PMID- 37601810
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230918
IS  - 2041-7314 (Print)
IS  - 2041-7314 (Electronic)
IS  - 2041-7314 (Linking)
VI  - 14
DP  - 2023 Jan-Dec
TI  - Promoting angiogenesis and diabetic wound healing through delivery of protein 
      transduction domain-BMP2 formulated nanoparticles with hydrogel.
PG  - 20417314231190641
LID - 10.1177/20417314231190641 [doi]
LID - 20417314231190641
AB  - 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 
      alpha-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.
CI  - (c) The Author(s) 2023.
FAU - Suh, Jae Wan
AU  - Suh JW
AUID- ORCID: 0000-0001-9386-6484
AD  - Department of Orthopaedic Surgery, Dankook University College of Medicine, 
      Cheonan, South Korea.
FAU - Lee, Kyoung-Mi
AU  - Lee KM
AD  - Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul, 
      South Korea.
FAU - Ko, Eun Ae
AU  - Ko EA
AD  - Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul, 
      South Korea.
FAU - Yoon, Dong Suk
AU  - Yoon DS
AD  - Department of Biomedical Science, Hwasung Medi-Science University, Hwaseong-Si, 
      Gyeonggi-Do, South Korea.
FAU - Park, Kwang Hwan
AU  - Park KH
AUID- ORCID: 0000-0002-2110-0559
AD  - Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul, 
      South Korea.
FAU - Kim, Hyun Sil
AU  - Kim HS
AD  - Department of Oral Pathology, Oral Cancer Research Institute, Yonsei University 
      College of Dentistry, Seoul, South Korea.
FAU - Yook, Jong In
AU  - Yook JI
AD  - Department of Oral Pathology, Oral Cancer Research Institute, Yonsei University 
      College of Dentistry, Seoul, South Korea.
FAU - Kim, Nam Hee
AU  - Kim NH
AD  - Department of Oral Pathology, Oral Cancer Research Institute, Yonsei University 
      College of Dentistry, Seoul, South Korea.
FAU - Lee, Jin Woo
AU  - Lee JW
AD  - Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul, 
      South Korea.
AD  - Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of 
      Medicine, Seoul, South Korea.
LA  - eng
PT  - Journal Article
DEP - 20230816
PL  - England
TA  - J Tissue Eng
JT  - Journal of tissue engineering
JID - 101550131
PMC - PMC10434183
OTO - NOTNLM
OT  - Diabetic wound healing
OT  - angiogenesis
OT  - bone morphogenetic protein-2
OT  - lipid nanoparticle
OT  - protein transduction domain
COIS- The author(s) declared the following potential conflicts of interest with respect 
      to the research, authorship, and/or publication of this article: J.I.Y. is an 
      inventor of the patent related to this work filed by MET Life Sciences Co., Ltd. 
      (Korean Patent Number: 10-2227966, PCT Application Number: PCT/KR2020/007011). 
      N.H.K., H.S.K., and J.I.Y. are the founders of MET Life Sciences Co., Ltd. and 
      shareholders. All other authors declare that they have no competing interests.
EDAT- 2023/08/21 06:42
MHDA- 2023/08/21 06:43
PMCR- 2023/08/16
CRDT- 2023/08/21 05:06
PHST- 2023/04/25 00:00 [received]
PHST- 2023/07/12 00:00 [accepted]
PHST- 2023/08/21 06:42 [pubmed]
PHST- 2023/08/21 06:43 [medline]
PHST- 2023/08/21 05:06 [entrez]
PHST- 2023/08/16 00:00 [pmc-release]
AID - 10.1177_20417314231190641 [pii]
AID - 10.1177/20417314231190641 [doi]
PST - epublish
SO  - J Tissue Eng. 2023 Aug 16;14:20417314231190641. doi: 10.1177/20417314231190641. 
      eCollection 2023 Jan-Dec.