Tissue Eng Regen Med.  2017 Jun;14(3):211-220. 10.1007/s13770-017-0059-9.

Local Delivery of CTGF siRNA with Poly(sorbitol-co-PEI) Reduces Scar Contraction in Cutaneous Wound Healing

• Cho KH
• Singh B
• Maharjan1
• Jang Y
• Choi YJ
• Cho CS

• KMID: 2395078
• DOI: http://doi.org/10.1007/s13770-017-0059-9

Abstract

Healing process in scarring inevitably produces a considerable amount of non-organized dense collagen-rich matrix called scar thus impairing the native structure of skin. Connective tissue growth factor (CTGF) overexpression within healing tissues is known to play an imperative role in collagen production stimulated by transforming growth factor-beta in cutaneous wound healing. Undoubtedly, the knockdown of CTGF expression through siRNA-mediated gene silencing could simply impede the scarring process. However, the less stability and low transfection of siRNAs themselves urge a safe carrier to protect and transfect them into cells at a high rate avoiding toxicities. Here, we developed a degradable poly(sorbitol-co-PEI) (PSPEI), prepared by polymerization of sorbitol diacrylate with low molecular weight polyethylenimine, which has high transfection efficiency but low cytotoxicity, and utilized it in siCTGF delivery to silence the expression of CTGF in an animal model of cutaneous wound healing. Unlike contracted scar in normal healing, there was no or less contraction in the healed skin of mice treated with siCTGF using PSPEI. Histologically, the healed tissues also had distinct papillary structures and dense irregular connective tissues that were lacking in the control scar tissues. This study exemplifies a successful treatment of cutaneous wound healing using a polymer system coupled with RNA interference. Hence, the approach holds a great promise for developing new treatments with novel targets in regenerative medicines.

Keyword

Connective tissue growth factor; Poly(sorbitol-co-PEI); siRNA; Scar contraction; Wound healing

MeSH Terms

Animals
Cicatrix*
Collagen
Connective Tissue
Connective Tissue Growth Factor
Gene Silencing
Mice
Models, Animal
Molecular Weight
Polyethyleneimine
Polymerization
Polymers
Regenerative Medicine
RNA Interference
RNA, Small Interfering*
Skin
Sorbitol
Transfection
Wound Healing*
Wounds and Injuries*
Collagen
Connective Tissue Growth Factor
Polyethyleneimine
Polymers
RNA, Small Interfering
Sorbitol