Two-dimensional nanovermiculite and polycaprolactone electrospun fibers composite scaffolds promoting diabetic wound healing

(2022) 20:343 Huang et al. Journal of Nanobiotechnology https://doi.org/10.1186/s12951-022-01556-w Journal of Nanobiotechnology Open Access RESEARCH Two‑dimensional nanovermiculite and polycaprolactone electrospun fibers composite scaffolds promoting diabetic wound healing Xingtai Huang1†, Qirui Wang2†, Runyi Mao1, Zeying Wang1, Steve G.F. Shen1,3*, Juan Mou4* and Jiewen Dai1* Abstract Background: Promoting diabetic wound healing is still a challenge, and angiogenesis is believed to be essential for diabetic wound healing. Vermiculite is a natural clay material that is very easy to obtain and exhibits excellent properties of releasing bioactive ions, buffering pH, adsorption, and heat insulation. However, there are still many unsolved difficulties in obtaining two-dimensional vermiculite and using it in the biomedical field in a suitable form. Results: In this study, we present a versatile organic–inorganic composite scaffold, which was constructed by embedding two-dimensional vermiculite nanosheets in polycaprolactone electrospun fibers, for enhancing angiogenesis through activation of the HIF-1α signaling pathway and promoting diabetic wound healing both in vitro and in vivo. Conclusions: Together, the rational-designed polycaprolactone electrospun fibers-based composite scaffolds integrated with two-dimensional vermiculite nanosheets could significantly improve neo-vascularization, re-epithelialization, and collagen formation in the diabetic wound bed, thus promoting diabetic wound healing. This study provides a new strategy for constructing bioactive materials for highly efficient diabetic wound healing. Keywords: Electrospun fibers, Vermiculite nanosheets, Diabetic wound healing, Angiogenesis, Composite scaffolds † Xingtai Huang and Qirui Wang contributed equally to this work *Correspondence: ; ; 1 Department of Oral and Cranio‑Maxillofacial Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, No. 639, Zhizaoju Road, 200011 Shanghai, China 3 Shanghai University of Medicine and Health Sciences, Shanghai 201318, China 4 The Key Laboratory of Resource Chemistry of Ministry of Education, Shanghai Key College of Chemistry and Materials Science, Shanghai Normal University, Shanghai 200234, China Full list of author information is available at the end of the article © The Author(s) 2022. 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The Creative Commons Public Domain Dedication waiver (http://creativeco mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Huang et al. Journal of Nanobiotechnology (2022) 20:343 Page 2 of 19 Graphical Abstract Introduction Skin serves as the body’s first line of protection against external environmental elements such as physical, chemical, and biological stimuli [1]. One of the most harmful outcomes of diabetes mellitus is a persistent and nonhealing skin wound [2]. Diabetic wounds are characterized by vascular impairment and delayed wound healing due to the long-term, unfavorable stimulation of high glucose, as opposed to the rapid and systematic healing processes of normal cutaneous wounds [3]. Cells and tissues are deprived of oxygen and nutrients when there is a lack of vasculature and blood circulation [4], and adequate vascularization through a tissue engineering approach may be a possible choice for promoting wound healing [5, 6]. The incorporation of clay minerals for promoting wound healing formulations is supported by its excellent biocompatibility with various skin cell types in previous studies [7, 8]. As a natural clay material, vermiculite (VMT), which exhibits the properties of releasing ions, buffering pH, adsorption, and heat insulation, has been widely used in a variety of applications, such as theranostics [9], energy resource engineering [10], and environmental management [11]. VMT belongs to the 2:1 aluminosilicate family, which consists of an octahedral layer of magnesium oxide (MgO) and ferric oxide (Fe2O3) sandwiched between two identical tetrahedral layers of silicon dioxide (SiO2) and aluminum oxide (Al2O3). The sandwiched layers are closely connected through water or metal ions, forming the three-dimensional (3D) structures of clay particle formations. To prepare two-dimensional (2D) clay nanosheets with the sandwiched layer as a unit, various exfoliation techniques based on breaking the linkage between the sandwiched layers, such as aqueous exfoliation [12], ion-assisted aqueous exfoliation [13], and organic polymer-assisted organic solution exfoliation [14], have been developed. However, there are still many unsolved difficulties. In addition, vermiculite nanosheets (VMT NSs) can be utilized as carriers for the sustained release of bioactive ions [15]. Direct powder application, however, has the disadvantages of being difficult to fix, poor adherence, and being easily detached [16]. Thus, clay nanosheets in two dimensions need to be evenly disseminated in polymers to create hybrid composites [17]. Integrating VMT NSs and polymers together to create a bioactive organic–inorganic hybrid platform may be an effective way of accelerating skin wound healing. The electrospun fibrous membrane has recently generated substantial interest in skin tissue regeneration due to its impressive properties, including extracellular matrixlike structure, porous linked 3D network, huge surfaceto-volume ratio, and customizable surface shape field [18–20]. In a variety of studies, bioactive components such as genes, cytokines, growth factors, and other biomolecules have been incorporated into bioactive electrospun fibrous dressings to accelerate wound healing [21–23]. Unfortunately, the direct addition of ectogenous growth factors into electrospun scaffolds has a number of drawbacks, including protein instability, high costs, and unfavorable side effects [24, 25]. The VMT NSs presented in this study have superior advantages, i (...truncated)