Spatially confined induction of endochondral ossification by functionalized hydrogels for ectopic engineering of osteochondral tissues

Despite the various reported approaches to generate osteochondral composites by combination of different cell types and materials, engineering of templates with the capacity to autonomously and orderly develop into cartilage-bone bi-layered structures remains an open challenge. Here, we hypothesized...

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Veröffentlicht in:Biomaterials 2018-07, Vol.171, p.219-229
Hauptverfasser: Stüdle, Chiara, Vallmajó-Martín, Queralt, Haumer, Alexander, Guerrero, Julien, Centola, Matteo, Mehrkens, Arne, Schaefer, Dirk J., Ehrbar, Martin, Barbero, Andrea, Martin, Ivan
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container_end_page 229
container_issue
container_start_page 219
container_title Biomaterials
container_volume 171
creator Stüdle, Chiara
Vallmajó-Martín, Queralt
Haumer, Alexander
Guerrero, Julien
Centola, Matteo
Mehrkens, Arne
Schaefer, Dirk J.
Ehrbar, Martin
Barbero, Andrea
Martin, Ivan
description Despite the various reported approaches to generate osteochondral composites by combination of different cell types and materials, engineering of templates with the capacity to autonomously and orderly develop into cartilage-bone bi-layered structures remains an open challenge. Here, we hypothesized that the embedding of cells inducible to endochondral ossification (i.e. bone marrow derived mesenchymal stromal cells, BMSCs) and of cells capable of robust and stable chondrogenesis (i.e. nasal chondrocytes, NCs) adjacent to each other in bi-layered hydrogels would develop directly in vivo into osteochondral tissues. Poly(ethylene glycol) (PEG) hydrogels were functionalized with TGFβ3 or BMP-2, enzymatically polymerized encapsulating human BMSCs, combined with a hydrogel layer containing human NCs and ectopically implanted in nude mice without pre-culture. The BMSC-loaded layers reproducibly underwent endochondral ossification and generated ossicles containing bone and marrow. The NC-loaded layers formed cartilage tissues, which (under the influence of BMP-2 but not of TGFβ3 from the neighbouring layer) remained phenotypically stable. The proposed strategy, resulting in orderly connected osteochondral composites, should be further assessed for the repair of osteoarticular defects and will be useful to model developmental processes leading to cartilage-bone interfaces.
doi_str_mv 10.1016/j.biomaterials.2018.04.025
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subjects Endochondral ossification
Human bone marrow derived mesenchymal stromal cells
Human nasal chondrocytes
Osteochondral tissue engineering
Poly(ethylene glycol) hydrogel
TGFβ3-functionalization
title Spatially confined induction of endochondral ossification by functionalized hydrogels for ectopic engineering of osteochondral tissues
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