Applied Osmotic Loading for Promoting Development of 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.

Download Full-text

Extended Long-Term Culture of MSC-Laden Agarose Constructs Does Not Produce Functional Tissue Comparable to Primary Chondrocytes

ASME 2010 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2010-19643 ◽

2010 ◽

Cited By ~ 1

Author(s):

Alice H. Huang ◽

Robert L. Mauck

Keyword(s):

Mechanical Properties ◽

3D Culture ◽

Biochemical Properties ◽

Clinical Use ◽

Promising Alternative ◽

Chondrogenic Medium ◽

Primary Chondrocytes ◽

The Poor

Articular cartilage lines the surfaces of joints and transmits the forces arising from locomotion. The poor ability of cartilage to self-repair has motivated efforts to engineer replacements that recapitulate this load-bearing function. While chondrocyte-laden constructs have been generated with near-native mechanical properties, limitations in chondrocyte availability may preclude their clinical use. Therefore, mesenchymal stem cells (MSCs), which can undergo chondrogenesis in 3D culture, have emerged as a promising alternative [1]. However, although MSCs deposit a cartilaginous matrix, mechanical and biochemical properties are lower than those achieved with chondrocytes [1, 2]. Using microarray analysis, we recently showed that limitations in functional MSC chondrogenesis may stem from incomplete or incorrect molecular induction; molecular differences were observed between donor-matched differentiated chondrocytes and newly differentiated MSCs over 8 weeks of culture [2]. While some genes remained consistently low in MSCs compared to chondrocytes, others gradually increased with time, approaching chondrocyte levels by 8 weeks. As these molecules may underlie the functional disparity between chondrocytes and MSCs, we hypothesized that longer culture durations may improve MSC-seeded construct properties and chondrogenesis. To test this hypothesis, we characterized the evolution of functional properties of MSC- and chondrocyte-seeded constructs over 4 months of in vitro culture in pro-chondrogenic medium.

Download Full-text

Characterization of Carbon Nanotube-Conjugated Collagen Composite Matrix Mechanics

ASME 2007 Summer Bioengineering Conference ◽

10.1115/sbc2007-176643 ◽

2007 ◽

Author(s):

John R. Twomey ◽

Vivek Sundaram ◽

Krishna Madhavan ◽

Wei Tan

Keyword(s):

Mechanical Properties ◽

Type I Collagen ◽

High Stress ◽

Type I ◽

Composite Matrix ◽

Matrix Mechanics ◽

Tissue Constructs ◽

Engineered Tissue ◽

Walled Carbon Nanotubes

In the case of vascular grafts, enhanced mechanical properties of engineered tissue constructs are required in order to function properly in mechanically-active physiologic conditions. It is proposed that a composite matrix constructed of type I collagen, fibronectin, and covalently-functionalized single-walled carbon nanotubes (SWNTs) will provide the desired mechanical properties required for the development of implantable tissues capable of withstanding high-stress environments.

Download Full-text

Dynamic Compression Stimulates the Development of Equilibrium Aggregate Modulus in Tissue Engineered Cartilage Constructs

10.1115/imece2000-2518 ◽

2000 ◽

Author(s):

Robert L. Mauck ◽

Glyn D. Palmer ◽

Christopher C.-B. Wang ◽

Michael A. Soltz ◽

Wilmot B. Valhmu ◽

...

Keyword(s):

Tissue Engineering ◽

Articular Cartilage ◽

Material Properties ◽

Dynamic Compression ◽

Biochemical Properties ◽

Functional Material ◽

Load Bearing ◽

Tissue Constructs ◽

Free Swelling ◽

Engineered Cartilage

Abstract A major challenge facing the tissue engineering of articular cartilage is the ability to grow tissue constructs that have the proper mechanical and biochemical properties that permit cartilage to serve its load-bearing function. This study tested the hypothesis that physiologic deformational loading enhances the formation of functional material properties in cell-seeded agarose constructs (versus free-swelling constructs).

Download Full-text

Dynamics of Nanoparticle Chain Aggregates of Carbon Under Tension

MRS Proceedings ◽

10.1557/proc-778-u4.4 ◽

2003 ◽

Vol 778 ◽

Author(s):

Rajdip Bandyopadhyaya ◽

Weizhi Rong ◽

Yong J. Suh ◽

Sheldon K. Friedlander

Keyword(s):

Mechanical Properties ◽

Carbon Black ◽

Polymer Film ◽

Elastic Behavior ◽

Small Strains ◽

Transmission Electron ◽

Chain Aggregates ◽

Nanoparticle Chains ◽

Reinforcing Filler

AbstractCarbon black in the form of nanoparticle chains is used as a reinforcing filler in elastomers. However, the dynamics of the filler particles under tension and their role in the improvement of the mechanical properties of rubber are not well understood. We have studied experimentally the dynamics of isolated nanoparticle chain aggregates (NCAs) of carbon made by laser ablation, and also that of carbon black embedded in a polymer film. In situ studies of stretching and contraction of such chains in the transmission electron microscope (TEM) were conducted under different maximum values of strain. Stretching causes initially folded NCA to reorganize into a straight, taut configuration. Further stretching leads to either plastic deformation and breakage (at 37.4% strain) or to a partial elastic behavior of the chain at small strains (e.g. 2.3% strain). For all cases the chains were very flexible under tension. Similar reorientation and stretching was observed for carbon black chains embedded in a polymer film. Such flexible and elastic nature of NCAs point towards a possible mechanism of reinforcement of rubber by carbon black fillers.

Download Full-text