title: RNAi functionalized collagen-chitosan/silicone membrane bilayer dermal equivalent for full-thickness skin regeneration with inhibited scarring.
abstract: Scar inhibition of dermal equivalent is one of the key issues for treatment of full thickness skin defects. To yield a bioactive RNAi functionalized matrix for skin regeneration with inhibited scarring, collagen-chitosan/silicone membrane bilayer dermal equivalent (BDE) was combined with trimetylchitosan (TMC)/siRNA complexes which could induce suppression of transforming growth factor-β1 (TGF-β1) pathway. The RNAi-BDE functioned as a reservoir for the incorporated TMC/siRNA complexes, enabling a prolonged siRNA release. The seeded fibroblasts in the RNAi-BDE showed good viability, internalized the TMC/siRNA complexes effectively and suppressed TGF-β1 expression constantly until 14 d. Application of the RNAi-BDE on the full-thickness skin defects of pig backs confirmed the in vivo inhibition of TGF-β1 expression by immunohistochemistry, real-time quantitative PCR and western blotting during 30 d post surgery. The levels of other scar-related factors such as collagen type I, collagen type III and α-smooth muscle actin (α-SMA) were also down-regulated. In combination with the ultra-thin skin graft transplantation for 73 d, the regenerated skin by RNAi-BDE had an extremely similar structure to that of the normal one. Our study reflects the latest paradigm of tissue engineering by incorporating the emerging biomolecule siRNA. The 3-D scaffolding materials for siRNA delivery may have general implications in generation of bioactive matrix as well.
authors.affiliation: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.forename: Lie
authors.initials: L
authors.lastname: Ma
authors.forename: Jun
authors.initials: J
authors.lastname: Liang
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
authors.forename: Jianying
authors.initials: J
authors.lastname: Teng
authors.forename: Changyou
authors.initials: C
authors.lastname: Gao
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002417:Cattle; D048271:Chitosan / Q000494:pharmacology*; D002921:Cicatrix / Q000473:pathology / Q000628:therapy; D003094:Collagen / Q000494:pharmacology*; D020405:Dermis / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008051:Lipid Bilayers / Q000494:pharmacology*; D046529:Microscopy, Electron, Transmission; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012038:Regeneration / Q000187:drug effects*; D012828:Silicones / Q000494:pharmacology*; D017768:Skin, Artificial; D013552:Swine; D013556:Swine, Miniature; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
chemical_list: D008051:Lipid Bilayers; D034741:RNA, Small Interfering; D012828:Silicones; D053773:Transforming Growth Factor beta1; D003094:Collagen; D048271:Chitosan