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High concentration of ascorbic acid (vitamin C) has been found in corneal epithelium of various species. However, the specific functions and mechanisms of ascorbic acid in the repair of corneal epithelium are not clear. In this study, it was found that ascorbic acid accelerates corneal epithelial wound healing in vivo in mouse. In addition, ascorbic acid enhanced the stemness of cultured mouse corneal epithelial stem/progenitor cells (TKE2) in vitro, as shown by elevated clone formation ability and increased expression of stemness markers (especially p63 and SOX2). The contribution of ascorbic acid on the stemness enhancement was not dependent on the promotion of Akt phosphorylation, as concluded by using Akt inhibitor, nor was the stemness found to be dependent on the regulation of oxidative stress, as seen by the use of two other antioxidants (GMEE and NAC). However, ascorbic acid was found to promote extracellular matrix (ECM) production, and by using two collagen synthesis inhibitors (AzC and CIS), the increased expression of p63 and SOX2 by ascorbic acid was decreased by around 50%, showing that the increased stemness by ascorbic acid can be attributed to its regulation of ECM components. Moreover, the expression of p63 and SOX2 was elevated when TKE2 cells were cultured on collagen I coated plates, a situation that mimics the in vivo situation as collagen I is the main component in the corneal stroma. This study shows direct therapeutic benefits of ascorbic acid on corneal epithelial wound healing and provides new insights into the mechanisms involved. Stem Cells Translational Medicine 2017;6:1356–1365

The optimal functionality of the native corneal stroma is mainly dependent on the well-ordered arrangement of extracellular matrix (ECM) and the pressurized structure. In order to develop an in vitro corneal model, it is crucial to mimic the in vivo microenvironment of the cornea. In this study, the influence of surface topography and mechanical strain on keratocyte phenotype and ECM formation within a biomimetic 3D corneal model is studied. By modifying the surface topography of materials, it is found that patterned silk fibroin film with 600 grooves mm -1 optimally supports cell alignment and ECM arrangement. Furthermore, treatment with 3% dome-shaped mechanical strain, which resembles the shape and mechanics of native cornea, significantly enhances the expression of keratocyte markers as compared to flat-shaped strain. Accordingly, a biomimetic 3D corneal model, in the form of a collagen-modified, silk fibroin-patterned construct subjected to 3% domeshaped strain, is created. Compared to traditional 2D cultures, it supports a significantly higher expression of keratocyte and ECM markers, and in conclusion better maintains keratocyte phenotype, alignment, and fusiform cell shape. Therefore, the novel biomimetic 3D corneal model developed in this study serves as a useful in vitro 3D culture model to improve current 2D cultures for corneal studies.The outermost epithelium, Bowman's layer, the stroma, Descemet's membrane, and the innermost endothelium. [2] The stroma, which constitutes up to 90% of the corneal thickness, is composed of well-organized collagen fibrils and quiescent stromal cells called keratocytes. [3,4] The structure of the stroma is important for the transparency and consequently the vision. The properties of the stroma are based on the combination of the orthogonal lamellar arrangement of aligned collagen fibrils (mainly collagen I and V) [5][6][7][8] and the spacing of these fibrils and the regulation of collagen diameter achieved by proteoglycans (such as lumican and keratocan). [9][10][11][12] It has been shown that keratocytes during in vitro cell culture conditions easily differentiate, as shown by reduced expression of the typical keratocyte markers, including keratocan, CD34, and ALDH3A1. [13,14] However, most of the in vitro corneal studies are conducted on 2D monolayers. [15][16][17] To overcome the limitations of 2D monolayer cell cultures, several 3D corneal in vitro models have been developed using tissue-engineered strategies and a number of biomaterials, such as colla gen, silk, chitosan, and other synthetic polymers. [14,18] Among the various materials, collagen is the most commonly used, as it is the main constituent of native cornea, and collagen-based corneal 3D models have shown promising results as substrates for the culture of corneal cells. [19][20][21] However, few of the 3D corneal in vitro models can replicate the in vivo microenvironment of the native cornea, due to the complexity of the corneal structure and the uniqueness of the mechanical environment created by the ...

No abstract

Large-sized bone defects are a great challenge in clinics and considerably impair the quality of patients’ daily life. Tissue engineering strategies using cells, scaffolds, and bioactive molecules to regulate the microenvironment in bone regeneration is a promising approach. Zinc, magnesium, and iron ions are natural elements in bone tissue and participate in many physiological processes of bone metabolism and therefore have great potential for bone tissue engineering and regeneration. In this review, we performed a systematic analysis on the effects of zinc, magnesium, and iron ions in bone tissue engineering. We focus on the role of these ions in properties of scaffolds (mechanical strength, degradation, osteogenesis, antibacterial properties, etc.). We hope that our summary of the current research achievements and our notifications of potential strategies to improve the effects of zinc, magnesium, and iron ions in scaffolds for bone repair and regeneration will find new inspiration and breakthroughs to inspire future research.