Nanoceria Can Act as the Cues for Angiogenesis in Tissue-Engineering Scaffolds: Toward Next-Generation in Situ Tissue Engineering

Abstract

Next-generation tissue engineering exploits the body’s own regenerative capacity by providing an optimal niche via a scaffold for the migration and subsequent proliferation of endogenous cells to the site of injury, enhancing regeneration and healing and bypassing laborious in vitro cell-culturing procedures. Such systems are also required to have a sufficient angiogenic capacity for the subsequent patency of implanted scaffolds. The exploitation of redox properties of nanodimensional ceria (nCeO2) in in situ tissue engineering to promote cell adhesion and angiogenesis is poorly investigated. As a novel strategy, electrospun polycaprolactone based tissue-engineering scaffolds loaded with nCeO2 were developed and evaluated for morphological and physicomechanical features. In addition, in vitro and in vivo studies were performed to show the ability of nCeO2-containing scaffolds to enhance cell adhesion and angiogenesis. These studies confirmed that nCeO2-containing scaffolds supported cell adhesion and angiogenesis better than bare scaffolds. Gene-expression studies had shown that angiogenesis-related factors such as HIF1α and VEGF were up-regulated. Overall results show that incorporation of nCeO2 plays a key role in scaffolds for the enhancement of angiogenesis, cell adhesion, and cell proliferation and can produce a successful outcome in in situ tissue engineering.

Cerium- and Iron-Oxide-Based Nanozymes in Tissue Engineering and Regenerative Medicine

“…In situ tissue engineering does not incorporate cells into their materials, but rather utilizes the body's own regenerative capacity [85]. Polycaprolactone (PCL) scaffolds were fabricated by electrospinning, incorporating different percentages (w/w) of CO-NPs (PCL-CO-NPs) [86]. As shown in Figure 3A, highly porous networks of PCL-CO-NPs fibers were obtained.…”

“…Expression of hypoxia-inducing factor 1α (HIF-1α) (F), vascular endothelial growth factor (VEGF) (G), tumor necrosis factor α (TNF-α) (H), and cyclooxygenase (COX) (I) in tissues isolated from implanted scaffolds; * p < 0.05, ** p < 0.001, *** p < 0.0001 vs. control. Reprinted with permission from Reference[86]. Copyright 2018, American Chemical Society.…”

<p>Silver Decorated Mesoporous Carbons for the Treatment of Acute and Chronic Wounds, in a Tissue Regeneration Context</p>

“…79,80 Several studies in literature report ability of different nanomaterials in exerting pro-angiogenic effects. In particular, gene expression analysis results concerning increased VEGF show Copper, Cerium or Yttriumcontaining nanoparticles to act through an hypoxia-induced mechanism, [81][82][83] whereas ZnO or Europium hydroxide nanoparticles to act through direct Ros generation. 84,85 Silver-doped C3 materials showed a significant VEGFA increase in transcript levels, as compared to untreated cells at both time points, in comparison to polystyrene, particularly at 7 days (1.42, 1.14 and 1.76-fold -p<0.0001; p<0.01; p<0.0001 for C3, C3Ag2 and C3Ag10, respectively), thus showing their angiogenic potential as well ( Figure 12A).…”

Cerium Oxide Nanoparticles (Nanoceria): Hopes in Soft Tissue Engineering

“…Incorporating CNPs into polymeric matrices is also a common method to make composites for diverse tissue engineering applications, such as accelerated excisional wound healing [ 22 ]. Moreover, three-dimensional (3D) engineered scaffolds containing CNPs were found to be suitable substitutes for replacing damaged skin tissue [ 23 , 24 ]. As the application of hard materials in soft tissue engineering brings new hope in the concept of modern therapies, we tried to clearly show the pros and cons of CNPs in reconstructive strategies applied for the skin, cardiac, neural, and ophthalmic tissues.…”