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Adam Weglein,DO, DABMA,CAQ Founder: Regenerative Ortho Med

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Presentation on theme: "Adam Weglein,DO, DABMA,CAQ Founder: Regenerative Ortho Med"— Presentation transcript:

1 Adam Weglein,DO, DABMA,CAQ Founder: Regenerative Ortho Med

2  Discuss the basic science of wound healing as it relates to PRP  Review some current evidence based literature on PRP  Ozone treatments with PRP


4  Ozone in orthopedics

5  Tissue heals through a immune cell mediated response that is regulated by tissue growth factors which are held in platelets  PRP- is the idea of increasing the concentration of healing factors in tissue like tendons, ligaments and cartilage to help enhance healing.

6  Definition: 200,000 Platelets/ micoliter( Red Cross

7  The idea of promoting a natural healing response  Very good safety profile  Simple and easy to set up  Ability to implement in clinic setting  Over 6,000 studies on Pubmed

8  I was introduced to prolo/ PRP during my sports medicine fellowship at South Pointe, Cleveland Clinic.  Assistant Clinical Professor University of Texas Houston Medical School  Certified Regenerative Injection Techniques, AAOM  Founder: The Regenerative Ortho Med Institute( specializing in PRP, BMAC, prolo) 

9  Started in 1980s  H. Ward- stealers-  Knee MCLsuperbowl XLIII

10  Ideal concentration?? Good question!  Most 3-8 times baseline  Upper threshold of benefit  Studies indicate that inhibition above 10ng/mL  (Kevy Harvard) work indicates above 5 million seeing drop off in neovascular benefit  Needs research for case and age of patient

11  PRP- provides growth factors- >neovascularization  PRP caused up regulation of  local GFs TGF-Beta1 for 1 st week post prp,  increased IGF-1 for 4 weeks tenocytes post prp

12  Circulate for 7-10 days  Contain 800 proteins with 1,500 bio active factors  Growth factors, peptide hormones, chemoattractants- macs, neutrophils, stem cells

13  Collagen  Serotonin  PAF- platelet Activating factor  Calcium  Mag  In vitro- bone material- osteocondral scaffold  Platelets release- + feedback loop  Thromboxane A2  ADP  Thrombin  Decreased in PRP  Caffine  propofol

14  Activated platelets  Cytoskeleton restructure- filopodia  Degranulation  Large initial burst of GF  Anti- inflammatory cytokine hepatcyte GF( inhibit NF kappa B, and IL -1)

15  Centrifuge system used  Starting whole blood  Hematocrit- product.  Hydration status  Inflammatory status  Lipemia-diet increased platelets  Testosterone level

16  Ideal world a pre PRP CBC should be done along with PRP sample to ensure platelet concentration  Very Important for research studies  May consider if patient fails first PRP treatment  MRI or ultrasound for diagnostic

17  WBC rich PRP  WBC poor PRP  Activated PRP  Non activated PRP  RBC rich PRP  RBC poor PRP  PRP- Prolo  PRP-ozone  PRP-BMAC

18  Presence 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 muscle  Still controversy  More studies needed??

19  In high concentrations respiratory burst can cause tissue damage, mmp 2,9,13,15, IL-1, IL-6 chondro toxic  Block GAGs in Hyaluronan  Monocytes- TGF-B, VEGF, bFGF- suppress inflammation- necessary for healing tissue  Macrophages are essential to in vivo healing  Essential for ligamentous tissue debridement for ligament healing.  Used for large dermal area with concern of infection

20  Low concentration in general in prp  Carry O2  Fe -> free radicals and tissue destruction apoptosis  Best to use lower Hct level  Ask your Centrifuge Rep HCT level?

21 Alpha Granules  Platelet derived growth factor (PDGF)  Transforming growth factor (TGF)  Epidermal growth factor (EGF)  Vascular endothelial growth factor (VEGF)  Fibroblast growth factor (FGF)  Connective tissue growth factor (CTGF) Dense Granules  Serotonin  ADP  Histamine  Calcium  Mag  Lamda granules  Remove infection  Plasminogen- fracture repair

22 22 Platelet Derived Growth Factor (PDGF)  Powerful chemoattractant- stem cells  Cell proliferation – osteoblasts ( Marko poulou et al.)  Angiogenesis Transforming Growth Factor – Beta (TGF-B)  Plays a major role in matrix formation and healing, chondrogenesis. Orthop Relat Res 2001;391(suppl):S171–81 Platelet Growth Factor Overview

23 Epidermal Growth Factor (EGF)  Linked to angiogenesis and collagen deposition at wound sites.  Shown to stimulate wound repair in fibroblasts and epithelial cells.

24 Vascular Endothelial Growth Factor (VEGF)  Stimulates endothelial growth and angiogenesis Fibroblast Growth Factor (FGF)  Family of growth factors involved in angiogenesis, wound healing

25  IGF-1 stored in Plasma  679 proteins( albumin, Ig, complement, CF)  Fibronectin, vitronectin- induce chemotaxis of stem cells, fibroblasts, osteoblasts.  Calcium- activation of PRP and contractile myofibroblasts- in vitro  Human growth hormone

26  IGF-1  Improve healing in equine tendon  Improve healing in cartilage  Being used in hydro dissection of nerves  as filler to form bio scaffold, cosmetics and MMT  Neurol Res. 2004 Mar;26(2):204-10.The multifunctional role of IGF-1 in peripheral nerve regeneration.Rabinovsky ED.SourceMichael E. DeBakey


28  Ligament  Tendon  Inside the joint  Nerve  Muscle

29  Involves taking patients own blood about 20cc-180cc then spinning down to Platelet Rich portion  Then identify target under MSK ultrasound  1% lido, sterile prep  Then inject PRP  Post injection physical therapy

30  Acute muscle, Tendon, ligament injury  Chronic tendonosis/ ligament injury  Chronic Spine disorders ( facet, SIJ)  Osteoarthritis  Intra operative use as surgical adjunct to tissue healing


32 Angel ® Whole Blood Separation Cytomedix™ Corporation




36 Platelet Sensor System

37 PRP Sample Volume and Platelet Concentration Patient Specific Application PRP Sample Volume and Platelet Concentration Patient Specific Application

38  Sanchez M, et al; “Application of Autologous Growth Factors on Skeletal Muscle Healing”, World Congress on Regenerative Medicine Podium Presentation, May 18, 2005  Study: 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.

39  Mishra A, Pafelko T, Coetzee; “Treatment of Chronic Severe Elbow Tendinosis with PRP”, American Journal of Sports Medicine, 34:1774-1778, 2006  Study: 140 patients-> 15 months of rehab- conservative tx  20 patients were randomized to evaluate effectiveness of PRP –VS. bupiv  1,2, and 6 months all PRP patients had lower pain and greater ROM  Conclusion: Treatment of chronic epicondylar pain with PRP should be considered prior to surgical intervention.

40 ▪ Gosens, Peerbooms, et al. American Journal of Sports Medicine 2011 ▪ Randomized controlled trial; Level of evidence, 1  100 patients randomized steroid vs prp  VAS/dash  At 2 years cortisone dash went to baseline unlike prp


42  OCL talus  PRP vs HA  Randomized ( level 2)  32 patients (18-60 age)  3 injections  Follow at 28 weeks  American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale (AHFS); a visual analog scale (VAS) for pain  OCL 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.

43  Have treated OA with PRP in most joints in the body  Hip  Knee  Ankle  Finger  Spine  SI joint  Shoulder

44  Mild to moderate OA  Frequency of treatments is done on a case by case  Mild OA often need only one PRP  Moderate OA may take up to 3 PRP done at two week to monthly intervals  Often combined with HA injections

45  Hunziker et al. TGF-B promotes chondrogenesis. Orthop Relat Res 2001;391(suppl):S171–81  Full 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):290-296.

46  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).

47  Sanchez, Anitua et al 2008. Clinical trial to evaluate intra-articular PRP vs hyaluron for knee OA  Observational, retrospective cohort study. ␣  60 patients, 3 weekly injections. (30 PRP 30 HA  At week 5, 33% of PRP group improved vs 10% of hyaluronan group

48  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

49 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

50  PRP increased hyaluronic acid concentration, stabilizing angiogenesis in ten patients with osteoarthritic knees  Anitua 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

51  “….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 approved  All 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 Br J Sports Med 2010:44:1072-1081 Slide courtesy of Joanne Borg-Stein, MD

52  Therapeutic Effects of Topical Application of Ozone on Acute Cutaneous Wound Healing-J Korean Med Sci. 2009 June; 24(3): 368–374  upregulation of platelet derived growth factor (PDGF), (TGF-β) and (VEGF) expressions, but not fibroblast growth factor expression in the ozone group on day 7

53  Bocci et al 1999- Ca chelated platelets in PRP insensitive to ozone  IOA 13 th ozone world congress 1997 pretreatment of PRP with ozone inhibited aggregation  ROS- activate platelets

54  Frequency  Combining 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!!!

55  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


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