Functional Tissue Engineering of Articular Cartilage Through Dynamic Loading of Chondrocyte-Seeded Agarose Gels

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 ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Compressive Strain ◽  
Fold Increase ◽  
Physiological Strain ◽  
Equilibrium Modulus ◽  
Free Swelling ◽  
Dynamically Loaded ◽  
Engineered Tissue ◽  
Natural Tissue ◽  
Engineered Cartilage

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]

scholarly journals Integrating melt-electrowriting and inkjet bioprinting for engineering structurally organized articular cartilage

2021 ◽  
Author(s):  
Alexandre DUFOUR ◽  
Xavier Barceló Gallostra ◽  
Conor OKeeffe ◽  
Kian F Eichholz ◽  
Stanislas Von Euw ◽  
...  
Keyword(s):  
Polymer Network ◽  
Fold Increase ◽  
Compressive Properties ◽  
Native Tissue ◽  
Engineer Cartilage ◽  
Helium Ion ◽  
Engineered Tissue ◽  
Engineered Cartilage ◽  
Cellular Aggregates ◽  
Polymeric Structures

Successful cartilage engineering requires the generation of biological grafts mimicking the structure, composition and mechanical behaviour of the native tissue. Here melt-electrowriting (MEW) was used to produce arrays of polymeric structures whose function was to orient the growth of cellular aggregates spontaneously generated within these structures, and to provide tensile reinforcement to the resulting tissues. Inkjeting was used to deposit defined numbers of cells into MEW structures, which self-assembled into an organized array of spheroids within hours, ultimately generating a hybrid tissue that was hyaline-like in composition. Structurally, the engineered cartilage mimicked the histotypical organization observed in skeletally immature synovial joints. This biofabrication framework was then used to generate scaled-up (50mm x 50mm) cartilage implants containing over 3,500 cellular aggregates in under 15 minutes. After 8 weeks in culture, a 50-fold increase in the compressive properties of these MEW reinforced tissues were observed, while the tensile properties were still dominated by the polymer network, resulting in a composite construct demonstrating tension-compression nonlinearity mimetic of the native tissue. Helium ion microscopy further demonstrated the development of an arcading collagen network within the engineered tissue. This hybrid bioprinting strategy provides a versatile and scalable approach to engineer cartilage biomimetic grafts for biological joint resurfacing.

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 ◽  
...  
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).

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 An Instrumented Bioreactor for Mechanical Stimulation and Real-Time, Nondestructive Evaluation of Engineered Cartilage Tissue

2012 ◽  
Vol 6 (2) ◽  
Author(s):  
Jenni R. Popp ◽  
Justine J. Roberts ◽  
Doug V. Gallagher ◽  
Kristi S. Anseth ◽  
Stephanie J. Bryant ◽  
...  
Keyword(s):  
Nondestructive Evaluation ◽  
Mechanical Stimulation ◽  
Ultrasonic Transducer ◽  
Testing Machine ◽  
Cartilage Tissue ◽  
Matrix Deposition ◽  
Intermittent Compression ◽  
Engineered Tissue ◽  
Engineered Cartilage

Mechanical stimulation is essential for chondrocyte metabolism and cartilage matrix deposition. Traditional methods for evaluating developing tissue in vitro are destructive, time consuming, and expensive. Nondestructive evaluation of engineered tissue is promising for the development of replacement tissues. Here we present a novel instrumented bioreactor for dynamic mechanical stimulation and nondestructive evaluation of tissue mechanical properties and extracellular matrix (ECM) content. The bioreactor is instrumented with a video microscope and load cells in each well to measure tissue stiffness and an ultrasonic transducer for evaluating ECM content. Chondrocyte-laden hydrogel constructs were placed in the bioreactor and subjected to dynamic intermittent compression at 1 Hz and 10% strain for 1 h, twice per day for 7 days. Compressive modulus of the constructs, measured online in the bioreactor and offline on a mechanical testing machine, did not significantly change over time. Deposition of sulfated glycosaminoglycan (sGAG) increased significantly after 7 days, independent of loading. Furthermore, the relative reflection amplitude of the loaded constructs decreased significantly after 7 days, consistent with an increase in sGAG content. This preliminary work with our novel bioreactor demonstrates its capabilities for dynamic culture and nondestructive evaluation.

Numerical Study on Mechanical Behavior of Tissue-Engineering Repaired Cartilage in Sliding Load Condition

2013 ◽  
Vol 441 ◽  
pp. 598-601
Author(s):  
Yu Zhou ◽  
Hai Ying Liu ◽  
Yu Tao Men ◽  
Li Lan Gao ◽  
Bao Shan Xu ◽  
...  
Keyword(s):  
Numerical Study ◽  
Compressive Strain ◽  
Load Condition ◽  
Repair Process ◽  
Cartilage Defects ◽  
Biphasic Model ◽  
Artificial Cartilage ◽  
Repairing Effect ◽  
Intensity Of Exercise ◽  
Engineered Cartilage

Mechanical state has a major impact on the repairing effect of tissue-engineered cartilage. The unusual state could result in the degeneration of artificial and host cartilage. A repaired cartilage defects was simulated by finite element simulation based on fiber-reinforced biphasic model in sliding load condition. The results showed that in the surrounding area of defects Mises stress, compressive strain and pore pressure are affected by the amount of compression and modulus of materials. Inadequate modulus leads to the declining mechanical bearing ability in defected position, while excessive modulus leads to increasing difference between the pressure on the two sides of bonding surface between artificial cartilage and host cartilage. During the repair process, it is suggested to choose the artificial cartilage modulus with both reasonable bearing ability and less stress concentration should be considered, and the intensity of exercise should also decrease to reduce the amount of compression.

Mechanical basis for lingual deformation during the propulsive phase of swallowing as determined by phase-contrast magnetic resonance imaging

2007 ◽  
Vol 103 (1) ◽  
pp. 255-265 ◽  
Author(s):  
Samuel M. Felton ◽  
Terry A. Gaige ◽  
Timothy G. Reese ◽  
Van J. Wedeen ◽  
Richard J. Gilbert
Keyword(s):  
Strain Rate ◽  
Phase Contrast ◽  
Compressive Strain ◽  
Local Strain ◽  
Styloid Process ◽  
Tongue Pressure ◽  
Orthogonal Expansion ◽  
Physiological Strain ◽  
Phase Contrast Mri ◽  
Contrast Magnetic Resonance

The tongue is an intricately configured muscular organ that undergoes a series of rapid shape changes intended to first configure and then transport the bolus from the oral cavity to the pharynx during swallowing. To assess the complex array of mechanical events occurring during the propulsive phase of swallowing, we employed tongue pressure-gated phase-contrast MRI to represent the tissue's local strain rate vectors. Validation of the capacity of phase-contrast MRI to represent local compressive and expansive strain rate was obtained by assessing deformation patterns induced by a synchronized mechanical plunger apparatus in a gelatinous material phantom. Physiological strain rate data were acquired in the sagittal and coronal orientations at 0, 200, 400, and 600 ms relative to the gating pulse during 2.5-ml water bolus swallows. This method demonstrated that the propulsive phase of swallowing is associated with a precisely organized series of compressive and expansive strain rate events. At the initiation of propulsion, bolus position resulted from obliquely aligned compressive and expansive strain, vertically aligned compressive strain and orthogonal expansion, and compressive strain aligned obliquely to the styloid process. Bolus reconfiguration and translocation resulted from a combination of compressive strain occurring in the middle and posterior tongue aligned obliquely between the anterior-inferior and the posterior-superior regions with commensurate orthogonal expansion, along with bidirectional contraction in the distribution of the transversus and verticalis muscle fibers. These data support the concept that propulsive lingual deformation is due to complex muscular interactions involving both extrinsic and intrinsic muscles.

scholarly journals Challenges in Fabrication of Tissue-Engineered Cartilage with Correct Cellular Colonization and Extracellular Matrix Assembly

2018 ◽  
Vol 19 (9) ◽  
pp. 2700 ◽  
Author(s):  
Mikko Lammi ◽  
Juha Piltti ◽  
Juha Prittinen ◽  
Chengjuan Qu
Keyword(s):  
Extracellular Matrix ◽  
Articular Cartilage ◽  
Pore Size ◽  
Cartilage Tissue ◽  
Cellular Interactions ◽  
Matrix Assembly ◽  
Small Pore ◽  
Culture Models ◽  
Open Question ◽  
Engineered Cartilage

A correct articular cartilage ultrastructure regarding its structural components and cellularity is important for appropriate performance of tissue-engineered articular cartilage. Various scaffold-based, as well as scaffold-free, culture models have been under development to manufacture functional cartilage tissue. Even decellularized tissues have been considered as a potential choice for cellular seeding and tissue fabrication. Pore size, interconnectivity, and functionalization of the scaffold architecture can be varied. Increased mechanical function requires a dense scaffold, which also easily restricts cellular access within the scaffold at seeding. High pore size enhances nutrient transport, while small pore size improves cellular interactions and scaffold resorption. In scaffold-free cultures, the cells assemble the tissue completely by themselves; in optimized cultures, they should be able to fabricate native-like tissue. Decellularized cartilage has a native ultrastructure, although it is a challenge to obtain proper cellular colonization during cell seeding. Bioprinting can, in principle, provide the tissue with correct cellularity and extracellular matrix content, although it is still an open question as to how the correct molecular interaction and structure of extracellular matrix could be achieved. These are challenges facing the ongoing efforts to manufacture optimal articular cartilage.

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