title: Helicoidal multi-lamellar features of RGD-functionalized silk biomaterials for corneal tissue engineering.
abstract: RGD-coupled silk protein-biomaterial lamellar systems were prepared and studied with human cornea fibroblasts (hCFs) to match functional requirements. A strategy for corneal tissue engineering was pursued to replicate the structural hierarchy of human corneal stroma within thin stacks of lamellae-like tissues, in this case constructed from scaffolds constructed with RGD-coupled, patterned, porous, mechanically robust and transparent silk films. The influence of RGD-coupling on the orientation, proliferation, ECM organization, and gene expression of hCFs was assessed. RGD surface modification enhanced cell attachment, proliferation, alignment and expression of both collagens (type I and V) and proteoglycans (decorin and biglycan). Confocal and histological images of the lamellar systems revealed that the bio-functionalized silk human cornea 3D constructs exhibited integrated corneal stroma tissue with helicoidal multi-lamellar alignment of collagen-rich and proteoglycan-rich extracellular matrix, with transparency of the construct. This biomimetic approach to replicate corneal stromal tissue structural hierarchy and architecture demonstrates a useful strategy for engineering human cornea. Further, this approach can be exploited for other tissue systems due to the pervasive nature of such helicoids in most human tissues.
authors.affiliation: Department of Biomedical Engineering, School of Engineering, Tufts University, 4 Colby St Medford, MA 02155, USA.
authors.forename: Eun Seok
authors.initials: ES
authors.lastname: Gil
authors.forename: Biman B
authors.initials: BB
authors.lastname: Mandal
authors.forename: Sang-Hyug
authors.initials: SH
authors.lastname: Park
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Marchant
authors.forename: Fiorenzo G
authors.initials: FG
authors.lastname: Omenetto
authors.forename: David L
authors.initials: DL
authors.lastname: Kaplan
mesh_terms: D001672:Biocompatible Materials / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D003315:Cornea / Q000187:drug effects / Q000502:physiology*; D003319:Corneal Stroma / Q000166:cytology / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D009842:Oligopeptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D047011:Silk / Q000737:chemistry* / Q000494:pharmacology*; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D001672:Biocompatible Materials; D015415:Biomarkers; D009842:Oligopeptides; D012333:RNA, Messenger; D047011:Silk; C047981:arginyl-glycyl-aspartic acid; D004247:DNA
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