Return to flip book view

Message About Dr. Nasiek:Dariusz J. Nasiek, M.D. is a board certifi ed pain specialist and anesthesiologist. He completed his residency and fellowship training at St. Vincent’s Hospital and Medical Center in NYC and has been in private practice in New York and New Jersey since 1996.Dr. Nasiek holds board certifi cations from the American Board of Anesthesiology, the American Board of Pain Medicine, and the American Board of Interventional Pain Physicians – he is one of a small group of triple certifi ed pain specialists. Dr. Nasiek is considered an expert in Platelet Rich Plasma (PRP) injections with hundreds of procedures performed on his patients.Dr. Dariusz J. Nasiek, M.D. serves as a Medical Director of Anesthesiology at Hackensack Surgical Center in Hackensack, NJ; he is a founding partner of Allied Neurology and Interventional Pain Practice with offi ces in New York and New Jersey. Dariusz J. Nasiek, M.D. is the founder of PRP Centers of America (PCA), a group of medical practices dedicated to the diagnosis and nonsurgical treatments of chronic pain and musculoskeletal maladies. The centers implement the use of the PRP therapies for a revolutionary approach in regenerative medicine (RM).www.PRPcenters.comDNasiek@PRPcenters.com866.400.14149 780988ISBN 978-0-9885190-0-851900851495$14.95PRPPlatelet Rich PlasmaA New Paradigm ofRegenerative Medicine Dariusz J. Nasiek, MD, DABA, DABPM, DABIPP

4

5Foreword“The doctor of the future will give no medicine, but will interest his patients in the care of the human frame with diet and the preven-tion of disease.” Thomas A. Edison.The treatment of the conditions that are described in this book exemplifi es the use of our own body to exact a cure. Scientists and physicians have found that the use of the bodies’ blood platelets in treatment can not only repair damage caused by injury, but can also regenerate the damaged tissue.Platelets have been implicated in the formation of clots in vital or-gans by impeding the blood fl ow and by clotting. However, more recent studies have shown that platelets also attract stem cells, which play an essential role in regeneration and repair.This book offers more information on treatment with PRP (Platelet Rich Plasma) as a therapy for tissue damage and injury. It also of-fers a glimpse into the future of utilizing stem cell therapy.Congratulations to the author for bringing this information to our attention.Alfred Mauro, M.D.Medical Director, Pain Management of New Jersey, PABoard Certifi ed Anesthesiologist and Pain ManagementSpecialist.

DedicationThis book is dedicated to my dear parentsStefania and Ludwik Nasiekfor the enormous emphasisthey placed upon my education,and for their contribution towards it.I would also like to acknowledge all the teachers and mentorswho have guided me through my life.

Copyright © 2012 by Dariusz J. Nasiek, M.D.All rights reserved. No part of this book may be reproduced in any form or by any electronic, pho-tocopying, recording, mechanical means including information storage and retrieval systems, or otherwise, without the prior written permission from the author. The only exception is by a reviewer, who may quote short excerpts in a review.THIS BOOK IS INTENDED FOR INFORMATIONAL PURPOSES ONLY. It is not the purpose of this book to give medical advice. The information contained herein is not a substitute for a thorough examination and consultation by a physician.ISBN 978-0-9885190-0-8Composed and produced by Master Printing USA, Inc.

Table of ContentsIntroduction: Overview and Avoiding Surgery 11Part I A BASIC UNDERSTANDING 15Chapter 1 Platelet Anatomy and Physiology 17Chapter 2 Understanding How Tissue Heals 23Part II CLINICAL APPLICATIONS 29Chapter 3 Historic Overview 31Chapter 4 Clinical Application of PRP Injections 35Chapter 5 Clinical Studies 41Chapter 6 Clinical Application of PRP for Cervical 55 and Lumbar Facet SyndromeChapter 7 Comparing PRP Injections with Synvisc® 59 Injections and Stem Cell TherapyChapter 8 Rehabilitation and Physical Therapy 63Chapter 9 Seeing the PRP Process 69 and Understanding the Techniques for the Application of the PRPChapter 10 Future Studies 85Part III A NEW PARADIGM 89Chapter 11 Regenerative Medicine 91Chapter 12 Facts, Concepts and Frequently Asked 95 QuestionsChapter 13 The Safety and Success 101 of the PRP Procedure Glossary 105

10

11IntroductionIf you have ever struggled through a long-term rehabilitation from a nagging physical injury, you are not alone.You may have even learned a few lessons yourself from your own experience and research during the healing process. You might know that the classical approach in Orthopedic Medicine and Surgery relies largely on stabilizers such as ACE bandages, slings, casts, plates, and screws which are used to immobilize broken bones, hurt joints, and painful tendons.This phase of healing is a period of inactivity during which your body slowly repairs the damage. Over time, with some consistent rehabilitation, the body regains its effi ciency and returns to its for-mer fl exibility.For most people, the arduous and painstaking process of rehabili-tation is the only option available.Recently though, professional athletes like Tiger Woods, suffering from a sore knee, and Chris Canty, defensive tackle for the New York Giants hampered with a hamstring injury, have discovered a noninvasive process called Platelet Rich Plasma therapy. This pro-cess put them back on their feet faster and got them back in the game sooner.The news is now out.

12Platelet Rich Plasma delivers a potent one-two-punch:1. It is more effective than the traditional approach.2. It regenerates damaged and irreparable tissues or organs.It is more effective as it uses platelets and relies upon growth fac-tors derived from cells responsible for repair and regeneration.The regeneration is done by stem cells. Although stem cell therapy has been controversial in the past, for many years platelets and growth factors have been used to effec-tively speed up the healing process.This book will do more than just educate you about the process and benefi ts of platelet therapy.It will explain in plain language why Platelet Rich Plasma in con-junction with physical therapy put active individuals and athletes back on their feet faster and got them back in the game sooner.It will also discuss other noninvasive pain management options that have benefi ted patients, including the revolutionary stem cell therapy.Most importantly, you will gain a clinical perspective on the effi -ciency of Platelet Rich Plasma from an expert in the fi eld of pain management, as well as a greater understanding about why and when Platelet Rich Plasma Injections are the best option.

13Avoiding SurgeryIf you have ever had to decide whether having surgery in order to eliminate a nagging long-term physical injury is your best option, it is likely that this was a diffi cult decision for you to make.To opt for the surgery or not is a tough choice. Especially, when there is no clear cut indication for having a surgical procedure and when the surgery is not immediately considered a life saving solu-tion.If you were patient of mine, we would discuss why I believe that any nonurgent or nonemergency surgery should be avoided in lieu of a minimally invasive therapy.It is better to carefully observe how your injury has developed. This observation could result in a noninvasive solution. Sometimes, the injury might even heal naturally.My rationale for this approach is simple.First of all, each surgical procedure carries inherent risks, even though the risk is low, it should be avoided if possible.Secondly, surgery is an irreversible process and it should be avoid-ed at all costs if nonsurgical or minimally invasive options exist.And fi nally, it is wise to incorporate lifestyle modifi cations before arriving at the point of no return.

14

15PART IA BASIC UNDERSTANDING

16

17Chapter 1Platelet Anatomy and Physiology

18

19Blood componentsBlood contains a liquid component and cells.The liquid component is called plasma. It is made mostly of water and acts as a transport medium for cells. Plasma contains fi brino-gen, a protein that acts like a net at a wound site where it catches platelets to form a blood clot.Red blood cells (RBC) that transport oxygen account for 93% of all blood cells. White blood cells (WBC) that fi ght infection, kill germs and carry off dead blood cells make up 1% of the total blood volume while platelets make up the remaining 6% (1).Platelets are responsible for hemostasis, but also play a pivotal role in healing because they are rich in growth factors and cytokines.Growth factors derived from activated platelets play a role in the construction of new connective tissue, revascularization, bone mineralization and they have anti-infl ammatory and antibacterial properties (7) (8).PlateletsPlatelets are the smallest component of blood cells. They are derived from fragmentation of mother cells - megakaryocytes – formed in the bone marrow. Platelets are small cell fragments measuring 23 microns. They are considered cell fragments because they do not have a nucleus containing DNA and are unable to multiply (1). However, they contain organelles and structures such as micro-tubules and are able to produce chemical products in the form of granulesin platelets. Because of these organelles, platelets synthe-size and release large amounts of biologically active proteins that promote tissue regeneration (6).There are three types of granules: alpha, delta, and lambda.Alpha granules, the most important of the three, are formed during the original megakaryocytes maturation. The granules measure 200-500 nm in diameter. Alpha granules contain platelet factor 4,

20transforming growth factor-β1, platelet-derived growth factor, fi -bronectin, B-thromboglobulin, vWF, fi brinogen, and coagulation factors V and XIII. Each platelet has approximately 50-80 alpha granules. They contain bioactive proteins and play a role in hemo-stasis and tissue healing. Activated platelets excrete the contents of these granules into their canalicular systems and into the sur-rounding blood vessels.Delta granules, also known as dense granules, contain ADP or ATP, calcium, and serotonin.Lambda granules, like lysosomes, contain hydrolytic enzymes. The average lifespan of a platelet is 5 to 9 days. Platelets are a nat-ural source of growth factors. They circulate in the blood and are involved in hemostasis, leading to the formation of blood clots and tissue repair leading to tissue regeneration.Platelets release a multitude of growth factors including plate-let-derived growth factor (PDGF), a potent chemotactic agent, and transforming growth factor (TGF) beta, which stimulates the depo-sition of extracellular matrix. Both of these growth factors have been shown to play a signifi cant role in the repair and regeneration of connective tissue like muscles, tendons and ligaments.Other healing-associated growth factors produced by platelets in-clude: basic fi broblast growth factor (bFGF), insulin-like growth factor 1 (IGF), platelet-derived epidermal growth factor (PDGF), and vascular endothelial growth factor (VEGF).Thus far, over 1100 types of proteins inside the platelets have been identifi ed by researchers.The most common platelet proteins include:1. Platelet-derived growth factor - PDGF2. Transforming growth factor - TGF3. Platelet-derived epidermal growth factor - PDEGF4. Vascular endothelial growth factor - VEGF5. Insulin-like growth factor - IGF

216. Basic fi broblast growth factor - bFGF7. Epidermal growth factor - EGF8. Cytokines9. ChemokinesLocal application of these factors in increased concentrations through Platelet-rich plasma (PRP) has been used as an adjunct to wound healing over the past several decades.PRP also has antibacterial effects (8). Platelets and leucocytes can release a variety of small antibacterial peptides upon contact with pathogens via a nonoxidative mechanism. Another advantage of those peptides is that they promote potent microbial killing activi-ties with very little toxicity to normal cells. PRP helps with the an-timicrobial activities of immune system defenses that help protect against infection.Finally, PRP enhances the gene expression of:1. Cellular matrix proteins2. Collagen production3. Tenocyte proliferation4. Mitogenic activity - the ability to increase the division and production of new cells. Many growth factors found in plate-lets are also involved in the homeostasis of articular carti-lage. They have been studied in vitro and have been shown to assist in cartilage repair (9).There is constant reference to healing, regeneration, rebuilding throughout the book. From beginning to end the book leaves no doubt that the regeneration process is the physiological basis for tissue repair and the foundation of the new paradigm of regenera-tive medicine.Important facts about platelets• Platelets are produced in the bone marrow, from fragmenta-tion of megakaryocytes - large mother cells.• The physiological range for platelet concentration is 150-400 ×109 per liter. By comparison platelet-rich plasma (PRP) for medical use contains at least 2- 5 times that number.

22• Approximately 1011 platelets are produced each day by an average healthy adult.• The lifespan of circulating platelets is 5 to 9 days.• Platelet production is regulated by a hormone produced by the liver and kidneys called thrombopoietin.• Each mother cell, megakaryocyte, produces between 5,000 and 10,000 platelets.• Reserve platelets are stored in the spleen, and are released when needed by sympathetically-induced splenic contraction.• Old platelets are destroyed by phagocytosis in the spleen and in the liver.Platelet functionThe main function of platelets is the maintenance of hemostasis. This is achieved primarily by the formation of thrombi, which oc-curs when the endothelium of blood vessels is damaged.The second signifi cant function of the platelets is to assist in the regeneration of damaged tissue through the delivery of growth fac-tors and the attraction of stem cells to the injured area.References1. Campbell, Neil A. Biology (2008). (8th ed.).2. Maton, Anthea; Jean Hopkins, Charles William McLaughlin, Susan Johnson, Maryan-na Quon Warner, David LaHart, Jill D. Wright Human Biology and Health (1993).3. O’Connell SM, Impeduglia T, Hessler K, Wang XJ, Carroll RJ, Dardik H Wound Repair Regen 2008, 16 (6): 74956.4. Knighton DR, Ciresi K, Fiegel VD, Schumerth S, Butler E, Cerra F., Surg Gynecol Ob-stet 1999. 170 (1): 5660.5. McAleer JP, Sharma S, Kaplan EM, Persich, Adv Skin Wound Care 2006, 19 (7): p 35463.6. Marx RE, Platelet-rich plasma (PRP): what is PRP and what is not PRP? Implant Dent. 2001 10(4): p.225-228.7. Samson S, Gerhardt M, Mandelbaum B, Platelet rich plasma injection grafts for mus-clocutaneus injuries: a review. Curr Rev Musculoscelet Med (2008) 1 165-174.8. Moojen DJ. et al. Antimicrobial activity of platelet-leukocyte gel against Staphylococ-cus aureus. J. Orthop. Res. 2008; 26(3): 404-410.9. Kajikawa Y. et al. Platelet-rich plasma enhances the initial mobilization of circula-tion-derived cells for tendon healing. J. Cell Physiol. 2008; 215(3): 837-845.

23Chapter 2Understanding How Tissue Heals

24

25It would be benefi cial to understand how the tissue heals and what role platelets play in this process.Healing is the restoration of damaged living tissue to normal or near normal function. It is the process by which the cells regener-ate and repair to reduce the size of a damaged area. Healing incor-porates both the removal (cleaning) and the replacement (rebuild-ing) of a dead tissue (1) (2) (3).The replacement can happen in two ways:1. by regeneration: the necrotic (dead) cells are replaced by new cells that form tissue similar to the original.2. by repair: injured tissue is replaced with scar tissue.Of course, the regeneration method is superior to that of a mere repair as it returns full function to the damaged tissue or organ. Most organs will heal using a combination of both mechanisms. The body has a predictable response to tissue injury. The purpose of this response is to promote the best recovery and healing of the injured area. Until recently, medical interventions in this process were meant to provide an optimal environment for it to occur in. New regenerative medicine specialists aspire to steer the healing process into a speedy and full regeneration (2) (3).Healing is a complex and dynamic process of restoring cellular structures and tissue layers.The three phases of healing are:1. Acute infl ammatory phase2. Repair phase3. Remodeling phaseAlthough these categories overlap slightly, they can be further di-vided into fi ve distinct phases:1. The clotting phase2. The infl ammatory phase3. The proliferative phase

264. The maturation phase5. The remodeling phaseAnd while the process of tissue healing may be considered a series of separate events, in actuality the entire process occurs in tandem on different planes at the same time and is much more complex than it seems.Within these broad phases is a complex and coordinated series of events that include chemotaxis, phagocytosis, neocollagenesis (formation of new collagen), collagen degradation, and collagen remodeling.In addition, angiogenesis, epithelization, and the production of new glycosaminoglycans (GAGs) and proteoglycans are vital to the healing process (6). (The defi nitions of these anatomical and phys-iological terms can be found in the glossary of terms in the back of the book).Clotting phase: The healing of a wound begins with clot forma-tion to stop bleeding and to reduce infection by trapping foreign bacteria, viruses and fungi. This happens immediately after the in-jury. Clotting is followed by an invasion of neutrophils (white blood cells) beginning 3 to 24 hours after the wound has occurred, with mitosis (divisions and multiplications) beginning in epithelial cells after 24 to 48 hours. Platelets are responsible for the clot forma-tion.Infl ammation phase: The infl ammatory response is what causes pain, swelling, redness, and warmth around an injured area. This is the body’s way of protecting itself. The swelling causes stabiliza-tion in the area. Because of the increased blood fl ow the area gets warmer, increased permeability occurs, and the tissue swells. In the infl ammatory phase the blood delivers macrophages and other phagocytic cells that kill bacteria, debris, and damaged tissue (1) (2).The blood also releases chemical factors such as growth factors that encourage fi broblasts, epithelial cells and endothelial cells to mi-grate to the area and divide to form new capillaries. Platelets are responsible for delivering growth factors to the healing site.

27Proliferative phase: This phase occurs when the infl ammation has subsided and your body begins to repair the injured area. In the proliferative phase, immature granulation tissue containing plump active fi broblasts is formed. Fibroblasts quickly produce abundant type III collagen, which heals the scar left by an open wound. While regenerating, granulation tissue moves from the border of the inju-ry towards the center. As granulation tissue matures, the fi broblasts produce much less collagen and become more spindly in appearance. They begin to produce the much stronger type I collagen. Some of the fi broblasts mature into myofi broblasts which contain the same type of actin (contracting protein) found in smooth muscle. This enables them to contract and reduce the size of the wound. Platelets are respon-sible for the initial delivery of growth factors to speed the process of proliferation and rebuilding of the damaged tissue (2) (3).Maturation phase: During the maturation phase the unnec-essary vessels formed in the granulation tissue are removed by apoptosis (programmed cell death), and type III collagen is largely replaced by type I collagen. In the beginning, the collagen is sim-ilar to sticky glue. It needs to be aligned in order to perform its function. The primary result of this phase is an improvement in the quality, orientation and tensile strength of the collagen. Collagen which was originally disorganized is now cross-linked and aligned along tension lines. This phase can last a year or longer. Ultimately, a scar made of collagen containing a small number of fi broblasts remains. Rehabilitation and physical therapy play a major role in the maturation phase of tissue regeneration.Remodeling phase: Tissue remodeling lasts the longest, some-times for years. During this phase tissue is remodeled as a result of old cells being replaced by new cells in response to stress, loading pressure and other numerous physiological and pathological fac-tors. The fi nal appearance and function depends on many factors. Rehabilitation plays a major role in the maturation phase of tis-sue remodeling.

28The healing process may result in one of the following outcomes:1. SCAR formation - nonfunctional tissue2. Reparation of partially functional tissue3. Formation of NORMAL TISSUE - fully functional tissuePlatelets are involved in many phases of tissue healing and are crit-ical in the normal process of repair and regeneration (6). The addi-tion of supranatural levels of platelets allows the process of regen-eration to go faster and smoother with a fi nal result of NORMAL TISSUE formation (5).References1. Grey Joseph E., Harding Keith G., ABC of Wound Healing (ABC Series). (2006)2. Stocum, David L., Wound Repair, Regeneration and Artifi cial Tissues (Molecular Biol-ogy Intelligence Unit Series). ( 1995 )3. Heister, L, A. General System of Surgery in Three Parts; Containing the Doctrine and Management. (2012)4. Einhorn TA, The science of fracture healing. J Orthop Trauma 2005, 19 (suppl.) 4-6.5. Alsousou J. et al The biology of platelet-rich plasma and its application in trauma and orthopaedic surgery. The Journal of Bone & Joint Surgery (Br), 2009, Vol.91-B, No.8. p. 987-995.6. Nurden AT. et al. Platelets and wound healing. Frontiers in Bioscience. 2008; 13: 3532-3548.

29PART IICLINICAL APPLICATIONS

30

31Chapter 3Historic Overview

32

33PRP and its various forms were originally used in clinical practice as an adjunct to surgery to assist in the healing of various tissues, especially to promote tissue healing in prosthetic surgery. PRP pro-motes the healing of the tissues around the implant and controls blood loss in prosthetic surgery (1).Initially PRP was used in oral surgery (2). Subsequently, PRP has seen various orthopedic applications and has been used in surgery of the hip, shoulder, and in knee procedures (4). More recently PRP injections have been used for the management of muscle, tendon, and cartilage injuries, as well as in sports medicine and for pain management (3). The newest applications of PRP can be seen in the fi eld of plastic surgery and cosmetic medicine where it is used to regenerate old skin, remove wrinkles and to avoid collagen vol-ume loss (5).Allogeneic fi brin glue, which is derived from the same organism, was originally introduced in 1970.The fi rst reference of PRP in clinical trials dates back to 1987 when after open heart surgery PRP was used to prevent the need for a homologous blood product transfusion.In 1990, autologous fi brin gel or fi brin serum (also known as fi brin glue) was used in haemostatic and adhesive preparation.In 2003, the fi rst scientifi c support for the management of carti-lage problems was described. Since then, the application of PRP has rapidly expanded throughout the medical world. This progress is described in multiple articles, reviews, and books that have been published touting its benefi ts.The results are benefi cial for three important reasons:1. Relative ease of use2. Low cost3. Alternative to major surgical procedures. (This is particular-ly true for athletes with sports injuries who need to get back in the game quickly, but also for older patients when speed of recovery is important and surgery avoidance is a high pri-ority.)

34References1. Bergoff W. et al. Platelet-rich plasma application during closure following total knee arthroplasty. Orthopedics. 2006: 29 (7) p. 590-598.2. Garg AK. The use of platelet rich plasma to enhance the success of bone grafts around dental implants. Dent. Implantol. Update. 2000; 11(3): 17-213. Anitua E. et al. The potential impact of the preparation rich in growth factors (PRGF) in different medical fi elds. Biomaterials 2007; 28: p.4551-45604. Everts PA et al. Platelets gel and fi brin sealant reduce allogenic blood transfusions in total knee arthroplasty. Acta Anaesthesiologica Scand. 2006; 50 (5) p.593-5995. Epply BL et al. Platelet rich plasma: a review of biology and applications in plastic surgery. Plast Reconstructive Surg. 2006; 118 (6) p.147-159

35Chapter 4Clinical Application of PRP Injections

36

37Clinical application of PRP is growing as new studies are being pub-lished and new areas of treatments are being developed every year.PRP in the treatment of tendon injuriesChronic tendon disorders are quite common in athletes and in ac-tive people. Surrounding tissue such as synovium and peritendon tissue are also affected. Tendinopathy is characterized by swelling, pain, and loss of full range of motion. PRP is a treatment option for the management of a chronic tendon injury. Positive effects on tendon healing have been established in animal and human studies. Mechanical testing indicates that there has been improvement in maturation of the tendon and cartilage when compared with controls. There has also been an increase in the formation of new bones and cartilage at the healing site.Most of the studies involving PRP in humans are on the Achilles tendon, patellar tendon, wrist extensor and supraspinatus tendon. These studies indicate that there is evidence that PRP injections into the Achilles tendon facilitate early recovery from the proce-dure after surgery. There are also studies suggesting that the injec-tions of PRP are benefi cial in chronic patellar tendinopathy (1) (2) (3).Platelet-derived growth factors show the important role of growth factors in repair of damaged ligaments and homeostasis. Platelets are involved during the early stage of medial collateral ligament and ACL healing and regeneration.PRP in the treatment of cartilage injuriesPRP has been used as a treatment for the management of articular cartilage injuries of the knee, hip, and ankle. The most common-ly reported method of clinical application consists of multiple in-tra-articular injections of PRP (3) (4) (5).Favorable results in pain reduction and improved function have been reported. Intra-articular injections were compared to a com-mon nonsurgical treatment such as hyaluronan injections, and

38they demonstrated better pain control and improvement in the physical function.It has been shown that several growth factors may improve cell regeneration. Regenerative effects of PRP have been documented both on patients and and in the laboratory. Studies report the use of PRP to augment ACL reconstruction. One study documented a 48% decrease in the amount of time it took to achieve a complete homogenous graft signal when measured by MRI. These reports suggest that the intra-articular injections have been successfully used to reduce pain and improve function (4) (5).Platelet-derived growth factors also play an important role in me-niscus homeostasis and repair. Platelets are involved during the early stage of meniscal regeneration and healing.PRP in the treatment of muscle injuriesMuscle strains and sprains along with muscle contusions are very common in sports and general activities. In the general population, muscle strains can be extremely painful and may be responsible for the increase in the level of pain and absence from work or school.Despite the advances in conservative measures like rehabilitation, the pain relief process can be long and the possibility of re-injury is high.The management of muscle injuries through conservative mea-sures includes the following:1. Stretching and strengthening regimen2. Gradual return to activity3. Injections of local anesthetic and steroids into the musclesNone of these techniques guarantee a full recovery.PRP has the ability to speed up the recovery process in muscle in-juries rehabilitation (6).

39Despite the limitations of PRP, scientifi c studies have measuredthe use of this noninvasive pain management protocol to facilitatethe healing of injuries and help patients return to activities sooner.While only minor scientifi c support exists for the use of PRP in themanagement of muscle pain, its usage has increased.References1. Sanchez M. et al. Comparison of surgically repaired Achilles tendon tears using plate-let-rich fi brin matrices. Am. J. Sports Med. 2007; 35(2): 245-251.2. Sanchez M. et al. Management of post-surgical Achilles tendon complications with a preparation rich in growth factors: a study of two cases. Injury EXTRA. 2009; 40:11- 15.3. De Vos RJ. Et al. Platelet-rich plasma injection for chronic Achilles tendon tendinopa-thy: a randomized controlled trial. JAMA. 2010; 303(2): 144-149.4. Sanchez M et al. Intra-articular injection of an autologous preparation rich in growth factors for the treatment of knee OA: a retrospective cohort study. Clin. Exp. Rheuma-tol. 2008; 26(5): 910-913.5. Kon E. et al. Platelet-rich plasma: intra-articular knee injections produced favorable results on degenerative cartilage lesions. Knee Surg Sports Traumatol Arthroscop 2010; 18(4): 472-479.6. Hammond JW. et al. Use of autologous platelet-rich plasma to treat muscle strain injuries. Am. J. Sports Med. 2009; 37(6): 1135-1142.

40

41Chapter 5Clinical Studies

42

43Multiple medical studies have shown that PRP therapy can acceler-ate the healing of tissues and help with injuries such as tendonitis, ligament tears, osteoarthritis, and most recently facet arthropa-thies and disc degeneration (1).Clinical studies in various areas are provided here to demonstrate the positive outcomes of PRP use. The following studies were care-fully chosen to demonstrate different areas of application and re-fl ect various study designs. They refl ect a relatively young fi eld that is expanding to include new applications and new areas which ac-company the need for further research.We’ll start with seven clinical studies in vivo, done with a live body, followed by a fi nal study in vitro, done on an animal, in a labora-tory. While each of these are lengthy, formidable studies, you will fi nd a brief commentary after each conclusion to help you under-stand its overall value.

44Study 1The American Journal of Sports Medicine 2010.Positive effect of autologous platelet concentrate in lateral epicon-dylitis in a double-blind randomized controlled trial-platelet-rich plasma versus corticosteroid injection with a one-year follow-up.Author: Joost C. PeerboomsBackground: Platelet-rich plasma (PRP) has shown to be a general stimulation for repair.Purpose: To determine the effectiveness of PRP compared with corticosteroid injections in patients with chronic lateral epicondylitis.Results: For the purpose of the study successful treatment was defi ned as more than 25% reduction of pain in the visu-al analog pain scale. The results showed that, according to the visual analog pain scale scores, 49% in the corticosteroid group and 73% of PRP group had successful outcome follow-ing the study.Conclusion: Treatment of patients with chronic lateral epicondylitis with PRP injections reduces pain and signifi -cantly increases function exceeding the effects of corticoste-roid injections.Summary: PRP treatment has helped a majority of patients to reduce their pain and enjoy greater mo-bility as compared to the results of those patients receiving steroid injections. This improvement was sustained over time with no reported compli-cations.

45Study 2International Journal of Sports Medicine 2010.Treatment of Achilles tendinopathy with platelet-rich plasma.Author: K. GawedaBackground: Achilles tendinopathy commonly impedes the functioning of an active person, but condition improves when the treatment of PRP injections is being implemented.Purpose: The aim of the study was to evaluate the effec-tiveness of Achilles tendinopathy treatment with autologous platelet-rich plasma (PRP).Results: 14 prospectively selected patients were evaluat-ed using the American Orthopedic Foot and Ankle Society (AOFAS) scale and Ultrasonography (US). During follow-up visits, a signifi cant improvement was observed in the clinical and imaging results of all the patients. Only two of the pa-tients complained of pain at the end of 18 month follow-up studies.Conclusion: A signifi cant improvement in functional evaluation scores with simultaneous lack of complications suggests a substantial value of PRP treatment. The study showed very high patient satisfaction and activity improve-ment; these results are encouraging.Summary: PRP injections have helped patients with Achilles tendinopathy to function better, with fewer complications.

46Study 3Clinical and Experimental Rheumatology 2008.Intra-articular injection of an autologous preparation rich in growth factors for the treatment of knee osteoarthritis (OA): A retrospective cohort study.Author: M. SanchezBackground: Platelets derived from blood, which form a preparation rich in growth factors (PRGF), have the poten-tial to enhance the capability of cartilage to repair itself.Purpose: The goal of this study was to explore whether the PRGF could be used for treatment of osteoarthritis of the knee.Results: 30% of patients with osteoarthritis were treated with PRGF and another 30% were treated with hyaluronan as a control group. After fi ve weeks, the observed success rate in improvement of pain perception was 33.4% in the PRGF group and 10% in the hyaluronan group. Intra-artic-ular administration of PRGF, along with biocompatibility and nonimmunogenicity, is an attractive approach to osteo-arthritis treatment. The autologous nature of this therapy is very relevant to osteoarthritis management since the disease affects primarily people over the age of 60, who are most prone to drug-toxicity.Conclusion: There is a higher success rate when using PRGF for treatment of patients with osteoarthritis of the knee than when using hyaluronan.Summary: PRP injections have helped to relieve osteoarthritic (OA) knee pain more effectively than hyaluronan (Synvics) injections.

47Study 4Knee Surgical Sports Traumatology and Arthroscopy2010. Platelet-rich plasma: intra-articular knee injections pro-duced favorable results on degenerative cartilage lesions.Author: Elizaveta KonBackground: Platelet-rich plasma (PRP) is a natural con-centrate of autologous blood growth factors experimented with in different fi elds of medicine in order to test its poten-tial to enhance tissue regeneration.Purpose: The aim of this study was to explore this novel approach to treat degenerative lesions of articular cartilage of the knee.Results: 100 consecutive patients, affected by a chronic degenerative condition of the knee, were treated with PRP intra-articular injections. The patients were evaluated at 6 and 12 month intervals with an objective visual analog pain scale used for clinical evaluation. A statistically signifi cant improvement of all cases was seen from the time of basal evaluation to the end of the therapy and then during the fol-low-up period 6-12 months later. 80% of patients were sat-isfi ed with the treatment results.Conclusion: PRP injections have a clinical relevance in re-ducing infl ammatory and degenerative articular processes and improving knee function and quality of life. The short-term results of the study were encouraging and indicated that treatment using autologous PRP intra-articular injec-tion is safe and may be useful for the treatment of early de-generative pathology of the knee.Summary: Following PRP injections patients en-joyed both short and long-term improvement in knee function and mobility. PRP is safe and may be an effective approach for treating early signs of aging in the knees.

48Study 5Injury, International Journal Care of Injured 2009. Platelet-Rich Plasma: New Clinical Application: a pilot study for treatment of jumper’s knee.Author: Elizaveta KonBackground: PRP growth factors help to improve pain stemming from jumper’s knee.Purpose: The aim of the study was to explore this novel approach to treating chronic patellar tendonitis with PRP injections by gathering and assessing the number, timing, severity, duration, and resolution of related adverse events occurring among study participants before and after treat-ment. Another purpose was to analyze the results obtained to determine feasibility, safety, indications, and application of this method in further studies.Results: 20 male athletes with a history of pain in the knee prepatellar region received PRP treatment and were evalu-ated at six month follow-up. No severe adverse events were observed, and statistically signifi cant improvements in all scores were recorded in all patients.Conclusion: The results suggest that this method, which aids the regeneration of tissue and which otherwise has low healing potential, may be safely used for the treatment of jumper’s knee. Treatment with PRP injection in a regenera-tive area has the potential to reduce pain and allow the ma-jority of patients to go back to full tendon-loading activity.Summary: Following PRP injections, tissue regen-eration in the knee was improved and there was an increased potential for pain relief.

49Study 6American Journal of Sports Medicine 2006. Treatment ofchronic elbow tendonitis with buffered platelet-rich plasma.Author: Allan MishraBackground: Elbow epicondylar tendonitis is a common problem that is usually resolved with nonoperative measur-ers. When these measures fail, however, patients are inter-ested in an alternative nonsurgical intervention.Purpose: The purpose of the study was to determine the effects of treatment of chronic severe elbow tendonitis with buffered platelet-rich plasma to reduce pain and increase function in patients who considered surgery.Results: 140 patients with elbow epicondylitis were eval-uated in this study. Eight weeks after the treatment with platelet-rich plasma patients noted 60% improvement in the visual analog pain scale scores versus 16% improvement in the control group. After six months, the patients treated with platelet-rich plasma noted 81% improvement in their visual analog pain scale. At the fi nal follow-up, there was a 93% reduction in pain compared with the visual analog pain scale scores before the treatment.Conclusion: Treatment of patients with chronic elbow tendonitis with buffered platelet plasma reduced pain sig-nifi cantly in this investigation. Platelet-rich plasma should be considered before surgical intervention. No PRP patients had worsened after treatment and there were no complica-tions in the study.Summary: PRP has been shown to be very effective in treating elbow tendonitis and is a viable alter-native to surgery.

50Study 7Journal Tissue Engineering 2007. Intervertebral disc (IVD) regeneration using platelet-rich plasma and biodegradable gela-tin hydrogel microspheres.Author: Masateru NagaeBackground: Platelet-rich plasma has the potential to re-generate intervertebral discs.Purpose: The purpose of the study was to determine the potential of growth factors to regenerate intervertebral discs and treat IVD degeneration. In addition, the therapeutic ef-fect of the combined administration of PRP and biodegrad-able gelatin hydrogel microspheres on degenerated IVD was investigated in a vivo animal study.Results: Histologically, notable progress in interverte-bral disc degeneration was observed in the control and PRP group. In contrast, progress of IVD degeneration was remarkably suppressed over the 8-week period in the PRP group. Intense immunostaining, for proteoglycans in the nucleus pulposus (NP) and inner layer of annulus fi brosus (AF), was observed 8 weeks after administration of PRP-im-pregnated microspheres. Almost all microspheres were in-distinct 8 weeks after the injection, and there were no appar-ent side effects in this study.Conclusion: Results suggest that the combined adminis-tration of PRP and gelatin hydrogel microspheres into the intervertebral disc may be a promising therapeutic modality for inhibiting intervertebral disc degeneration inhibition.Summary: PRP injection into an intervertebral disc helps to regenerate the disc with no side effects.

51Study 8American Journal of Sports Medicine 2008. Platelet-rich plasma enhanced tendon repair. A cell culture study in vitro.Author: Marieke De MosBackground: Autologous platelet-rich plasma (PRP) ap-plication appears to improve tendon healing in traumatic tendon injuries, but basic knowledge of how PRP promotes tendon repair is needed.Purpose: The intent of this study was to evaluate the effect of platelet-rich plasma, as well as endogenous growth factors produced by human tenocytes, on cell collagen production.Results: Platelet number in PRP increased 2.55. Both PRCR and PPCR increased cell number and total collagen.Conclusion: In human tenocyte cultures PRCR and PPCR stimulate cell proliferation and total collagen production. Autologous PRP application appears effective in the healing of chronic traumatic tendon injuries and tendinopathies. PRP clot releasate stimulates cell proliferation, collagen deposition, and enhances the gene expression of matrix de-grading enzymes and endogenous growth factors produced by human tendon cells which may promote the return to normal function after traumatic injuries.Summary: PRP injections stimulate cell growth and collagen production which help to improve the healing of tendons.

52With the growing number of successful clinical applications for PRP in medical literature comes the need for larger and better de-signed clinical trials to document the healing properties of PRP.I chose the fi rst seven human studies to help you gain an under-standing of the effects of PRP on actual patients, while the fi nal study was performed on animals in the laboratory.Here is a brief summary of the above eight studies:• PRP treatment has helped patients to reduce their pain and enjoy greater mobility as compared to the results of patients receiving steroid injections (study 1).• PRP injections have helped patients with Achilles tendinop-athy function better, with fewer complications (study 2).• PRP injections have helped to relieve osteoarthritic knee pain more effectively than Synvisc injections (study 3).• Patients enjoyed both short and long-term improvement in knee function and mobility after PRP injections (study 4).• PRP is safe and may be an effective approach in treating ear-ly signs of aging in the knees (study 4).• Tissue regeneration in the knee was improved and there was an increased potential for pain relief. This is another exam-ple of how PRP can accelerate healing (study 5).• PRP has been shown to be very effective in treating elbow tendonitis and is a viable alternative to surgery (study 6).• There were no side effects after treatment when PRP injec-tions were combined with hydrogel to effectively treat inter-vertebral disc degeneration (study 7). • PRP injections stimulate cell growth and collagen produc-tion which helps to improve the healing of tendons (study 8).

53References1. Alsousou J. et al. The biology of platelet-rich plasma and its application in trauma and orthopaedic surgery: a review of the literature. J. Bone Joint Surg. Br. 2009; 91(8): 987-996.2. Marx RE: Platelet-rich plasma: Evidence to support its use. J. Oral Maxillofac. Surg. 2004;62:489-496.

54

55Chapter 6Clinical Application of PRP for Cervicaland Lumbar Facet Arthropathy

56

57In practice, physicians are using PRP to treat neck and lower back pain originating from painful cervical and lumbar facets. This con-dition is known as cervical and lumbar facet syndrome and also as facet arthropathy. Results when using PRP to treat this condition are very favorable (1).Facet arthropathy is similar to other joint arthropathies where treatment with PRP has almost always been successful. The regen-erative properties of PRP help to reduce pain and increase mobility following an injury. This treatment also works on healing in many degenerative conditions (2).Traumatic neck and back pain is very often related to whiplash in-juries with the following symptoms: nonradiating neck/back pain, becoming worse with extension or posterior tilt, tenderness in the projection of the facet joints, and positive facetogenic maneuvers. This type of acceleration/deceleration injury can occur as a result of a rear end accident or an abrupt stop of the car.Confi rmation of the diagnosis is identifi ed by positive response to the medial branch block. Upon completion of the block (if the block is positive), the result will be that of temporary pain relief and increased range of motion.More clinical trials are needed to document the increase of PRP in clinical applications and explain why the ligaments and muscles heal faster after PRP injections. Because there are no standardized protocols available regarding blood collection and PRP prepara-tion, more needs to be done to standardize these areas. Physical Medicine and Rehabilitation protocols following PRP injections also need to be established to facilitate recovery after injections.In our practice, every patient follows a structured physical therapy (PT) protocol. Following the PRP injection our PT protocol incor-porates the following:1. 24-48 hours of rest followed by a minimal amount of PT.2. A more comprehensive PT protocol begins 72 hours after the initial injection.

583. The PT is done for 3-4 weeks followed by a medical evalua-tion.4. Additional PRP injections are performed in 4 week intervals.Ad 1. A relative rest period following the PRP injection is neces-sary to provide the opportunity for the platelets to work at the site of injury and to reduce the intensity of the pain where the actual injection was performed. Excessive movements may displace the PRP matrix from the point of injection.Ad 2. Physical therapy (PT) protocol requires 2 to 3 visits per week and incorporates techniques that facilitate the maturation and re-modeling phases of the healing phases as described in chapter 2.Ad 3. & 4. Upon evaluation, the decision to continue PRP injections is based on the relief of symptoms and the ability to perform a full range of motion exercises.Three PRP injections followed by physical therapy seems to be the optimal protocol in most cases with a high success rate of function recovery and the elimination of neck and back pain.References1. Nasiek, D. PRP helps to regenerate injured facets joints following MVA injury (study in progress). 2. Mei-Dan O. et al. Autologous platelet-rich plasma: a revolution in soft tissue sports injury management? The Physician and Sports Medicine, psm. (2010),12.p 1835.

59Chapter 7Comparing PRP Injections with Synvisc®Injections and Stem Cell Therapy

60

61Injections of blood product in the form of PRP have been used suc-cessfully for many years throughout various medical and surgical fi elds.Let’s compare PRP injections with Synvisc® and stem cell injec-tions.Synvisc® injections vs. PRP injectionsPreviously developed injections such as Synvisc® were and are still used to treat osteoarthritis of the knee. They are successful in eliminating pain and improving function. Synvisc-One®, which is a natural hyaluronic acid derivative, is used for treatment of pain due to osteoarthritis (OA) of the knee in patients who have failed to respond adequately to conservative nonpharmacological therapy such as physical therapy (PT), manipulation, and simple analge-sics like acetaminophen. It can provide up to 6 months of osteo-arthritic knee pain relief with just one injection (1). Synvisc® is made from a natural substance that lubricates and cushions the joint. The injections of the viscous products provide lubrication to the joint. The product has no biological activity itself and needs to be administered repeatedly in order to provide relief (1).PRP injections, on the other hand, are biologically active and stim-ulate healing, repair, and tendon regeneration. More studies are necessary in order to uncover the full potential of their effects as they speed up the recovery and healing process (2).Stem cell injections vs. PRP injectionsNew frontiers have been tested with new injections that target spe-cifi c cells. Omnipotent stem cells can be utilized to regenerate spe-cifi c tissues rather than to provide nonspecifi c healing properties. Direct stem cell injections are the latest process in development. Stem cells delivered from bone marrow aspiration and from fatty tissue aspiration present great biological healing potential. They can infl uence faster regeneration and promote the development of new tissues. Stem cells have the remarkable potential to develop into many different cell types in the body. They serve as an internal repair system, dividing without limit to replenish other cells. When a stem cell divides, each new cell has the potential either to remain

62a stem cell or become another type of cell with a more specialized function, and under certain conditions it can be induced to become a tissue cell, organ cell or cell with specialized functions. Research on stem cells continues to advance knowledge of how healthy cells replace damaged cells.PRP injections, like stem cells, are biologically active and stimu-late healing, repair, and regeneration. PRP depends on growth fac-tors to speed the recovery and the recruitment or facilitation of the stem cells from the vicinity and/or circulation. The PRP uses the attributes of the stem cells, but at a restricted level. More studies will help to uncover their full potential as they speed up the recov-ery and healing process through recruitment of the stem cells.References1. Manufactures insert from injectible Synvisc® and Synvisc-one® products.2. Anitua E. et al. Platelet-released growth factors enhance the secretion of hyaluronic acid and induce hepatocyte growth factor production by synovial fi broblasts from ar-thritic patients. Rheumatology. 2007; 46(12): 1769-72.

63Chapter 8Rehabilitation and Physical Therapy

64

65Rehabilitation and physical therapy are the most important con-tributing factors to insure complete restoration and recovery after PRP injections.Traditionally the convalescence process included the following:1. Eliminating or reducing activities2. Adding passive types of therapy3. Using nonsteroidal anti-infl ammatory drugs like Aspirin, Motrin, and AleveI will explain why this is not the best and fastest road to recovery.First, physical activity in any form speeds up recovery (1)(2).Secondly, both active and passive therapy need to be incorporated (4).Finally, while the anti-infl ammatory medication may help in the short term, in the long term it will slow down the healing process and may lead to undesirable outcomes such as tendinopathy and chronic pain.In our practice, we advise our patients to follow these important steps in physical therapy and rehabilitation following the PRP in-jections:1. Rest for the fi rst 24-48 hours after PRP procedure to prevent displacement of the newly-formed PRP mash at the injection site.2. Implementation of advised and slow range-of-motion activities with the addition of physical therapy after the fi rst 48 hours.3. Resuming activities and a full physical therapy protocol after 72 hours.4. Restriction on the use of steroidal and nonsteroidal anti-infl am-matory medication for a period of 4 weeks.5. Intake of Tylenol or weak painkillers to reduce pain and facilitate an exercise program.

66Ad 1-4. The goal of physical therapy is to improve function, de-crease pain, and increase strength.Ad 5. The goal of medication is to create a pain-free physical ther-apy experience and to allow for continuation of normal activities. Incorporating physical activity and a moderate exercise program in conjunction with physical therapy will immediately increase the water content and the blood fl ow in healthy tendons and in those tendons with tendinosis (1). An increase in water content and blood fl ow in the vicinity of the injury will speed up the recovery. Increased blood circulation brings more platelets and growth fac-tors to the injured area which leads to a quicker recovery (1). According to many experts, exercise may prevent or reduce the production of the chemical agents responsible for producing pain in tendinosis (2). These agents, associated with symptomatic ten-dinosis, include substance-P, Glutamate, Calcitonin, and other active peptides, amongst others. These neuropeptides may be re-sponsible for tendinosis pain. However, patients who exercise have lower levels of these substances in their blood (2). The same is true following physical therapy.As you may know, exercise stimulates the production of colla-gen synthesis, an enzyme responsible for stimulation of collagen production. This suggests that exercise may increase the size of a tendon because it increases the production of collagen type I (5). This may be of further benefi t because fi broblasts, which help re-pair damaged areas of tendons, normally synthesize a greater pro-portion of type III collagen (type III collagen is not as strong and resembles scar tissue). As a result, physical therapy exercises may strengthen tendons and protect them from subsequent overuse (5).Weight-bearing exercises have long been known to strengthen ten-dons by increasing blood fl ow, oxygen uptake, and metabolic rate (3)(4). They also prevent collagen degradation and improve colla-gen synthesis in healthy tendons. The same may be true for repair-ing injured tendons. Weight lifting may also strengthen degenera-tive tendons in the same way it does in healthy ones (4).

67It is important to participate in physical activity to be able to de-pend on yourself and resume a normal life, but it should be done in a controlled rehabilitation setting from the onset of treatment. Otherwise, unsupervised physical and/or sports activity may actu-ally cause or aggravate damage, tendinosis, etc. On the other hand, exercise under the supervision of a medical doctor and physical therapist will promote faster healing and optimize the regenera-tion process.References1. Alfredson H. et al., The chronic painful Achilles and patellar tendon: research on basic biology and treatment. Scandinavian Journal of Med. Science Sports. 2005; 15 p.252-2592. Puffe T. et al., Mechanical factors infl uence the expression of endostatin an inhibitor of angiogenesis in tendons. Journal of Orthopedic Res. 2003; 21, p. 610- 6163. Shalabi A. et al., Immediate Achilles tendon response after strength training evaluated by MRI. Medical Science Sports Exerc. 2004; 36, p. 1841-18464. Tipton CM. et al. The infl uence of physical activity on ligaments and tendons. Medical Science Sports. 1975; 7, p. 165-1755. Maffulli N. et al. Tenocytes from ruptured and tendinopathic Achilles tendons produce greater quantities of type III collagen than from normal Achilles tendons: an in vitro model of human tendon healing. American Journal Sports Medicine. 2000; 28, p.499-505

68

69Chapter 9Seeing the PRP Process and Understandingthe Techniques for the Application of the PRP

70

71The following photographs will illustrate the technical aspects of the process from admission to discharge.1. Arrival at the surgical center.2. Admission protocol with a registered nurse at the surgicalcenter.

723. Discussion with the surgeon, documenting and obtaining informed patient consent.

73PREPARATIONThe preparation of the PRP occurs in an operating room or preop-erative area of the hospital, outpatient facility or physician’s offi ce. It begins with blood collection. A sterile technique is used when withdrawing and preparing PRP.4. Blood drawing.

74Blood drawing. Final stage.5. Blood processing. Preparing for centrifugation.

75Centrifugation.Blood sample following centrifugation.

76Transfer of PRP for activation.Transfer of PRP to the sterile syringe for injection.

77PREPARATION FOR INJECTIONA strict aseptic sterile technique is followed when preparing the surgical fi eld for injection. The sterile technique and antibacterial properties of the PRP make an infection unlikely.6. Positioning of the patient in the operating room on the operating room table.7. Preparation of the surgical fi eld.

78VISUALIZATIONPRP is considered most effective when injected as close as possi-ble to the site of the injured tissue. The process recommended to ensure the accuracy of needle placement includes two visualization techniques, ultrasound and fl uoroscopy.Ultrasonography allows the visualization of tissues with the use of ultrasonic waves. It works on the principle that sound is refl ected at different speeds by tissues of different densities.Ultrasonograpy does not use radiation and is a portable technolo-gy. Resolution and penetration depend upon wave frequency.Fluoroscopy allows for the examination of internal structures of the body by means of a live continuous X-ray image. Some struc-tures with high mineral bone content are opaque to conventional X-rays. Live fl uoroscopy, with the use of contrast, provides live im-ages of high resolution for examination of bones and joints during the time of procedure or surgery.8. Identifi cation of abnormality by means of ultrasound guidance.

79Ultrasound machine.8A. Identifi cation of the pathology using C-arm (X-ray machine).

80APPLICATIONPRP can be used both percutaneously by means of a syringe injec-tion or by direct placement during an open surgical procedure in the form of fl uid injection, gel or gelatinous structure positioned directly into or on the surgical fi eld.PRP can be mixed with other biological materials such as bone grafts or ligament grafts and then injected into the tissue. PRP can also be applied directly to the surface of the skin.Most commonly the PRP is applied in a liquid form injected direct-ly from a syringe under guidance of ultrasound and/or fl uoroscop-ic visualization.9. Injection of local anesthetic with or without sedation anesthesia.

81ACTIVATION OF PRP BEFORE/DURING APPLICATIONActivation of PRP is critical when obtaining the blood using an-ticoagulation. PRP activation may take place immediately before application or can occur after application in-vivo within the inject-ed tissues. Currently, there is no consensus over the timing of PRP activation.PRP can be activated outside of the tissue in-vitro (done in a lab-oratory) and then injected into the tissue. The major in-vitro ac-tivating factors are calcium chloride and autologously-prepared thrombin.PRP can be activated in the tissue in-vivo (done with a live body) and placed directly where needed to allow the local environment to activate it immediately at the injection site. By relying on the collagen activation in the tissue, PRP can be injected while inactive and then become activated by the presence of collagen in the tissue during the procedure or surgery.Following application, the platelets actively secrete proteins from the granules within ten minutes of clotting. The majority of these proteins are growth factors and they are secreted within the fi rst hour. After the initial outburst of growth factors, the platelets syn-thesize and secrete additional growth factors for the remaining days of their lifespan.10. Actual injection of PRP.

8211. Application of dressing.

8312. Return to the recovery room and discharge instructions:(a) 24-hours of immobilization(b) Avoidance of Aspirin, Advil and similar products(c) Prescription of analgesics(d) Physical therapy as per protocol13. Follow-up visit.A course of physical therapy will be determined following PRP.This is done to improve function, increase strength and improve the outcome of the injection procedure.Additional injections may be recommended.The goal is to avoid surgical procedure and to speed up the recovery process.

84

85Chapter 10Future Studies on PRP Therapy

86

87 As we have discussed, the medical literature as of 2012 has rel-atively few credible and large studies on PRP therapies. Since ex-tensive data is diffi cult to fi nd and interpret, evaluation of PRP has been challenging. Why has so little been written and published on the subject, de-spite the fact that this effective noninvasive therapy has been avail-able for a quarter of the century? Is it possible that a potential confl ict of interest exists within the pharmaceutical industry, due to its lack of interest in the devel-opment of technology that cannot be patented, and then used for profi t? The simple answer to these two critical questions might be that PRP is a blood product and not a drug. There is no incentive to promote a pharmaceutical product ob-tained directly from the patient’s own blood. This has resulted in the lack of funding for past and present studies and will continue to hinder future medical trials. At one time a recombinant growth therapy using growth factors was proposed. The process of chemical and biological synthesis of molecules was involved in regeneration and healing. Unfortunate-ly, these efforts failed due to the extremely high cost of recombi-nant synthesis of the growth factors and their inability to achieve good therapeutic results with a single growth factor application (growth factors usually work in conjunction with one another). Without the resources and funds available, it is very diffi cult to perform clinical trials on a larger scale. Domestic institutions and non-profi t organizations like the National Institute of Health, the National Cancer Institute, or government agencies, should be involved in facilitating this type of research, but they are not. In an article published in The American Journal of Sports Med-icine in 2005, “Outcome of Surgery for Chronic Achilles Tendinop-athy”, Cheryl Tallon and co-authors (1) suggest that for any future studies to be considered credible, the following guidelines should be included:1. Studies should be large-scale, randomized, controlled and prospective.2. The patient selection criteria should be specifi c and well documented. The number of patients who do not complete the study should also be considered.3. Post procedural/postoperative evaluation should include MRI, ultrasound and other objective studies such as histo-

88logical assessment - in addition to clinical evaluation.4. When evaluating the results of the pain relief and improved range of motion studies, the quantitative research should be documented in order to ensure its objectivity.5. Postoperative rehabilitation should be documented in de-tail. This would provide a full description of the protocol and patient compliance. Postoperative rehabilitation is extreme-ly important and may play a vital role in the rehabilitation process following the PRP injection. It seems that at present the pharmaceutical industry may not contribute to the growth of PRP treatment and signifi cant clinical studies will not become available. However, I intend to diligently continue documenting the positive results patients have achieved with PRP therapy in conjunction with physical therapy (PT). I also intend to recommend PRP therapy to three groups of patients who may benefi t most from it.1. Surgical candidates: When surgery is presented as the only option, a trial of the PRP therapy may be successful and the surgery may be avoided altogether.2. Young athletes: Since greatest healing potential exists in younger patients, this is where PRP shows most promise.3. Injury victims: The majority of studies done on injured tendons, joints, and muscles have validated the benefi t of PRP. Whether you are a patient considering surgery, an injured ath-lete or recovering from an injury, PRP used in conjunction with physical therapy is a viable and cost effective option. It has benefi t-ed many individuals seeking to be active again.References1. Tallon, Ch. et al. Outcome of Surgery for Chronic Achilles Tendinopathy, The Ameri-can Journal of Sports Medicine, Vol.29, No. 3, p.315-320.

89PART IIIA NEW PARADIGM

90

91Chapter 11Regenerative Medicine

92

93As previously mentioned, the classical approach in Orthopedic Medicine and Surgery relies mainly on stabilizers or immobilizers such as ace bandages, slings, casts, plates, and screws, which are used to immobilize broken bones, hurt joints, and painful tendons. Even the most advanced surgical technique called ORIF (Open Reduction Internal Fixation) depends on fi xation and stabilization with mere plates and screws.The recovery phase of the classical approach, during which the body gradually repairs the damage, is slow and ineffi cient. In time, along with some consistent physiotherapy, the body recovers its former effi ciency and patients regain their previous physical fi tness.For years, this long and painstaking healing process was the only one available.This is not the case any longer. Recently the medical world has giv-en birth to a new paradigm of regenerative medicine.Regenerative Medicine is a science, which seeks to strengthen the healing process and create new tissue. This tissue repairs, replaces and restores the function and the structures that have been lost due to injury or disease.Repair refers to the healing of injured tissue or replacement of lost tissue by cell proliferation and synthesis of new extracellular ma-trix. Unfortunately, repaired tissue generally fails to replicate the structure, composition, and function of the normal organ.In this context, regeneration refers to the formation of entirely new tissue that essentially duplicates the original organ.Regenerative Medicine focuses on two principal techniques:1. To signifi cantly enhance and increase normal therapeutic properties.2. To reproduce the previously damaged and irreparable tissue or organs in order to replace them.

94The fi rst approach (enhancing and increasing normal healing) uses platelets and depends upon growth factors obtained from cells re-sponsible for repair and regeneration.This can be accomplished in clinical medicine through PRP injec-tions and PRP therapy.The second approach (reproducing the previously damaged and irreparable tissue or organs) depends upon omnipotent cells avail-able to regenerate the area of irreparable damage. These cells are known as stem cells.The injection of stem cells obtained from bone marrow or fat aspi-rate facilitates the regeneration of the damaged tissue. Although in the past, stem cell therapy has been riddled with con-troversy, platelets and growth factors have been used successful-ly for many years to accelerate the healing process. This process, at least partially, depends upon the recruitment and activation of stem cells from the periphery and from blood circulation. As a result, stem cell therapy has recently become part of mainstream medical therapy.New frontiers have been tested with injections that target specifi c cells. It is possible that omnipotent stem cells can be utilized to re-generate specifi c tissues rather than to provide nonspecifi c healing properties. Direct stem cell injections, as well as the recruitment of stem cells from the bloodstream, are the latest process in develop-ment.

95Chapter 12Facts, Concepts, and FrequentlyAsked Questions

96

97Now that you have a solid understanding of the reasons why Plate-let Rich Plasma (PRP) is an important pain management option, this brief summary will help you tie all of the concepts together.First, ten simple facts to remember:1. PRP stands for Platelet Rich Plasma injection and the sub-stance is derived from the patient’s own blood.2. PRP has a higher than normal concentration of platelets.3. PRP is used to deliver above normal concentration of growth factors to the patient’s cells.4. PRP has been used by many medical and surgical special-ists including Sports Medicine Specialists, Orthopedic Sur-geons, Pain Management Specialists, Oral Surgeons, Podia-trists, and Plastic Surgeons.5. PRP application in Sports Medicine has increased over the past few years with high-profi le athletes receiving extensive media coverage after treatment.6. PRP supports and speeds up the healing of muscle strains, tendon and ligament sprains, and tendinopathy.7. PRP usage in Pain Management may decrease pain and has-ten recovery from common pain syndromes.8. PRP clinical studies in Veterinary Medicine and Animal Re-search show promising results.9. PRP usage in human studies is underway and has already shown highly satisfactory and promising clinical results.10. PRP application can benefi t a broad range of medical spe-cialists including pain management specialists, orthopedic surgeons, sports medicine physicians, physiotherapists, chi-ropractors, and acupuncturists.

98Secondly, six key aspects of PRP and how it works:1. PRP is a blood product derived from the patient’s own blood. To increase the concentration of the existing blood platelets and growth factors, the blood is centrifuged at a high speed and spun to separate the red blood cells from platelets and plasma. This is done immediately before application of the PRP; the resulting substance is used within minutes of its preparation.2. Any contamination during the preparation of PRP is very unlikely as there is minimal contact with the outside envi-ronment. The blood is collected, processed and reinjected within minutes in the same physical location.3. As part of PRP, both platelets and plasma contain funda-mental growth factors.4. After injury the pain area has low or minimal blood fl ow. The level of delivered nutrients and healing factors decreas-es, and the healing process slows down. The injection of PRP directly to the site of injury increases the supply of growth factors and nutrients which enhance and stimulate healing of the wound.5. The extensive range of medical applications comes from the ability of PRP to support the healing of many tissues. Spe-cifi cally, PRP enhances fi broblast events involved in tissue healing including chemotaxis, cell proliferation, proteosyn-thesis, repair, extracellular matrix deposition, and tissue re-modeling.6. By providing additional growth factors, PRP accelerates the regeneration process. This in turn may enhance the recovery process and the patient’s faster return to normal activities. PRP has also been successfully used to improve the out-comes of surgical procedures in orthopedic, podiatric, spi-nal, maxillofacial, and cosmetic surgery.

99Finally, important answers to the most essential and frequently asked questions.What is the science behind PRP?The science of wound healing and tissue repair is complex and oc-curs on multiple levels. The molecular response is a chemical pro-cess mediated by many factors. These factors are released from plasma and platelets after an activation phase. The presence of an increased level of growth factors signifi cantly speeds up the pro-cess of regeneration.How is PRP prepared and applied?A sample of the patient’s blood is obtained in the same way any blood sample is extracted for blood analysis. After antiseptic skin preparation, a tourniquet is applied, and a needle is inserted into the peripheral vein.The tube is labeled with the patient’s name and placed in the cen-trifuge. The spinning of the sample at a high speed takes minutes after which the PRP is ready for injection. The PRP will remain with the patient until it is subsequently injected by the physician.Typically, patients are seen every four to six weeks until healing is complete. Generally, two to six visits are necessary for each area being treated.There are many systems used for PRP preparation. They vary in the amount of blood they use and the centrifuging peak and trough times.In my clinical experience, using the Cascade Platelet Rich Plasma Therapy System of Musculoskeletal Transplant Foundation in Edi-son, New Jersey has been successful. This product has led to quick recovery and greater patient satisfaction.

100What are the results?The clinical use of PRP is gaining acceptance and popularity be-cause of its effectiveness and simplicity. The regenerative effects of PRP on human tissues and organs translate into clinical benefi ts. This alternative to surgical intervention has greatly benefi ted the general public as well as athletes, both occasional and professional. The biological effect of PRP is being researched further to deter-mine if there are even greater clinical applications.Is PRP good for all types of injuries?PRP is good for less severe injuries where there is no complete sep-aration of the tendon or ligament tissue. A complete rupture will require surgery, while an incomplete rupture, sprain or strain will be well served by a regenerative PRP injection.Is PRP good for arthritis?PRP is helpful for pain relief. If viscosupplementation therapy with Synvisc® and steroid injection with Depomedrol® fails, PRP may be a viable option. The same is true if the patient refuses surgery or is a poor candidate for joint replacement therapy.How long will it take for the PRP results to be visible?Because PRP therapy is a regenerative process, it takes time - one to two months - before the results are clearly visible. Repeated PRP procedures may be necessary before complete healing occurs.Why PRP and not surgery?While surgery is more expensive and requires much more time for recovery, in well-selected cases, PRP offers similar results at a low-er cost and in signifi cantly less time.

101Chapter 13The Safety and Successof the PRP Procedure

102

103PRP is an autologous preparation. This means that the donor and recipient are the same person, which prohibits an immunogenic reaction and disease transmission. It is safe as it is generated from the body of the same individual (1).The blood preparation is collected in a sterile container and re-mains there throughout the entire process of preparation. Only after antiseptic skin preparation has been completed is the tourni-quet applied and the needle inserted into the vein. It is also highly unlikely that a PRP preparation would become contaminated since there is minimal contact with the outside environment.There is no evidence of any systemic effects of local PRP injections (2).The aforementioned clinical studies conducted on patients validate a wide range of success and safety. The results of these studies in-clude:- PRP treatment has helped patients to reduce pain and enjoy greater mobility as compared to the results of those patients re-ceiving steroid injections.- PRP has helped patients with Achilles tendinopathy function bet-ter with fewer complications.- Patients enjoyed both short and long-term improvement in knee function and mobility. PRP is safe and may be an effective approach to treating early signs of aging in the knees.- Tissue regeneration in the knee was improved with an increased potential of pain relief. This is another example of PRP accelerated healing.- PRP has proved very effective in the treatment of elbow tendon-itis. It is a viable alternative to surgery.- PRP has also been clinically used for backaches. There were no side effects of PRP therapy when combined with hydrogel to effec-tively treat intervertebral disc degeneration.

104The role of PRP in tissue healing and regeneration introduces a new era in regenerative medicine. Standards regarding the effec-tiveness of PRP in a clinical setting are being established for fu-ture applications. These standards support the use of PRP for the healing of muscles, tendons, ligaments, cartilage and other pain generating and deteriorating tissue. In the future, this healing will be done by omnipotent cell lines, growth factors and bioactive pro-teins.Combining biological advancements with the art of medicine (knowledge, experience, clinical judgment, and intuition) is cen-tral for proper transition of these new therapies and their future implementation in routine medical care.References1. Foster T. et al. Platelet-rich Plasma. From Basic Science to Clinical Applications. The American Journal of Sports Medicine, Vol.37, No 11:2259-2273.2. Redler L. et al. Platelet-Rich Plasma Therapy: A Systematic Literature Review and Ev-idence for Clinical Use. The Physician and Sportsmedicine, Feb. 2011, No1, Vol39, 42-51.

105Glossary

106

107Achilles Tendon InjuryThe Achilles tendon is the tendon extension of two muscles, gas-trocnemius and soleus, that passes behind the ankle. It is the thick-est and strongest tendon in the body. The most common Achilles tendon injuries are Achilles tendinosis and Achilles tendon rup-ture. Achilles tendinosis is the soreness or stiffness of the tendon, generally due to overuse. Achilles tendinitis, infl ammation of the tendon, was thought to be the cause of most tendon pain, until sci-entists discovered no evidence of infl ammation. The clinical term of tendinopathy should be given to the combination of tendon pain, swelling and impaired performance. Treatment of damage to the tendon is generally nonoperative. Orthotics can provide early re-lief to the tendon by the correction of misalignments. Nonsteroidal anti-infl ammatory drugs (NSAIDs) are generally to be avoided as they make the more common tendinopathy (degenerative) injuries worse although they may infrequently be indicated for the tendini-tis (infl ammatory) injuries which are rare. Physiotherapy by eccen-tric calf stretching under resistance is commonly recommended, usually in conjunction with podiatric insoles or heel cushioning. The pain in Achilles tendinopathy arises from the nerves associat-ed with neovascularization. PRP injections show promise in non-healing Achilles tendon injury when other therapies have failed. Steroid injections should be avoided as they may weaken the Achil-les tendon and lead to rupture. Surgical intervention is reserved for total rupture of the Achilles tendon.ActinA protein found in muscle, which together with myosin, functions in muscular contraction and relaxation.AllogenicBeing genetically different although obtained from the same spe-cies.AutologousDerived or transplanted from the body of the same individual.

108CartilageA strong but fl exible connective tissue found in various parts of the body, including the joints, the outer ear, and the larynx. During the embryonic development of most vertebrates, the skeleton forms as cartilage before most of it hardens into bone.CellThe smallest living units of the body which group together to form tissues and help the body perform specifi c functions.ChemotaxisDirectional movement of an organism or cells in response to the infl uence of chemical stimulation. Chemotaxis is a cellular func-tion, particularly of neutrophils and monocytes, whose phagocytic activity is infl uenced by chemical factors released by invading mi-croorganisms.EpicondylitisPainful infl ammation of the muscles and soft tissue around an epi-condyle.- lateral epicondylitis, lateral humeral epicondylitis, tennis el-bow - painful infl ammation of the tendon at the outer border of the elbow resulting from overuse of lower arm muscles (as in twisting of the hand).- medial epicondylitis, golfer’s elbow is an infl ammatory con-dition of the medial epicondyle of the elbow. EpithelizationThe healing process of covering (a wound, for example) with epi-thelial tissue.FibroblastA cell in connective tissue that synthesizes collagen.

109FunctionThe physiological activity of an organ or body part. Special, nor-mal, or proper operation of any part or organ.Hyaluronic Acid A gellike aminoglycan that is found in the tissue space, the synovial fl uid of joints, and the vitreous humor of the eyes; acts as a binding, lubricating, and protective agent.Infl ammationA response of body tissues to injury or irritation, characterized by pain, swelling, redness and heat.Injection nounIn medicine, a fl uid injected into the body, especially for medicinal purposes.Injection verbThe act of putting a liquid into the body by means of a syringe• intradermal injection - an injection into the skin• intramuscular injection - an injection into a muscle• intravenous injection - an injection into a vein• subcutaneous injection - an injection under the skinJumper’s knee or Patellar Tendinopathy(often incorrectly called Patellar tendinitis) It is a relatively com-mon cause of pain in the inferior patellar region in athletes. It be-gins as infl ammation in the patellar tendon where it attaches to the patella and may progress by tearing or degenerating the tendon. It is an overuse injury from repetitive overloading of the extensor mechanism of the knee. The microtears exceed the body’s heal-ing mechanism unless the activity is stopped. The injury occurs in many athletes, but is most common in sports such as soccer, volleyball, or basketball which require explosive movements. Early stages may be treated conservatively. PRP offers an excellent op-portunity for noninvasive, nonsurgical option to aid a speedy re-

110turn to normal activities. Uncommonly, it may require surgery to remove myxoid degeneration in the tendon.Leukocytes White Blood Cells (WBCs)Cells of the immune system involved in defending the body against infectious disease and foreign materials. There are fi ve different and diverse types of leukocytes: 1.Neutrophils, 2. Basophils, 3. Eo-sinophils, 4. Monocytes 5. Lymphocytes. All of them are produced and derived from a multipotent cell in the bone marrow known as a hematopoietic stem cell. Leukocytes are found throughout the body, including the blood and lymphatic system.LysosomeCellular organelles that contain acidic hydrolase enzymes (diges-tive enzymes) that break down waste materials and cellular debris.Muscle A body tissue composed of sheets or bundles of cells that contract to produce movement or increase tension. Muscle cells contain fi l-aments made of the proteins actin and myosin, which lie parallel to each other. When a muscle is signaled to contract, the actin and myosin fi laments slide past each other in an overlapping pattern. • Skeletal muscle powers voluntary movement of the skeleton and is made up of bundles of elongated cells (muscle fi bers), each of which contains many nuclei. • Smooth muscle provides the contractile force for the internal organs and is controlled by the au-tonomic nervous system. Smooth muscle cells are spindle-shaped and each contains a single nucleus. • Cardiac muscle makes up the muscle of the heart and consists of a meshwork of striated cells.MyosinThe most common protein in muscle cells, responsible for the elas-tic and contractile properties of muscle. It combines with actin to form actomyosin.

111NeutrophilA cell, especially an abundant type of granular white blood cell, that is highly destructive of microorganisms. It is the chief phago-cytic leukocyte.OrganA differentiated part of the body that performs a specifi c function.OrganelleA differentiated structure within a cell, such as a mitochondrion, vacuole, or chloroplast, which performs a specifi c function.PainAn unpleasant sensory and emotional sensation occurring in vary-ing degrees of severity as a consequence of injury, disease, or emo-tional disorder.PhagocytosisThe process by which a cell, such as a white blood cell, ingests mi-croorganisms, other cells, and foreign particles.Plantar FasciitisA painful infl ammatory or degenerative process of the plantar fas-cia – tendinosis structure at the bottom of the foot. Longstand-ing cases of plantar fasciitis often demonstrate more degenerative changes than infl ammatory changes and are termed plantar fasci-osis. The plantar fascia is a thick fi brous band of connective tissue originating on the bottom surface of the calcaneus (heel bone) and extending along the sole of the foot towards the fi ve toes. This con-dition occurs in 10% of the population within the span of a lifetime and is associated with constant weight gain and obesity. Diffi culty and decreased dorsifl exion of the ankle is also present. The pain is usually felt on the underside of the heel and may be debilitating.

112PlasmaThe clear, yellowish fl uid portion of blood, lymph, or intramuscu-lar fl uid in which cells are suspended. It differs from serum in that it contains fi brin and other soluble clotting elements.PlateletFragments of protoplasm found in vertebrate blood; essential for blood clotting and tissue regeneration.Prolotherapy (“Proliferative Injection Therapy”)Involves injecting an otherwise nonpharmacological and nonactive irritant solution into the body, generally in the region of tendons or ligaments for the purpose of strengthening weakened connective tissue and alleviating musculoskeletal pain. Prolotherapy is also known as “proliferation therapy” or “regenerative injection ther-apy.” Regenerative MedicineAdvanced medicine described as the creation of tissue that pro-vide, repair, replace or restore structures and functions absent or lost due to congenital defects, aging, disease, or damage. Regener-ative medicine helps natural healing processes to work faster, or uses special materials to regrow missing or damaged tissue.Rotator Cuff SyndromeThe tendons at the ends of the rotator cuff muscles (supraspinatus, infraspinatus, teres minor and subscapularis) can become stretched, sprained, or partially or completely torn, leading to pain and restrict-ed movement of the arm. A torn rotator cuff can occur following a trauma to the shoulder or it can occur through the “wear and tear” of tendons, most commonly those of the supraspinatus under the acromion. It is an injury frequently sustained by athletes whose du-ties involve making repetitive throws. It is commonly associated with motions that require repeated overhead motions or forceful pulling motions. The purpose of the initial treatment is to reduce pain and swelling. As with all muscle injuries, R.I.C.E. is an acronym for initial response and therapy recommended by health providers.

113• Rest means ceasing movement of the affected area.• Icing uses cold to reduce infl ammation.• Compression limits swelling.• Elevation involves placing the area higher to reduce infl am-mation and swelling.Initial therapy involves physical therapy modalities, strengthening exercises and range of motion exercises. If a partial tear is pres-ent, the rest may require more time for healing. If conservative measures fail PRP shows promise in all but the most severe cases of complete separation and may help to avoid surgical interven-tion through its regenerative properties. Depending on severity of symptoms, further imaging with radiograph or MRI may be war-ranted to see if an underlying bone injury exists. Partial rotator cuff tear may require PRP injection, while fracture and/or complete separation will require surgery.SerumBlood serum, a blood component which is collected after coagula-tion.Stem Cell TreatmentsA type of intervention strategy that introduces new cells into dam-aged tissue in order to treat disease or injury. Many medical re-searchers believe that stem cell treatments have the potential to change the face of human disease and alleviate suffering. The abil-ity of stem cells to self-renew and give rise to subsequent gener-ations with variable degrees of differentiation capacities, offers signifi cant potential for generation of tissues that can potentially replace diseased and damaged areas in the body, with minimal risk of rejection and side effects (1).

114SyndromeA group of symptoms that collectively indicate or characterize a disease or abnormal condition.Syndromes:Tennis ElbowA condition where the outer part of the elbow becomes sore and tender. The condition is also known as lateral epicondylitis (“in-fl ammation of the outside elbow bone”), a misnomer as histologic studies have shown no infl ammatory process. Other descriptions for tennis elbow are lateral epicondylosis, lateral epicondylal-gia, or simply lateral elbow pain. Tennis elbow is an overuse injury occurring in the lateral side of the elbow region, more specifi cally, occurring at the common extensor tendon that originates from the lateral epicondyle. While the common name tennis elbow suggests that people who play tennis may develop this condition, other ac-tivities of daily living may also cause it. The main factor precipi-tating tennis elbow is overexertion. Athletes as well as those who use the same repetitive motion for many years, especially in their profession, suffer from tennis elbow. It is also common in indi-viduals who performed motions they were unaccustomed to and occurs most commonly in the right arm.Golfer’s Elbow or medial epicondylitisThis is an infl amatory/degenerative condition of the medial epi-condyle of the elbow.Jumper’s Knee (see above)

115Sports MedicineAn area of health and special services that applies medical and sci-entifi c knowledge to prevent, recognize, manage, and rehabilitate injuries related to sport, exercise, or recreational activity.SynoviumA thin membrane in synovial (freely moving) joints that lines the joint capsule and secretes synovial fl uid.TendonA band of tough, inelastic fi brous tissue that connects a muscle to its boney attachment.TendinosisSometimes called chronic tendinitis, chronic tendinopathy or chronic tendon injury. It is damage to a tendon at the cellular lev-el (the suffi x “-osis” implies a pathology of chronic degeneration without infl ammation). It is thought to be caused by microtears in the connective tissue in and around the tendon, leading to an increase in tendon repair cells. This may lead to reduced tensile strength, thus increasing the chance of tendon rupture. Tendinosis is often misdiagnosed as tendinitis.TendinitisMeaning infl ammation of a tendon (the suffi x “itis” denotes diseas-es characterized by infl ammation), is a type of tendinopathy. The term tendinitis should be reserved for tendon injuries that involve large-scale acute injuries accompanied by infl ammation.TissuePart of an organism consisting of an aggregation of cells having a similar structure and function.

116Statement:Dr. Dariusz J. Nasiek, M.D. has no confl icts of interest to disclose. No benefi ts in any form have been received or will be received from a commercial party related directly or indirectly to the sub-ject of this publication.

About Dr. Nasiek:Dariusz J. Nasiek, M.D. is a board certifi ed pain specialist and anesthesiologist. He completed his residency and fellowship training at St. Vincent’s Hospital and Medical Center in NYC and has been in private practice in New York and New Jersey since 1996.Dr. Nasiek holds board certifi cations from the American Board of Anesthesiology, the American Board of Pain Medicine, and the American Board of Interventional Pain Physicians – he is one of a small group of triple certifi ed pain specialists. Dr. Nasiek is considered an expert in Platelet Rich Plasma (PRP) injections with hundreds of procedures performed on his patients.Dr. Dariusz J. Nasiek, M.D. serves as a Medical Director of Anesthesiology at Hackensack Surgical Center in Hackensack, NJ; he is a founding partner of Allied Neurology and Interventional Pain Practice with offi ces in New York and New Jersey. Dariusz J. Nasiek, M.D. is the founder of PRP Centers of America (PCA), a group of medical practices dedicated to the diagnosis and nonsurgical treatments of chronic pain and musculoskeletal maladies. The centers implement the use of the PRP therapies for a revolutionary approach in regenerative medicine (RM).www.PRPcenters.comDNasiek@PRPcenters.com866.400.14149 780988ISBN 978-0-9885190-0-851900851495$14.95PRPPlatelet Rich PlasmaA New Paradigm ofRegenerative Medicine Dariusz J. Nasiek, MD, DABA, DABPM, DABIPP