-PTD-BMP2-loaded dressing enhanced wound closure in diabetic mice.
LNP-PTD-BMP2 induced greater tube formation in human umbilical vein endothelial cells compared to control and rhBMP2.
LNP-PTD-BMP2 increased the recruitment capacity of skin cells involved in healing.
Wounds treated with LNP-PTD-BMP2 showed improved re-epithelialization rates and higher collagen deposition.
Treatment with LNP-PTD-BMP2 resulted in greater neovascularization, indicated by more CD31- and α-SMA-positive cells.
LNP-PTD-BMP2 exhibited a longer half-life than rhBMP2 and localized around wounds.
Simplified
Decreased 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 (). We aimed to determine whether a 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.
Key numbers
4.1×
Increase in Collagen Deposition
Collagen deposition in -PTD-BMP2 group compared to rhBMP2 group.
81.3%
Wound Closure Rate
Wound gap closure in HaCaT cells treated with -PTD-BMP2 at 48 hours.
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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.
