Failed Rotator Cuff:

What now?

Scott Steinmann MD

Professor of Orthopedic Surgery

Mayo Clinic

Biology of Repair

Molecules of Growth and Repair

• Basic fibroblast growth factor (bFGF)

• Insulin-like growth factor (IGF)

• Platelet-derived growth factor (TGF) β

These molecules have been noted to be

expressed in a supraspinatus rabbit tendon

defect model M. Kobayashi, E. Itoi, et al., J Shoulder Elbow Surg (2006)

Sheep Tendon Study

3 groups with Infraspinatus detachment and repair

• Group 1: Osteoinductive BMP on type I collagen sponge

• Group 2: Only collagen sponge

• Group 3: Only tendon repair

Rodeo SA, et al. J Bone Joint Surg Am. 2007

Sheep Tendon Study

• Volume of newly formed bone and soft tissue was greatest in

BMP treated animals (MRI)

• Specimens with BMP had greater load to failure loads at 6 and

12 weeks

• However when normalized for tissue volume, no difference

between the groups

• Growth factors results in the formation of poor-quality scar

tissue rather than true tissue regeneration

Rodeo SA, et al. J Bone Joint Surg Am. 2007

Sheep Tendon Study Caveats:

• The placement of the sponge directly between the

tendon and the bone may have acted as a block to

tissue formation

• Subtle immune response against the bovine-derived

collagen sponge might have led to inhibition of

tissue formation

• In the same sheep model a porcine patch led to

greater stiffness, but no change in failure loads

Schlegel et al, Am J Sports, 2006

Rodeo SA, et al. J Bone Joint Surg Am. 2007

What about a patch?

Animal Model of Rotator Cuff Graft

• Canine Model

• Full-thickness tendon defect induced in the infraspinatus at the myotendinous junction

• Repaired with an acellular dermal matrix graft (GraftJacket®, Wright Medical, Arlington, TN) or excised autologous tendon

• Survival times 6 weeks, 3 months, 6 months.

Adams et al, Arthroscopy, 2006

Histological evaluation- 3 months survival

Dog 152, area adjacent to GJ, OM 200x

Adams et al, Arthroscopy, 2006

Ultimate Stress

0

5

10

15

20

Time 0 6 Weeks 3 Months 6 Months

Ult

ima

te S

tre

ss

(M

Pa

)

Control

Dermal matrix graft

Adams et al, Arthroscopy, 2006

Canine Rotator Cuff Study Human Dermal Graft

Sometimes you need a patch?

16 year old female hockey player

Rotator Cuff Tear

Two prior attempts at repair

Bare Humeral

Head

Completed Repair

Prior open Supraspinatus and Subscapularis Repair

55yo Revision Massive Tear

55yo Revision Massive Tear Dermal Graft Patch

Got PRP?

What is platelet-rich plasma (PRP)?

First understand the stages of healing

1) Inflammation lasts days

2) Cellular and matrix development lasts weeks

3) Tissue formation and maturation lasts months

4) Tissue remodeling lasts years

What is PRP?

Cellular/Matrix proliferation stage

• Injury allows for hematoma/fibrin clot

• Platelets in the fibrin clot provide initial growth

factors

• Can we increase the healing response by

adding PRP, stem cells, etc?

What is PRP? • Common steps in preparation:

• 1) Withdraw patients blood (9 –

100mL)

• 2) Centrifugation

• 3) 3 layers – RED, WHITE,

YELLOW

Layers -

• RED: Erythrocytes

• WHITE: Leukocytes/Inflammatory

cytokines

• YELLOW: plasma, platelets and

growth factors

Mei-Dan and Carmont, Sports Med Rev, 2011

What is PRP?

• Platelets – anuclear cells, circulate in blood for 7-

10days

• Key role in coagulation

• Contain Alpha granules – secrete molecules when

activated

• Molecules are: Platelet-derived growth factor (PDGF),

Transforming growth factor β, VEGF, etc.

• Platelets have analgesic properties (protease-activated

receptor 4 peptides

What is PRP?

But the commercial preparations have

significant differences –

• Speed and number of centrifugations

• Use of anticoagulant

• Presence or absence of leukocytes

• Use of an activator

PRP controversy

• Higher number of platelets is NOT a better

system

• Concentrations above 1.8 x 106 platelets/μl may

have an inhibitory effect

• Platelet activation: some systems don’t others

use exogenous (bovine) or endogenous thrombin

• Calcium chloride used as an activator to avoid

immune reaction to exogenous thrombin

PRP controversy

Leukocytes:

• Contain matrix metalloproteinases 8 and 9

• Release of reactive oxygen species may increase

tissue damage

• But contain growth factors such as VEGF

Does PRP work?

• Basic science studies have shown a culture of

tenocytes in a broth of growth factors increase

angiogenesis

• But does this translate into improved rotator cuff

healing rates in our patients?

World’s Literature on PRP

2011 • 13 human in vivo articles

• 3 elbow tendinopathy

• 2 rotator cuff

• 3 Achilles tendon

• 3 ACL studies

• 3 prospective cohort studies – rotator cuff

• Only 1 prospective, randomized, double-blind

studies (level 1) rotator cuff

Taylor et al, Clin J Sport Med, 2011

PRP outcome studies

• Prospective, randomized, controlled, double blind study

• Biomet, 6ml injected between bone/tendon “dry”

subacromial space

• 26 patients RC repair +PRP, 27 pts control

• Pain scores lower in PRP+ (1 - 30days post-op only)

• No difference in strength at 6 – 24 months

• MRI at 2 years – no significant difference in healing rates

Randelli et al, JSES, 2011

PRP outcome studies

• Matched groups (not

randomized)

• 20 each group PRP+ and

PRP-

• Single surgeon

• PRP (Cascade system) , no

thrombin activation or

leukocytes (growth factors

released over several days

Barber et al, Arthroscopy, 2011

PRP Outcome Studies

• PRP construct compressed

between tendon and

reattachment site (not injected

so more technically

challenging)

• MRI studies at 4 months

<3cm healed: 50% control

group

86% PRP group

• No significant difference

between groups ASES or

Constant scores

Barber et al, Arthroscopy, 2011

PRP Outcome Studies

• 19 pts with PRP, 23 without

PRP

• Gel spheres (COBE, spectra LRS Turbo,

Caridian BCT, Lakewood, CO) placed on

suture and placed between

tendon and bone – plasma

collected the day before surgery

• NO difference in ROM,

strength, functional scores, or

overall satisfaction

• Retear rate by MRI at 9 months,

no significant difference

Jo et al, AJSM, 2011

PRP outcome studies

• Randomized study

• 36 patients PRPM with RC repair

• 31 patients no augmentation

• PRPM placed on suture interface between tendon and

bone

• Ultrasound at 6 and 12 weeks

• 67% PRPM intact 81% no augment intact

• ASES scores no statistical difference

• Is PRP detrimental?

Rodeo et al, ASES closed meeting, 2010

PRP outcome studies

• Prospective, cohort study

• RC tears up to 3 cm in length, applying 5-6 cc

PRP, at least one triple loaded metal suture anchor

• 48 PRP+ patients, 47 PRP- patients

• 6 month F/U ultrasound

• No statistically significant effect on healing time

by ultrasound

Buford, AANA annual meeting 2011

Prospective, Randomized Study on PRP

• 30 patients PRGF applied at end of repair

• 30 patients no PRGF

• VAS, SST, UCLA and ASES scores

• 3 month follow-up

• No complications

• Trend toward higher SST and VAS scores in

Non-PRGF group!

• Few MRI/Ultrasound, but early clinical results same

Weber, ASES open meeting, 2010

Use of platelet rich plasma gel on wound healing:

A systematic review and meta-analysis.

• 8577 publications

• 24 eligible

• Wound healing more likely in wounds treated with PRP

• Infection rates lower in PRP treated subjects

• PRP subjects had better QoL scores and less narcotic –

may- result in less wound pain

• (study funded by Cytomedix –a wound healing

company)

Carter MJ, Fylling CP, Parnell LK, ePlasty 2011

Genetically modified Stem Cells

The real future?

Genetically Modified MMPs may improve healing

• Rotator cuff tears heal via a scar tissue interface:

weaker and may lead to retear

• Membrane type 1 matrix matalloproteinase

(MT1-MMP) is upregulated during

embryogenesis at developing bone-tendon sites

• Can this process be used to direct healing away

from scar tissue and more toward tendon

regeneration?

Genetically Modified MMPs may improve healing

• Rat model

• 30 rats detachment and repair of supraspinatus tendon –

Mesenchymal Stem Cells (MSCs)

• 30 rats detachment and repair of supraspinatus tendon –

transduced MSCs modified to overexpress MT1 –

MMP

• At 4 weeks, the MMP group had more fibrocartilage

and higher ultimate load to failure/ultimate stress

compared to the MSC only group

Gulotta et al, AJSM, 2010

Summary

• Patches may play a role when the muscle

remains viable and the tendon is gone

• Growth factors soaked in collagen sponges may

not improve strength of repair

• PRP can grow tenocytes in a petri dish, but does

that translate to better rotator cuff repair?

• MMP upregulation of stem cells might be the

future but a product is years away

Gonda Building - Rochester

Thank You