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Promoting angiogenesis and diabetic wound healing through delivery of protein transduction domain-BMP2 formulated nanoparticles with hydrogel

Authors
 Jae Wan Suh  ;  Kyoung-Mi Lee  ;  Eun Ae Ko  ;  Dong Suk Yoon  ;  Kwang Hwan Park  ;  Hyun Sil Kim  ;  Jong In Yook  ;  Nam Hee Kim  ;  Jin Woo Lee 
Citation
 JOURNAL OF TISSUE ENGINEERING, Vol.14, 2023-08 
Journal Title
JOURNAL OF TISSUE ENGINEERING
Issue Date
2023-08
Keywords
Diabetic wound healing ; angiogenesis ; bone morphogenetic protein-2 ; lipid nanoparticle ; protein transduction domain
Abstract
Decreased angiogenesis contributes to delayed wound healing in diabetic patients. Recombinant human bone morphogenetic protein-2 (rhBMP2) has also been demonstrated to promote angiogenesis. However, the short half-lives of soluble growth factors, including rhBMP2, limit their use in wound-healing applications. To address this limitation, we propose a novel delivery model using a protein transduction domain (PTD) formulated in a lipid nanoparticle (LNP). We aimed to determine whether a gelatin hydrogel dressing loaded with LNP-formulated PTD-BMP2 (LNP-PTD-BMP2) could enhance the angiogenic function of BMP2 and improve diabetic wound healing. In vitro, compared to the control and rhBMP2, LNP-PTD-BMP2 induced greater tube formation in human umbilical vein endothelial cells and increased the cell recruitment capacity of HaCaT cells. We inflicted large, full-thickness back skin wounds on streptozotocin-induced diabetic mice and applied gelatin hydrogel (GH) cross-linked by microbial transglutaminase containing rhBMP2, LNP-PTD-BMP2, or a control to these wounds. Wounds treated with LNP-PTD-BMP2-loaded GH exhibited enhanced wound closure, increased re-epithelialization rates, and higher collagen deposition than those with other treatments. Moreover, LNP-PTD-BMP2-loaded GH treatment resulted in more CD31- and α-SMA-positive cells, indicating greater neovascularization capacity than rhBMP2-loaded GH or GH treatments alone. Furthermore, in vivo near-infrared fluorescence revealed that LNP-PTD-BMP2 has a longer half-life than rhBMP2 and that BMP2 localizes around wounds. In conclusion, LNP-PTD-BMP2-loaded GH is a viable treatment option for diabetic wounds.
Files in This Item:
T202305494.pdf Download
DOI
10.1177/20417314231190641
Appears in Collections:
2. College of Dentistry (치과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Orthopedic Surgery (정형외과학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Nam Hee(김남희) ORCID logo https://orcid.org/0000-0002-3087-5276
Kim, Hyun Sil(김현실) ORCID logo https://orcid.org/0000-0003-3614-1764
Park, Kwang Hwan(박광환) ORCID logo https://orcid.org/0000-0002-2110-0559
Yook, Jong In(육종인) ORCID logo https://orcid.org/0000-0002-7318-6112
Lee, Kyoung Mi(이경미) ORCID logo https://orcid.org/0000-0002-9038-8162
Lee, Jin Woo(이진우) ORCID logo https://orcid.org/0000-0002-0293-9017
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/196473
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