Article, 2024

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

Small, ISSN 1613-6829, 1613-6810, Volume 20, 24, Page e2309164, 10.1002/smll.202309164

Contributors

Alizadeh, Sanaz [1] Samadikuchaksaraei, Ali 0000-0002-2108-9927 [1] Jafari, Davod [1] Orive, Gorka 0000-0002-0773-300X [2] [3] [4] Dolatshahi-Pirouz, Alireza 0000-0001-6326-0836 [5] Pezeshki-Modaress, Mohamad 0000-0002-3859-1745 (Corresponding author) [1] Gholipourmalekabadi, Mazaher 0000-0001-6287-6831 (Corresponding author) [1] [6]

Affiliations

  1. [1] Iran University of Medical Sciences
    2. [NORA names: Iran; Asia, Middle East];
  2. [2] Bioaraba, NanoBioCel Research Group, Vitoria‐Gasteiz, 01006, Spain
    3. [NORA names: Spain; Europe, EU; OECD];
  3. [3] Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER‐BBN), Vitoria‐Gasteiz, 01006, Spain
    4. [NORA names: Spain; Europe, EU; OECD];
  4. [4] University of the Basque Country
    5. [NORA names: Spain; Europe, EU; OECD];
  5. [5] Technical University of Denmark
    6. [NORA names: DTU Technical University of Denmark; University; Denmark; Europe, EU; Nordic; OECD];

Abstract

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.

Keywords

CuO, CuO NPs, HUVEC cells, HUVECs, NP scaffolds, adhesion, alcohol, angiogenesis, attempt, biocompatibility, biocompatible properties, cell adhesion, cells, concentration, concentrations of CuO NPs, copper ions, copper oxide nanoparticles, core-shell, core-shell structure, core-shell system, cytotoxic effects, cytotoxicity, delivery, delivery of copper ions, diabetic wound dressing, diabetic wound healing, diabetic wounds, dose-dependent cytotoxicity, dressing, effect, electrospinning technique, emulsion, emulsion electrospinning technique, enhanced diabetic wound healing, expression, formation, genes, healing, higher levels, immune responses in vivo, in vitro, in vivo, induce angiogenesis, interaction, ions, levels of tube formation, micro/nanofibrous scaffolds, microenvironment, model, nanoparticle delivery, nanoparticles, oxide nanoparticles, parts, presence, pro-angiogenesis, pro-angiogenesis genes, properties, rat model, rats, release, responses in vivo, scaffolds, structure, study, sustained delivery, system, technique, tube, tube formation, wound, wound dressing, wound healing

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