Tissue-engineered dermo-epidermal skin grafts prevascularized with adipose-derived cells

Klar, Agnes S.; Güven, Sinan; Biedermann, Thomas; Luginbühl, Joachim; Böttcher‐Haberzeth, Sophie; Meuli‐Simmen, Claudia; Meuli, Martin; Martín, Iván; Scherberich, Arnaud; Ernst, Rolf

doi:10.1016/j.biomaterials.2014.02.049

Cited by 148 publications

(145 citation statements)

References 66 publications

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“…[25] Fibrin is a versatile biopolymer that has a critical role in blood clotting, cellular-matrix interactions, wound healing, and angiogenesis, [29][30][31] and is widely used as a biomaterial for engineered adipose, dermal, and cardiovascular tissues. [32][33][34] Like most other natural materials though, the main disadvantages of using fibrin as a scaffold are low mechanical stiffness and rapid degradation, [35,36] both of which can be mitigated by incorporation of PEG, an FDA-approved polymer with a wide range of medical and industrial applications. [25,37,38] Based on this data, we hypothesized that subcutaneously injecting AFSC-seeded fibrin/PEG hydrogels in immunodeficient mice would both induce a fibrin-driven angiogenic response and promote AFSC-derived neovascularization.…”

mentioning

confidence: 99%

In situ vascularization of injectable fibrin/poly(ethylene glycol) hydrogels by human amniotic fluid‐derived stem cells

Benavides

Brooks

Cho

et al. 2015

J Biomedical Materials Res

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One of the greatest challenges in regenerative medicine is generating clinically-relevant engineered tissues with functional blood vessels. Vascularization is a key hurdle faced in designing tissue constructs larger than the in vivo limit of oxygen diffusion. In this study, we utilized fibrin-based hydrogels as a foundation for vascular formation, poly(ethylene glycol) (PEG) to modify fibrinogen and increase scaffold longevity, and human amniotic fluid-derived stem cells (AFSC) as a source of vascular cell types (AFSC-EC). AFSC hold great potential for use in regenerative medicine strategies, especially those involving autologus congenital applications, and we have shown previously that AFSC-seeded fibrin-PEG hydrogels have the potential to form three-dimensional vascular-like networks in vitro. We hypothesized that subcutaneously injecting these hydrogels in immunodeficient mice would both induce a fibrindriven angiogenic host response and promote in situ AFSC-derived neovascularization. Two weeks post-injection, the average maximum invasion distance of host murine cells into the subcutaneous fibrin/PEG scaffold was 147±90µm after one week and 395±138µm after two weeks, the average number of cell-lined lumen per mm 2 was significantly higher in hydrogels

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mentioning

confidence: 99%

In situ vascularization of injectable fibrin/poly(ethylene glycol) hydrogels by human amniotic fluid‐derived stem cells

Benavides

Brooks

Cho

et al. 2015

J Biomedical Materials Res

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“…Recapitulating these biological processes in printed tissues is challenging and requires a proper spatiotemporal interplay between vascular cells, resident cells and surrounding ECM. Although several strategies have been explored to promote vascularization in skin constructs [62,88], engineering branched vascularization in 3D hierarchical architectures remains a great challenge. Bioprinting technologies are attractive to engineer a vascular tree within thick constructs by the precise layer by layer deposition of multiple cell types and ECMlike bioinks into prescribed spatial locations at high resolution [202].…”

Section: Printed Vascularized Skin Constructsmentioning

confidence: 99%

“…Typically, these wounds require extensive hospitalization, labour intensive clinical procedures and costly wound care products, representing a major burden over total world healthcare expenditure [9,153,175]. Several skin therapies and wound care products have been developed and tested through pre-clinical and randomized controlled clinical trials with the ultimate goal of promoting the repair and regeneration of functional skin [44,49,84,86,88,103,124,189,195,212]. Traditional treatments are based on the use of grafts (which includes auto-, allo-and xenograft varieties), herbal and animalderived compounds, silver-containing and traditional dressings.…”

Section: Introductionmentioning

confidence: 99%

Advances in bioprinted cell-laden hydrogels for skin tissue engineering

et al. 2017

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Bioprinting technologies are powerful additive biofabrication techniques to produce cellular constructs for skin tissue engineering owing to their unique ability to precisely pattern living and non-living materials in predefined spatial locations. This unique feature, combined with the computer controlled printing and medical imaging techniques, enable researchers and clinicians to generate patient specific constructs partly replicating the intricate compositional and architectural organization of the skin. Bioprinting has been used to automatically dispense hydrogels with skin cells located in prescribed sites that promote skin formation in vitro and in vivo. Current skin bioprinting approaches mostly rely on the sequential printing of fibroblasts and keratinocytes embedded within a homogeneous hydrogel. Although such approaches have already been translated to pre-clinical scenarios, they still present limitations in terms of fully replicating the cellular and extracellular matrix (ECM) heterogeneity in native skin. The success of bioprinting for skin repair strongly depends on the design of printable bioinks capable of supporting the function of printed cells and stimulating the production of new ECM components. To better mimic the human skin, novel developments in dedicated bioprinting technologies, in the design of bioinks, as well as in the printing of vascularised constructs are necessary. This paper presents an overview regarding the use of bioprinting for skin tissue engineering applications. The operating principles of bioprinting technologies are outlined along with requirements of printed skin constructs. Finally, preclinical results are summarized and future perspectives for the field are highlighted.

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“…92,93 Very recently, Klar et al suggested that SVF possesses similar percentages of stromal and endothelial cells, demonstrating that when in-corporated in 3D fibrin or collagen, SVF cells were capable of de novo formation of microvascular networks, causing a rapid anastomosis with the host vasculature and a sustained epidermal coverage. 92 Moreover, when applied to burn wounds, increased VEGF production and reduced inflammation was observed. 93 Likewise, in a scenario of diabetic wounds, VEGF and bFGF expression was also increased, 94 accelerating the wound-healing process.…”

Section: Hypoxiamentioning

confidence: 99%