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

IF 6.7 1区 工程技术 Q1 CELL & TISSUE ENGINEERING Journal of Tissue Engineering Pub Date : 2023-01-01 DOI:10.1177/20417314231190641
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
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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.

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通过递送蛋白质转导结构域bmp2配方纳米颗粒与水凝胶促进血管生成和糖尿病伤口愈合。
糖尿病患者血管生成减少导致伤口愈合延迟。重组人骨形态发生蛋白-2 (rhBMP2)也被证明可以促进血管生成。然而,包括rhBMP2在内的可溶性生长因子的半衰期较短,限制了它们在伤口愈合应用中的应用。为了解决这一限制,我们提出了一种新的递送模型,使用在脂质纳米颗粒(LNP)中配制的蛋白质转导结构域(PTD)。我们的目的是确定明胶水凝胶敷料装载lnp配方的PTD-BMP2 (LNP-PTD-BMP2)是否可以增强BMP2的血管生成功能并改善糖尿病伤口愈合。在体外实验中,与对照和rhBMP2相比,lnp - ppd - bmp2诱导人脐静脉内皮细胞更大的管状形成,并增加HaCaT细胞的细胞募集能力。我们对链脲霉素诱导的糖尿病小鼠背部皮肤造成大的全层伤口,并将含有rhBMP2、LNP-PTD-BMP2的微生物转谷氨酰胺酶交联的明胶水凝胶(GH)涂在这些伤口上。与其他治疗相比,使用负载lnp - ppd - bmp - 2的GH治疗的伤口表现出更强的伤口愈合、更高的再上皮化率和更高的胶原沉积。此外,lnp - ppd - bmp2负载GH处理导致更多的CD31-和α- sma阳性细胞,表明比rhbmp2负载GH或单独GH处理更大的新生血管能力。此外,体内近红外荧光显示LNP-PTD-BMP2的半衰期比rhBMP2长,并且BMP2定位于伤口周围。总之,lnp - ptd - bmp2负载GH是治疗糖尿病伤口的可行选择。
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来源期刊
Journal of Tissue Engineering
Journal of Tissue Engineering Engineering-Biomedical Engineering
CiteScore
11.60
自引率
4.90%
发文量
52
审稿时长
12 weeks
期刊介绍: The Journal of Tissue Engineering (JTE) is a peer-reviewed, open-access journal dedicated to scientific research in the field of tissue engineering and its clinical applications. Our journal encompasses a wide range of interests, from the fundamental aspects of stem cells and progenitor cells, including their expansion to viable numbers, to an in-depth understanding of their differentiation processes. Join us in exploring the latest advancements in tissue engineering and its clinical translation.
期刊最新文献
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