineered proteins into composite structures, biomaterials are created with 3D patterns that emerge over time in response to cell-secreted enzymes. These dynamic 3D structures enable the delivery of multiple drugs with precise spatial and temporal resolution and also enable the design of biomaterials that adapt to changing scaffold needs.
Straley
Karin
K
Stanford University, Stanford, CA 94305, USA.
Heilshorn
Sarah C
SC
D001672:Biocompatible Materials; D032701:Biomimetics; D002448:Cell Adhesion; D002468:Cell Physiological Phenomena; D002477:Cells / Q000166:cytology*; D004549:Elastin / Q000032:analysis / Q000737:chemistry; D005353:Fibronectins / Q000096:biosynthesis / Q000737:chemistry; D006801:Humans; D009416:Nerve Regeneration / Q000502:physiology*; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D017933:Peripheral Nervous System / Q000502:physiology / Q000503:physiopathology; D011994:Recombinant Proteins / Q000096:biosynthesis; D013119:Spinal Cord Injuries / Q000503:physiopathology / Q000628:therapy; D023822:Tissue Engineering / Q000379:methods*; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D054457:Tissue Scaffolds; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D001672:Biocompatible Materials; D005353:Fibronectins; D011994:Recombinant Proteins; D004549:Elastin; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator