adam weglein,do, dabma,caq founder: regenerative ortho med
TRANSCRIPT
Adam Weglein,DO, DABMA,CAQFounder: Regenerative Ortho Med
www.houstonsportsdoctor.com
Platelet Rich Plasma and ozone
Objectives
Discuss the basic science of wound healing as it relates to PRP
Review some current evidence based literature on PRP
Ozone treatments with PRP
Brazil Regenerative Orthopedic conference 2012
Ozone in orthopedics
Tissue healing
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.
Platelet Rich Plasma
Definition: 200,000 Platelets/ micoliter( Red Cross
Why PRP
The idea of promoting a natural healing response
Very good safety profileSimple and easy to set upAbility to implement in clinic setting Over 6,000 studies on Pubmed
My exposure to PRP
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)
www.houstonsportsdoctor.com
PRP background
Started in 1980s H. Ward- stealers-
Knee MCLsuperbowl XLIII
PRP
Ideal concentration?? Good question!Most 3-8 times baselineUpper 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
PRP mechanism of action
PRP- provides growth factors->neovascularization
PRP caused up regulation of local GFs TGF-Beta1 for 1st week post
prp, increased IGF-1 for 4 weeks tenocytes
post prp
Platelets
Circulate for 7-10 daysContain 800 proteins with 1,500 bio
active factors Growth factors, peptide hormones,
chemoattractants- macs, neutrophils, stem cells
Platelet Activation
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
Platelet Activation
Activated platelets Cytoskeleton restructure- filopodia Degranulation Large initial burst of GF Anti- inflammatory cytokine hepatcyte
GF( inhibit NF kappa B, and IL -1)
Factors affecting PRP platelet count
Centrifuge system used Starting whole blood Hematocrit- product. Hydration status Inflammatory status Lipemia-diet increased platelets Testosterone level
Pre PRP
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
treatmentMRI or ultrasound for diagnostic
PRP subtypes ?? Yes indeed.
WBC rich PRPWBC poor PRPActivated PRPNon activated PRPRBC rich PRPRBC poor PRPPRP- Prolo
PRP-ozone PRP-BMAC
WBC poor PRP
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??
WBC rich PRP
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
RBC- PRP
Low concentration in general in prpCarry O2Fe -> free radicals and tissue
destruction apoptosis
Best to use lower Hct level Ask your Centrifuge Rep HCT level?
Alpha GranulesPlatelet 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 GranulesSerotoninADPHistamineCalciumMag
Lamda granules Remove infection Plasminogen-
fracture repair
PRP-GF
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
PRP growth factors
Epidermal Growth Factor (EGF) Linked to angiogenesis and collagen
deposition at wound sites. Shown to stimulate wound repair in
fibroblasts and epithelial cells.
PRP growth factor overview Vascular Endothelial Growth Factor (VEGF)
Stimulates endothelial growth and angiogenesis
Fibroblast Growth Factor (FGF) Family of growth factors involved in
angiogenesis, wound healing
Plasma 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 vitro
Human growth hormone
PPP
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
Phases of wound healing
Target tissue
LigamentTendon Inside the jointNerve Muscle
PRP-Platelet Rich Plasma
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
Clinical indications
Acute muscle, Tendon, ligament injury
Chronic tendonosis/ ligament injuryChronic Spine disorders ( facet, SIJ)Osteoarthritis Intra operative use as surgical
adjunct to tissue healing
PRP- joints
Angel® Whole Blood Separation
Cytomedix™ Corporation
Platelet Sensor System
PRP Sample Volume and Platelet ConcentrationPatient Specific Application
Whole Blood Volume 3 cc 4 cc 5 cc 6 cc 7 cc 8 cc 9 cc 10 cc 11 cc 12 cc 13 cc 14 cc 15 cc 16 cc 17 cc 18 cc 19 cc 20 cc
Final Volume of PRP
40 cc 8.0 6.0 4.8 4.0 3.4 3.0 2.7 2.4 2.2 2.0 1.8 1.7 1.6 1.5 1.4 1.3 1.3 1.2
50 cc 10.0 7.5 6.0 5.0 4.3 3.7 3.3 3.0 2.7 2.5 2.3 2.1 2.0 1.9 1.8 1.7 1.6 1.5
60 cc 12.0 9.0 7.2 6.0 5.1 4.5 4.0 3.6 3.3 3.0 2.8 2.6 2.4 2.2 2.1 2.0 1.9 1.8
70 cc 14.0 10.5 8.4 7.0 6.0 5.2 4.7 4.2 3.8 3.5 3.2 3.0 2.8 2.6 2.5 2.3 2.2 2.1
80 cc 16.0 12.0 9.6 8.0 6.8 6.0 5.3 4.8 4.4 4.0 3.7 3.4 3.2 3.0 2.8 2.7 2.5 2.4
90 cc 18.0 13.5 10.8 9.0 7.7 6.7 6.0 5.4 4.9 4.5 4.1 3.8 3.6 3.4 3.2 3.0 2.8 2.7
100 cc 15.0 12.0 10.0 8.6 7.5 6.7 6.0 5.4 5.0 4.6 4.3 4.0 3.7 3.5 3.3 3.2 3.0
110 cc 16.5 13.2 11.0 9.4 8.2 7.3 6.6 6.0 5.5 5.1 4.7 4.4 4.1 3.9 3.7 3.5 3.3
120 cc 18.0 14.4 12.0 10.3 9.0 8.0 7.2 6.5 6.0 5.5 5.1 4.8 4.5 4.2 4.0 3.8 3.6
130 cc 15.6 13.0 11.1 9.7 8.6 7.8 7.1 6.5 6.0 5.6 5.2 4.9 4.6 4.3 4.1 3.9
140 cc 16.8 14.0 12.0 10.5 9.3 8.4 7.6 7.0 6.4 6.0 5.6 5.2 4.9 4.7 4.4 4.2
150 cc 18.0 15.0 12.8 11.2 10.0 9.0 8.2 7.5 6.9 6.4 6.0 5.6 5.3 5.0 4.7 4.5
160 cc 16.0 13.7 12.0 10.6 9.6 8.7 8.0 7.4 6.8 6.4 6.0 5.6 5.3 5.0 4.8
170 cc 17.0 14.5 12.7 11.3 10.2 9.3 8.5 7.8 7.3 6.8 6.4 6.0 5.7 5.4 5.1
180 cc 18.0 15.4 13.5 12.0 10.8 9.8 9.0 8.3 7.7 7.2 6.7 6.3 6.0 5.7 5.4
Platelet Concentration
(Fold over whole blood
input)
PRP in muscle
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.
PRP Tendon
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.
PRP Tendon
▪ Gosens, Peerbooms, et al. American Journal of Sports Medicine 2011
▪ Randomized controlled trial; Level of evidence, 1100 patients randomized steroid vs
prpVAS/dashAt 2 years cortisone dash went to
baseline unlike prp
PRP-tendon
Gosens two year follow up on tennis elblow Cortisone vs PRP Results
TREATMENT 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 YEARS
Gosens, Peerbooms, et al. American Journal of Sports Medicine 2011
Platelet-Rich Plasma or Hyaluronate in the Management of Osteochondral Lesions of the Talus, Omer Mei-Dan et al.
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.
Osteoarthritis
Have treated OA with PRP in most joints in the body Hip Knee Ankle Finger Spine SI joint Shoulder
OA PRP
Mild to moderate OAFrequency 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 intervals
Often combined with HA injections
Early OA PRP research
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.
PRP 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).
Sanchez, Anitua et al 2008. Clinical trial to evaluate intra-articular PRP vs hyaluron for knee OA
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
PRP 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
Demonstrated consistent anti-inflammatory effects of PRP. Am J Sports Med November 2011 39 2362-2370; 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
PRP-increased hyaluronic Acid
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
IOC consensus paper on the use of platelet rich plasma in sports medicine
“….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
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
Ozone research growth factors
Ozone with PRP
Bocci et al 1999- Ca chelated platelets in PRP insensitive to ozone
IOA 13th ozone world congress 1997 pretreatment of PRP with ozone inhibited aggregation
ROS- activate platelets
There is much that we don’t know
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!!!
Putting 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
Thank you