Helicoidal multi-lamellar features of RGD-functionalized silk biomaterials for corneal tissue engineering.
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.
Gil
Eun Seok
ES
Department of Biomedical Engineering, School of Engineering, Tufts University, 4 Colby St Medford, MA 02155, USA.
Mandal
Biman B
BB
Park
Sang-Hyug
SH
Marchant
Jeffrey K
JK
Omenetto
Fiorenzo G
FG
Kaplan
David L
DL
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
D001672:Biocompatible Materials; D015415:Biomarkers; D009842:Oligopeptides; D012333:RNA, Messenger; D047011:Silk; C047981:arginyl-glycyl-aspartic acid; D004247:DNA
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