scholarly journals Applied osmotic loading for promoting development of engineered cartilage

2013 ◽  
Vol 46 (15) ◽  
pp. 2674-2681 ◽  
Author(s):  
Sonal R. Sampat ◽  
Matthew V. Dermksian ◽  
Sevan R. Oungoulian ◽  
Robert J. Winchester ◽  
J. Chloë Bulinski ◽  
...  
Keyword(s):  
Osmotic Loading ◽  
Engineered Cartilage

Applied Osmotic Loading for Promoting Development of Engineered Cartilage

2012 ◽  
Author(s):  
Sonal R. Sampat ◽  
Drew A. Robinson ◽  
George P. Ackerman ◽  
Matthew V. Dermksian ◽  
Gerard A. Ateshian ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
3D Culture ◽  
Biochemical Properties ◽  
Tissue Constructs ◽  
Osmotic Loading ◽  
Chondrogenic Lineage ◽  
Engineered Tissue ◽  
Proteoglycan Content ◽  
Engineered Cartilage

The avascular nature of cartilage and the harsh joint loading environment lead to a poor intrinsic healing capacity after injury, motivating the development of cell-based therapies for repair. Synovium-derived stem cells (SDSCs) have the potential for differentiating down a chondrogenic lineage and are thought to aid in articular cartilage repair after damage in vivo1. In the present study, we adopt a two-pronged strategy for growing clinically relevant cartilage grafts. Firstly, we compare the potential of SDSCs versus chondrocytes for engineering functional constructs. Secondly, we investigate the effect of extracellular osmolarity on mechanical and biochemical properties of SDSCs and similarly passaged chondrocytes in 3D culture. This approach is motivated by the fact that the in situ osmotic environment of chondrocytes varies with proteoglycan content and tissue deformation, altering the regulation of chondrocyte activity through mechanotransduction pathways2. We test the hypothesis that application of a hypertonic, more physiologic osmotic environment (created by addition of NaCl and KCl) relative to hypotonic media (300 mOsm), during 3D culture of SDSCs or chondrocytes in agarose hydrogels, improves the biochemical composition and mechanical properties of engineered tissue constructs.

Osmotic or Chemical Activation of the TRPV4 Ion Channel Enhances the Development of Chondrocyte-Based Tissue Engineered Cartilage

2013 ◽  
Author(s):  
Christopher J. O’Conor ◽  
Halei C. Benefield ◽  
Wolfgang Liedtke ◽  
Farshid Guilak
Keyword(s):  
Ion Channel ◽  
Mechanical Loading ◽  
Functional Properties ◽  
Articular Chondrocytes ◽  
Metabolic Response ◽  
Chemical Activation ◽  
Osmotic Loading ◽  
Novel Strategy ◽  
Engineered Cartilage ◽  
Biophysical Effects

Dynamic mechanical loading can enhance the formation of engineered cartilage, potentially through secondary biophysical effects such as changes in interstitial osmolarity. This study examined the effects of daily osmotic loading, as well as direct activation of the osmosensitive ion channel TRPV4, on the biochemical and functional properties of chondrocyte-laden cartilage constructs. Osmotic loading, as well as exposure to the TRPV4-specific agonist GSK1016790A, enhanced extracellular matrix (ECM) accumulation, and TRPV4 activation enhanced the functional properties of the constructs. This study implicates the Ca ++-permeable TRPV4 ion channel in the metabolic response of articular chondrocytes to osmotic and mechanical loading. Furthermore, these results suggest that targeting TRPV4, either directly with channel agonists, or indirectly via osmotic loading, may provide a novel strategy for enhancing tissue engineered cartilage construct maturation.

scholarly journals Heparan Sulfate Deficiency in Cartilage: Enhanced BMP-Sensitivity, Proteoglycan Production and an Anti-Apoptotic Expression Signature after Loading

2021 ◽  
Vol 22 (7) ◽  
pp. 3726
Author(s):  
Matthias Gerstner ◽  
Ann-Christine Severmann ◽  
Safak Chasan ◽  
Andrea Vortkamp ◽  
Wiltrud Richter
Keyword(s):  
Heparan Sulfate ◽  
Pain Perception ◽  
Biological Process ◽  
Transcriptome Profiling ◽  
Mrna Levels ◽  
Unconfined Compression ◽  
Expression Signature ◽  
Hypomorphic Allele ◽  
Underlying Mechanisms ◽  
Engineered Cartilage

Osteoarthritis (OA) represents one major cause of disability worldwide still evading efficient pharmacological or cellular therapies. Severe degeneration of extracellular cartilage matrix precedes the loss of mobility and disabling pain perception in affected joints. Recent studies showed that a reduced heparan sulfate (HS) content protects cartilage from degradation in OA-animal models of joint destabilization but the underlying mechanisms remained unclear. We aimed to clarify whether low HS-content alters the mechano-response of chondrocytes and to uncover pathways relevant for HS-related chondro-protection in response to loading. Tissue-engineered cartilage with HS-deficiency was generated from rib chondrocytes of mice carrying a hypomorphic allele of Exostosin 1 (Ext1), one of the main HS-synthesizing enzymes, and wildtype (WT) littermate controls. Engineered cartilage matured for 2 weeks was exposed to cyclic unconfined compression in a bioreactor. The molecular loading response was determined by transcriptome profiling, bioinformatic data processing, and qPCR. HS-deficient chondrocytes expressed 3–6% of WT Ext1-mRNA levels. Both groups similarly raised Sox9, Col2a1, and Acan levels during maturation. However, HS-deficient chondrocytes synthesized and deposited 50% more GAG/DNA. TGFβ and FGF2-sensitivity of Ext1gt/gt chondrocytes was similar to WT cells but their response to BMP-stimulation was enhanced. Loading induced similar activation of mechano-sensitive ERK and P38-signaling in WT and HS-reduced chondrocytes. Transcriptome analysis reflected regulation of cell migration as major load-induced biological process with similar stimulation of common (Fosl1, Itgα5, Timp1, and Ngf) as well as novel mechano-regulated genes (Inhba and Dhrs9). Remarkably, only Ext1-hypomorphic cartilage responded to loading by an expression signature of negative regulation of apoptosis with pro-apoptotic Bnip3 being selectively down-regulated. HS-deficiency enhanced BMP-sensitivity, GAG-production and fostered an anti-apoptotic expression signature after loading, all of which may protect cartilage from load-induced erosion.

scholarly journals Ultrasound Elastography for Estimation of Regional Strain of Multilayered Hydrogels and Tissue-Engineered Cartilage

2015 ◽  
Vol 43 (12) ◽  
pp. 2991-3003 ◽  
Author(s):  
Chen-Yuan Chung ◽  
Joseph Heebner ◽  
Harihara Baskaran ◽  
Jean F. Welter ◽  
Joseph M. Mansour
Keyword(s):  
Ultrasound Elastography ◽  
Regional Strain ◽  
Engineered Cartilage

Finite Element Modeling of Osmotic Swelling in Tissue-Engineered Cartilage

2008 ◽  
Author(s):  
Liming Bian ◽  
Terri Ann N. Kelly ◽  
Eric G. Lima ◽  
Gerard A. Ateshian ◽  
Clark T. Hung
Keyword(s):  
Articular Cartilage ◽  
Potential Role ◽  
Swelling Pressure ◽  
Type Ii Collagen ◽  
Type Ii ◽  
Osmotic Swelling ◽  
Fixed Charges ◽  
Central Regions ◽  
Significant Research ◽  
Engineered Cartilage

Proteoglycans and Type II collagen represent the two major biochemical constituents of articular cartilage. Collagen fibrils in cartilage resist the swelling pressure that arises from the fixed charges of the glycosaminoglycans (GAGs), and together they give rise to the tissue’s unique load bearing properties. As articular cartilage exhibits a poor intrinsic healing capacity, there is significant research in the development of cell-based therapies for cartilage repair. In some of our tissue engineering studies, we have observed a phenomenon where chondrocyte-seeded hydrogel constructs display cracking in their central regions after significant GAG content has been elaborated in culture. A theoretical analysis was performed to gain greater insights into the potential role that the spatial distribution of proteoglycan and collagen may play in this observed response.

scholarly journals Vascularization of tissue engineered cartilage - Sequential in vivo MRI display functional blood circulation

Biomaterials ◽  
2021 ◽  
pp. 121002
Author(s):  
Peter Apelgren ◽  
Matteo Amoroso ◽  
Karin Säljö ◽  
Mikael Montelius ◽  
Anders Lindahl ◽  
...  
Keyword(s):  
Blood Circulation ◽  
Engineered Cartilage
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