<i>In Vivo</i>Cellular Infiltration and Remodeling in a Decellularized Ovine Osteochondral Allograft

Novak, Tyler; Gilliland, Kateri Fites; Xu, Xin; Worke, Logan J.; Ciesielski, Aaron; Breur, Gert J.; Neu, Corey P.

doi:10.1089/ten.tea.2016.0149

Cited by 28 publications

(27 citation statements)

References 44 publications

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“…Therefore, a decellularized osteochondral ECM scaffold that can maintain osteochondral hierarchy was generated to promote osteochondral regeneration. Although several studies have reported the use of such materials 22,37 , vital aspects such as cell removal rate, retention of histological stratification, biocompatibility (in vitro and in vivo), and effective preservation of ECM components have not yet been evaluated in decellularized osteochondral ECM scaffolds. While in our study, through the integrated decellularization process, our osteochondral ECM scaffold was generated through complete elimination of fullthickness cellular components.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, preparing an osteochondral ECM scaffold by decellularization can provide a means of recreating osteochondral tissue architecture. Recently, though several studies have reported that osteochondral ECM scaffold was fabricated and applied to osteochondral defect repairing, its evaluation in cell removal effect, stratified structure retention and regeneration mechanism were still uncertain 21,22 .…”

Section: Introductionmentioning

confidence: 99%

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Biphasic hierarchical extracellular matrix scaffold for osteochondral defect regeneration

Lin

Chen

Qiu

et al. 2018

Osteoarthritis and Cartilage

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Biphasic hierarchical extracellular matrix scaffold for osteochondral defect regeneration

Lin

Chen

Qiu

et al. 2018

Osteoarthritis and Cartilage

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“…We chose to use a 1% cross linked hydrogel, rather than a 2% hydrogel, to maintain larger pores (~15 µm pore diameter 10 ) for facilitating migration within the hydrogel domains of the tissue clay 25 . Furthermore, chondrocyte migration into tissue ECM has been previously observed at the edges of large acellular ECM implants, but only extending into the tissue about 25-100 µm from the edge [26][27][28] . Thus, pulverizing the cartilage ECM until the microparticle diameter is <250 µm and embedding in a hydrogel with 15 µm pores facilitates chondrocyte migration towards matrix-bound TGF-β1.…”

Section: Chondrocyte Migration Into Tissue Particles Is Attributed Tomentioning

confidence: 99%

Percolation of Microparticle Matrix Promotes Cell Migration and Integration while Supporting Native Tissue Architecture

Barthold

Martin

Sridhar

et al. 2020

Preprint

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Cells embedded in the extracellular matrix of tissues play a critical role in maintaining homeostasis while promoting integration and regeneration following damage or disease. Emerging engineered biomaterials utilize decellularized extracellular matrix as a tissue-specific support structure; however, many dense, structured biomaterials unfortunately demonstrate limited formability, fail to promote cell migration, and result in limited tissue repair. Here, we developed a reinforced composite material of densely packed acellular extracellular matrix microparticles in a hydrogel, termed tissue clay, that can be molded and crosslinked to mimic native tissue architecture. We utilized hyaluronic acid-based hydrogels, amorphously packed with acellular articular cartilage tissue particulated to ~125-250 microns in diameter and defined a percolation threshold of 0.57 (v/v) beyond which the compressive modulus exceeded 300kPa. Remarkably, primary chondrocytes recellularized particles within 48 hours, a process driven by chemotaxis, exhibited distributed cellularity in large engineered composites, and expressed genes consistent with native cartilage repair. We additionally demonstrated broad utility of tissue clays through recellularization and persistence of muscle, skin, and cartilage composites in a subcutaneous in vivo mouse model. Our findings suggest optimal strategies and material architectures to balance concurrent demands for large-scale mechanical properties while also supporting integration of dense musculoskeletal and connective tissues.

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“…Therefore, the ability of CDM to support both cartilage [35] and bone [41] regeneration empowers CDM to serve as a single, compositionally homogenous substrate for engineering osteochondral constructs. Additionally, CDM can be remodeled in vivo [42]. However, the in vivo degradation profile of CDM is uneven, random, and irregular over time [43], which contributes to the failure of CDM constructs in long-term, high load bearing, osteochondral repair [44].…”

Section: Introductionmentioning

confidence: 99%

Regulation of Decellularized Tissue Remodeling via Scaffold-Mediated Lentiviral Delivery in Anatomically-Shaped Osteochondral Constructs

Rowland¹,

Glass

Ettyreddy

et al. 2018

Preprint

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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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In VivoCellular Infiltration and Remodeling in a Decellularized Ovine Osteochondral Allograft

Cited by 28 publications

References 44 publications

Biphasic hierarchical extracellular matrix scaffold for osteochondral defect regeneration

Biphasic hierarchical extracellular matrix scaffold for osteochondral defect regeneration

Percolation of Microparticle Matrix Promotes Cell Migration and Integration while Supporting Native Tissue Architecture

Regulation of Decellularized Tissue Remodeling via Scaffold-Mediated Lentiviral Delivery in Anatomically-Shaped Osteochondral Constructs

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