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

Author(s):  
Lindsay E. Kugler ◽  
Kenneth W. Ng ◽  
Christopher J. O’Conor ◽  
Gerard A. Ateshian ◽  
Clark T. Hung

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.

Author(s):  
Christopher J. O’Conor ◽  
Kenneth W. Ng ◽  
Lindsay E. Kugler ◽  
Gerard A. Ateshian ◽  
Clark T. Hung

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).


Author(s):  
Adam Griebel ◽  
C. C. van Donkelaar ◽  
Corey P. Neu

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.


Author(s):  
Shujiang Zhang ◽  
Yongchang Yao

: 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.


2016 ◽  
Vol 104 (11) ◽  
pp. 2764-2774 ◽  
Author(s):  
Amir Mellati ◽  
Meisam Valizadeh Kiamahalleh ◽  
S. Hadi Madani ◽  
Sheng Dai ◽  
Jingxiu Bi ◽  
...  

2019 ◽  
Vol 11 (40) ◽  
pp. 36359-36370 ◽  
Author(s):  
Yaqiang Li ◽  
Yanqun Liu ◽  
Xiaowei Xun ◽  
Wei Zhang ◽  
Yong Xu ◽  
...  

2016 ◽  
Vol 4 (20) ◽  
pp. 3562-3574 ◽  
Author(s):  
E. A. Aisenbrey ◽  
S. J. Bryant

Three dimensional hydrogels are a promising vehicle for delivery of adult human bone-marrow derived mesenchymal stem cells (hMSCs) for cartilage tissue engineering.


Author(s):  
Hui Wang ◽  
Zhonghan Wang ◽  
He Liu ◽  
Jiaqi Liu ◽  
Ronghang Li ◽  
...  

Although there have been remarkable advances in cartilage tissue engineering, construction of irregularly shaped cartilage, including auricular, nasal, tracheal, and meniscus cartilages, remains challenging because of the difficulty in reproducing its precise structure and specific function. Among the advanced fabrication methods, three-dimensional (3D) printing technology offers great potential for achieving shape imitation and bionic performance in cartilage tissue engineering. This review discusses requirements for 3D printing of various irregularly shaped cartilage tissues, as well as selection of appropriate printing materials and seed cells. Current advances in 3D printing of irregularly shaped cartilage are also highlighted. Finally, developments in various types of cartilage tissue are described. This review is intended to provide guidance for future research in tissue engineering of irregularly shaped cartilage.


Author(s):  
Natalia Vapniarsky ◽  
Lilia Moncada ◽  
Carissa Garrity ◽  
Alice Wong ◽  
Barbro Filliquist ◽  
...  

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.


Author(s):  
C. C. van Donkelaar ◽  
M. Khoshgoftar ◽  
L. M. Kock ◽  
K. Ito

Tissue engineered cartilage has reached the level of maturity where the cells, either chondrocytes, BMSC’s or other cells are stimulated to produce a tissue of which the biochemical content qualitatively resembles that of native cartilage. Quantitatively, the proteoglycan content approaches that of native content in long term cultures, but to obtain native collagen fractions is still challenging. Engineered cartilage matrix is either homogeneously distributed, or shows gradual variation from the periphery to the center, caused by nutritional effects.


2018 ◽  
Vol 83 ◽  
pp. 195-201 ◽  
Author(s):  
Xingchen Yang ◽  
Zhenhui Lu ◽  
Huayu Wu ◽  
Wei Li ◽  
Li Zheng ◽  
...  

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