scholarly journals Design of an Endoreactor for the Cultivation of a Joint-Like-Structure

2009 ◽  
Vol 3 (2) ◽  
Author(s):  
E. May ◽  
J. L. Herder ◽  
J. H. Kuiper ◽  
S. Roberts ◽  
S. Sivananthan ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Joint Replacement ◽  
Compliant Mechanism ◽  
Dynamic Compression ◽  
Activity Level ◽  
Body Motion ◽  
Loading Frequency ◽  
Promising Alternative ◽  
Cartilage Formation ◽  
And Cartilage

To avoid revision surgeries in artificial joint replacements and to allow young people to have a joint replacement, using biological joint replacement created by tissue engineering is a promising alternative. Several research groups have tissue engineered bone [Warnke 2004] and cartilage [Chung 2007] separately. The tissue engineering of a joint, consisting of bone and cartilage is the next frontier. The present study focuses on the design of a novel device, named Endoreactor, that is employing the mechanosensitivity of cells to create a joint-like-structure (JLS) consisting of a bone and cartilage sandwich, similar to an amphiarthrosis, by applying a mechanical loading regime to a stem cell seeded scaffold construct during endocultivation. This way, the patients who will eventually need the new joint will serve as their own bioreactor, having the joint grow in their own body. In the JLS, the outside layers are designed to become bone, using a 6 mm thick scaffold with high stiffness. The center layer is a 4 mm thick scaffold which is compliant so as to experience more strain than the outside scaffolds to stimulate cartilage formation. Compression is realized by placing the JLSs between the long links of a kite-shaped four-bar linkage. This Endoreactor is powered by natural body motion through connection to the musculoskeletal system of the host, which in the experimental phase is a Gottingen minipig. The loading frequency and rest versus active time is dictated by the activity level of the minipig. This results in a natural loading pattern that is employed for the stimulation of cartilage formation in the JLS. A tensile force created during ambulation is converted into compressive action between the two long links of the mechanism. A mechanical stop limits the motion. This way controlled intermittent dynamic compression between 2.5% and 12.5% is realized in the cartilage layer of the JLS. All functions are integrated into a single piece compliant mechanism which is produced out of titanium using 3D rapid prototyping by selective laser melting technology. The mechanism can be fitted with cages that hold the scaffolds for bone and cartilage in place and protect them from external loads while being implanted. A safety spring was added to accommodate for large actuation excursions. A number of prototypes were produced and tested for fatigue, plastic deformation, failure load, and displacements of the long links at the JLS locations under different axial loads. These tests confirmed the proper mechanical functioning of the Endoreactor. Work with animal models making use of the device to culture an amphiarthosis-like joint is foreseen in the near future. This work was carried out at part of MYJOINT: Living Bioreactor—Growing a New Joint in a Human Back, EU FP6-2004-NEST-C-1, Proposal No. 028861.

scholarly journals AB0039 AGRIN REPAIRS BONE AND CARTILAGE IN VIVO

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1052.1-1052
Author(s):  
S. Eldridge ◽  
A. Barawi ◽  
H. Wang ◽  
A. Roelofs ◽  
M. Kaneva ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Cartilage Repair ◽  
Joint Replacement ◽  
Critical Size ◽  
Joint Surface ◽  
Cartilage Defects ◽  
Osteochondral Defects ◽  
Cartilage Formation ◽  
And Cartilage

Background:Cartilage defects in the joints are reported in 61% of all arthroscopies1&2. The size of the cartilage repair market is estimated to be $2.195 million by 20253. Cartilage defects can evolve into osteoarthritis, in which abnormal load results in cartilage breakdown, joint pain and reduced mobility. Osteoarthritis is the leading cause of permanent disability and absenteeism and affects up to 1/3 of the people over 60yrs. In western countries osteoarthritis costs 1.5-2% of the GDP4. Joint replacement with a prosthesis restores some degree of independence but in up to 20% of patients it does not meet expectations 5 and has a limited life span. There is no pharmacological intervention that arrests or reverts the course of osteoarthritis, despite the desperate need.We previously published that agrin plays an important role in cartilage homeostasis6. The addition of agrin to chondrocytes in vivo resulted in enhanced cartilage formation, suggesting a potential role for agrin in cartilage repair.Objectives:Investigate the potential of agrin for use in cartilage repair.Methods:Critical size osteochondral defects were generated in mice and sheep and injected intraarticularly with type I collagen gel containing agrin or vehicle. Animals were monitored for 8 weeks or 6 months respectively. MicroCT, histological analysis, qPCR, linage tracking, reporter assays, chondrogenesis assay, immunohistochemistry were performed.Results:A single intraarticular administration of agrin induced regeneration of critical-size osteochondral defects in mice, restoring the tissue architecture and bone-cartilage interface. Agrin stem cells to the site of injury and, through simultaneous activation of CREB and suppression of canonical WNT signalling, induced GDF5 expression and differentiation into stable articular chondrocytes, forming stable articular cartilage. In sheep, agrin treatment resulted in regeneration of bone and cartilage, which promoted increased ambulatory activity.Conclusion:Agrin orchestrates repair morphogenesis at the joint surface by modulating multiple signalling pathways, supporting the therapeutic use of agrin for joint surface regeneration.References:[1]Curl, W. W. et al. Cartilage injuries: a review of 31,516 knee arthroscopies. Arthrosc. J. Arthrosc. Relat. Surg. Off. Publ. Arthrosc. Assoc. N. Am. Int. Arthrosc. Assoc. 13, 456–460 (1997).[2]Hjelle, K., Solheim, E., Strand, T., Muri, R. & Brittberg, M. Articular cartilage defects in 1,000 knee arthroscopies. Arthrosc. J. Arthrosc. Relat. Surg. Off. Publ. Arthrosc. Assoc. N. Am. Int. Arthrosc. Assoc. 18, 730–734 (2002).[3]Cartilage Repair Market Size, Share, Industry Analysis 2018-2025 | AMR. Allied Market Research https://www.alliedmarketresearch.com/cartilage-repair-market.[4]Hiligsmann, M. et al. Health economics in the field of osteoarthritis: an expert’s consensus paper from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). Semin. Arthritis Rheum. 43, 303–313 (2013).[5]Dieppe, P., Lim, K. & Lohmander, S. Who should have knee joint replacement surgery for osteoarthritis? Int. J. Rheum. Dis. 14, 175–180 (2011).[6]Eldridge, S., et al. Agrin mediates chondrocyte homeostasis and requires both LRP4 and α-dystroglycan to enhance cartilage formation in vitro and in vivo. Annals of the rheumatic diseases 75 (6), 1228-1235 (2016).Acknowledgements:We thank the technical staff in the ARM Lab and Staff at the University of Aberdeen’s Animal Facility and Microscopy and Histology Facility for support. Funding: We gratefully acknowledge funding support of this work by the MRC (MR/L022893/1, MR/N010973/1,and MR/P026362/1), Versus Arthritis (19667, 21515, 20886, and 21621), Rosetrees Trust (A1205), the Medical College of St Bartholomew’s Hospital Trust, and the William Harvey Research Foundation.Disclosure of Interests:Suzanne Eldridge: None declared, Aida Barawi: None declared, Hui Wang: None declared, Anke Roelofs: None declared, Magdalena Kaneva: None declared, Zeyu Guan: None declared, Helen Lydon: None declared, Bethan Thomas: None declared, Anne-Sophie Thorup: None declared, Beatriz F Fernandez: None declared, Sara Caxaria: None declared, Danielle Strachan: None declared, Ahmed Ali: None declared, Kanatheepan Shanmuganathan: None declared, Costantino Pitzalis: None declared, James Whiteford: None declared, Fran Henson: None declared, Andrew McCaskie: None declared, Cosimo De Bari: None declared, Francesco Dell’Accio Consultant of: F.D. has received consultancy fees from Samumed and UCB.

scholarly journals A Case Report of Spindle Cell Carcinoma with Osteoid and Cartilage Formation in the Tongue

Reports ◽  
2021 ◽  
Vol 4 (1) ◽  
pp. 5
Author(s):  
Sawako Ono ◽  
Takuma Makino ◽  
Hiroyuki Yanai ◽  
Hotaka Kawai ◽  
Kiyofumi Takabatake ◽  
...  
Keyword(s):  
Case Report ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Spindle Cell ◽  
Spindle Cell Carcinoma ◽  
Cartilage Formation ◽  
And Cartilage

Spindle cell carcinoma (SCSCC) with osteoid and/or cartilage formation in the head and neck is rare; only one case was reported in the tongue. Herein, we report an SCSCC with osteoid and cartilage formation of the tongue developed in an 85-year-old man, and then review the report.

scholarly journals Tissue Engineering of Muscles and Cartilages Using Polyelectrolyte Hydrogels

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Hyuck Joon Kwon
Keyword(s):  
Tissue Engineering ◽  
In Vivo Studies ◽  
Current Status ◽  
Polyelectrolyte Gel ◽  
Polyelectrolyte Gels ◽  
Joint Surfaces ◽  
Functional Replacement ◽  
And Cartilage

The prevalent nature of osteoarthritis that causes the erosion of joint surfaces and loss of mobility and muscle dystrophy that weakens the musculoskeletal system and hampers locomotion underlies the importance of developing functional replacement or regeneration of muscle and cartilage tissues. Polyelectrolyte gels have high potential as cellular scaffolds due to characteristic properties similar to biological matrixes. A number of in vitro and in vivo studies demonstrated that polyelectrolyte gels are useful for replacement and regeneration of muscle and cartilage tissues. In addition, it was also found that polyelectrolyte gels have high biocompatibility, durability, and resistance to biodegradation. Moreover, polyelectrolyte gels can overcome their drawbacks of mechanical behavior by introducing double network into the gel. This paper reviews the current status and recent progress of polyelectrolyte gel-based tissue engineering for repairs of muscle and cartilage tissues.

scholarly journals An ECHO of Cartilage: In Silico Prediction of Combinatorial Treatments to Switch Between Transient and Permanent Cartilage Phenotypes With Ex Vivo Validation

2021 ◽  
Vol 9 ◽  
Author(s):  
Sakshi Khurana ◽  
Stefano Schivo ◽  
Jacqueline R. M. Plass ◽  
Nikolas Mersinis ◽  
Jetse Scholma ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Model Checking ◽  
Cell Fate ◽  
Growth Plate ◽  
Ex Vivo ◽  
Boolean Model ◽  
Zonal Distribution ◽  
Cell Fate Decisions ◽  
Hypertrophic Cartilage ◽  
Cartilage Formation

A fundamental question in cartilage biology is: what determines the switch between permanent cartilage found in the articular joints and transient hypertrophic cartilage that functions as a template for bone? This switch is observed both in a subset of OA patients that develop osteophytes, as well as in cell-based tissue engineering strategies for joint repair. A thorough understanding of the mechanisms regulating cell fate provides opportunities for treatment of cartilage disease and tissue engineering strategies. The objective of this study was to understand the mechanisms that regulate the switch between permanent and transient cartilage using a computational model of chondrocytes, ECHO. To investigate large signaling networks that regulate cell fate decisions, we developed the software tool ANIMO, Analysis of Networks with interactive Modeling. In ANIMO, we generated an activity network integrating 7 signal transduction pathways resulting in a network containing over 50 proteins with 200 interactions. We called this model ECHO, for executable chondrocyte. Previously, we showed that ECHO could be used to characterize mechanisms of cell fate decisions. ECHO was first developed based on a Boolean model of growth plate. Here, we show how the growth plate Boolean model was translated to ANIMO and how we adapted the topology and parameters to generate an articular cartilage model. In ANIMO, many combinations of overactivation/knockout were tested that result in a switch between permanent cartilage (SOX9+) and transient, hypertrophic cartilage (RUNX2+). We used model checking to prioritize combination treatments for wet-lab validation. Three combinatorial treatments were chosen and tested on metatarsals from 1-day old rat pups that were treated for 6 days. We found that a combination of IGF1 with inhibition of ERK1/2 had a positive effect on cartilage formation and growth, whereas activation of DLX5 combined with inhibition of PKA had a negative effect on cartilage formation and growth and resulted in increased cartilage hypertrophy. We show that our model describes cartilage formation, and that model checking can aid in choosing and prioritizing combinatorial treatments that interfere with normal cartilage development. Here we show that combinatorial treatments induce changes in the zonal distribution of cartilage, indication possible switches in cell fate. This indicates that simulations in ECHO aid in describing pathologies in which switches between cell fates are observed, such as OA.

BONE AND CARTILAGE FORMATION BY PERIOSTEUM

1955 ◽  
Vol 37 (4) ◽  
pp. 717-730 ◽  
Author(s):  
Jonathan Cohen ◽  
Pierre Lacroix
Keyword(s):  
Cartilage Formation ◽  
And Cartilage
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