Bioprinting of biomimetic self-organised cartilage with a supporting joint fixation device

2021 ◽  
Vol 14 (1) ◽  
pp. 015008
Author(s):  
Ross Burdis ◽  
Farhad Chariyev-Prinz ◽  
Daniel J Kelly
Keyword(s):  
Complete Solution ◽  
Cartilage Tissue ◽  
Synovial Joint ◽  
Fixation Device ◽  
Collagen Network ◽  
Parallel Fibre ◽  
Engineered Tissue ◽  
Self Organisation ◽  
Engineered Cartilage

Abstract Despite sustained efforts, engineering truly biomimetic articular cartilage (AC) via traditional top-down approaches remains challenging. Emerging biofabrication strategies, from 3D bioprinting to scaffold-free approaches that leverage principles of cellular self-organisation, are generating significant interest in the field of cartilage tissue engineering as a means of developing biomimetic tissue analogues in vitro. Although such strategies have advanced the quality of engineered cartilage, recapitulation of many key structural features of native AC, in particular a collagen network mimicking the tissue’s ‘Benninghoff arcade’, remains elusive. Additionally, a complete solution to fixating engineered cartilages in situ within damaged synovial joints has yet to be identified. This study sought to address both of these key challenges by engineering biomimetic AC within a device designed to anchor the tissue within a synovial joint defect. We first designed and fabricated a fixation device capable of anchoring engineered cartilage into the subchondral bone. Next, we developed a strategy for inkjet printing porcine mesenchymal stem/stromal cells (MSCs) into this supporting fixation device, which was also designed to provide instructive cues to direct the self-organisation of MSC condensations towards a stratified engineered AC. We found that a higher starting cell-density supported the development of a more zonally defined collagen network within the engineered tissue. Dynamic culture was implemented to further enhance the quality of this engineered tissue, resulting in an approximate 3 fold increase in glycosaminoglycan and collagen accumulation. Ultimately this strategy supported the development of AC that exhibited near-native levels of glycosaminoglycan accumulation (>5% WW), as well as a biomimetic collagen network organisation with a perpendicular to a parallel fibre arrangement (relative to the tissue surface) from the deep to superficial zones via arcading fibres within the middle zone of the engineered tissue. Collectively, this work demonstrates the successful convergence of novel biofabrication methods, bioprinting strategies and culture regimes to engineer a hybrid implant suited to resurfacing AC defects.

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.

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.

Effects of Media Stirring and Presence of Nutrient Channels on Functional Properties of Large Engineered Cartilage Constructs

2013 ◽  
Author(s):  
Alexander D. Cigan ◽  
Robert J. Nims ◽  
Michael B. Albro ◽  
Clark T. Hung ◽  
Gerard A. Ateshian
Keyword(s):  
Functional Properties ◽  
Orbital Motion ◽  
Scale Up ◽  
Cartilage Tissue Engineering ◽  
Cartilage Tissue ◽  
Different Types ◽  
Effects Of Media ◽  
Inhomogeneous Properties ◽  
Engineered Cartilage

Cartilage tissue engineering is a promising approach for the replacement of degraded joint cartilage in osteoarthritis (OA) patients. Current strategies employ smaller constructs (∼20 mm 2), however OA generally does not become symptomatic until defects reach ≥ 5 cm 2. Therefore, small constructs may not ultimately be clinically relevant for treatment of OA. Attempts to scale up construct size are met with challenges, as inhomogeneous properties develop as a result of poor nutrient availability at the construct center due to cellular consumption at the periphery [1]. Previously, the incorporation of ∅1 mm nutrient channels in large (∅10 mm) constructs was found to improve Young’s modulus (E Y) and glycosaminoglycan (GAG) content and reproduce their native values [2]. Rotational mixing has been shown to improve properties of micro-channeled constructs [3]. As a major goal of our research is to optimize channel size and arrangement to improve the quality of large engineered cartilage constructs, it is essential to develop a simple but effective method for convecting media through channeled constructs. Therefore, this study seeks to compare the functional properties of large constructs that are subjected to different types of media stirring, by rocking or orbital motion, and to determine whether either of these conditions favors the quality of constructs with nutrient channels.

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.

scholarly journals P1398 Echocardiographic continuous monitoring of exercise stress test using probe fixation device

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
K Wdowiak-Okrojek ◽  
P Wejner-Mik ◽  
Z Bednarkiewicz ◽  
P Lipiec ◽  
J D Kasprzak
Keyword(s):  
Image Quality ◽  
Physical Exercise ◽  
Stress Test ◽  
Exercise Stress Test ◽  
Bicycle Ergometer ◽  
Exercise Stress ◽  
Fixation Device ◽  
The Mean ◽  
First Time

Abstract Background Stress echocardiography (SE) plays an important role among methods of noninvasive diagnosis of ischemic disease. Despite the advantages of physical exercise as the most physiologic stressor, it is difficult (bicycle ergometer) or impossible (treadmill) to obtain and maintain the acoustic window during the exercise. Recently, an innovative probe fixation device was introduced and a research plan was developed to assess the feasibility of external probe fixation during exercise echocardiography on a supine bicycle and upright treadmill exercise for the first time. Methods 37 subjects (36 men, mean age 39 ± 16 years, 21 healthy volunteers, 16 patients with suspected coronary artery disease) were included in this study. This preliminary testing stage included mostly men due to more problematic probe fixation in women. All subjects underwent a submaximal exercise stress test on a treadmill (17/37) or bicycle ergometer (11/37). Both sector and matrix probes were used. We assessed semi-quantitatively the quality of acquired apical views at each stage – the four-point grading system was used (0-no view, 1-suboptimal quality, 2-optimal quality, 3-very good quality), 2-3 sufficient for diagnosis. Results The mean time required for careful positioning of the probe and image optimization was 12 ± 3 min and shortened from 13,7 to 11,1 minutes (mean) in first vs second half of the cohort documenting learning curve. At baseline, 9 patients had at least one apical view of quality precluding reliable analysis. Those patients were excluded from further assessment. During stress, 17 patients maintained the optimal or very good quality of all apical views, whereas in 11 patients the quality significantly decreased during the stress test and required probe repositioning. The mean image quality score at baseline was 2,61 ± 0,48 and 2,25 ± 0,6 after exercise. Expectedly, good image quality was easier to obtain and maintain in the supine position (score 2,74 ± 0,44) points as compared with upright position (score 2,25 ± 0,57). Conclusion This preliminary, unique experience with external probe fixation device indicates that continuous acquisition and monitoring of echocardiographic images is feasible during physical exercise, and for the first time ever - also on the treadmill. This feasibility data stem from almost exclusively male patients and the estimated rate of sufficient image quality throughout the entire test is currently around 60%. We are hoping, that gaining more experience with the product could increase the success rate on exercise tests. Abstract P1398 Figure. Treadmill and ergometer stress test

Tissue-Engineered Cartilage in Three-Dimensional Cultured Chondrocytes by Ultrasound Stimulation and Collagen Sponge as Scaffold

2009 ◽  
Author(s):  
Toshihiko Shiraishi ◽  
Ietomo Matsunaga ◽  
Shin Morishita ◽  
Ryohei Takeuchi ◽  
Tomoyuki Saito ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Three Dimensional ◽  
Collagen Sponge ◽  
Cartilage Tissue ◽  
Mechanical Environment ◽  
Ultrasound Stimulation ◽  
Scaffold Structure ◽  
Matrix Production ◽  
Engineered Cartilage ◽  
Cultured Chondrocytes

This paper describes the effects of ultrasound stimulation on chondrocytes in three-dimensional culture in relation to the production of regenerative cartilage tissue, using collagen sponges as a carrier and supplementation with hyaluronic acid (used in the conservative treatment of osteoarthritis). It has been shown that cell proliferation and matrix production can be facilitated by considering the mechanical environment of the cultured chondrocytes and the mechanical properties of the scaffold structure used in the culture and of the stimulation used.

Mechanical quality of tissue engineered cartilage: Results after 6 and 12 weeksin vivo

2000 ◽  
Vol 53 (6) ◽  
pp. 673-677 ◽  
Author(s):  
Georg N. Duda ◽  
Andreas Haisch ◽  
Michaela Endres ◽  
Christian Gebert ◽  
Daniel Schroeder ◽  
...  
Keyword(s):  
Mechanical Quality ◽  
Engineered Cartilage

scholarly journals Attenuation of Trauma-induced Osteoarthritis by Repetitive Intra-articular Administration of Peripheral Blood Derived Mesenchymal Stem Cells

2021 ◽  
Author(s):  
Weiping Lin ◽  
Zhengmeng Yang ◽  
Liu Shi ◽  
Haixing Wang ◽  
Qi Pan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Articular Cartilage ◽  
Subchondral Bone ◽  
Peripheral Blood ◽  
Cartilage Degradation ◽  
Cartilage Tissue ◽  
Synovial Joint ◽  
Post Surgery ◽  
Sham Surgery

Abstract Background: Osteoarthritis (OA) is a chronic joint disease, characterized by articular cartilage degradation, subchondral bone hardening, and inflammation of the whole synovial joint. There is no pharmacological treatment in slowing down OA progression, leading to costly surgical interventions eventually. Cell therapy using chondrocytes or progenitor cells from different sources has been reported in clinical trials for OA management with some success, but outcomes are varied. Peripheral blood derived mesenchymal stem cells (PB-MSCs) are promising cells owing to their easy collection, superior migration, and differentiation potentials. In the current study, we evaluated the effect of intra-articular administration of PB-MSCs on the progression of OA in mice.Methods: C57BL/6J mice (8-10 weeks old male) were subjected to destabilization of the medial meniscus surgeries (DMM) on their right joints following protocols as previously reported. The mice after DMM were randomly treated with saline (vehicle control), PB-MSCs, or adipose tissue derived MSCs (AD-MSCs) (n = 7 per group). The mice treated with sham surgery were regarded as sham controls (n = 7). PB-MSCs and AD-MSCs were harvested and cultured according to previous published protocols, and pre-labeled with BrdU for 48 h before use. PB-MSCs or AD-MSCs (5 × 105 cells/mouse; passage 3~5) were injected into the right knee joints thrice post-surgery (except sham surgery group). The mice were euthanized at 8 weeks post-surgery and knee joint samples were collected for micro-CT and histological examinations.Results: PB-MSCs administration significantly reduced hardening of subchondral bone comparing to vehicle controls. Safranin O staining showed that PB-MSCs treatment ameliorated degeneration of articular cartilage, which is comparable to AD-MSCs treatment. The expression of catabolic marker MMP13 was significantly reduced in articular cartilage of PB-MSCs-treated groups comparing to vehicle controls. Co-expression of BrdU and Sox9 were detected, indicating injected PB-MSCs differentiated towards chondrocytes in situ. Reduced level of IL-6 in the peripheral sera of PB-MSCs- and AD-MSCs-treated mice was also determined. Conclusions: Repetitive administration of PB-MSCs or AD-MSCs halted OA progression through inhibiting cartilage degradation and inflammation. PB-MSCs may become a promising cell source for cartilage tissue repair and alleviation of OA progression.

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