ARTICULAR CARTILAGE REGENERATION – ADVANCES IN MEDICAL GROWTH FACTOR GENERATION

Image Credits: Sports Health 

“Health is a large word. It embraces not the body only, but the mind and spirit as well; …and not today’s pain or pleasure alone, but the whole being and outlook of a man.”
– James H. West

Introduction

Progress is a continuous effort. In all fields, there’s a desire for growth and change. One of the best things that has happened in 2020 is the advancement of aerospace and the resuming of activities that are gearing us towards the limits of our solar system. There is a Universe within us as well, and there are always continuing increases in the technologies that are dedicated to improving our health and well being. In the area of cellular and molecular biotechnology, there is a noticeable transition toward the over-production of therapeutic and anabolic growth factors. With this development, it will one day be a useful application for the treatment of osteoarthritis (OA). As a regenerative treatment, the overproduction of growth factors will facilitate self healing, once the relevant environment is created. 

The vision for such therapies is the utilization of GP293 cells to generate the therapeutic proteins and anabolic growth factors that will enhance the restoration and regeneration of the cartilage. Scientific studies have indicated that there is a reduction in healing capacity with the onset of the aging process. With growth factor enhancers however, this will no longer be a limitation. Utilizing the Tissue Gene-C therapy, biologic treatments will be facilitated in this regard. With live cells as a baseline, the ability for utilization of cells to be biological drug delivery systems will be the wave of the future. 

With new innovations currently being developed and deployed, regenerative medicine is emerging as the go to therapy for degenerative diseases such as OA. As a start, as a patient, you can imagine that an injection will one day…be able to restore your joints.

What are Growth Factors? 

Growth Factors (GF’s) are proteins that facilitate the internal healing processes. The primary function of growth factors is to catalyze growth, proliferation, migration, survival and differentiation of target cell types. In the physical realms, catalysts are elements in a reaction that speed up a reaction. Biological catalysts like growth factors facilitate similar mechanisms in biological reactions. Their presence helps to improve reaction rates, and generation rates of critical healing components in your body. Growth factors are regulators and determine what the specialised function and phenotype of cells will be, as well as how they will interact with other elements in the cells in the genetic expression process. GF’s have been found to be effective on the majority of cell types, with the exception of cells like mature neurons. 

As biological catalysts, the GF’s are small and stable polypeptides which are naturally secreted within the body’s cellular system. Secreted into the extracellular matrix, they then get to work and regulate several body functions. It’s really an amazing biologic marvel. When sourced from stem cells, the GF’s generated can facilitate the healing process and stabilize tissue regeneration and maintenance, as well as heal wounds in the skin. Articular cartilage benefits greatly from the presence of stem cell derived GF’s. Studies have shown that in terms of the articular cartilage classification both IGF-1 and FGF have proven to be beneficial to articular cartilage repair. Within the transforming growth factor-β (TGF-β) superfamily, the system is encoded by 33 genes that work to facilitate wound healing and immunoregulation. 

TGF-β has action on articular cartilage, that is found to be dependent on a variety of factors. The current studies indicate that in vivo and in vitro performance can often differ. Some of the impactors to healing can include the nature of the internal environment of the patient. It reacts differently for instance in a young healthy joint, versus an ageing joint. Studies have shown that TGF-β is actually more active in OA joints. This indication is one of the reasons that it is being targeted as a treatment of OA. As a smart reactor, the TGF-β is showing signs of specificity, which is what is needed for any drug – be it synthetically generated, or biologically induced. The lock and key and target mechanisms are key to ensuring that specific conditions such as OA are treatable, without any adverse side effects to the body. 

How are these Growth Factors delivered? 

With the current state of the art technology in cellular and molecular biotechnology, live carriers of the GF will be injected into the cavity of the knee joint. Via the utilization of what is classified as “transfected and irradiated protein packaging eukaryotic cell lines”, these carrier cells will be the generators of the GF proteins. Generating the relevant cells for healing, the appropriate combinations of the GF’s necessary to heal the joint will be easily delivered. The healing cocktail which typically will contain cells such as chondrocytes and mesenchymal stem cells (MSCs) to enable maximum success. 

What is Osteoarthritis? 

Statistically, osteoarthritis is the most prevalent joint condition. Induced by a multitude of root causes, it is ultimately one of those conditions that has a wealth of treatments ranging from the utilization of wholistic healing methods such as joint healing oils, or the administration of surgery to facilitate the healing or replacement of the joint. 

Joints are the union of two or more bones. As a mechanical unit, the free flow of the joint is facilitated by the natural lubricating agents known as cartilage. Cartilage is soft protective tissue that lines the exterior of the bone. Under the condition of osteoarthritis, the cartilage degenerates and exposes the bones to each other. The painful condition results in limited mobility of the patients. While the majority of osteoarthritis cases take place in older patients, who have reduced healing capabilities, athletes and active individuals who place stress on their joints, can also develop arthritis. If left untreated, arthritis can induce disability. 

Causes of Osteoarthritis

It was highlighted in the previous introduction that cartilage degeneration is what ultimately leads to the joint damage associated with osteoarthritis. Joint damage as a whole has several root causes. If you had an injury for instance that resulted in the dislocation of a joint, there can also be resultant joint damage that can also inflict symptoms of osteoarthritis. Osteoarthritis does have genetic links, so ensure that your family medical history is assessed, and you’ll be able to identify with your doctor’s help, if you or your family members are at risk of the condition.

The Science of Cartilage 

As a tough, flexible coating to the bone, when cartilage degenerates, the friction between the joint’s bones can cause the exposed surfaces to become jagged. Cartilage, with time and age, is not a naturally self healing mechanism, because there is limited blood supply to the area. Biologics however, is beginning to enable the facilitation of healing by introducing the appropriate growth factors that will enable the cartilage to rebuild. The symptoms that patients experience include: pain as an initial indicator of a joint issue. With inflammation, the joint will swell and tenderness be experienced. As the joints lose their flexibility, there will be stiffness experienced, often in the morning upon rising. Your orthopaedic surgeon will assess your condition and determine the best way for you to approach your treatment. With all health conditions, with time, you can actually initiate healing via the facilitation of the right internal chemistry. A good and proper diet, can reduce the internal inflammation that you experience. 

THE STAGES OF OSTEOARTHRITIS

Osteoarthritis has the following five classifications:

Stage 0 – Normal 

Stage 1 – Minor 

Stage 2 – Mild 

Stage 3 – Moderate 

Stage 4- Severe

Consult with your orthopaedic surgeon to identify what stage of the progression you are on, if you are diagnosed with osteoarthritis. Cartilage loss is most prevalent in the higher tiers of the osteoarthritis scale. You are also at risk of increases in swelling and inflammation, and joint instability. 

ORTHOPAEDIC CONSULTATION

There are some conditions that take a long time to actually develop and diagnose. Osteoarthritis is one of those conditions. It is often during the periods of intense pain that one would be led to an orthopaedic specialist for the root cause of this discomfort. During your consultation, your orthopaedic surgeon will usually utilize a diagnostic tool such as an X-ray or an MRI image, in order to see the internal functions of the joint. For further details of your internal chemistry, blood tests, joint fluid tests and other tests can be conducted in order to eliminate additional root causes. From the surface, Rheumatoid Arthritis and Osteoarthritis do have almost identical symptoms. The critical tests will provide your orthopaedic specialist with the decision making tools that will enable your condition to be diagnosed. As a progressive and degenerative condition that causes the joints to stiffen, mobility is often a challenge with OA. 

How Growth Factors can improve OA

Based on the aforementioned mechanism of generation, GF’s are proving to important to generation and synthesis of articular cartilage. In the orthopaedic realm, bioactive GFs are currently being trialled in order to test their ability to heal chrondal injuries and inhibit the arthritic process. Scientific studies have identified a few relevant growth factors, that have been outlined below: 

Types of Growth Factors.PNG

With the advent of the application of a combination of these growth factors, it will be possible to facilitate the healing of cartilage, as well as bone repair and regeneration. As the demand for recombinant therapeutic proteins is on the rise, the accumulated knowledge and applications of these therapies will one day help to combat a condition that plagues many. With the current potential list of growth factors, these novel biological agents for cartilage regeneration show a very promising future. As study and treatments evolve, the cartilage degeneration that is identified in the age group of individuals over 50, it will be possible to “turn back the hands of time” and restore the limbs and joints to full capacity. Additional GF therapies will have applications in areas such as sports injury. 

For further details, consult with your orthopaedic specialist. You may actually qualify for a trial if the conditions and research facilities are in your local area. 

References:

https://www.preprints.org/manuscript/202007.0674/v1/download

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Dr. Gordon Slater

Dr. Slater is one of the first foot and ankle surgeons in Australia to adopt minimally invasive surgical techniques. He routinely uses MIS to treat a range of conditions, including bunions.

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Dr Gordon Slater is a highly-skilled surgeon specialising in foot and ankle conditions and sports injuries. Dr Slater is one of the first foot and ankle surgeons in Australia to adopt minimally invasive surgical techniques. He routinely uses MIS to treat a range of conditions, including bunions. MIS  has many advantages including shorter operating times, reduced post-operative pain, reduced risk of infection, minimal scarring and better cosmetic outcomes.

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