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Cardiovascular tissue regeneration system based on multiscale scaffolds comprising double-layered hydrogels and fibers.

ABSTRACT: We report a technique to reconstruct cardiovascular tissue using multiscale scaffolds incorporating polycaprolactone fibers with double-layered hydrogels comprising fibrin hydrogel surrounded by secondary alginate hydrogel. The scaffolds compartmentalized cells into the core region of cardiac tissue and the peripheral region of blood vessels to construct cardiovascular tissue, which was accomplished by a triple culture system of adipose-derived mesenchymal stem cells (ADSCs) with C2C12 myoblasts on polycaprolactone (PCL) fibers along with human umbilical vein endothelial cells (HUVECs) in fibrin hydrogel. The secondary alginate hydrogel prevented encapsulated cells from migrating outside scaffold and maintained the scaffold structure without distortion after subcutaneous implantation. According to in vitro studies, resultant scaffolds promoted new blood vessel formation as well as cardiomyogenic phenotype expression of ADSCs. Cardiac muscle-specific genes were expressed from stem cells and peripheral blood vessels from HUVECs were also successfully developed in subcutaneously implanted cell-laden multiscale scaffolds. Furthermore, the encapsulated stem cells modulated the immune response of scaffolds by secreting anti-inflammatory cytokines for successful tissue construction. Our study reveals that multiscale scaffolds can be promising for the remodeling and transplantation of cardiovascular tissue.

SUBMITTER: Kook YM

PROVIDER: S-EPMC7683622 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Cardiovascular tissue regeneration system based on multiscale scaffolds comprising double-layered hydrogels and fibers.

Kook Yun-Min YM Hwang Soonjae S Kim Hyerim H Rhee Ki-Jong KJ Lee Kangwon K Koh Won-Gun WG

Scientific reports 20201123 1

We report a technique to reconstruct cardiovascular tissue using multiscale scaffolds incorporating polycaprolactone fibers with double-layered hydrogels comprising fibrin hydrogel surrounded by secondary alginate hydrogel. The scaffolds compartmentalized cells into the core region of cardiac tissue and the peripheral region of blood vessels to construct cardiovascular tissue, which was accomplished by a triple culture system of adipose-derived mesenchymal stem cells (ADSCs) with C2C12 myoblasts ...[more]

PMID: 33230134

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Project description:Articular cartilage has limited capacity for regeneration and when damaged cannot be repaired with currently available metallic or synthetic implants. We aim to bioengineer a microfibre-reinforced hydrogel that can capture the zonal depth-dependent mechanical properties of native cartilage, and simultaneously support neo-cartilage formation. With this goal, a sophisticated bi-layered microfibre architecture, combining a densely distributed crossed fibre mat (superficial tangential zone, STZ) and a uniform box structure (middle and deep zone, MDZ), was successfully manufactured via melt electrospinning and combined with a gelatin-methacrylamide hydrogel. The inclusion of a thin STZ layer greatly increased the composite construct's peak modulus under both incongruent (3.2-fold) and congruent (2.1-fold) loading, as compared to hydrogels reinforced with only a uniform MDZ structure. Notably, the stress relaxation response of the bi-layered composite construct was comparable to the tested native cartilage tissue. Furthermore, similar production of sulphated glycosaminoglycans and collagen II was observed for the novel composite constructs cultured under mechanical conditioning w/o TGF-ß1 supplementation and in static conditions w/TGF-ß1 supplementation, which confirmed the capability of the novel composite construct to support neo-cartilage formation upon mechanical stimulation. To conclude, these results are an important step towards the design and manufacture of biomechanically competent implants for cartilage regeneration. STATEMENT OF SIGNIFICANCE: Damage to articular cartilage results in severe pain and joint disfunction that cannot be treated with currently available implants. This study presents a sophisticated bioengineered bi-layered fibre reinforced cell-laden hydrogel that can approximate the functional mechanical properties of native cartilage. For the first time, the importance of incorporating a viable superficial tangential zone (STZ) - like structure to improve the load-bearing properties of bioengineered constructs, particularly when in-congruent surfaces are compressed, is demonstrated. The present work also provides new insights for the development of implants that are able to promote and guide new cartilaginous tissue formation upon physiologically relevant mechanical stimulation.

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Cardiovascular tissue regeneration system based on multiscale scaffolds comprising double-layered hydrogels and fibers.

Publications

Cardiovascular tissue regeneration system based on multiscale scaffolds comprising double-layered hydrogels and fibers.

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