During the past several decades, advances have been made in the treatment of musculoskeletal disorders. Many of these advances have been the result of improvements in diagnostic imaging and surgical techniques. While it is possible to repair soft tissues reliably during surgery, the long-term outcomes are not always as successful as the immediate surgical result. One of the primary reasons for suboptimal surgical outcomes is the fact that surgical fixation (anchors, screw, sutures) will eventually fail if the repaired structures cannot heal themselves and regain their native strength.
Recently, attention has shifted towards optimizing the biology of the healing environment in an attempt to stimulate the body’s natural healing process and improve outcomes. The structures that we are trying to repair, eg, the rotator cuff or meniscus, often are of poor vascularity and have limited capacity to heal. Methods that hold the potential to improve the biological milieu at the repair site have become available over recent years. One of these methods is the use of platelet-rich plasma. Platelet-rich plasma can be used in both the nonoperative and operative settings to improve or stimulate the healing response. The focus of this article is to review the current literature pertaining to platelet-rich plasma and to discuss its potential role in the treatment of musculoskeletal pathology.
Platelet-rich plasma is essentially plasma that has been processed to contain a high concentration of platelets and growth factors. Platelet-rich plasma is derived from a patient’s whole blood. The blood is spun down in a centrifuge, which allows the red blood cells to be removed. Most systems require a second centrifuging step to create the final product. Once the red blood cells are removed, the remaining plasma is again centrifuged, which allows the platelet-rich layer to be extracted. The platelet-rich plasma can then be activated with thrombin or calcium chloride. This activation step causes the platelets to begin releasing growth factors. Platelet-rich plasma can also be injected in its inactivated form allowing it to be activated once it is within the body.
There are many different proprietary methods of creating platelet-rich plasma but the essential concepts behind creating the platelet-rich plasma are similar for each system. The platelet-rich plasma contains platelets as well as specific growth factors (Table). These growth factors include: transforming growth factor beta (TGF-?), platelet-derived growth factor (PDGF), insulin-like growth factor (IGF), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and fibroblast growth factor-2 (FGF-2). Many of these factors have been shown to enhance one or more phases of bone and soft tissue healing. Insulin-like growth factor is thought to stimulate osteoblast proliferation and differentiation. Platelet-derived growth factor, EGF, and FGF-2 have been shown to stimulate proliferation of osteoblastic progenitors as well as to affect the mitogenesis of mesenchymal stem cells and to stimulate epidermal cell proliferation. Transforming growth factor beta is believed to stimulate collagen synthesis. Angiogenic factors, including VEGF and FGF-2, are believed to enhance early angiogenesis and revascularization.1
In order to understand the mechanism of action of platelet-rich plasma, it is necessary to review the normal healing process of musculoskeletal tissue. The repair response of musculoskeletal tissues starts with the formation of a blood clot and degranulation of platelets. This degranulation of platelets releases growth factors and cytokines into the local environment. This in turn results in chemotaxis of inflammatory cells as well as the activation and proliferation of local progenitor cells.
It is believed that platelet-rich plasma can augment or stimulate healing by turning on the same biological healing process that normally occurs in the human body after musculoskeletal injury.
Among all the anti-inflammatory cytokines, IL-10 is a cytokine with potent anti-inflammatory properties, repressing the expression of inflammatory cytokines such as TNF-α, IL-6 and IL-1 by activated macrophages.
What is the Composition of Platelet-Rich Plasma (PRP)?
PRP is a biologic isolated from whole blood that is preferentially enriched for platelets. While platelets are the primary component of PRP, preparations may also contain other cellular components such as white blood cells (WBCs) and peripheral stem cells. These components all play a biological role in the healing process and are provided at concentrated levels in PRP. Thus, PRP may help optimize the conditions for healing of bone and soft tissue. Platelets Platelets play a critical role in several aspects of the healing process. Activated platelets release adhesion molecules that support clot formation for hemostasis. They also release several antimicrobial peptides that deliver infection control properties. Most importantly, as it relates to healing, platelets also release numerous growth factors, including PDGF, TGF-β, VEGF, and SDF-1α30,33 that have been shown to orchestrate the key biological processes, including angiogenesis, inflammation resolution and tissue regeneration. WBCs WBCs (or leukocytes) play a key role in protecting the body from infection and coordinating the inflammatory response. The three primary classes of cells found in the WBC population each provide unique biological functionalities: Granulocytes (or neutrophils) • The “immediate response” cells for prevention of infection • Key mediators of inflammatory response through phagocytosis and release of reactive oxygen species (ROS) Lymphocytes • T-lymphocytes help regulate the function of other immune cells and directly attack various infected cells and tumors • B-lymphocytes make antibodies, which are proteins that target unwanted bacteria, viruses and other foreign materials Monocytes • Assist in pathogen recognition • Eventually become macrophages, which engulf and destroy pathogens The illustration below shows how WBCs travel through the body to address inflammatory conditions. Stem Cells Stem cells are at the core of the tissue regeneration process. They are required to rebuild and repair damaged tissue at an injury site.6 Platelets release several growth factors, such as SDF-1α, that function to induce migration of stem cells to the damaged tissue during the healing process. PRP provides these growth factors in high concentrations. In addition, some PRP preparations also contain stem cells isolated directly from the blood sample during processing, which can directly support tissue regeneration. Why PRP? The concept behind the clinical use of PRP is to harness the natural biological components of a patient’s blood―primarily platelets―which may help optimize the conditions for healing, improve inflammatory response, control infection and promote angiogenesis.13,17,18 Compared with other biologics, such as concentrated BMA and adipose tissue, PRP possesses higher concentrations of platelets. Platelets facilitate healing through release of many growth factors actively involved in this process. Thus, PRP offers the physician an alternative to widespread treatments, such as steroid injections. Such treatments provide short-term relief by masking symptoms such as pain and inflammation that are the result of an injury, rather than actually addressing the cause of the injury directly through repair of damaged tissue.
Platelet-rich plasma (PRP) is a biologic isolated from whole blood that is preferentially enriched for platelets. The high concentration of platelets may help improve inflammatory response, infection control, and promotion of angiogenesis and tissue regeneration.
WBCs
WBCs (or leukocytes) play a key role in protecting the body from infection and coordinating the inflammatory response. The three primary classes of cells found in the WBC population each provide unique biological functionalities:
GRANULOCYTES (OR NEUTROPHILS)
- The “immediate response” cells for prevention of infection
- Key mediators of inflammatory response through phagocytosis and release of reactive oxygen species (ROS)
LYMPHOCYTES
- T-lymphocytes help regulate the function of other immune cells and directly attack various infected cells and tumors
- B-lymphocytes make antibodies, which are proteins that target unwanted bacteria, viruses and other foreign materials
MONOCYTES
- Assist in pathogen recognition
- Eventually become macrophages, which engulf and destroy pathogens
Regenerative Pain Medicine seeks to address the cause of chronic musculoskeletal pain by reversing damage to and degeneration of connective tissue caused by traumatic injury, repetitive motion injury, or the aging process. By injecting stem cells from one’s own tissues directly into the problem areas, we attempt to regenerate normal tissue, eliminate dysfunction and pain, and restore health.
Damaged and degenerated ligaments, tendons, muscles, and joint surfaces cause pain and dysfunction. Damaged and degenerated connective tissues have decreased blood flow, entrapped nerve ending, and accumulation of metabolic waste. The goal of Regenerative Pain Medicine is to restore health to these compromised tissues. Restoration of health to these tissues decreases or can eliminate pain and normalize function.
CONDITIONS WE ARE INVESTIGATING:
- Osteoarthritis of any joint
- Back Pain (from any cause except cancer)
- Neck Pain/Headaches (except true hormonal headaches or fibromyalgia syndrome with no history of trauma)
- Sports Injuries (such as tendonitis/tendonosis, rotator cuff tear, ACL tear, torn meniscus, chronic ankle sprains, chronic shoulder dislocations, Achilles tendonosis, etc)
- Overuse Injuries (plantar fasciitis, carpal tunnel syndrome, texters/quilters thumb, TMJ syndrome, etc)
- Bone spurs
- Avascular Necrosis
More On Healing
Healthy organisms are capable of healing themselves after injury. Injury to musculoskeletal structures triggers a critically important inflammatory pathway followed by a healing cascade. Anti-inflammatory drugs such as ibuprofen hinder this healing cascade. The majority of healing occurs in the first eight weeks after an injury. During this time the body produces growth factors in order to stimulate growth of new tissue. After this time, if healing is not complete there is a localized decrease blood flow, entrapment of nerve endings, and accumulation of metabolic waste. In essence, these tissues turn from normal connective tissue into scar tissue. As a direct result, nerve receptors in these tissues chronically fire pain signals. Sub-optimal healing leads to structures that do not have sufficient tensile strength (lax ligaments or joint capsules). Stretched ligaments are no longer able to stabilize their corresponding joint. This leads to muscle spasm in an attempt to stabilize joints and arthritis. Arthritis, similarly, is degeneration of joint surface tissue secondary to macro or micro trauma.
Most chronic musculoskeletal pain conditions are due to degenerative processes, not inflammatory processes. Most back and neck pain is due to damaged, degenerated tissues, not herniated discs even if herniated discs are present.
Those patients who are not truly good candidates for surgery and for whom alternative medicine has not been effective are often those who experience the best outcomes with Regenerative Pain Medicine.
For the most part, conventional management of musculoskeletal pain conditions involves palliative drug therapies until the condition becomes bad enough to warrant surgery. Arthroscopic surgery for arthritis has been definitively proven to not be effective long-term. Statistics for disc surgery for back/neck pain are not always completely successful. Alternative modalities such as chiropractic, massage, and acupuncture frequently can sometimes be curative for mild to moderate conditions, but often only give a temporary pain relief for advanced cases.
Regenerative Pain Medicine’s principle interventions are platelet rich plasma and bone marrow derived stem cells. Because Regenerative Pain Medicine seeks to harness the body’s own healing abilities to cure the cause of pain.