Crosslinkable hydrogels derived from cartilage, meniscus, and tendon tissue.
Abstract: Decellularized tissues have proven to be versatile matrices for the engineering of tissues and organs. These matrices usually consist of collagens, matrix-specific proteins, and a set of largely undefined growth factors and signaling molecules. Although several decellularized tissues have found their way to clinical applications, their use in the engineering of cartilage tissue has only been explored to a limited extent. We set out to generate hydrogels from several tissue-derived matrices, as hydrogels are the current preferred cell carriers for cartilage repair. Equine cartilage, meniscus, and tendon tissue was harvested, decellularized, enzymatically digested, and functionalized with methacrylamide groups. After photo-cross-linking, these tissue digests were mechanically characterized. Next, gelatin methacrylamide (GelMA) hydrogel was functionalized with these methacrylated tissue digests. Equine chondrocytes and mesenchymal stromal cells (MSCs) (both from three donors) were encapsulated and cultured in vitro up to 6 weeks. Gene expression (COL1A1, COL2A1, ACAN, MMP-3, MMP-13, and MMP-14), cartilage-specific matrix formation, and hydrogel stiffness were analyzed after culture. The cartilage, meniscus, and tendon digests were successfully photo-cross-linked into hydrogels. The addition of the tissue-derived matrices to GelMA affected chondrogenic differentiation of MSCs, although no consequent improvement was demonstrated. For chondrocytes, the tissue-derived matrix gels performed worse compared to GelMA alone. This work demonstrates for the first time that native tissues can be processed into crosslinkable hydrogels for the engineering of tissues. Moreover, the differentiation of encapsulated cells can be influenced in these stable, decellularized matrix hydrogels.
Publication Date: 2015-02-09 PubMed ID: 25557049PubMed Central: PMC4394887DOI: 10.1089/ten.TEA.2014.0362Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
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 describes the process of transforming cartilage, meniscus, and tendon tissues (harvested from horses) into crosslinkable hydrogels, to explore their potential use in tissue engineering. The study also investigates how these tissue-derived hydrogels affect the differentiation of certain cells, particularly chondrocytes and Mesenchymal Stromal Cells (MSCs).
Processing of Native Tissues into Hydrogels
- The study aimed to create hydrogels from native tissues, as these hydrogels could potentially facilitate cartilage repair.
- The native tissues used for the study were cartilage, meniscus, and tendons, sourced from horses.
- These tissues were decellularized, a process that removes all the cells from a tissue, leaving behind a matrix of collagen, growth factors, and several other elements. This provides a structure for new cells to grow in, and is an important step in many tissue engineering processes.
- Once decellularized, the tissues were digested enzymatically to get tissue digests. They were then functionalized with methacrylamide groups. The tissues allowing them to create structural crossover points, or ‘crosslinks’, forming hydrogels.
- After being photo-crosslinked, these tissue hydrogels underwent mechanical characterization, a process that identifies their mechanical properties.
Addition of Tissue-derived Matrices to GelMA
- GelMA, or Gelatin Methacrylamide, is another type of hydrogel and was also tested in conjunction with the tissue-derived matrices.
- This hydrogel’s base is made from gelatin, which is desirable for tissue engineering due to its non-toxic, biocompatible properties.
- By integrating the tissue-derived matrices to GelMA, the researchers aimed to investigate if these combined hydrogels could influence the chondrogenic differentiation of MSCs. Meaning, if they could influence the process by which these stem cells develop into chondrocytes—essential for cartilage formation.
Chondrocytes and MSCs Culture and Analysis
- Chondrocytes and MSCs were encapsulated into the hydrogels and cultured in vitro for up to 6 weeks.
- After this culture period, the gene expression of specific markers, including COL1A1, COL2A1, ACAN, MMP-3, MMP-13, and MMP-14, was analyzed. These genes are associated with cartilage formation and degradation.
- Furthermore, the creation of cartilage-specific matrix and hydrogel stiffness was also observed.
- While the researchers noticed that the addition of tissue-derived matrices to GelMA influenced the chondrogenic differentiation of MSCs, no significant improvement was observed.
- For chondrocytes, the tissue-derived matrix gels performed worse compared to the GelMA hydrogel alone.
Conclusion
- This research successfully demonstrated that native tissues could be processed into crosslinkable hydrogels, opening new possibilities for tissue engineering.
- Nonetheless, the performance of these hydrogels, with respect to cell differentiation and properties, will require further study to prove their clinical value.
Cite This Article
APA
Visser J, Levett PA, te Moller NC, Besems J, Boere KW, van Rijen MH, de Grauw JC, Dhert WJ, van Weeren PR, Malda J.
(2015).
Crosslinkable hydrogels derived from cartilage, meniscus, and tendon tissue.
Tissue Eng Part A, 21(7-8), 1195-1206.
https://doi.org/10.1089/ten.TEA.2014.0362 Publication
Researcher Affiliations
- 1 Department of Orthopaedics, University Medical Center Utrecht , Utrecht, The Netherlands .
MeSH Terms
- Animals
- Cartilage / cytology
- Cell Differentiation / drug effects
- Cell Survival / drug effects
- Chondrocytes / cytology
- Chondrocytes / drug effects
- Compressive Strength / drug effects
- Cross-Linking Reagents / pharmacology
- DNA / metabolism
- Elastic Modulus / drug effects
- Extracellular Matrix / drug effects
- Extracellular Matrix / metabolism
- Gene Expression Regulation / drug effects
- Glycosaminoglycans / metabolism
- Horses
- Hydrogels / pharmacology
- Menisci, Tibial / cytology
- Mesenchymal Stem Cells / cytology
- Tendons / cytology
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