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Three-dimensional multilayered fibrous constructs for wound healing applications.

ABSTRACT: Electrospun materials are promising scaffolds due to their light-weight, high surface-area and low-cost fabrication, however, such scaffolds are commonly obtained as ultrathin two-dimensional non-woven meshes, lacking on topographical specificity and surface side-dependent properties. Herein, it is reported the production of three-dimensional fibrous materials with an asymmetrical inner structure and engineered surfaces. The manufactured constructs evidence fibrous-based microsized conical protrusions [length: (10 ± 3) × 10(2) ?m; width: (3.8 ± 0.8) × 10(2) ?m] at their top side, with a median peak density of 73 peaks per cm(2), while their bottom side resembles to a non-woven mesh commonly observed in the fabrication of two-dimensional electrospun materials. Regarding their thickness (3.7 ± 0.1 mm) and asymmetric fibrous inner architecture, such materials avoid external liquid absorption while promoting internal liquid uptake. Nevertheless, such constructs also observed the high porosity (89.9%) and surface area (1.44 m(2) g(-1)) characteristic of traditional electrospun mats. Spray layer-by-layer assembly is used to effectively coat the structurally complex materials, allowing to complementary tailor features such as water vapor transmission, swelling ratio and bioactive agent release. Tested as wound dressings, the novel constructs are capable of withstanding (11.0 ± 0.3) × 10(4) kg m(-2) even after 14 days of hydration, while actively promote wound healing (90 ± 0.5% of wound closure within 48 hours) although avoiding cell adhesion on the dressings for a painless removal.

SUBMITTER: Reis TC

PROVIDER: S-EPMC4729609 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Three-dimensional multilayered fibrous constructs for wound healing applications.

Reis Tiago C TC Castleberry Steven S Rego Ana M B AM Aguiar-Ricardo Ana A Hammond Paula T PT

Biomaterials science 20160201 2

Electrospun materials are promising scaffolds due to their light-weight, high surface-area and low-cost fabrication, however, such scaffolds are commonly obtained as ultrathin two-dimensional non-woven meshes, lacking on topographical specificity and surface side-dependent properties. Herein, it is reported the production of three-dimensional fibrous materials with an asymmetrical inner structure and engineered surfaces. The manufactured constructs evidence fibrous-based microsized conical protr ...[more]

PMID: 26584183

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Project description:Development of natural protein-based fibrous scaffolds with tunable physical properties and biocompatibility is highly desirable to construct three-dimensional (3D), fully cellularized scaffolds for wound healing. Herein, we demonstrated a simple and effective technique to construct electrospun 3D fibrous scaffolds for accelerated wound healing using a photocrosslinkable hydrogel based on gelatin methacryloyl (GelMA). We found that the physical properties of the photocrosslinkable hydrogel including water retention, stiffness, strength, elasticity and degradation can be tailored by changing the light exposure time. We further observed that the optimized hydrogel fibrous scaffolds which were soft and elastic could support cell adhesion, proliferation and migration into the whole scaffolds, facilitating regeneration and formation of cutaneous tissues within two weeks. Such tunable characteristics of the fibrous GelMA scaffolds distinguished them from other reported substrates developed for reconstruction of wound defects including glutaraldehyde-crosslinked gelatin or poly (lactic-co-glycolic acid) (PLGA), whose physical and chemical properties were difficult to modify to allow cell infiltration into the 3D scaffolds for tissue regeneration. We anticipate that the ability to become fully cellularized will make the engineered GelMA fibrous scaffolds suitable for widespread applications as skin substitutes or wound dressings.Statement of significanceIn present study, we generate three-dimensional photocrosslinkable gelatin (GelMA)-based fibrous scaffolds with tunable physical and biological properties by using a combined photocrosslinking/electrospinning approach. The developed GelMA fibrous scaffolds can not only support cell viability and cell adhesion, but also facilitate cell migration and proliferation, accelerating regeneration and formation of cutaneous tissues. In addition, the physical properties of the engineered fibrous GelMA hydrogel including water retention capability, mechanical properties and biodegradability can be tuned to accommodate different patients' needs, making it a promising candidate for skin tissue engineering.

Project description:Tissue engineering is an essential component of developing effective regenerative therapies. In this study, we introduce a promising method to create scaffold-free three-dimensional (3D) tissue engineered multilayered microstructures from cultured cells using the "3D tissue fabrication system" (Regenova®; Cyfuse, Tokyo, Japan). This technique utilizes the adhesive nature of cells. When cells are cultured in nonadhesive wells, they tend to aggregate and form a spheroidal structure. The advantage of this approach is that cellular components can be mixed into one spheroid, thereby promoting the formation of extracellular matrices, such as collagen and elastin. This system enables one to create a predesigned 3D structure composed of cultured cells. We found that the advantages of this system to be (1) the length, size, and shape of the structure that were designable and highly reproducible because of the computer controlled robotics system, (2) the graftable structure could be created within a reasonable period (8 days), and (3) the constructed tissue did not contain any foreign material, which may avoid the potential issues of contamination, biotoxicity, and allergy. The utilization of this robotic system enabled the creation of a 3D multilayered microstructure made of cell-based spheres with a satisfactory mechanical properties and abundant extracellular matrix during a short period of time. These results suggest that this new technology will represent a promising, attractive, and practical strategy in the field of tissue engineering. Impact statement The utilization of the "three dimensional tissue fabrication system" enabled the creation of a three-dimensional (3D) multilayered microstructure made of cell-based spheres with a satisfactory mechanical properties and abundant extracellular matrix during a short period of time. These results suggest that this new technology will represent a promising, attractive, and practical strategy in the field of tissue engineering.

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Three-dimensional multilayered fibrous constructs for wound healing applications.

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Three-dimensional multilayered fibrous constructs for wound healing applications.

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