De novo neo-hyaline-cartilage from bovine organoids in viscoelastic hydrogels
Open accessAbstract
Regenerative therapies for articular cartilage are currently clinically available. However, they are associated with several drawbacks that require resolution. Optimizing chondrocyte expansion and their assembly, can reduce the time and costs of these therapies and more importantly increase their clinical success. In this study, cartilage organoids were quickly mass produced from bovine chondrocytes with a new suspension expansion protocol. This new approach led to massive cell proliferation, high viability and the self-assembly of organoids. These organoids were composed of collagen type II, type VI, glycosaminoglycans, with Sox9 positive cells, embedded in a pericellular and interterritorial matrix similarly to hyaline cartilage. With the goal of producing large scale tissues, we then encapsulated these organoids into alginate hydrogels with different viscoelastic properties. Elastic hydrogels constrained the growth and fusion of the organoids inhibiting the formation of a tissue. In contrast, viscoelastic hydrogels allowed the growth and fusion of the organoids into a homogenous tissue that was rich in collagen type II and glycosaminoglycans. The encapsulation of organoids to produce in vitro neocartilage also proved to be superior to the conventional method of encapsulating 2D expanded chondrocytes. This study describes a multimodal approach that involves chondrocyte expansion, organoid formation and their assembly into neohyaline-cartilage which proved to be superior to the current standard approaches used in cartilage tissue engineering. STATEMENT OF SIGNIFICANCE: In this manuscript, we describe a new and simple methodology to quickly mass produce self-assembling cartilage organoids. Due to their matrix content and structure similarities with native cartilage, these organoids on their own have the potential to revolutionize cartilage research and the manner in which we study signaling pathways, disease progression, tissue engineering, drug development, etc. Furthermore, these organoids and their fast mass production were combined with a key relatively ignored hydrogel characteristic, viscoelasticity, to demonstrate their fusion into a neo-tissue. This has the potential to open the door for large scale cartilage regeneration such as for entire joint surfaces.
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The viscoelastic properties of a material affect matrix remodeling, cell spreading, migration, differentiation, and consequently, organoid fate.
“The viscoelastic properties of a material affect matrix remodeling, cell spreading, migration, differentiation, and consequently, organoid fate139–141.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [141]
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- Authors
- Crispim, J. F., & Ito, K.
- Affiliations
- Eindhoven University of Technology (NL)
- Corresponding author
- Crispim, João F.
- Ito, Keita
- Venue
- Acta Biomaterialia
- Publisher
- Elsevier BV
- Published
- 2021-07
- Volume
- 128
- Pages
- 236-249
- ISSN
- 1742-7061 (ISSN-L)
- OpenAlex
- W3155900515
- Cited by
- 71
- References
- 78
- Citations by year
- 2026: 10 · 2025: 18 · 2024: 20 · 2023: 12 · 2022: 8 · 2021: 3
- FWCI
- 8.13
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Acta Biomaterialia (publishedVersion, cc-by)
- PubMed (publishedVersion)
- TU/e Research Portal (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Keywords
- cartilage organoids, hyaline cartilage regeneration, chondrocyte expansion, viscoelastic hydrogels, alginate hydrogel, organoid fusion, self-assembly, type II collagen, glycosaminoglycans, SOX9, bovine chondrocytes, cartilage tissue engineering
- MeSH terms
- Animals, Cartilage, Articular, Cattle, Hyalin, Organoids, Chondrocytes, Hydrogels, Tissue Engineering, Hyaline Cartilage
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