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

  • Ki-Hyun Cho
  • Bijay Singh
  • Sushila Maharjan
  • Yoonjeong Jang
  • Yun-Jaie Choi
  • Chong-Su ChoEmail author
Original Article

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.

Keywords

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

Notes

Acknowledgements

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Minister of Science, ICT and Future Planning (MIST) (NRF-2014R1A1A2007163).

Compliance with ethical standards

Conflict of interest

The authors have no potential conflicts of interest.

Ethical statement

This study was conducted under the approval of animal ethics committee at Seoul National University (SNU-130520-7).

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Copyright information

© The Korean Tissue Engineering and Regenerative Medicine Society and Springer Science+Business Media Dordrecht 2017

Authors and Affiliations

  • Ki-Hyun Cho
    • 1
  • Bijay Singh
    • 1
    • 2
  • Sushila Maharjan
    • 1
    • 2
  • Yoonjeong Jang
    • 3
  • Yun-Jaie Choi
    • 1
  • Chong-Su Cho
    • 1
    Email author
  1. 1.Department of Agricultural Biotechnology, Research Institute for Agriculture and Life SciencesSeoul National UniversitySeoulKorea
  2. 2.Research Institute for Bioscience and BiotechnologyKathmanduNepal
  3. 3.Research Institute for Veterinary Science and College of Veterinary MedicineSeoul National UniversitySeoulKorea

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