4Brazil Regenerative Orthopedic conference 2012 Ozone in orthopedics
5Tissue healingTissue heals through a immune cell mediated response that is regulated by tissue growth factors which are held in plateletsPRP- is the idea of increasing the concentration of healing factors in tissue like tendons, ligaments and cartilage to help enhance healing.
6Platelet Rich PlasmaDefinition: 200,000 Platelets/ micoliter( Red Cross
7Why PRP The idea of promoting a natural healing response Very good safety profileSimple and easy to set upAbility to implement in clinic settingOver 6,000 studies on Pubmed
8My exposure to PRPI was introduced to prolo/ PRP during my sports medicine fellowship at South Pointe, Cleveland Clinic.Assistant Clinical Professor University of Texas Houston Medical SchoolCertified Regenerative Injection Techniques, AAOMFounder: The Regenerative Ortho Med Institute( specializing in PRP, BMAC, prolo)
9PRP background Started in 1980s H. Ward- stealers- Knee MCLsuperbowl XLIII
10PRP Ideal concentration?? Good question! Most 3-8 times baseline Upper threshold of benefitStudies indicate that inhibition above 10ng/mL(Kevy Harvard) work indicates above 5 million seeing drop off in neovascular benefitNeeds research for case and age of patient
11PRP mechanism of action PRP- provides growth factors->neovascularizationPRP caused up regulation oflocal GFs TGF-Beta1 for 1st week post prp,increased IGF-1 for 4 weeks tenocytes post prp
12Platelets Circulate for 7-10 days Contain 800 proteins with 1,500 bio active factorsGrowth factors, peptide hormones, chemoattractants- macs, neutrophils, stem cells
16Pre PRPIdeal world a pre PRP CBC should be done along with PRP sample to ensure platelet concentrationVery Important for research studiesMay consider if patient fails first PRP treatmentMRI or ultrasound for diagnostic
18WBC poor PRPPresence of WBCs in prp can lead to catabolic breakdown of tissue and negative affect of matrix synthesis in tendons( Mcmarrel/ Foster et al.)Thought to be beneficial for muscleStill controversyMore studies needed??
19WBC rich PRPIn high concentrations respiratory burst can cause tissue damage, mmp 2,9,13,15, IL-1, IL-6 chondro toxicBlock GAGs in HyaluronanMonocytes- TGF-B, VEGF, bFGF- suppress inflammation- necessary for healing tissueMacrophages are essential to in vivo healingEssential for ligamentous tissue debridement for ligament healing.Used for large dermal area with concern of infection
20RBC- PRP Low concentration in general in prp Carry O2 Fe -> free radicals and tissue destruction apoptosisBest to use lower Hct levelAsk your Centrifuge Rep HCT level?
22Platelet Growth Factor Overview PRP-GFPlatelet Derived Growth Factor (PDGF)Powerful chemoattractant- stem cellsCell proliferation – osteoblasts ( Marko poulou et al.)AngiogenesisTransforming Growth Factor – Beta (TGF-B)Plays a major role in matrix formation and healing, chondrogenesis. Orthop Relat Res 2001;391(suppl):S171–81
23PRP growth factorsEpidermal Growth Factor (EGF)Linked to angiogenesis and collagen deposition at wound sites.Shown to stimulate wound repair in fibroblasts and epithelial cells.
24PRP growth factor overview Vascular Endothelial Growth Factor (VEGF)Stimulates endothelial growth and angiogenesisFibroblast Growth Factor (FGF)Family of growth factors involved in angiogenesis, wound healing
25Plasma growth factors PPP IGF-1 stored in Plasma679 proteins( albumin, Ig, complement, CF)Fibronectin, vitronectin- induce chemotaxis of stem cells, fibroblasts, osteoblasts.Calcium- activation of PRP and contractile myofibroblasts- in vitroHuman growth hormone
26PPP IGF-1 Improve healing in equine tendon Improve healing in cartilageBeing used in hydro dissection of nervesas filler to form bio scaffold, cosmetics and MMTNeurol Res Mar;26(2): The multifunctional role of IGF-1 in peripheral nerve regeneration.Rabinovsky ED.SourceMichael E. DeBakey
28Target tissueLigamentTendonInside the jointNerveMuscle
29PRP-Platelet Rich Plasma Involves taking patients own blood about 20cc-180cc then spinning down to Platelet Rich portionThen identify target under MSK ultrasound1% lido, sterile prepThen inject PRPPost injection physical therapy
30Clinical indications Acute muscle, Tendon, ligament injury Chronic tendonosis/ ligament injuryChronic Spine disorders ( facet, SIJ)OsteoarthritisIntra operative use as surgical adjunct to tissue healing
36Platelet Sensor System The Angel System integrates LED lasers and detectors to specifically detect and distinguish oxyhemoglobin (red cells), platelets and leukocytes. Using this detection platform the Angel will produce a highly concentrated platelet sample that can range from 7X to greater than 18X of that found in the patients input sample. The concentration will vary dependent on the size of the sample processed as well as the distribution of platelet size and density in the individual patient.
37PRP Sample Volume and Platelet Concentration Patient Specific ApplicationThe table above is intended to guide appropriate dilution of the platelet concentrate to achieve a wide range of desired platelet concentrations.
38PRP in muscleSanchez M, et al; “Application of Autologous Growth Factors on Skeletal Muscle Healing”, World Congress on Regenerative Medicine Podium Presentation, May 18, 2005Study: 20 patient prospective muscle injury pilot study with 6 month follow-up – Ultrasound guided injection of PRP within the injured muscle enhanced healing (echo-graphic images) and functional capacities 50% faster than the control group.
39PRP TendonMishra A, Pafelko T, Coetzee; “Treatment of Chronic Severe Elbow Tendinosis with PRP”, American Journal of Sports Medicine, 34: , 2006Study: 140 patients-> 15 months of rehab- conservative tx20 patients were randomized to evaluate effectiveness of PRP –VS. bupiv1,2, and 6 months all PRP patients had lower pain and greater ROMConclusion: Treatment of chronic epicondylar pain with PRP should be considered prior to surgical intervention.
40PRP Tendon 100 patients randomized steroid vs prp VAS/dash Gosens, Peerbooms, et al. American Journal of Sports Medicine 2011Randomized controlled trial; Level of evidence, 1100 patients randomized steroid vs prpVAS/dashAt 2 years cortisone dash went to baseline unlike prp
41PRP-tendon Gosens two year follow up on tennis elblow Cortisone vs PRP ResultsTREATMENT OF PATIENTS WITH CHRONIC LATERAL EPICONDYLITIS WITH PRP REDUCES PAIN AND INCREASES FUNCTION SIGNIFICANTLY, EXCEEDING THE EFFECT OF CORTICOSTEROID INJECTION EVEN AFTER A FOLLOW-UP OF 2 YEARSGosens, Peerbooms, et al. American Journal of Sports Medicine 2011
42Platelet-Rich Plasma or Hyaluronate in the Management of Osteochondral Lesions of the Talus, Omer Mei-Dan et al.OCL talusPRP vs HARandomized ( level 2)32 patients (18-60 age)3 injectionsFollow at 28 weeksAmerican Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale (AHFS); a visual analog scale (VAS) for painOCL lesions of the ankle treated with intra-articular injections of PRP and HA resulted in a decrease in pain scores and an increase in function for at least 6 months. Platelet-rich plasma treatment led to a significantly better outcome than HA.
43Osteoarthritis Have treated OA with PRP in most joints in the body Hip KneeAnkleFingerSpineSI jointShoulder
44OA PRP Mild to moderate OA Frequency of treatments is done on a case by caseMild OA often need only one PRPModerate OA may take up to 3 PRP done at two week to monthly intervalsOften combined with HA injections
45Early OA PRP researchHunziker et al. TGF-B promotes chondrogenesis. Orthop Relat Res 2001;391(suppl):S171–81Full Thickness cartilage defects in rabbits demonstrated better mechanical properties (Cugot 06).␣Frisbie, et al. Clinical biochemical and histological effects of intra-articular administration of autologous conditioned serum in horses with experimentally induced osteoarthritis. Am J Vet Res. 2007;68(3):
46PRP OA 2007 International cartilage repair society meeting Warsaw: PR- amplification of chondrocyte proliferation with convincing clinical effects on degenerative knee OA.(Konet al)- PRP encouraged chondrogenesis with an injectable scaffold while seeded with chondrocytes in rabbit ears. (Wu et al 2007).
47Observational, retrospective cohort study.␣ Sanchez, Anitua et al Clinical trial to evaluate intra-articular PRP vs hyaluron for knee OASanchez, Anitua et al Clinical trial to evaluate intra-articular PRP vs hyaluron for knee OAObservational, retrospective cohort study.␣60 patients, 3 weekly injections. (30 PRP 30 HAAt week 5, 33% of PRP group improved vs 10% of hyaluronan group
48PRP OA Kon, et al. 2009: PRP in 115 arthritic knees › Notable improvement in functional and pain scores which remained positive at 6 mos.›Mild degradation of the scores at 1 year› Better outcome in lower grades of arthritis and younger patients
49Demonstrated consistent anti-inflammatory effects of PRP Demonstrated consistent anti-inflammatory effects of PRP . Am J Sports Med November ; published online before print August 19, 2011, Gerben et al.Prior studies have demonstrated anabolic effect of PRP on chondrocyte cells inducing proliferation. ␣ Demonstrated consistent anti-inflammatory effects of PRP.␣ Counteracts the catabolic environment and inflammatory response by inhibiting IL-1 beta mediated effects on human osteoarthritic chondrocytes.␣ Inhibits Nuclear factor kappa B activation (Key in OA pathogenesis) Similar to NSAIDs, Glucocorticoids and proteasome
50PRP-increased hyaluronic Acid PRP increased hyaluronic acid concentration, stabilizing angiogenesis in ten patients with osteoarthritic kneesAnitua E, Sanchez M, Nurden AT, et al: Platelet-released growth factors enhance the secretion of hyaluronic acid and induce hepatocyte growth factor production by synovial fibroblasts from arthritic patients. Rheumatology 2007;46:1769–72
51IOC consensus paper on the use of platelet rich plasma in sports medicine Br J Sports Med 2010:44:Slide courtesy of Joanne Borg-Stein, MD“….proceed with caution in the use of PRP in athletic sporting injuries. We believe more work on the basic science needs to be undertaken….”WADA:Intramuscular injections prohibited until 2011, when approvedAll other routes of administration, such as intra-articular, intra-or peritendinous are permitted and require a declaration of use.Isolated growth factors are prohibited: IGF-1, VEGF, PDGF
52Ozone research growth factors Therapeutic Effects of Topical Application of Ozone on Acute Cutaneous Wound Healing-J Korean Med Sci June; 24(3): 368–374upregulation of platelet derived growth factor (PDGF), (TGF-β) and (VEGF) expressions, but not fibroblast growth factor expression in the ozone group on day 7
53Ozone with PRPBocci et al Ca chelated platelets in PRP insensitive to ozoneIOA 13th ozone world congress 1997 pretreatment of PRP with ozone inhibited aggregationROS- activate platelets
54There is much that we don’t know FrequencyCombining HA with PRP at same time vs separate injections( pending publication in Singapore very positive)Interaction with other modalities? Case studies show better affect with combined tradition Prolo/ NPT and PRP/ stem cells.Exciting times ahead!!!
55Putting it all together I have used ozone in combination with a number of refractory PRP OA Pts in joints with outstanding results.I have found that the addition of PRP to ozone to be better than Ozone in patient reported outcomes at 6 weeks post injection