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Growth Factors
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Growth Factors

Loss of cartilage usually occurs when the usual balance of building (synthesis) and breaking down (degradation) of tissue that helps to maintain a healthy joint becomes imbalanced. This leads to a steady decline in the quality and quantity of cartilage structure. These types of conditions are associated with significant disabilities and long-term (chronic) pain.

At a cellular level, these problems worsen because the cells that restore cartilage are incapable of secreting enough new material to combat the degradation or that there is simply not enough living cells to do the job. With this in mind, several avenues of research have been focused on method of stimulating the cellular regeneration of the damaged tissue.

Growth factors are really a broad range of diverse substances that are capable of activating and stimulating the growth and repair of damaged tissue as well as protect cells from death. They therefore offer a very promising avenue for both treatment and further study.

Cartilage degradation and subsequent osteoarthritis is more common in people aged over 50 years, but people of any age have a significantly increased risk of cartilage and joint damage that may lead to post-traumatic osteoarthritis after sports or other joint injuries.

Growth factor treatments offer potential benefits to prevent osteoarthritis (especially at its early stages) later in life, as well as being an immediate consideration after sports injury, when the prevention of further damage is a priority.

The information here offers an explanation of how growth factors work, the evidence for the specific types thought to be best for cartilage repair, the main advantages and risks and any common questions on the topic.

Intended audience

This article is intended for anyone suffering from damage to their articular cartilage and their families who would like to find out about growth factors, as well as anyone interested in cartilage problems.

What are growth factors?

Growth factors are a family of diverse substances found naturally in the body that promote and stimulate biological processes and growth. They are a crucial part of the self-regulation of the body (homeostasis), in which an internal balance occurs between mechanisms of growth (including repair and regeneration) and degradation, both of which are important in maintaining a healthy body (You might think about a home: to keep it “new”, it would be important to remove worn area (degradation) and then refurbish (repair and regeneration)).

Numerous growth factors are responsible for maintaining healthy cartilage in the joints, both promoting cartilage restoration and counterbalancing dedicated substances that break cartilage down.

For example, the bone morphogenetic proteins (BMP) are a family of restorative growth factors that were named years before their activity on cartilage was known. Subsequently, they have been studied for their therapeutic applicability in cartilage repair. Administration of extra BMP growth factors would, ideally, restore cartilage, and be effective regardless of the patient’s age, sex or the cause of cartilage damage.

Two of these proteins in particular, known as BMP-2 and BMP-7 (the latter also known as Osteogenic Protein-1, or OP-1) have been identified as powerful treatments for restoring damaged bone and cartilage. BMP-2 is approved in several countries for treating damaged spine and bone. However, it is only in the past decade that they have been examined more intently for cartilage repair.

In initial culture-dish experiments with engineered growth factors, BMP-7/OP-1 in particular produced the components of cartilage, as well as protected important cells from death and inhibited inflammation. In animal studies, it had a clear potential for halting the degradation of cartilage, as well promoting its repair. While complete restoration of cartilage has not yet been achieved, future studies will look at different formulations, delivery methods and other aspects that are hoped to improve outcomes significantly.

The delivery of these therapeutic agents is the focus of considerable study. Alongside simple injection, other approaches for delivery at the wound/damage site include scaffolds of bio-engineered structures that mimic the natural 3D environment of the body. This may help in the long-term delivery of growth factors over weeks or months, although it is still not clear what length of time of application would be enough.

Although less well-studied, two other agents are worth mentioning. Fibroblast growth factor 18 (FGF-18) stimulates connective tissue cells (fibroblasts) and platelet-rich plasma (PRP), which is a mixture of many proteins and growth factors, made by separating components of a patient’s own blood. PRP may have a role in wound-healing. Therapeutic injection of PRP into the joint may “rebalance” the pro-inflammatory and anti-inflammatory factors in the joint or, in some cases, it might reinvigorate tissue growth.

What are the advantages and disadvantages of Growth Factors?

What are the advantages of Growth Factors?

BMP-7/OP-1 has been tested in animal studies without any reported side effects, such as unwanted bone formation in the tissue space, free-floating debris or inflammation.

The use of growth factors soon after injury is thought to be extremely promising in reducing, or even stopping, cartilage degeneration as well as controlling pain. It may even improve surgical outcomes – time will tell.

What are the disadvantages of Growth Factors?

Animal studies have shown great potential for halting damage to or partially repairing cartilage reproducing the same structure of cartilage tissue (as it is in the case of BMP-7/OP-1). However, complete restoration remains to be achieved.

While large, randomised trials in humans are still needed, many companies own the rights to different approaches. Therefore, trials involving a combination of different growth factor approaches will likely have to wait until this issue is resolved.

Some growth factors, like PRP (as it is derived from the patient’s own blood), are already available in many countries. However, well-defined clinical studies on large cohorts of patients and standardisation of PRP production are necessary to validate these novel techniques and therapies.

Frequently Asked Questions (FAQs)

Can I enrol in a trial using growth factors for cartilage repair?

Discuss with your Orthopaedic surgeon if there are any ongoing trials within your country.

Are growth factors available as a treatment for cartilage repair in humans?

Some growth factors, like PRP, are already available in many countries. However, well-defined clinical studies on large cohorts of patients and standardization of PRP production are necessary to validate these novel techniques and therapies. At the current time, further studies need to be completed before growth factors can be established as a standard treatment for cartilage repair. The ideal therapy in the future will most probably be multi-varied and will target multiple mechanisms. Growth factors might become an important part of the treatment mix.

Further reading

More information can be found in a selection of papers on the topic:

  • S Chubinskaya, M Hurtig and D C Rueger. OP-1/BMP-7 in cartilage repair. Int Orthop.(2007); 31(6): 773–78
  • DD Anderson et al. Post-Traumatic Osteoarthritis: Improved Understanding and Opportunities for Early Intervention. J Orthop Res (2011); 29:802–809
  • L A Fortier et al. The Role of Growth Factors in Cartilage Repair. Clin Orthop Relat Res (2011); 469:2706–2715
Loss of cartilage usually…
ICRShttps://cartilage.org/content/uploads/icrs.jpg
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