mazzocca isakos 10am june 3 biologics rcr · bone marrow concentr ate can result in healing of...

$: Mazzocca ISAKOS 10am June 3 Biologics RCR · Bone marrow concentr ate can result in healing of acute full-thickness cartilage defects that is superior to that after microfracture$
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Biologic Augmentation for Multiple Failed Rotator Cuff Repairs in Middle Aged Adults

Augustus D Mazzocca MS, MD

Director of the UCONN Musculoskeletal Institute

Chairman Department of Orthopaedic Surgery

Professor University of Connecticut

New England Musculoskeletal Institute

[email protected]

USA

The following relationships exist and have been fully disclosed and approved by the

STATE OF CONNECTICUT ETHICS BOARD1.Royalties and stock options-NONE

2.Consulting income-ARTHREX INC

3.Research and educational support –ARTHREX INC

4.Other support-Educational and Research grants from OREF, Donaghue Foundation

COMITTEES LEADERSHIPProgram Chairman for the 2014 AOSSM International Sports Medicine

Meeting

Research Committee of the Arthroscopy Association of North America (AANA) 2010 to Present

Continuing Education Committee of the American Shoulder and Elbow Surgeons (ASES) 2009 to Present

Founder and Executive Committee Member of the New England Shoulder and Elbow Society (NESES) 2003 to Present

Thanks toGerber C, Crosby L, Cote MP, Russell RP, McCarthy MB, Obopilwe E, Solovyova O,

Apostolakos JM, Hirose T, Beitzel K, Romeo AA, Imhoff A, Porcellini G, Cerciello S, Spoliti M,

Bradley J, Shepard D, Arnoczky S, Rodeo S, Shea KP, Steinman S, Edgar C, & Arciero RA

This Research has been presented at the AOSSM 2010, 2011 AANA 2011, 2012

2009 and 2011 ISAKOS Meeting2009 and 2011 European Shoulder and Elbow Society,

Mazzocca et al AJSM 2009, JBJS 2012.Arthroscopy 2011, 2012Beitzel et al Arthroscopy 2011 and AJSM 2012

Introduction1.Review of Literature for failed rotator

cuff repairs

2.Biologic analysis of non healing tissue

3.Operative solutions for failed rotator cuff repairs

Arthroscopic Revision RCR

BMA/PRP/Dermal graft

BMA/PRP Clots

BMA/PRP/DBM

Latissimus Dorsi Transfer

Superior Capsular Reconstruction

Reverse Arthroplasty

4.Algorithm for revision RCR

Chronic Tear-poor tissue quality

Factors Predicting Rotator Cuff Retears: An analysis of 1000

Consecutive Rotator Cuff repairs• Overal Retear rate was 17% (27% in Full

thickness and 5% partial Thickness Repairs)

• Rotator Cuff Tear size and Age was a better predictor of failure than Tissue Quality or other injuries

• In this study Diabetic status did not demonstrate a relationship to retear rate

Le and Murrell AJSM 2014

Failed Rotator Cuff Repair (RCR)Confirmed on MRI

SYMPTOMATIC• Pain with activity

• Night Pain & Awakening• Weakness

• Loss of ROM

Observe at 1 year intervals with repeat

MRI

ASYMPTOMATIC• Small Tear or gap

• No Pain• Full ROM

• Happy/low demand/older

Offer Operative Intervention

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OPERATIVE INTERVENTIONSymptomatic Failed RCR

•Non-retracted tears•No x-ray changes

•Good muscle/tendon

quality

•Proximal migrationhumeral head x-ray• > 70 years of age

•Horrible pain at rest•Massive RC tear

• > 1 primary RCR•Young patient•Retracted tear

•Changes on x-ray

ArthroscopicRevision RCR

Reverse Ball and Socket Prosthesis

Superior Capsular Reconstruction NOT a

Latissimus DorsiTransfer

OR

Arthroscopic RCR with concentrated bone marrow and

allograft patch

Rotator Cuff Repair procedures in a single surgeon’s practice (ADM) from 2002-May 2017

“20% revision feels like 80%”Rotator Cuff

Related Procedures

n =1487

Primary Rotator Cuff Repair

n =1093 (74%)

Reverse TSA

n = 117 (8%)

Revision Rotator Cuff Repair

n = 277 (18%)

Arthroscopic revision RCR

n = 153 (10%)

Latissimus DorsiTransfer

(Nov 2009- 2013)

n = 45 (3 %)

BMA Patch

(Oct 2009 – July 2014)

n = 36 (2%)

Autologous cBMA Clots

(Nov 2014 – Present)

n = 43 (3%)

This has been a 11 year biologic journey (2006-2017) which

unfortunately is not over• Latissimus Dorsi Transfers

– 2006-2013 (n=35)

• RCR using BMA Patch (Double Syringe)– 2009-2014 (n= 29)

• RCR using BMA Clot (Angel System)– 2014-2016

• Multiple cBMA Clots (n = 12)

• 30cc cBMA “Mega Clot” (n = 13)

• Superior Capsule Reconstruction (n = 10)

• FlexiGRAFT (n = 6)

Clinical Data-Rotator Cuff Repairs have a 30-94% failure rate

Boileau JBJS 2005

65 ARCR (tension band technique) assessed with MRI or CT arthrogram

71%(46/65) Watertight

4%(3/65) Partial Repair

25% (16/65) Recurrent Tear

Galatz JBJS 2004

18 RCR>2cm evaluated at 1and 2 yrs with Ultrasound

17/18 Recurrent Tear

Gerber JBJS 2000

29 Massive RCR evaluated with MRI

17/29(58%)Repair Intact

12/29(42%) re tear

Ozbaydar Acta Ortho 2005

16 RCR mini open nonretracted

3/16(19%) Re Tear

13/16(81%) intact

Large or Massive generally do not heal or retearWhile smaller tears have a lower retear rate

Biology and RCR: What's New in 2017PRP alone not enhancing primary rotator cuff repair.

Gwiner et al Act Ortho 2016

DiBenedetto et al Bio 2016

Flury et al AJSM 2016

Fu et al Clin Rehab 2016

Saltzman et al Arthro 2016

Samuelson et al Arthro 2016

Mesenchymal Stem cells can be obtained from all over the body-most common Bone marrow and Adipose

FDA Title 21 part 1271 section 351-Low Risk

minimal manipulation

homologous use

noncombination product

Nonsystemic effect

Miller et al AJSM 2011-41% of all RCR failed and 80% of these failed within 3 Months-Never healed!!!!

Gamradt et al JSES 2010-At 3 months following repair, the majority of blood flow to the repair is derived from the peribursal soft tissues and the anchor site. The tendon, particularly those with a defect at 3 months, is relatively avascular

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quality




•Changes on x-ray




OR

Arthroscopic RCR with concentrated bone marrow and

allograft patch

Limited Reports on Revision RCR• DeOrio JK, Cofield RH. Results of a second attempt at surgical repair of a

failed initial rotator-cuff repair. J Bone Joint Surg Am. Apr 1984;66(4):563-567.

• Djurasovic M, Marra G, Arroyo JS, Pollock RG, Flatow EL, Bigliani LU. Revision rotator cuff repair: factors influencing results. J Bone Joint Surg Am. Dec 2001;83-A(12):1849-1855.

• Neviaser RJ. Evaluation and management of failed rotator cuff repairs. Orthop Clin North Am. Apr 1997;28(2):215-224.

• Bigliani LU, Cordasco FA, McIlveen SJ, Musso ES. Operative treatment of failed repairs of the rotator cuff. J Bone Joint Surg Am. Dec 1992;74(10):1505-1515.

• Lo IK, Burkhart SS. Arthroscopic revision of failed rotator cuff repairs: technique and results. Arthroscopy. Mar 2004;20(3):250-267.

• Trantalis, J. N.; Boorman, R. S.; Pletsch K.; Lo, I. K.: Medial Rotator Cuff Failure After Arthroscopic Double-Row Rotator Cuff Repair. Arthroscopy, 24(6): 727-31, 2008.

• Keener JD,Wei AS,Kim HM,Paxon ES,Teefy SA,Galatz LM. Revision Arthroscopic Rotator Cuff Repair:Repair Integrity and Clinical Outcome. JBJS-A 2010 92 (590-598)

Less pain

Unpredictable functional improvement

Arthroscopic Revisions

165 Arthroscopic revisions• 35 Failures (21%)

• 130 Success (79%)

Most are single RCR failure

Younger patients

(compliance or Trauma)

The Anchor, Suture, and Knot are all intact-it is the tendon that has pulled away

from the bone

Gerber Critical Shoulder Angle-Age,Trauma and Large CSA can predict

RC tears

XR’s:

• No OA / AVN / bone loss

• minimal superior migration (A-H distance =4 mm)

• Critical Shoulder Angle = 38*

• Acromial Index (Lateral extension of acromion) = 0.75

CSA:normal = 33

OA = 28RTC = 38Viehofer and Gerber JOR 2015

Moor and Gerber Ortho and Trauma 2014

How can we improve?

Multiple Cell Types Present at Tendon/Bone Interface

Benjamin & Ralphs, J. Anat., 1998

H&E

Calcified Fibrocartilage

Bone

Uncalcified Fibrocartilage

Tide Mark

Articular Cartilage

Tendon-Dense fibrous connective

Tissue

Supraspinatus Tendon Insertion:Bone-Calcified Fibrocartilage-Fibrocartilage-Tendon

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Not Scar Tissue but Tendon Attempting to Heal

This tissue had cells and a wavy collagen pattern

with increased vascularity

Scar tissue has a distinctly irregular collagen pattern

No Cells

Biologic Categories that will enhance the bodies own ability to improve tendon healing?

Growth Factors and Platelet Rich Plasma-Can modulate various aspects of healing but have a specific does and time response

Cell Based Therapies and Scaffolds-Mesenchymal stem cells as well as various extracellular patches may improve healing

Increasing vascularity during Rotator cuff healing-poor vascularity exists at the healing cite and agents such as glyceryl trinitrate improved healing (Paoloni et al AJSM 2005)

Matrix Metalloproteinase -play a role in extracellular matrix production. Tissue inhibitors of Matrix Metalloproteinase’s (TIMMP) such as Doxycyline can improve healing

We have research and experience on the first two

In 2017, have we evolved into both a Cell Based Approach (BMA) as well as a Signal Based Approach (PRP) to

Assist in Rotator Cuff Revisions?

Mesenchymal Stem Cells (MSC)• Synonyms:

– Connective Tissue Progenitors (CTP) – Mesenchymal Progenitor Cells (MPC)

• Able to differentiate into mesenchymal tissuelike bone, tendon, cartilage etc.

• Highly Proliferative while retaining their growth and multilineage potential (but not immortal)

• Commonly defined by:– Colony Formation – Surface Markers (CD105+,CD73+; Negative for CD34, CD45 & CD14) – Differentiation into mesenchymal cell lines

Dominici et al., Cytotherapy, 2006Chamberlain et al., StemCells, 2007Koch et al. BMC Biotechnology 2007Beitzel et al Arthroscopy 2011

Mesenchymal Stem Cells are found in Bone, Fat, and Muscle. They can differentiate into tendon and bone for improved healing of Rotator Cuff repairs.

Neural- crest

Pericyte Myofibroblast

Mesenchymal Progenitor

PeriodontalLigament

ADULT OR

EMBRYONIC

STEM CELL

Hemangio-blast

Endothelial

Hematopoietic Chondrocyte

Mesenchymal Progenitor

Adipocyte

Osteoblast

Neuro- ectoderm

HematopoieticSupport Cells

Endodermal Skeletal Muscle

Tendon &LigamentInterstitial

Fibroblasts

Pericyte Myofibroblast

Osteoblast

Mesoderm

Different Ways to ObtainBone Marrow Cells

Aspiration is easily achieved during arthroscopic RCR using a bone marrow trocar

Stem cells can be isolated in the OR within 5 minutes

Cannulated anchors isanother way to obtain bone

marrow for healing

Vented Anchors and the “Crimson Duvet” technique

may assist with healing

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Rotator Cuff Repair aided with Bone Marrow and Stem Cells

Ellera, 2012, KSSTA

– Conventional rotator cuff repair complemented by the aid of mononuclear autologous stem cells,

• At 12 mo, 12 of the 14 tears had healed

Hernigou, 2014, Orthop

– Biologic augmentation of rotator cuff repair with mesenchymal stem cells during arthroscopy improves healing and prevents further tears: a case- controlled study

After 10 years, tendon integrity was found in

87 % (BMC) vs. 44 % (control)

Literature showing healing with Stem Cells

Hernigou et al., JBJS 2005 Autologous bone-marrow grafting efficacy appears to be related to number of progenitors in the graft / aspirated bone marrow should be concentrated (60 Humans)

Fortier et al., JBJS 2010Bone marrow concentrate can result in healing of acute full-thickness cartilage defects that is superior to that after microfracture alone (12 adult horses)

Okamoto et al., JBJS 2010 Transplantation of whole bone marrow cells may be a better treatment for Achilles tendon rupture than cultured mesenchymal stem cells. (BM vs. MSC 87 rats)

Ota et al AJSM 2011- Stem cell application to muscle improved and accelerated healing

Stem Cells Defined by:

1.Differentiation into bone, fat, tendon,and muscle

2.Colony Forming Units (CFU)

3.Morphology

4.FACS Analysis (CD 73, 90, 45) FACS

CFU

Bone Marrow–Derived Mesenchymal Stem Cells Obtained During Arthroscopic Rotator Cuff Repair Surgery Show Potential for Tendon Cell Differentiation After Treatment With Insulin

Augustus D. Mazzocca, M.S., M.D., Mary Beth R. McCarthy, B.S., David Chowaniec, B.S.,Mark P. Cote, D.P.T., Christopher H. Judson, M.D., John Apostolakos, B.S., Olga Solovyova, B.S.,

Knut Beitzel, M.A., M.D., and Robert A. Arciero, M.D. Arthroscopy, 27 (2011), 1459-71

How, When, and What Do We Count as a Colony?

This is important to know when you review the literature

How DO We Count Colony Forming Units?

• After counting the nucleated cells, the cBMA is plated into a tissue culture dish and checked daily for the appearance of colonies. 1,2

• A Colony Forming Unit (CFU) is defined as > 8 cells in a cluster that has adhered to the tissue culture

plastic

• The colonies are counted and expressed as the Concentration of CTP:

# of CFU/1.0 cc cBMA• From these 2 numbers CTP prevalence can be calculated:

CTP Concentration/ # of Nucleated cells = CTP Prevalence

CFU

1. McLain, R. F., et al. (2005). “t." J Bone Joint Surg Am 87(12): 2655-2661.

2. Muschler, G. F., et al. (2001). J Orthop Res 19(1): 117-125.

Nucleated Cells are Important to Count Because they are a Predictor of the Amount of

Stem cells Obtained

• A 0.01ml sample of cBMA is added to 10 ml’s of isotonic saline and the number of nucleated cells are counted using a Coulter Counter or hemocytometer

• This # is expressed as:

million of nucleated cells/ 1.0cc cBMA

• We count nucleated cells because they are good predictor of how many stem cells we have

• The number of nucleated cells are used to calculate the prevalence of stem cells in a sample.1

Coulter Counter

1. Pittenger, M.F., et al., Multilineage potential of adult human mesenchymal stem cells.Science, 1999. 284(5411): p. 143-7.

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Why Are There Inconsistencies?

Each cBMA Plate is Assessed on a Daily Basis for the Appearance of Colonies. Once Colonies appear, 25% of the most Representative Part of

the Plate is Counted.• The plate is first scanned microscopically on

4X power to asses the density of the cells. Time = 20 min.

• The quadrant most representative of the entire plate is then chosen for colony counting.

• 2- lines are drawn to delineate the quarters of the plated and to help identify the area you are in when looking through the microscope.

• Colonies are ALWAYS counted using a 10X Magnification.

• A manual cell counter is used to count colonies.

• The final number is then multiplied by 4 to give total # of CFU’s/ml cBMA

Typical View of Colonies at 48 hrs. How Many Can You Count?

Myself (Yellow Circles) Counted: 13 CFU’s

Lab Director (Red Circles) Counted 23 CFU’s

Colonies Must be Counted Before they Begin to Proliferate (Grow)

Colonies Can appear anytime between 2-10 days

Perfect! Colonies are easy to spot Too late! Hard to tell one colony from another

48 hrs. 96 hrs.10x Mag 10x Mag

You can see from this Picture that 1-CFU can have 100’s of Cells

Can you count the number of cells?No and neither can we…cells are piled on top of each other

48 hrs. 10x Mag

Quote taken from a paper published in 1997 by Dr. George Muschler-it’s a know fact that

there are inconsistencies in these numbers

If more that 60 colonies were present in a field, significant overlap of individual colonies could result in underestimation of the true number! 1

Majors, A. K., et al. (1997). "Characterization of human bone marrow stromal cells withrespect to osteoblastic differentiation." J Orthop Res 15(4): 546-557.

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Take Home Points!• Not everyone counts colonies the same way.

• 1-CFU does NOT equal 1-cell in fact it can be hundreds of cells

• Only 25% of each plate counted!

• There are differences between labs!

• Even in our lab we have inconsistencies!

• It is important that colonies are counted by the same experienced person and that person counts in a consistent fashion each time.

Pittenger, M. F., et al. (1999). "Multilineage potential of adult human mesenchymal stem cells.”Science 284(5411): 143-147.

Very interesting but how is this #@$% clinically applicable




quality




•Changes on x-ray




OR

ARCR with cBMA/PRPBMA/PRP/DBMSuperior capsular

Reconstruction

Can we obtain Human Stem Cells without increasing surgical morbidity,

time, and number of procedures?

YESRapid Isolation of Human Stem Cells (Connective Tissue Progenitor Cells) from the Proximal Humerus During Arthroscopic Rotator Cuff Surgery

Augustus D. Mazzocca, M.S., M.D., Mary Beth McCarthy, B.S., David Chowaniec, B.S., Mark P. Cote, P.T., D.P.T, Robert A. Arciero, M.D, Hicham Drissi, PhD

Am J Sports Med, 38 (2010), 1438-47

Rapid Isolation of Human Stem Cells (Connective Tissue Progenitor Cells) From the Distal Femur During Arthroscopic Knee Surgery

Knut Beitzel, M.A., M.D., Mary Beth McCarthy, B.S., Mark P. Cote, P.T., D.P.T.,David Chowaniec, B.S., Lauryn M. Falcone, Justine A. Falcone, Evan M. Dugdale,

Thomas M. DeBerardino, M.D., Robert A. Arciero, M.D., and Augustus D. Mazzocca, M.S., M.D.Arthroscopy, 28 (2012), 74-84

Is this safe to the patient?

The University of Connecticut Department of Safety and Quality Control

No increase in risk to the patient of the operative technical aspects of bone marrow aspiration from

the shoulder of knee

YES

No increase in complications with the aspirate group in fact less in this group

(n=120 aspirations)

Wound Infection

Abnormal Pain

Delayed Healing

Stiffness

ASPIRATE GROUP

0 0 3 (13%) 2 (8%)

CONTROL GROUP

1 (4%) 3 (13%) 3 (13%) 1 (4%)

No surgical complications (0%)

There were no incidence of RSD, DVT, wound irregularities, hematoma, or septic arthritis (0%)

Incidence of Complications:

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Aspirate Bone Marrow

BMA Processing Systems Available in 2017

Company Product Name

Thermogenesis Res-Q 60 BMC

Harvest BMAC

Arthrex Angel System

Biomet BioCUE

Baxter Bone Marrow Collection Kit

DePuy Selective Retention

Pall Corporation Purecell Select System

The ratio of BMA to ACD-A is critical for making GOOD autologous clots

If the ratio of ACD-A: BMA is NOT correct then clot stability is impaired.

Clot will not hold together well and will dissolve after 24 hrs.

Must be 1: 5.61-Part ACD-A to 5.6 parts BMA

Good ClotRobust but not too robust

Aspiration TechnologyNo difference in amount of MSC obtained from Fenestrated Cannula vs. Single Hole Cannula

Arthrex® Bone Marrow Aspiration System Harvest® Bone Marrow Aspiration System

Each system has a trocar with a 14g needle appropriately sized for use in the proximal humerus and to prevent cell damage during harvest.

Voss, Beitzel and Mazzocca 2017 Arthroscopy

Graduated depth marks ensure the Trocar depth is between 25-30mm

Insert BMA 14g needle and trocar into area of first anchor

Radiographic Determination of Safe

Trocar Penetration

30mm20mm 50mm

45 degree dead mans angle

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Insert the Trocar to 35-40 mm Depth, Attach the Syringe and draw up 17 cc’s of BM.

TOTAL VOLUME = 20 cc’s /syringe

- BMA will be aspirated through the same hole where the anchor for RC-Repair will be set

- At least 35 cc of bone marrow aspirate is needed (3 cc ACD-A + 17 cc BMA X2 syringes)

Always Process the BMA Using the filter provided in the Concentration

System and a 15% Hematocrit Setting

How many cells do we get and does the number matter?

Comparison of Mesenchymal Stem Cells (Osteoprogenitors) Harvested From Proximal Humerus and Distal Femur During Arthroscopic Surgery

Knut Beitzel, M.A., M.D., Mary Beth R. McCarthy, B.S., Mark P. Cote, D.P.T.,Thomas J.S. Durant, P.T., David M. Chowaniec, B.S., Olga Solovyova, B.S.,

Ryan P. Russell, M.A., Robert A. Arciero, M.D., and Augustus D. Mazzocca, M.S., M.D.Arthroscopy, 29 (2013), 301-8

Stem cells per 10cc syringe per million

How Do We Compare?

0

5

10

15

20

25

30

35

40

45

Mazzocca(No gradient)

Mazzocca(Unpublished

Data)

Mazzocca(AJSM 2010)

Shoulder

Mazzocca(Arthroscopy)

Knee

Heringou(JBJS 2005)Illiac Crest

Muschler(JBJS 2005)Illiac Crest

Muschler(JBJS 2005)

Vertebral Body

CF

Us/

106

Nu

clea

ted

Cel

ls

Stem Cells

n=21n=21

n=25

n= 60

n=23

n=25

n=63

4 min @ 800 rpm 5 min @1500 rpm 2-Step Expansion

The first procedures we did involved an allograft patch as a

scaffold to keep the cells in place

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Clinically we use ACP/PRP, Stem Cells and Human Dermis patches for

revision rotator cuff tears

The Positive Effects of Different Platelet-Rich Plasma Methods on Human Muscle, Bone, and Tendon Cells

Augustus D. Mazzocca, Mary Beth R. McCarthy, David M. Chowaniec, Evan M. Dugdale, Derek Hansen, Mark P. Cote, James P. Bradley,

Anthony A. Romeo, Robert A. Arciero and Knut BeitzelAm J Sports Med 2012 40: 1742 originally published online July 16, 2012

Platelet-Rich Plasma Differs According toPreparation Method and Human Variability

Augustus D. Mazzocca, MS, MD, Mary Beth R. McCarthy, BS, David M. Chowaniec, BS, Mark P. Cote, DPT, Anthony A. Romeo, MD,

James P. Bradley, MD, Robert A. Arciero, MD, and Knut Beitzel, MDJ Bone Joint Surg Am, 94 (2012), 308-16

Isolation of Human Stem Cells (Connective Tissue Progenitor Cells) From the Proximal Humerus During Arthroscopic Rotator Cuff Surgery

Augustus D. Mazzocca,* MS, MD, Mary Beth R. McCarthy, BS, David M. Chowaniec, BS,Mark P. Cote, PT, DPT, Robert A. Arciero, MD, and Hicham Drissi, PhD

Am J Sports Med 2010 38: 1438 originally published online April 7, 2010

Application of Allograft Scaffold, PRP and Cells to Revision RC Repair

Now that we have the cells, we need them to stay in place.

Will cells stay adhered during arthroscopic surgery?

Human Tendon Cell Response to 7 Commercially Available Extracellular Matrix Materials: An In Vitro StudyKevin P. Shea, M.D., Mary Beth McCarthy, B.S., Felicia Ledgard, B.S.,

Cristina Arciero, B.A., David Chowaniec, B.S., and Augustus D. Mazzocca, M.S., M.D.Arthroscopy, 26 (2010), 1181-8

YES

If the Cells are adherent are they still alive? Over time?

YES0 Time (30 min attachment) • 21 d in Culture

After 21 days in culture stem cells have multiplied Stain =Hematoxylin and Eosin 10X Magnification

Native allograft No Cells

Biomechanics of scaffolds soaked in Stem Cells and ACP

Does the positioning, material, or addition of stem cells harm the stability of transosseous

equivalent classic rotator cuff repair?

NOStability of Double-Row Rotator Cuff Repair Is Not Adversely Affected by

Scaffold Interposition Between Tendon and BoneKnut Beitzel, David M. Chowaniec, Mary Beth McCarthy, Mark P. Cote, Ryan P. Russell,

Elifho Obopilwe, Andreas B. Imhoff, Robert A. Arciero and Augustus D. MazzoccaAm J Sports Med 2012 40: 1148 originally published online February 28, 2012

All patients of a single surgeon’s practice (ADM) undergoing RC revision with biologic augmentation

(N=26)

(9/23/2009-9/24/2013)

Stable

N=13

Failed

N= 13

Clinical Failure

N=5

MRI Failure

N=8

In our clinical analysis we had a 50% Failure Rate

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All patients (Mazzocca) undergoing RC revision with biologic augmentation

(N=26)

(2009-2013)

Mean Age = 59

Stable

N=13

Complete dataN=10

Avg CTP/mL injected= 2,394

Failed

N= 13

Complete dataN=12


Hernigou et al 2014-much better success and more cells!!!

Not Revisions

All patients (Hernigou) undergoing primary RC with biologic

augmentation (N=45)

(2000-2005)

Mean Age = 61

Stable

N=39

Failed

N=6

Complete dataN=39


Complete dataN=6


MAZZOCCA HERNIGOU

7 Year Post Op – BMA Patch Augmentation

2006-2013N=35

We compared our BMA/PRP/Allograft Patch to our

Lat transfers

Not much difference in clinical outcome but a significant difference

in surgical mortality

Latissimus Dorsi TransferIndicated for patients that are young

with multiple failed RCR.N=35

Can reduce pain but will not reproducibly increase strength or ROM

Functional UCONN Outcomes N=34Latissimus Dorsi Transfer

N=12 Failures defined as no improvement in pain. 1 revised to a Reverse Prosthesis

N=12 Success with either no pain or significant improvement in pain with shoulder level or above motion

N=10 Fair-improvement but still having pain and less motion

Patch Vs Lat Outcomes

Biologic Augmentation (BA) when it worksGives great improvement compared to Lat failure and success

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There must be a better way

Making an Autologous Clot

1 CC BMA/PRP CLOTS2014-2015 (N=10)

Working toward making this process easy/efficient for use in PRIMARY Rotator

Cuff Repair

Multiple 3mm clots with cBMA (2015)

N=10

Our original idea was to make a clot and attach it to the suture for ease of repair. This did not work

consistently

Clot:Average Number of cells and cBMA Volume

(cc’s) Re-implanted

• Average Volume (cc’s) of cBMA

re-implanted = 4.33 + 2.1

• Average # of Stem Cells

re-implanted = 20,579.1 + 12,957

1 cc Clot Outcomes - 3 out 10 significant pain & confirmed failure

N = 10

Patient #

MonthsPost OP

SignificantPain (+/-)

ROM

CTPConcentration (# of CFU/cc

cBMA)

Complications?

1 12 - Active FF 180, ABD 180, Ex Rot 70 978

2 12 - Active FF 180, ABD 180, ex Rot 60 994

3 12 - Active FF 150, ABD 100, ex rot 30

1840 Confirmed Failure Via MRI



6 12 + Active FF 160, ABD 110, Ex Rot 60

1458 Confirmed Failure Via MRI, Non-compliant





9 7 - Active FF 180, ABD 180, Ex Rot 60

10 14 - Active FF 180, ABD 180 (w/ pain), Ex Rot 80


63 Year Old RHD Female w/ failed Right RCR –Treatment with 1 cc Clots

Preop Postop

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Patch vs. 1 cc Clot comparison-Clot clinically easier and improved

results

0

10

20

30

40

50

60

70

80

90

100

ASES SST Pain SANE

BMA Patch Augmentation vs. 1 cc Clot Augmentation

Pre Patch Post Patch Pre Clot Post Clot

We are now using a single “mega clot” to give the advantage of improved biology with a more consistent delivery system

30 cc BMA/PRP Mega ClotAugust 2015 – Present

(n=18)

Clot processing and implantation

- 0.6 cc PPP from blood- 0.1 cc PRP from blood- 0.1 cc PRP from BMA- 0.2 cc Thrombin

Wait 10-20 sec.

Ready for use

Cells after 24h and 48h still aliveGreen AliveRed Dead 24 h 48 h

Application of Clot

Medial Row of the RCR is completed

Injection area is localized with a spinal needle

Trocar Inserted

Lateral row completed

Subacromial Space

BMA trocar placed with Spinal needle guidance

Mega Clot Outcomes (n = 18) 3/18 failedPatient

#Months Post OP


Full ROM

CTP Concentration (# of CFU/cc

cBMA)

Complications?

1 10 - Active FF 170, ABD 170, EX rot 80 329

2 12 - Active FF 170, ABD 170, ex Rot 80 2034 Confirmed Retear Via MRI

3 3 - Active FF 180, ABD 170, EX Rot 45 4783 LOST TO FOLLOW UP

4 12 + Active FF 80, ABD 70, Ex Rot 70 2983 Confirmed Retear Via MRI

5 12 + Active FF 80, ABD 45, Ex Rot 70 1728 Confirmed Retear Via MRI, PostiveBelly Press & Jobst Test

6 12 + Active FF 180, ABD 180, Ex Rot 70 1678 ROM improving but still with pain (anteriorly located)

7 13 + Passive FF to 180, ABD 160, Ex Rot 45

675 Several Falls After Sx (patient admits needs to be placed in bubble)

8 7 + Active FF 160, ABD 140, Ex Rot 50 2834 Pain Relief using narcotics, all ROM with Pain

9 12 + FF 90, ABD 60, Ex Rot 30 3021 MRI Revealed Supraspinatur muscle retracted to the glenoid

10 3 Pain Improving Passive 150, ABD 140, Ex Rot 70 1765 Feels Much Better Already

11 3 + Passive FF 110, ABD 100, Ex Rot 60 with NO Pain

1789 NON-COMPLIANT WITH SLING

12 6 Pain Improving Active 170, ABD 170, Ex Rot 60 2890

13 6 Pain ImprovingPassive FF 160, ABD 110, Ex Rot

801745 Withheld from PT for healing purposes

58 Year Old RHD Female w/ massive failed RCR – PreOp Mega Clot

Preop 1 year Postop

6/1/2017

14

1 cc Clots vs Mega Clot Outcomes-This data indicates a trend for

improvement and ease of clinical use

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ASES SST Pain Sane

1 cc BMA/PRP Clot

Pre Clot Post Clot

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Mega Clot

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Bone marrow-derived mesenchymal stromal cells enhanced by PRP

maintain adhesion to scaffolds in arthroscopic simulation

Demineralized Bone Matrix (DBM)

Normal Human tendon (NHT)

Fibrin Scaffold/Clot (FC)

Is there a better way to hold onto the cells?

BMA/ PRP with DBM June 2016 – Present (n = 8)

bMSC had significantly greater adhesion on the DBM compared to FS and NHTPRP improved Cellular Adhesion in all three groups (DBM,FS, NHT)

P=0.02

N=6

Hoberman et al Arthroscopy 2017 In Press

DBM Scaffold/Clot:Average Number of cells and cBMA Volume (cc’s) Re-implanted using the Angel System

• Average Volume (cc’s) of cBMA

re-implanted = 5.0 + 1.41

• Average # of Stem Cells

re-implanted = 40,265 + 22,040.5

Implantation of BMA/PRP with DBM

DBM Outcomes – 7 out of 8 doing well

Patient # Months Post OP


Full ROM Complications?

1 8 + Active FF 100, ABD 100, EX rot 50

2 10 + Active FF 170, Abd 160, Ex rot 50

Revised to Reverse TSA

3 6 ‐ Active FF 180, ABD 80, Ex Rot 45

4 4 ‐ Active FF 80, ABD 40, Ex Rot 40

5 2 ‐ Active FF 170, ABD 160, EX Rot 70

Withheld from PT for healing purposes

6 2 ‐ Passive FF 170, ABD 150, Ex Rot 60

7 1 ‐ Passive FF 20, ABD 10, Ex Rot 10

8 1 + Passive FF 30, ABD 30, Ex Rot 10

6/1/2017

15

DBM Outcomes vs CFUs

Patient # Months Post OP Complications? CTP Concentration (# of CFU/cc cBMA)

1 8 Complicated by Adhesive capsulitis BUT RCR INTACT

2 10 Significant Pain Laterally 2947

3 6 Repeat MRI OrderedPositive Shoulder Hiking

1234

4 4 3256

5 2 Withheld from PT for healing purposes

1435

6 2 694

7 1 756

8 1 1156

49 Year Old RHD male carpenter w/ right failed RCR – PreOp DBM BMA/PRP

6 months Post Op

SUPERIOR CAPSULE RECONSTRUCTION

NOV 2015 – PRESENT (N=10)

YOUNGER PATIENT WITH IRREPARABLE ROTATOR

CUFF TEARHAMADA-1-3 YESHAMADA 4-6 NO

Injection Dermal Patch w/ cBMA and PRP

We have performed 10-SCR procedures using dermal allograft patch, cBMA and PRP

Patient # Date Age Gender # of CTP cells/106

nucleated Cells

# of CTP/1.0 cc

of BMA

1 11/10/15 42 M 20.8 512

2 11/17/15 61 M 69.7 2014

3 2/2/16 66 F 75.9 1789

4 2/9/16 54 F 70.3 2032

5 3/1/16 63 M 18.2 432

6 3/29/16 59 M 28.0 2829

7 3/29/16 63 M 105.6 2489

8 6/14/16 54 M 83.7 2234

9 5/9/2017 51 F

10 5/16/2017 57 M

SCR Failures Vs. Hamada Grading; analyzed by Dr. Bastian Scheiderer

Patient DOS Hamada Scale Failure?

1 11/10/2015 1 Yes

2 11/17/2015 2 Yes

3 2/2/2016 2 Yes

4 2/9/2016 3 Yes

5 3/1/2016 2 No

6 3/29/2016 2 Yes

7 3/29/2016 3 No

8 6/14/2016 1 Yes

9 5/9/2017 2 N/A

10 5/16/2017 3 N/A

6/1/2017

16

SCR doing well 6 mos Post OP6 Months Post Op Failed SCR –

PreOp Reverse TSA

6 Months Post Op Reverse TSA – Doing Well

Reverse Arthroplasty Outcomes

When SCR fails

Age cut off becoming younger

Reverse TSA- Significantly Improved Surgical Outcomes

Mean Follow Up = 2.0 years

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ROWE ASES SST CM Pain SANE

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Post

Mean Age = 72Median Age = 72

79 Year Old RHD active female w/ LT Cuff Tear Arthropathy – Pre Op Reverse TSA

Pre-Op 6 months Post Op

6/1/2017

17

2017 MSC Take Home Facts1. Mesenchymal Stem Cells exist in the proximal Humerus

2. Can easily withdraw increase volume of Bone Marrow(0-40cc) and spin with standard centrifuge

3. MSC can be found in increase volume aspiration but not as consistent

4. MSC able to adhere to various biologic scaffolds and proliferate

5. Multiple hole vs Single Hole aspiration does not make a difference

2017 Clot Take Home

Reproducible method to form a fibrin clot that cells live in. Too tight and they die. Too lose and it falls apart

Clinical outcomes have been inconsistent. Use of DBM or the mega clot increase OR time by 20-30min

2017 SCR/Reverse Take Home

SCR can decrease the force on the deltoid with a massive tear

Place graft in with arm abduction angle of 30-45 degrees. As tight as possible

Save remaining cuff with margin converegence

mazzocca isakos 10am june 3 biologics rcr · bone marrow concentr ate can result in healing of...

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