Rick Marinelli, ND, DAAPMClinical Professor, NCNM

President, Board of Directors, AAPM

Introduction to Platelet

Autografting

Normal Normal Collagen Collagen StructureStructure

Myotendinous Junction

The Fibro-Osseous Junction

Tendinopathy Results When Normal Healing

Fails

88

DELIVERING A CONCENTRATION OF AUTOLOGOUS PROTEINS TO THE DELIVERING A CONCENTRATION OF AUTOLOGOUS PROTEINS TO THE SURGICAL SITE MAY IMPROVE THE HEALING RATESURGICAL SITE MAY IMPROVE THE HEALING RATE

HemostaticHemostaticBarrierBarrier

InflammationInflammationDebridementDebridement

Tissue Tissue RegenerationRegeneration

Tissue Tissue RemodelingRemodeling

Tissue Tissue RemodelingRemodeling

Application of proteins from a platelet concentrate may

dramatically improve the early phases of the Healing Cascade

Body’s Response to Tissue Injury [Time]

99

SURGICAL PROCEDURES TISSUE AND CELLULAR INJURY

BODY’S NATURAL RESPONSE HEALING CASCADE.

COMPLETEHEALING

NATURAL HEALING CASCADE

CLOT /BARRIER

CLOT /BARRIER

INFLAMMATION

TISSUE REGENERATION

(Cell Proliferation)

TISSUE REMODELING

THE PROTEINS THAT CONTROL THE FIRST THREE STAGES OF THE HEALING CASCADE ARE FOUND IN SPECIFIC BLOOD COMPONENTS:o PLASMAo WHITE BLOOD CELLSo PLATELETS

INJURY

1010

THE ROLE OF AUTOLOGOUS PROTEINS IN THE THE ROLE OF AUTOLOGOUS PROTEINS IN THE HEALING CASCADEHEALING CASCADE

Initial Response to Tissue Initial Response to Tissue InjuryInjury

Autologous Proteins Controlling the Healing Autologous Proteins Controlling the Healing CascadeCascade

Clotting / SealingClotting / Sealing

InflammationInflammation(Remove Debris)(Remove Debris)

Tissue RegenerationTissue Regeneration(New Cell Growth)(New Cell Growth)

Autologous ProteinsAutologous Proteins•Fibrinogen Fibrinogen Fibrin Strands Fibrin Strands•Activated Platelet MembraneActivated Platelet Membrane

Autologous ProteinsAutologous Proteins•Platelet Signaling ProteinsPlatelet Signaling Proteins•WBC Signaling ProteinsWBC Signaling Proteins

Autologous ProteinsAutologous Proteins•Platelet Growth Factors (PDGF; TGF-Platelet Growth Factors (PDGF; TGF-ß; EGF)ß; EGF)•WBC Growth Factor (VEGF)WBC Growth Factor (VEGF)•Plasma Growth Factors (IGF)Plasma Growth Factors (IGF)•Adhesion Molecules (Fibronectin; SC Adhesion Molecules (Fibronectin; SC Factor; Victronectin;Vascular Cell Factor; Victronectin;Vascular Cell Adhesion FactorAdhesion Factor

1

2

3

1111

Platelet Rich Plasma Platelet Rich Plasma (PRP)(PRP)Scaffold

Signal Proteins and Adhesion Molecules

Undifferentiated Cells

1212

Growth FactorsGrowth Factors

Growth Factors

Receptor

Signaling

Molecules

Transcription

Factors

1313

Application of Autologous Platelet Gel:• Usable throughout surgical site• Creates an intricate network of fibrin polymers

working to that seal the wound, provide hemostasis, and contract the wound

• Provides a release of concentrated wound growth factors

• Stabilizes bone and soft tissue graft materials• Optimizes wound site for healing

Autologous Growth Factors Provide:• Enhanced healing• Enhanced angiogenesis• Improved bone regeneration• Hastened bone maturity• Increased collagen content• Enhanced wound strength• Bactericidal effect at wound site

“Leading to hastened and improved healing.”

Benefits of Platelet Gel(Physiologic Perspective)

1414

Dose-Dependent Mitogenic Effects of Platelet Releasate on Dose-Dependent Mitogenic Effects of Platelet Releasate on hMSC’shMSC’s

Mitogenic Stimulation of Human Mesenchymal Stem Cells by Platelet Releasate Suggests a Mechanism for Enhancement of Bone Repair by Platelet Concentrate, Poster AAOS Meeting 2002 Haynesworth, SE; Kadiyala, S; Liang, L; Bruder, SP; DePuy AcroMed, DePuy Orthopedics, and Case Western Reserve University.

QTY of hMSC’s

Conclusions:Conclusions:• Platelet Concentrate and VEGF stimulate chemotactic migration of Platelet Concentrate and VEGF stimulate chemotactic migration of

hMSC’s in a dose-dependent manner.hMSC’s in a dose-dependent manner.

• Platelet Concentrate stimulates proliferation of hMSC’s in a dose-Platelet Concentrate stimulates proliferation of hMSC’s in a dose-

dependent mannerdependent manner

How Many Platelets Is Enough?How Many Platelets Is Enough?

----Platelet Concentrates---

227 %INCREASE IN CELLPOPULATIONWITH 5 TIMESINCREASE INPLATELETS

1515

RESEARCH STUDIES RELATED TO THE EFFECT OF RESEARCH STUDIES RELATED TO THE EFFECT OF PLATELET CONCENTRATE ON CELL PROLIFERATIONPLATELET CONCENTRATE ON CELL PROLIFERATION

OSTEOBLASTS“…platelet-supplemented medium stimulates proliferation and maintains the differentiated function of human osteoblast-like cells. Platelets may play an important role in early healing of fractures and also may be useful as a cheap autologous source of multiple growth factors to enhance osteoblast proliferation”

M. Slater et al; Involvement of Platelets in Stimulating Osteogenic ActivityJournal of Orthopedic Research, Nov 1994

FIBROBLASTS“The results of this study demonstrate the efficacy of activated platelets bound on fibrinogen in the mitosis of fibroblasts, which is a response to growth factors secreted by platelets. Platelets without binding to fibrinogen showed no secretion of growth factors and had no effect on cell mitosis. These events may Contribute to wound healing and could be the first important step in this process”

R. Gfatter, et al; The mitosis of fibroblasts in cell cell culture is enhanced by Bibding GP IIb-IIa of activated platelets on fibrinogen Platelets, Vol 1, 2000

1616S. KEVY, et al, CENTER FOR BLOOD RESEARCH; PRESENTED AT SOCIETY FOR BIOMATERIALS APR 2001

GROWTH FACTOR LEVELS INCREASE LINEARLY WITH PLATELET CONCENTRATION

Transforming Growth Factor-ß (TGF-ß)

APCAPCAutologous Platelet ConcentrationAutologous Platelet Concentration

1717

GROWTH FACTOR LEVELS INCREASE LINEARLY with APC+

R2 = 0.9815

0

75

150

225

300

0 200 400 600 800 1000 1200 1400

Platelet Concentration (thousand/microliter)

TG

F-B

eta

(ng

/ml)

Platelet-Derived Growth Factor (PDGF) Transforming Growth Factor-ß (TGF-ß)

S. KEVY, et al, CENTER FOR BLOOD RESEARCH; PRESENTED AT SOCIETY FOR BIOMATERIALS APR 2001

1818

Paques P, Chastan C, et al; “Effect of Autologous Platelet Concentrate in Surgery for Idiopathic Macular Hole: Results of a Multicenter, Double-Masked, Randomized Trial”, Opthalmology, 106:932-938, 1999

110 patient double-masked randomized prospective macular hole study to evaluate the safety and efficacy of PRP – Injection of PRP significantly improved the anatomic success rate of surgery for idiopathic macular holes of less than 3 years duration.

PRP and Injection Therapy PRP and Injection Therapy

Barrett S, Erredge S; “Growth Factors for Chronic Plantar Fasciitis”, Podiatry Today, 37-42, 2004

9 patients with hypoechoic and thickened plantar fascia were injected with PRP to evaluate the efficacy of PRP with 1 week, 2 week and 1, 3, 6, and 12 month follow-up – All patients had improvement that was noted on diagnostic ultrasound and 6 patients had complete resolution after 2 months. At 1 year, 7 of 9 patients were completely healed.

Mishra A, Pafelko T, Coetzee; “Treatment of Chronic Severe Elbow Tendinosis with PRP”, American Journal of Sports Medicine, Preview, May 30, 2006

20 patients that failed non-operative treatment for chronic epicondylar pain were randomized to evaluate effectiveness of PRP – At 1,2, and 6 months all PRP patients had lower pain and greater ROM than control (bupivicaine). Treatment of chronic epicondylar pain with PRP should be considered prior to surgical intervention.

1919

Treatment of Chronic Severe Elbow Tendinosis with PRPMishra, A., Pafelko, T., Coetzee, 2005 AAOS Podium Presentation

Aim: Elbow epicondylar tendinosis is a common problem for patients whose work or activities require strong gripping or repetitive wrist movements.

140 patients with elbow epicondylar pain were evaluated in this study. Twenty of these patients met the strict chronic, severe inclusion criteria. All of the patients had failed non-operative treatment and were considering surgical treatment.

A single percutaneous application of platelet rich plasma (PRP, active group) or bupivicaine (control group) was used to treat these twenty patients.

2020

Treatment of Chronic Severe Elbow Tendinosis with PRPMishra, A., Pafelko, T., Coetzee, 2005 AAOS Podium Presentation

Results: Four weeks - PRP patients noted a 46% improvement in their visual analog pain scores versus a 17% improvement in control patients (p = 0.028).

Eight weeks - PRP patients noted a 60% improvement in their visual analog pain scores versus a 16% improvement control patients (p = 0001).

After eight weeks, 60% of the control patients either formally withdrew from the study or sought other treatments. Only the PRP patients were available for further evaluation.

Six months - PRP patients noted an 81% improvement in their visual analog pain scores (p = 0.0001). These PRP patients at the same follow-up period noted a 72% improvement in their Mayo elbow scores (p = 0.0001).

Text

Right Lateral Epicondyle

Text

Right Lateral Epicondyle