cues for further differentiation and proliferation.
These regeneration therapies have been tested in several animal models such as mouse, chicken, rabbit, sheep, and monkeys. Very few have been extended to human subjects. The clinical trial for the regeneration of tendons is the technology wherein the tenocytes are applied to the site of the wound that promotes regeneration. Similar to cartilage, scaffolds are also used to deliver these cells to the site of the wound.
Taking the treatment from animal models to human subjects requires the collaboration of cell and molecular biologists and surgeons to work together to concur on the cellular mechanics and delivery of the scaffold. There are several lobbyist groups such as the arthritis foundation that are pushing boundaries to take the therapy to the next level.
Ligament Regeneration
Ligaments are soft yet mechanical tissues that are capable of load bearing. They are of enormous mechanical strength, yet the regeneration process is not robust because of the decreased requirement of nutrients and oxygen for the ligament tissue. This results in the formation of weak tissue and so the regeneration of ligament has been gaining a fair amount of attention. One of the first therapy options for the purposes of regeneration is to apply biomolecules at the site of the wound. These biomolecules, such as TGF-beta and PDGF, promote the formation of ligament—inside the body. This process uses the human body as a bioreactor to generate the ligament. Some of the other options are very similar to those of cartilages and ligaments wherein stem cells are isolated from the body, differentiated in vitro, and then later applied to the site of the wound. Biomaterials and biomimetics are said to generate structure to generate the inserts of desirable shape.
Another important consideration in choosing scaffolding material in the case of ligaments is that, considering the function of ligaments, they need to be durable and strong. The load-bearing capacity of the scaffolding tissue is tested in vitro before it can be applied to the bone. Since ligaments are mostly tissue that are attached to bone and facilitate the easy movement of the joint, the shape and pliability of the scaffold are also very important. Natural and synthetic polymers can be used as scaffolds. The advantage of a natural polymer over synthetic polymer is that it offers a surface that is adherent for the cells. Natural polymers also do not release acidic chemicals on hydrolysis, but one of the significant disadvantages is that they are degradable, and once inside the body system, the degradation curve cannot be controlled as yet.
The regeneration of bone commonly involves the regeneration of soft tissues as well, because the bones and joints are held together with the help of cartilage, tendons, and ligaments. All the processes in concert with one another are required for efficient regeneration of the structural system. When a bone regenerates, the tendons and cartilage also need to regenerate to hold the structure in place. Combinations of scaffolds and different biomaterials for bone, cartilage, tendons, and ligaments are being theorized to facilitate a complete healing of the skeletal subunit.
Clinical Trials
Most of the clinical trials in the area of cartilage and tendon regeneration are focused on autologous regeneration. Most of the scaffold and biomaterial supplements are in the stages of animal model testing.
In autologous reconstruction of worn-out cartilage, cartilage is extracted from a different site in the patient. This extracted cartilage is carved ex vivo and then applied to the site of the wound that needs to regenerate. Clinical trials are in progress for supplementing this process with plasma platelets. These trials test individual factors such as injection mode, time of injection, volume of injection, and whether a single dose or a series of injections in smaller volumes is preferable. The scientific efficacy of the test parameters is evaluated to devise a therapeutic or surgical plan. At the end of clinical trials, the methodology is also assessed for patient benefit, affordable costs, and the risks involved in the implementation of the process. A joint patient-doctor approach is used to evaluate the aforementioned parameters.
Ligament tears are very common in athletes and sportsmen, who require a robust and quick fix to get the joints back in working condition. The anterior cruciate ligament (ACL) in the knee connects the two bones in the joint, and it is one of the most common ligament tears. In 2014, a clinical trial is in progress to test the replacement of this ligament with the polymer poly-L-Lactic acid. The polymer is inserted via the bone in both knees and it substitutes for the ACL.
Outlined above are some of the clinical trials that are devising therapeutic strategies. The cell replacement therapy and tissue engineering is yet to reach the clinical trials as far as tendons, ligaments, and cartilage are concerned.
Sharanya Kumar
Independent Scholar
See Also: Cartilage, Tendons, and Ligaments: Cell Types Composing the Tissue; Cartilage, Tendons, and Ligaments: Current Research on Isolation or Production of Therapeutic Cells; Cartilage, Tendons, and Ligaments: Development and Regeneration Potential; Cartilage, Tendons, and Ligaments: Major Pathologies; Cartilage, Tendons, and Ligaments: Stem and Progenitor Cells in Adults.
Further Readings
Kuo, C. K., J. E. Marturano, and R. S. Tuan. “Novel Strategies in Tendon and Ligament Tissue Engineering: Advanced Biomaterials and Regeneration Motifs.” Sports Medicine, Arthroscopy, Rehabilitation, Therapy & Technology, v.2/20 (2010).
Paoloni, J., R. J. De Vos, B. Hamilton, G. A. Murrell, and J. Orchard. “Platelet-Rich Plasma Treatment for Ligament and Tendon Injuries.” Clinical Journal of Sport Medicine, v.21/1 (2011).
Tuan, R. S., A. F. Chen, and B. A. Klatt. “Cartilage Regeneration.” Journal of the American Academy of Orthopaedic Surgeons, v.21/5 (2013).
Yang, G., B. B. Rothrauff, and R. S. Tuan (2013). “Tendon and Ligament Regeneration and Repair: Clinical Relevance and Developmental Paradigm.” Birth Defects Research Part C Embryo Today, v.99/3 (2013).
Cartilage, Tendons, and Ligaments: Major Pathologies
Cartilage, Tendons, and Ligaments: Major Pathologies
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Cartilage, Tendons, and Ligaments: Major Pathologies
The human skeletal system consists of bones, cartilage, and joints along with supplementary structures, including tendons and ligaments. Damage to the cartilage is associated with severe inflammation, skeletal stiffness, and range limitation. Similarly, since ligaments and tendons serve to connect the components of the skeletal system, damage to these structures is also associated with significant pain, swelling, restricted movement, and permanent disability. Major disease states associated with cartilage, tendons, and ligaments are treated through conventional modalities. However, current experimental research is investigating the significance of mesenchymal stem cells (MSC) in the use of cartilage, tendon, and ligament regeneration and repair. Mesenchymal stem cells are multipotent cells that can differentiate into different types of cell varieties, including chondrocytes. They can be obtained from umbilical cord tissue, developing buds of molars, adipose tissue, and amniotic fluid. The aim of the effort is to utilize MSCs in the attempt to maintain and regenerate these tissues.
Cartilage
Cartilage is a firm but flexible connective tissue consisting of cells and intracellular fibers embedded
