Advances in Application of Mechanical Stimuli in Bioreactors for Cartilage Tissue Engineering

2017 ◽  
Vol 23 (4) ◽  
pp. 399-411 ◽  
Author(s):  
Ke Li ◽  
Chunqiu Zhang ◽  
Lulu Qiu ◽  
Lilan Gao ◽  
Xizheng Zhang
Keyword(s):  
Tissue Engineering ◽  
Cartilage Tissue Engineering ◽  
Cartilage Tissue ◽  
Mechanical Stimuli

The Response of Tissue Engineered Cartilage to the Temporal Application of Transforming and Insulin-Like Growth Factors

2007 ◽  
Author(s):  
Christopher J. O’Conor ◽  
Kenneth W. Ng ◽  
Lindsay E. Kugler ◽  
Gerard A. Ateshian ◽  
Clark T. Hung
Keyword(s):  
Tissue Engineering ◽  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Cartilage Tissue Engineering ◽  
Cartilage Tissue ◽  
Mechanical Stimuli ◽  
Tissue Development ◽  
Engineering Research ◽  
Engineered Cartilage

Agarose has been used as an experimental scaffold for cartilage tissue engineering research due to its biocompatibility with chondrocytes, support of cartilage tissue development, and ability to transmit mechanical stimuli [1–3]. Tissue engineering studies have demonstrated that the temporal application of transforming growth factor (TGF) β3 for only 2 weeks elicits rapid tissue development that results in mechanical properties approaching native values [4]. However, it is not known whether this response to a 2-week exposure to growth factors is unique to TGF-β3. Therefore, the present study characterizes the response of tissue engineered cartilage to the temporal application of the anabolic growth factors TGF-β1, TGF-β3, and insulin-like growth factor I (IGF-I).

scholarly journals Tissue Engineering of Canine Cartilage from Surgically Debrided Osteochondritis Dissecans Fragments

2021 ◽  
Author(s):  
Natalia Vapniarsky ◽  
Lilia Moncada ◽  
Carissa Garrity ◽  
Alice Wong ◽  
Barbro Filliquist ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Thyroid Hormone ◽  
Cartilage Tissue Engineering ◽  
Collagen Content ◽  
Cartilage Tissue ◽  
Mechanical Stimuli ◽  
Primary Chondrocytes ◽  
Native Tissue ◽  
Tissue Constructs ◽  
Self Assembling

AbstractThis study in dogs explored the feasibility of using cartilage fragments removed and discarded during routine palliative surgery for osteochondritis dissecans (OCD) as a source of primary chondrocytes for scaffold-free cartilage tissue-engineering. Primary chondrocytes were obtained from three OCD donors and one age-matched healthy articular cartilage (HAC) donor. After monolayer expansion of primary cells, a three-dimensional spherical suspension culture was implemented. Following this stage, cells were seeded at a high density into custom-made agarose molds that allowed for size and shape-specific constructs to be generated via a method of cellular self-assembling in a scaffold-free environment. Fifty-eight neocartilage constructs were tissue-engineered using this methodology. Neocartilage constructs and native cartilage from shoulder joint were subjected to histological, mechanical, and biochemical testing. OCD and HAC chondrocytes-sourced constructs had uniformly flat morphology and histology consistent with cartilage tissue. Constructs sourced from OCD chondrocytes were 1.5-times (32%) stiffer in compression and 1.3 times (23%) stronger in tension than constructs sourced from HAC chondrocytes and only 8.7-times (81%) less stiff in tension than native tissue. Constructs from both cell sources consistently had lower collagen content than native tissue (22.9%/dry weight [DW] for OCD and 4.1%/DW for HAC vs. 51.1%/DW native tissue). To improve the collagen content and mechanical properties of neocartilage, biological and mechanical stimuli, and thyroid hormone (tri-iodothyronine) were applied to the chondrocytes during the self-assembling stage in two separate studies. A 2.6-fold (62%) increase in compressive stiffness was detected with supplementation of biological stimuli alone and 5-fold (81%) increase with combined biological and mechanical stimuli at 20% strain. Application of thyroid hormone improved collagen content (1.7-times, 33%), tensile strength (1.8-times, 43%), and stiffness (1.3-times, 21%) of constructs, relative to untreated controls. Collectively, these data suggest that OCD chondrocytes can serve as a reliable cell source for cartilage tissue-engineering and that canine chondrocytes respond favorably to biological and mechanical stimuli that have been shown effective in chondrocytes from other animal species, including humans.

Strains in Stratified Agarose Constructs as Determined by Displacement-Encoded MRI

2012 ◽  
Author(s):  
Adam Griebel ◽  
C. C. van Donkelaar ◽  
Corey P. Neu
Keyword(s):  
Tissue Engineering ◽  
Cartilage Tissue Engineering ◽  
Cartilage Tissue ◽  
Mechanical Stimuli ◽  
Healthy Cartilage ◽  
Mechanical Quality ◽  
Different Strains ◽  
Engineered Cartilage ◽  
External Stimuli

Osteoarthritis (OA) is a debilitating disease for which no satisfactory treatment exists. Tissue engineering-based strategies have shown considerable potential for repair. Agarose is frequently used as a scaffold material, as chondrocytes maintain their phenotype and cells remain responsive to mechanical stimuli. To improve the mechanical quality of tissue engineered cartilage, recent studies aimed to reproduce the depth-dependent structure of healthy cartilage. One approach to achieve this is by applying depth-dependent mechanical stimuli via cyclically sliding a glass cylinder over the cell-seeded agarose construct [1,2]. The different strains applied to the surface and the deeper regions are expected to induce stratified matrix synthesis and therefore stratified tissue stiffness. Consequently, with the same external stimuli, the internal strain distribution may alter with ongoing tissue development. Such effect is important to understand in order to optimize mechanical loading regimes for cartilage tissue engineering.

scholarly journals Harnessing Biomechanics to Develop Cartilage Regeneration Strategies

2015 ◽  
Vol 137 (2) ◽  
Author(s):  
Kyriacos A. Athanasiou ◽  
Donald J. Responte ◽  
Wendy E. Brown ◽  
Jerry C. Hu
Keyword(s):  
Tissue Engineering ◽  
Articular Cartilage ◽  
Biochemical Characterization ◽  
Articular Chondrocytes ◽  
Lysyl Oxidase ◽  
Cartilage Tissue Engineering ◽  
Cartilage Regeneration ◽  
Cartilage Tissue ◽  
Main Function ◽  
Mechanical Stimuli

As this review was prepared specifically for the American Society of Mechanical Engineers H.R. Lissner Medal, it primarily discusses work toward cartilage regeneration performed in Dr. Kyriacos A. Athanasiou's laboratory over the past 25 years. The prevalence and severity of degeneration of articular cartilage, a tissue whose main function is largely biomechanical, have motivated the development of cartilage tissue engineering approaches informed by biomechanics. This article provides a review of important steps toward regeneration of articular cartilage with suitable biomechanical properties. As a first step, biomechanical and biochemical characterization studies at the tissue level were used to provide design criteria for engineering neotissues. Extending this work to the single cell and subcellular levels has helped to develop biochemical and mechanical stimuli for tissue engineering studies. This strong mechanobiological foundation guided studies on regenerating hyaline articular cartilage, the knee meniscus, and temporomandibular joint (TMJ) fibrocartilage. Initial tissue engineering efforts centered on developing biodegradable scaffolds for cartilage regeneration. After many years of studying scaffold-based cartilage engineering, scaffoldless approaches were developed to address deficiencies of scaffold-based systems, resulting in the self-assembling process. This process was further improved by employing exogenous stimuli, such as hydrostatic pressure, growth factors, and matrix-modifying and catabolic agents, both singly and in synergistic combination to enhance neocartilage functional properties. Due to the high cell needs for tissue engineering and the limited supply of native articular chondrocytes, costochondral cells are emerging as a suitable cell source. Looking forward, additional cell sources are investigated to render these technologies more translatable. For example, dermis isolated adult stem (DIAS) cells show potential as a source of chondrogenic cells. The challenging problem of enhanced integration of engineered cartilage with native cartilage is approached with both familiar and novel methods, such as lysyl oxidase (LOX). These diverse tissue engineering strategies all aim to build upon thorough biomechanical characterizations to produce functional neotissue that ultimately will help combat the pressing problem of cartilage degeneration. As our prior research is reviewed, we look to establish new pathways to comprehensively and effectively address the complex problems of musculoskeletal cartilage regeneration.

The role of mechanical regulation in cartilage tissue engineering

2021 ◽  
Vol 16 ◽  
Author(s):  
Shujiang Zhang ◽  
Yongchang Yao
Keyword(s):  
Tissue Engineering ◽  
Cartilage Tissue Engineering ◽  
Cartilage Regeneration ◽  
Cartilage Tissue ◽  
Mechanical Stimuli ◽  
And Function ◽  
Engineered Cartilage ◽  
Potential Use

: Due to the lack of vascular distribution and the slow metabolism, cartilage tissue cannot repair itself, which remains a huge challenge for cartilage regeneration. Tissue engineering using stem cells appears to be a promising method for cartilage repair. Tissue engineers demonstrated that mechanical stimulation can enhance the quality of engineered cartilage, making it more similar to natural cartilage in structure and function. In this review, we summarize recent studies on the role of mechanical stimuli in chondrogenesis, focusing on the applications of extrinsic mechanical loading and the studies on mechanical properties of biomaterials in cartilage tissue engineering. This review will provide fresh insights into the potential use of mechanical stimuli for clinical use.

Scaffold Properties Play a Critical Role in the Retention of Synthesized Glycosaminoglycans in Tissue Engineered Cartilage

2007 ◽  
Author(s):  
Lindsay E. Kugler ◽  
Kenneth W. Ng ◽  
Christopher J. O’Conor ◽  
Gerard A. Ateshian ◽  
Clark T. Hung
Keyword(s):  
Tissue Engineering ◽  
Critical Role ◽  
Cartilage Tissue Engineering ◽  
Three Dimensional ◽  
Cartilage Tissue ◽  
Mechanical Stimuli ◽  
Chondrocyte Phenotype ◽  
Engineering Research ◽  
Engineered Cartilage ◽  
Scaffold Properties

Agarose has been used as a model scaffold for cartilage tissue engineering research due to its maintenance of chondrocyte phenotype, support of cartilage tissue development, and ability to transmit mechanical stimuli [1–4]. In a previous study, the temporal application of TGF-β3 for only 2 weeks resulted in explosive growth in the functional properties of tissue engineered cartilage [5]. The role of scaffolds in tissue engineering includes providing a physiologic three-dimensional environment for cells, decreased path lengths for diffusion and retention of cell elaborated matrix. In past studies by our laboratory, it was hypothesized that the scaffold properties in engineered cartilage plays a crucial role in the retention of synthesized glycosaminoglycan (GAG) molecules, a major extracellular matrix constituent of articular cartilage [6, 7]. This study focuses on testing this hypothesis using 3%, 2%, and 1% (wt/vol) agarose as scaffolds for engineered cartilage.

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