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ALTEX2017; 35(1); 65-76; doi: 10.14573/altex.1704171

Ex vivo model unravelling cell distribution effect in hydrogels for cartilage repair.

Abstract: The implantation of chondrocyte-laden hydrogels is a promising cartilage repair strategy. Chondrocytes can be spatially positioned in hydrogels and thus in defects, while current clinical cell therapies introduce chondrocytes in the defect depth. The main aim of this study was to evaluate the effect of spatial chondrocyte distribution on the reparative process. To reduce animal experiments, an ex vivo osteochondral plug model was used and evaluated. The role of the delivered and endogenous cells in the repair process was investigated. Full thickness cartilage defects were created in equine osteochondral plugs. Defects were filled with (A) chondrocytes at the bottom of the defect, covered with a cell-free hydrogel, (B) chondrocytes homogeneously encapsulated in a hydrogel, and (C, D) combinations of A and B with different cell densities. Plugs were cultured for up to 57 days, after which the cartilage and repair tissues were characterized and compared to baseline samples. Additionally, at day 21, the origin of cells in the repair tissue was evaluated. Best outcomes were obtained with conditions C and D, which resulted in well-integrated cartilage-like tissue that completely filled the defect, regardless of the initial cell density. A critical role of the spatial chondrocyte distribution in the repair process was observed. Moreover, the osteochondral plugs stimulated cartilage formation in the hydrogels when cultured in the defects. The resulting repair tissue originated from the delivered cells. These findings confirm the potential of the osteochondral plug model for the optimization of the composition of cartilage implants and for studying repair mechanisms.
Publication Date: 2017-09-08 PubMed ID: 28884783PubMed Central: PMC7116182DOI: 10.14573/altex.1704171Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research article discusses the use of hydrogels with strategically placed chondrocytes (cartilage cells) to enhance cartilage repair. Using an ex vivo (outside of a living organism) model, the study explores how the distribution of these cells affects the repair process and informs the development of cartilage implants.

Overview of the Study

  • The research aimed to understand the role of spatially-distributed chondrocytes in a hydrogel medium towards the cartilage healing process.
  • This has been explored using an ex vivo model, to reduce the dependency on live animal testing. The model used was an equine osteochondral plug (a piece of bone and cartilage surgically removed).
  • Different distribution strategies of chondrocytes in the hydrogel were tested – one with chondrocytes at the defect’s base, another with equal cell distribution across the gel and two mixed methods with varying cell densities.

Process and Findings

  • Cartilage defects were artificially created in the osteochondral plugs and then filled using the different hydrogel-cell composition strategies.
  • The plugs were then cultured for up to 57 days during which the repair tissue was observed, evaluated and compared to initial samples.
  • The mixed methods (combination of base placed cells and evenly distributed cells) showed the best results in terms of well integrated, complete fill of the defect.
  • Furthermore, it was also observed that the cells in the repair tissue originated from the chondrocytes originally delivered in the hydrogel, pertinently confirming their role in the wound healing process.

Implications of the Study

  • Crucially, the research highlighted the importance of the spatial distribution of chondrocytes in cartilage repair, underlining that where these cells are specifically placed in the hydrogel plays a role in optimizing how well the resulting tissue integrates and fills the defect.
  • The osteochondral plug model confirmed its potential utility in studying and refining cartilage implant compositions and understanding associated repair mechanisms. This could have future application in the clinical development of cartilage repair therapies or implant devices.

Cite This Article

APA
Mouser VHM, Dautzenberg NMM, Levato R, van Rijen MHP, Dhert WJA, Malda J, Gawlitta D. (2017). Ex vivo model unravelling cell distribution effect in hydrogels for cartilage repair. ALTEX, 35(1), 65-76. https://doi.org/10.14573/altex.1704171

Publication

ISSN: 1868-8551
NlmUniqueID: 100953980
Country: Germany
Language: English
Volume: 35
Issue: 1
Pages: 65-76

Researcher Affiliations

Mouser, Vivian H M
  • Department of Orthopaedics, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Dautzenberg, Noël M M
  • Department of Orthopaedics, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Levato, Riccardo
  • Department of Orthopaedics, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
van Rijen, Mattie H P
  • Department of Orthopaedics, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Dhert, Wouter J A
  • Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Malda, Jos
  • Department of Orthopaedics, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
  • Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Gawlitta, Debby
  • Department of Oral and Maxillofacial Surgery & Special Dental Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

MeSH Terms

  • Animal Testing Alternatives
  • Animals
  • Cartilage / physiology
  • Cells, Cultured
  • Chondrocytes / physiology
  • Horses
  • Hydrogels
  • Tissue Engineering / methods

Grant Funding

  • 647426 / European Research Council

Conflict of Interest Statement

Conflict of interest. The authors have no conflicts of interest to declare.

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