Regulation of Decellularized Tissue Remodeling via Scaffold-Mediated Lentiviral Delivery in Anatomically-Shaped Osteochondral Constructs Article Swipe
Christopher R. Rowland
,
Katherine A. Glass
,
Adarsh R. Ettyreddy
,
Catherine C. Gloss
,
Jared R.L. Matthews
,
Nguyen P.T. Huynh
,
Farshid Guilak
·
YOU?
·
· 2018
· Open Access
·
· DOI: https://doi.org/10.1101/261792
YOU?
·
· 2018
· Open Access
·
· DOI: https://doi.org/10.1101/261792
Cartilage-derived matrix (CDM) has emerged as a promising scaffold material for tissue engineering of cartilage and bone due to its native chondroinductive capacity and its ability to support endochondral ossification. Because it consists of native tissue, CDM can undergo cellular remodeling, which can promote integration with host tissue and enables it to be degraded and replaced by neotissue over time. However, enzymatic degradation of decellularized tissues can occur unpredictably and may not allow sufficient time for mechanically competent tissue to form, especially in the harsh inflammatory environment of a diseased joint. The goal of the current study was to engineer cartilage and bone constructs with the ability to inhibit aberrant inflammatory processes caused by the cytokine interleukin-1 (IL-1), through scaffold-mediated delivery of lentiviral particles containing a doxycycline-inducible IL-1 receptor antagonist (IL-1Ra) transgene on anatomically-shaped CDM constructs. Additionally, scaffold-mediated lentiviral gene delivery was used to facilitate spatial organization of simultaneous chondrogenic and osteogenic differentiation via site-specific transduction of a single mesenchymal stem cell (MSC) population to overexpress either chondrogenic, transforming growth factor-beta 3 (TGF-β3), or osteogenic, bone morphogenetic protein-2 (BMP-2), transgenes. Controlled induction of IL-1Ra expression protected CDM hemispheres from inflammation-mediated degradation, and supported robust bone and cartilage tissue formation even in the presence of IL-1. In the absence of inflammatory stimuli, controlled cellular remodeling was exploited as a mechanism for fusing concentric CDM hemispheres overexpressing BMP-2 and TGF-β3 into a single bi-layered osteochondral construct. Our findings demonstrate that site-specific delivery of inducible and tunable transgenes confers spatial and temporal control over both CDM scaffold remodeling and neotissue composition. Furthermore, these constructs provide a microphysiological, in vitro , joint, organoid model with site-specific, tunable, and inducible protein delivery systems for examining the spatiotemporal response to pro-anabolic and/or inflammatory signaling across the osteochondral interface.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/261792
- https://www.biorxiv.org/content/biorxiv/early/2018/02/08/261792.full.pdf
- OA Status
- green
- Cited By
- 1
- References
- 99
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2796366249
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W2796366249Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1101/261792Digital Object Identifier
- Title
-
Regulation of Decellularized Tissue Remodeling via Scaffold-Mediated Lentiviral Delivery in Anatomically-Shaped Osteochondral ConstructsWork title
- Type
-
preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2018Year of publication
- Publication date
-
2018-02-08Full publication date if available
- Authors
-
Christopher R. Rowland, Katherine A. Glass, Adarsh R. Ettyreddy, Catherine C. Gloss, Jared R.L. Matthews, Nguyen P.T. Huynh, Farshid GuilakList of authors in order
- Landing page
-
https://doi.org/10.1101/261792Publisher landing page
- PDF URL
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https://www.biorxiv.org/content/biorxiv/early/2018/02/08/261792.full.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
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https://www.biorxiv.org/content/biorxiv/early/2018/02/08/261792.full.pdfDirect OA link when available
- Concepts
-
Cell biology, Decellularization, Scaffold, Chondrogenesis, Endochondral ossification, Cartilage, Mesenchymal stem cell, Extracellular matrix, Chemistry, Gene delivery, Tissue engineering, Bone morphogenetic protein, Biomedical engineering, Anatomy, Biology, Genetic enhancement, Medicine, Gene, BiochemistryTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
1Total citation count in OpenAlex
- Citations by year (recent)
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2022: 1Per-year citation counts (last 5 years)
- References (count)
-
99Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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