Biocompatibility of helicoidal multilamellar arginine-glycine-aspartic acid-functionalized silk biomaterials in a rabbit corneal model

Wang, Liqiang; Ma, Ruijue; Du, Gaiping; Guo, Huiling; Huang, Yifei

doi:10.1002/jbm.b.33192

Cited by 30 publications

(23 citation statements)

References 36 publications

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“…The 3D silk‐based construct we developed has acceptable optical transparency, favorable mechanical strength, and excellent cell biocompatibility, which are the essential properties of an ideal corneal equivalent. It has been reported that patterned silk fibroin film has suitable biocompatibility with the corneal stroma in rabbit . More work needs to be done, including in vivo biocompatibility tests and in situ animal studies to evaluate the potential of this 3D silk‐based construct as a transplant biomaterial for cornea repair.…”

Section: Resultsmentioning

confidence: 99%

Surface Topography and Mechanical Strain Promote Keratocyte Phenotype and Extracellular Matrix Formation in a Biomimetic 3D Corneal Model

Zhang

Chen

Backman

et al. 2016

Adv Healthcare Materials

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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 ...

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Section: Resultsmentioning

confidence: 99%

Surface Topography and Mechanical Strain Promote Keratocyte Phenotype and Extracellular Matrix Formation in a Biomimetic 3D Corneal Model

Zhang

Chen

Backman

et al. 2016

Adv Healthcare Materials

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“…Transplantation with human cadaveric tissue is presently the only treatment option in most cases, but severe tissue shortage has led to an urgent need to develop bioengineered alternatives to donor corneal tissue [2][3][4][5][6][7][8][9][10][11][12]. Natural collagen-derived corneal scaffolds are the most mature of these [13][14][15][16][17][18][19], and we recently reported results from collagen-based scaffolds four years after implantation into diseased human corneas [13].…”

Section: Introductionmentioning

confidence: 99%

Composite core-and-skirt collagen hydrogels with differential degradation for corneal therapeutic applications

et al. 2016

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“…Furthermore, the materials need to sustain the tissue biological functions, therefore supporting cellular growth and organization in 3D, while being implantable in the target site. Silk can be successfully used to answer corneal tissue needs, due to its mechanical and optical properties, its ability to support corneal cell growth and it is well tolerated when implanted intra-stromally [20, 37, 41]. The current biomaterial alternatives mainly rely on nano-fibrillar polyester, natural polymers blended polyethylene glycol and polylactic acid composites, as well as a variety of collagen-based constructs [18, 53–57].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, silk films have been shown to be a suitable materials for corneal stroma reconstruction in a rabbit animal model [41]. Silk films can be further organized in a 3D multi-lamellar architecture for the growth of corneal stromal cells, by optimizing topography, surface chemistry, and the porosity of each layer [37].…”

Section: Introductionmentioning

confidence: 99%

3D Functional Corneal Stromal Tissue Equivalent Based on Corneal Stromal Stem Cells and Multi-Layered Silk Film Architecture

et al. 2017

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The worldwide need for human cornea equivalents continues to grow. Few clinical options are limited to allogenic and synthetic material replacements. We hypothesized that tissue engineered human cornea systems based on mechanically robust, patterned, porous, thin, optically clear silk protein films, in combination with human corneal stromal stem cells (hCSSCs), would generate 3D functional corneal stroma tissue equivalents, in comparison to previously developed 2D approaches. Silk film contact guidance was used to control the alignment and distribution of hCSSCs on RGD-treated single porous silk films, which were then stacked in an orthogonally, multi-layered architecture and cultured for 9 weeks. These systems were compared similar systems generated with human corneal fibroblasts (hCFs). Both cell types were viable and preferentially aligned along the biomaterial patterns for up to 9 weeks in culture. H&E histological sections showed that the systems seeded with the hCSSCs displayed ECM production throughout the entire thickness of the constructs. In addition, the ECM proteins tested positive for keratocyte-specific tissue markers, including keratan sulfate, lumican, and keratocan. The quantification of hCSSC gene expression of keratocyte-tissue markers, including keratocan, lumican, human aldehyde dehydrogenase 3A1 (ALDH3A1), prostaglandin D2 synthase (PTDGS), and pyruvate dehydrogenase kinase, isozyme 4 (PDK4), within the 3D tissue systems demonstrated upregulation when compared to 2D single silk films and to the systems generated with the hCFs. Furthermore, the production of ECM from the hCSSC seeded systems and subsequent remodeling of the initial matrix significantly improved cohesiveness and mechanical performance of the constructs, while maintaining transparency after 9 weeks.

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Biocompatibility of helicoidal multilamellar arginine-glycine-aspartic acid-functionalized silk biomaterials in a rabbit corneal model

Cited by 30 publications

References 36 publications

Surface Topography and Mechanical Strain Promote Keratocyte Phenotype and Extracellular Matrix Formation in a Biomimetic 3D Corneal Model

Surface Topography and Mechanical Strain Promote Keratocyte Phenotype and Extracellular Matrix Formation in a Biomimetic 3D Corneal Model

Composite core-and-skirt collagen hydrogels with differential degradation for corneal therapeutic applications

3D Functional Corneal Stromal Tissue Equivalent Based on Corneal Stromal Stem Cells and Multi-Layered Silk Film Architecture

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