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

2000 ◽  
Author(s):  
Robert L. Mauck ◽  
Glyn D. Palmer ◽  
Christopher C.-B. Wang ◽  
Michael A. Soltz ◽  
Wilmot B. Valhmu ◽  
...  

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).

2000 ◽  
Vol 122 (3) ◽  
pp. 252-260 ◽  
Author(s):  
Robert L. Mauck ◽  
Michael A. Soltz ◽  
Christopher C. B. Wang ◽  
Dennis D. Wong ◽  
Pen-Hsiu Grace Chao ◽  
...  

Due to its avascular nature, articular cartilage exhibits a very limited capacity to regenerate and to repair. Although much of the tissue-engineered cartilage in existence has been successful in mimicking the morphological and biochemical appearance of hyaline cartilage, it is generally mechanically inferior to the natural tissue. In this study, we tested the hypothesis that the application of dynamic deformational loading at physiological strain levels enhances chondrocyte matrix elaboration in cell-seeded agarose scaffolds to produce a more functional engineered tissue construct than in free swelling controls. A custom-designed bioreactor was used to load cell-seeded agarose disks dynamically in unconfined compression with a peak-to-peak compressive strain amplitude of 10 percent, at a frequency of 1 Hz, 3× (1 hour on, 1 hour off)/day, 5 days/week for 4 weeks. Results demonstrated that dynamically loaded disks yielded a sixfold increase in the equilibrium aggregate modulus over free swelling controls after 28 days of loading (100±16 kPa versus 15±8 kPa,p<0.0001). This represented a 21-fold increase over the equilibrium modulus of day 0 4.8±2.3 kPa. Sulfated glycosaminoglycan content and hydroxyproline content was also found to be greater in dynamically loaded disks compared to free swelling controls at day 21 (p<0.0001 and p=0.002, respectively). [S0148-0731(00)00703-2]


2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Tongguang Xiao ◽  
Weimin Guo ◽  
Mingxue Chen ◽  
Chunxiang Hao ◽  
Shuang Gao ◽  
...  

The scaffold is a key element in cartilage tissue engineering. The components of Wharton’s jelly are similar to those of articular cartilage and it also contains some chondrogenic growth factors, such as insulin-like growth factor I and transforming growth factor-β. We fabricated a tissue-engineered cartilage scaffold derived from Wharton’s jelly extracellular matrix (WJECM) and compared it with a scaffold derived from articular cartilage ECM (ACECM) using freeze-drying. The results demonstrated that both WJECM and ACECM scaffolds possessed favorable pore sizes and porosities; moreover, they showed good water uptake ratios and compressive moduli. Histological staining confirmed that the WJECM and ACECM scaffolds contained similar ECM. Moreover, both scaffolds showed good cellular adherence, bioactivity, and biocompatibility. MTT and DNA content assessments confirmed that the ACECM scaffold tended to be more beneficial for improving cell proliferation than the WJECM scaffold. However, RT-qPCR results demonstrated that the WJECM scaffold was more favorable to enhance cellular chondrogenesis than the ACECM scaffold, showing more collagen II and aggrecan mRNA expression. These results were confirmed indirectly by glycosaminoglycan and collagen content assessments and partially confirmed by histology and immunofluorescent staining. In conclusion, these results suggest that a WJECM scaffold may be favorable for future cartilage tissue engineering.


Author(s):  
Sonal R. Sampat ◽  
Drew A. Robinson ◽  
George P. Ackerman ◽  
Matthew V. Dermksian ◽  
Gerard A. Ateshian ◽  
...  

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.


Author(s):  
Eric G. Lima ◽  
Liming Bian ◽  
Francis B. Gonzales ◽  
Gerard A. Ateshian ◽  
Clark T. Hung

Injury to the diarthrodial joint is often associated with elevated levels of cytokines and other inflammatory molecules. While the influence of interleukin on articular cartilage has been well-studied, its effects on engineered cartilage are not. The presence of inflammatory factors in the injured joint would be expected to affect the performance of implanted engineered cartilage repair tissue [1] and this effect may be especially pronounced in underdeveloped tissues [2]. The current study addresses this issue by examining the influence of interleukin (IL-1α and IL-1β) on engineered cartilage mechanical and biochemical properties at sequential stages of development. Furthermore, dexamethasone, an anti-inflammatory steroid that has been shown in some cases to suppress interleukin-induced degradation of native cartilage [3], was examined in the context of engineered constructs.


Materials ◽  
2019 ◽  
Vol 12 (20) ◽  
pp. 3331 ◽  
Author(s):  
Chaudhry R. Hassan ◽  
Yi-Xian Qin ◽  
David E. Komatsu ◽  
Sardar M.Z. Uddin

Scaffold design plays an essential role in tissue engineering of articular cartilage by providing the appropriate mechanical and biological environment for chondrocytes to proliferate and function. Optimization of scaffold design to generate tissue-engineered cartilage has traditionally been conducted using in-vitro and in-vivo models. Recent advances in computational analysis allow us to significantly decrease the time and cost of scaffold optimization using finite element analysis (FEA). FEA is an in-silico analysis technique that allows for scaffold design optimization by predicting mechanical responses of cells and scaffolds under applied loads. Finite element analyses can potentially mimic the morphology of cartilage using mesh elements (tetrahedral, hexahedral), material properties (elastic, hyperelastic, poroelastic, composite), physiological loads by applying loading conditions (static, dynamic), and constitutive stress–strain equations (linear, porous–elastic, biphasic). Furthermore, FEA can be applied to the study of the effects of dynamic loading, material properties cell differentiation, cell activity, scaffold structure optimization, and interstitial fluid flow, in isolated or combined multi-scale models. This review covers recent studies and trends in the use of FEA for cartilage tissue engineering and scaffold design.


2020 ◽  
pp. 110215
Author(s):  
Matthew M. Grondin ◽  
Fang Liu ◽  
Michael F. Vignos ◽  
Alexey Samsonov ◽  
Wan-Ju Li ◽  
...  

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 319
Author(s):  
Promita Bhattacharjee ◽  
Mark Ahearne

Medical conditions such as trachoma, keratoconus and Fuchs endothelial dystrophy can damage the cornea, leading to visual deterioration and blindness and necessitating a cornea transplant. Due to the shortage of donor corneas, hydrogels have been investigated as potential corneal replacements. A key factor that influences the physical and biochemical properties of these hydrogels is how they are crosslinked. In this paper, an overview is provided of different crosslinking techniques and crosslinking chemical additives that have been applied to hydrogels for the purposes of corneal tissue engineering, drug delivery or corneal repair. Factors that influence the success of a crosslinker are considered that include material composition, dosage, fabrication method, immunogenicity and toxicity. Different crosslinking techniques that have been used to develop injectable hydrogels for corneal regeneration are summarized. The limitations and future prospects of crosslinking strategies for use in corneal tissue engineering are discussed. It is demonstrated that the choice of crosslinking technique has a significant influence on the biocompatibility, mechanical properties and chemical structure of hydrogels that may be suitable for corneal tissue engineering and regenerative applications.


Biomaterials ◽  
2011 ◽  
Vol 32 (25) ◽  
pp. 5773-5781 ◽  
Author(s):  
Nandana Bhardwaj ◽  
Quynhhoa T. Nguyen ◽  
Albert C. Chen ◽  
David L. Kaplan ◽  
Robert L. Sah ◽  
...  

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