Enhancing Diabetic Wound Healing Through Improved Angiogenesis: The Role of Emulsion-Based Core-Shell Micro/Nanofibrous Scaffold with Sustained CuO Nanoparticle Delivery

被引:11
|
作者
Alizadeh, Sanaz [1 ,2 ]
Samadikuchaksaraei, Ali [3 ]
Jafari, Davod [3 ]
Orive, Gorka [4 ,5 ,6 ,7 ]
Dolatshahi-Pirous, Alireza [8 ]
Pezeshki-Modaress, Mohamad [9 ,10 ,11 ]
Gholipourmalekabadi, Mazaher [1 ,2 ,3 ,12 ]
机构
[1] Iran Univ Med Sci, Cellular & Mol Res Ctr, Tehran 1449614535, Iran
[2] Iran Univ Med Sci IUMS, Fac Adv Technol Med, Dept Tissue Engn & Regenerat Med, Tehran, Iran
[3] Iran Univ Med Sci, Fac Allied Med, Dept Med Biotechnol, Tehran 1449614535, Iran
[4] Univ Basque Country UPV EHU, Sch Pharm, Lab Pharmaceut, NanoBioCel Grp, Paseo Univ 7, Vitoria 01006, Spain
[5] Biomed Res Networking Ctr Bioengn Biomat & Nanomed, Zaragoza, Spain
[6] UPV EHU Fdn Eduardo Anitua, Univ Inst Regenerat Med & Oral Implantol UIRMI, Vitoria, Spain
[7] NanoBioCel Res Grp, Bioaraba, Vitoria, Spain
[8] Tech Univ Denmark, Dept Hlth Technol, DK-2800 Lyngby, Denmark
[9] Iran Univ Med Sci, Burn Res Ctr, Tehran 1449614535, Iran
[10] Iran Univ Med Sci, Sch Med, Hazrat Fatemeh Hosp, Dept Plast & Reconstruct Surg, Tehran 1449614535, Iran
[11] Iran Univ Med Sci, Stem Cell & Regenerat Med Res Ctr, Tehran 1449614535, Iran
[12] Noavarn Salamat ZHINO PHC, NanoBiotechnol & Regenerat Med Innovat Grp, Tehran 1949635882, Iran
关键词
angiogenesis; copper; core-shell electrospinning; diabetic wound healing; sustained drug delivery; MECHANICAL-PROPERTIES; SILVER NANOPARTICLES; NANOFIBERS; NANOCOMPOSITES; ADHESION; RELEASE; GROWTH; MODEL; MATS; SIZE;
D O I
10.1002/smll.202309164
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Attempts are made to design a system for sustaining the delivery of copper ions into diabetic wounds and induce angiogenesis with minimal dose-dependent cytotoxicity. Here, a dual drug-delivery micro/nanofibrous core-shell system is engineered using polycaprolactone/sodium sulfated alginate-polyvinyl alcohol (PCL/SSA-PVA), as core/shell parts, by emulsion electrospinning technique to optimize sustained delivery of copper oxide nanoparticles (CuO NP). Herein, different concentrations of CuO NP (0.2, 0.4, 0.8, and 1.6%w/w) are loaded into the core part of the core-shell system. The morphological, biomechanical, and biocompatibility properties of the scaffolds are fully determined in vitro and in vivo. The 0.8%w/w CuO NP scaffold reveals the highest level of tube formation in HUVEC cells and also upregulates the pro-angiogenesis genes (VEGFA and bFGF) expression with no cytotoxicity effects. The presence of SSA and its interaction with CuO NP, and also core-shell structure sustain the release of the nanoparticles and provide a non-toxic microenvironment for cell adhesion and tube formation, with no sign of adverse immune response in vivo. The optimized scaffold significantly accelerates diabetic wound healing in a rat model. This study strongly suggests the 0.8%w/w CuO NP-loaded PCL/SSA-PVA as an excellent diabetic wound dressing with significantly improved angiogenesis and wound healing. A dual drug-delivery micro/nanofibrous core-shell system is engineered using polycaprolactone/sodium sulfated alginate-polyvinyl alcohol (PCL/SSA-PVA), as core/shell parts, by emulsion electrospinning technique to optimize sustained delivery of copper oxide nanoparticles (CuO NP). PCL/SSA-PVA 0.8Cu is considered an optimized scaffold with excellent sustained release and angiogenic properties for diabetic wound healing and now promises to proceed with clinical investigations.image
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页数:19
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