Growth Factor Therapy

Each of the over 350 joints in the human body is made of two opposing solid bones that are held together with tough connective tissues. These connective tissues stabilize the joint as well as divert about one third of the force away from the joint during activities to prevent cartilage damage (Stecco, C 1999).  Cartilage is the delicate shock absorbing structure at the ends of the opposing bones of the joint. Cartilage can withstand a tremendous amount of pressure but can be easily damaged if the connective tissues loosen or are damaged. 

 

The connective tissues provide the structure and scaffolding of the human body. They are found within the deepest layers of the muscle fibers to the thickest parts of the joints such as the well-known anterior cruciate ligament (ACL) of the knee. The connective tissues provide the home for different types of cells such as the bone and muscle cells that are called bones and muscles, respectively. The connective tissues that are visible are called the ligaments and fascia. The thicker connective tissues are called ligaments and the thinner connective tissues are called fascia.

Over a lifetime, the ligaments and fascia withstand huge amounts of force during normal daily activities such as during sitting, walking and sports which can result in damage. Microscopically, the ligaments and fascia sustain repetitive cycles of micro-injury and healing. These repeated episodes may result in delayed or incomplete healing. The accumulation of micro-injuries causes the ligaments and fascia to loosen, creating instability and eventually creates enough tissue damage to create noticeable joint stiffness and pain. The sudden appearance of symptoms may occur many years or decades later without notice. This also results in increased wear-and-tear within the delicate cartilage surfaces of the joints which show up as degeneration or arthritis on x-rays or MRIs (Fleming, 2005). This is process is called the degenerative cascade.

The degenerative cascade describes the wear-and-tear that is most often attributed to the aging process. The degenerative cascade can also develop after joint injuries, trauma or overuse. The most important part of the degenerative cascade is creep.  Creep describes the stretching of ligaments and fascia. Over time the tissues do no recoil back to their normal length and remain slightly stretched. This causes joint popping and crackling. Creep also injures tiny nerves within the ligaments and fascia whose primary job is to protect the joint from injury (Solomonow, 1999).  The nerves then become inflamed created a phenomenon called neurogenic inflammation which accelerates tissue degeneration.

Platelet-derived growth factors can restart the tissue healing process and decrease nerve inflammation (Dees et al. 2011, Montesano and Orci 1988, Nurden 2011). This phenomenon is better known as the three step healing cascade. The first step is called the inflammatory phase. It results in the formation of a tissue scaffold, activation of the growth factors, and attraction of white blood cells to remove bacteria and cellular debris (Clark 1996). The proliferative phase is the second step. Macrophages clean up the area and the fibroblasts and stem cells initiate the formation of new tissues and blood vessels. The final step is called remodeling. The initial collagen that was created in the first step is realigned and linked together. This allows for the creation of stronger type 1 collagen fibers from the weaker type 3 collagen fibers to create the tissue resilience that has long been absent. This healing phenomenon was first described in the treatment of chronic non-healing skin ulcers. A single application of platelet-derived growth factors reduced the healing time of these ulcers by a remarkable 50% (Knighton, 1990).

Platelet-derived growth factors are activated within the first hour of the healing cascade. These growth factors include platelet-derived growth factor (PDGF), transforming growth factor beta (TGF-b), vascular endothelial growth factor (VEGF), basic fibroblastic growth factor (bFGF), epidermal growth factor (EGF), Insulin-like growth factor (IGF-1) and hepatocyte growth factor (HGF). Their activity is robust within the first several days of activation. Afterwards, the majority of the healing occurs from the recruited cells and proteins such as pericytes and mesenchymal stem cells (Krampera, 2006)

 

My most impressive patient outcomes have occurred with the precise application of platelet-derived growth factors within connective tissues, often with the use of imaging-guidance. Within a month, patients can experience decreased pain and improved function.  Follow-up imaging has also demonstrated tissue healing. The outcomes are superior to repeated courses of physical therapy, medications, and steroid injections. I have had patients return to walking, running road races, rock climbing and horseback riding within weeks. I am most excited by the fact that the majority of patients experience long-term resolution of their condition.

 

References

  1. Anitua E, Andia I, Ardanza B et al. Autologous platelets as a source of proteins for healing and tissue regeneration. Thromb Haemost 2004;91(1):4–15.

  2. Anitua E, Andia I, Sanchez M, et al. Autologous preparations rich in growth factors promote proliferation and induce VEGF and HGF productions by human tendon cells in culture. J Orthop Res 2005;23:281–286.

  3. Clark RAF. Overview and general considerations of wound repair. In: Clark RAF (ed) The molecular and cellular biology of wound repair. 1996 Plenum Press, New York, pp 3–50.

  4. Dees C, Akhmetshina A, Zerr P, Reich N, Palumbo K, Horn A, Jungel A, Beyer C, Kronke G, Zwerina J, Reiter R, Alenina N, Maroteaux L, Gay S, Schett G, Distler O, Distler JH. Platelet-derived serotonin links vascular disease and tissue fibrosis. J Exp Med 2011;208(5):961–972.

  5. Fleming BC, Hulstyn MJ, Oksendahl HL, Fadale PD. Ligament injury, reconstruction, and osteoarthritis. Curr Opinion Orthop 2005; 16(5): 354-62.

  6. Knighton DR, Ciresi KF, Fiegel VD, et al. Stimulation of repair in chronic non healing cutaneous ulcers using platelet-derived wound healing formula. Surg Gynecol Obstet 1990;170(1):56–60.

  7. Krampera M, Pizzolo G, Aprili G, Franchini M. Mesenchymal stem cells for bone, cartilage, tendon and skeletal muscle repair. Bone. 2006;39(4):678- 683.

  8. Montesano R, Orci L. Transforming growth factor beta stimulates collagen-matrix contraction by fibroblasts: implications for wound healing. Proc Natl Acad Sci U S A 1988;85(13):4894–4897.

  9. Nurden AT. Platelets, inflammation and tissue regeneration. Thromb Haemost 2011;105(Suppl 1):S13–S33.

  10. Solomonow M, Zhou BH, Baratta RV, Lu Y, Harris M Biomechanics of increased exposure to lumbar injury caused by cyclic loading: Part 1. Loss of reflexive muscular stabilization. Spine. 1999 Dec 1;24(23):2426-34.

  11. Stecco C, Macchi V, Porzionato A, Duparc F, De Caro R. The fascia: the forgotten structure. Ital J Anat Embryol. 2011;116(3):127-38.

Andre Panagos, MD

820 Second Avenue, Suite 6D

New York, NY 10017

Tel. 212-682-6970, Fax. 212-682-6979

info@ssmny.com

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