scholarly journals Cartilage tissue engineering using pre-aggregated human articular chondrocytes

2008 ◽  
Vol 16 ◽  
pp. 92-99 ◽  
Author(s):  
F Wolf ◽  
◽  
C Candrian ◽  
D Wendt ◽  
J Farhadi ◽  
...  
Lab on a Chip ◽  
2014 ◽  
Vol 14 (23) ◽  
pp. 4475-4485 ◽  
Author(s):  
Siwei Li ◽  
Peter Glynne-Jones ◽  
Orestis G. Andriotis ◽  
Kuan Y. Ching ◽  
Umesh S. Jonnalagadda ◽  
...  

Bioengineering neocartilage grafts of human articular chondrocytes in a custom-built microfluidic perfusion bioreactor with integrated ultrasound standing wave trap.


2021 ◽  
Vol 11 (17) ◽  
pp. 7821
Author(s):  
Angeliki Dimaraki ◽  
Pedro J. Díaz-Payno ◽  
Michelle Minneboo ◽  
Mahdiyeh Nouri-Goushki ◽  
Maryam Hosseini ◽  
...  

The treatment of articular cartilage defects remains a significant clinical challenge. This is partially due to current tissue engineering strategies failing to recapitulate native organization. Articular cartilage is a graded tissue with three layers exhibiting different cell densities: the superficial zone having the highest density and the deep zone having the lowest density. However, the introduction of cell gradients for cartilage tissue engineering, which could promote a more biomimetic environment, has not been widely explored. Here, we aimed to bioprint a scaffold with different zonal cell densities to mimic the organization of articular cartilage. The scaffold was bioprinted using an alginate-based bioink containing human articular chondrocytes. The scaffold design included three cell densities, one per zone: 20 × 106 (superficial), 10 × 106 (middle), and 5 × 106 (deep) cells/mL. The scaffold was cultured in a chondrogenic medium for 25 days and analyzed by live/dead assay and histology. The live/dead analysis showed the ability to generate a zonal cell density with high viability. Histological analysis revealed a smooth transition between the zones in terms of cell distribution and a higher sulphated glycosaminoglycan deposition in the highest cell density zone. These findings pave the way toward bioprinting complex zonal cartilage scaffolds as single units, thereby advancing the translation of cartilage tissue engineering into clinical practice.


Author(s):  
Minwook Kim ◽  
Jason A. Burdick ◽  
Robert L. Mauck

Mesenchymal stem cells (MSCs) are an attractive cell type for cartilage tissue engineering in that they can undergo chondrogenesis in a variety of 3D contexts [1]. Focused efforts in MSC-based cartilage tissue engineering have recently culminated in the formation of biologic materials possessing biochemical and functional mechanical properties that match that of the native tissue [2]. These approaches generally involve the continuous or intermittent application of pro-chondrogenic growth factors during in vitro culture. For example, in one recent study, we showed robust construct maturation in MSC-seeded hyaluronic acid (HA) hydrogels transiently exposed to high levels of TGF-β3 [3]. Despite the promise of this approach, MSCs are a multipotent cell type and retain a predilection towards hypertrophic phenotypic conversion (i.e., bone formation) when removed from a pro-chondrogenic environment (e.g., in vivo implantation). Indeed, even in a chondrogenic environment, many MSC-based cultures express pre-hypertrophic markers, including type X collagen, MMP13, and alkaline phosphatase [4]. To address this issue, recent studies have investigated co-culture of human articular chondrocytes and MSCs in both pellet and hydrogel environments. Chondrocytes appear to enhance the initial efficiency of MSC chondrogenic conversion, as well as limit hypertrophic changes in some instances (potentially via secretion of PTHrP and/or other factors) [5–7]. While these findings are intriguing, articular cartilage has a unique depth-dependent morphology including zonal differences in chondrocyte identity. Ng et al. showed that zonal chondrocytes seeded in a bi-layered agarose hydrogel construct can recreate depth-dependent cellular and mechanical heterogeneity, suggesting that these identities are retained with transfer to 3D culture systems [8]. Further, Cheng et al. showed that differences in matrix accumulation and hypertrophy in zonal chondrocytes was controlled by bone morphogenic protein [9]. To determine whether differences in zonal chondrocyte identity influences MSC fate decisions, we evaluated functional properties and phenotypic stability in photocrosslinked hyaluronic acid (HA) hydrogels using distinct, zonal chondrocyte cell fractions co-cultured with bone marrow derived MSCs.


2006 ◽  
Vol 53 ◽  
pp. 67-69
Author(s):  
H. Otsuka ◽  
T. Satomi ◽  
Koji Ueno ◽  
Tetsuya Tateishi

Micropatterned PEGylated substrates with two-dimensional arrays of plasma-etched circular domains (diameter:100 micro-m) were prepared by coating of mercapto-functionalized poly(ethylene glycol) (PEG) on Au surface, followed by plasma-etching through a metal mask pattern with circular holes. The PEGylated region on the patterned substrate works to repel proteins, consequently, inhibits cell adhesion. Then the micro-patterning of bovine articular chondrocytes or rat primary hepatocytes hetero-spheroids underlaid with human umbilical endothelial cells (HUVEC) was achieved on the plasma-etched circular domains, exposing the base gold surface. Obtained results suggested that the efficiency of inhibiting non-specific protein adsorption significantly affects on construction of micro-patterned cell adhesion and hetero-spheroids. The formation of hetero-spheroid thus suggested is significantly modulated by suface properties, particularly non-fouling character of PEG region. These arrayed spheroids is promising materials for tissue and cell-based biosensors (TBB/CBB) as well as tissue engineering technologies.


2015 ◽  
Vol 137 (2) ◽  
Author(s):  
Kyriacos A. Athanasiou ◽  
Donald J. Responte ◽  
Wendy E. Brown ◽  
Jerry C. Hu

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.


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