Can we improve rotator cuff tendon biology and is augmentation helpful?

Mr Adnan Saithna, Consultant Sports Injury Knee and Shoulder Surgeon based at Southport, Ormskirk and Renacres Hospitals

The role for improving biology..

• High failure rates, particularly for massive tears

• Widely reported figures of 20-90%

• How can we optimise the biology:

Avoid treatments that impair biology

Optimise the repair

Optimise patient factors

Augmentation

PRP

Stem Cells

Patches

SR:Effect of glucocorticoidsMechanical properties of tendon, Dean et al

Effect of glucocorticoids

• significant negative effects on tendon cells in vitro, including reduced cell viability, cell proliferation and collagen synthesis

• There is increased collagen disorganisation and necrosis as shown by in vivo studies

• Directly affects microvascularisation of the footprint, Bonneviale et al

• 48 patients

Angiogenesis assessed by CD34 immunostaining from intra-op biopsy at repair

Correlated with success of repair at 1 year

Glucocorticoid injection significantly reduces CD34 staining (and microvascularity of footprint) 10% vs 16%

Microvascularity correlates with success of cuff healing after repair

16%

14%

4%

Association between rate of microvascularisation and Sugaya grade

Footprint preparation: Radiofrequency ablation• Ficklcherer, et al. Arthroscopy 2014

• Supraspinatus repair in 189 rats

Footprint either decorticated, untreated or treated with RFA

• Biomechanics of repair

Mean load to failure significantly reduced in RFA group

No diff decorticated/untreated

• Histological

Significantly reduced type II collagen in RFA group compared to others

Crimson duvet Snyder et al, TSES, 2009

RCT, Microfracture, Milano et al, Arthroscopy 2013

40 patients in each arm

Significantly improved healing rate in large tears (65 vs

52 %)

No difference in small tears

No difference in constant score

Similar findings Jo et al , AJSM 2013

Optimising patient factors:Smoking and cuff repairSystematic Review, Santiago-Torres, AJSM 2014

• Nicotine delays tendon to bone healing in rat model with lower load to failure at 10 and 28 days

• Clinical outcomes

3 studies

Balyk et al and Mallon et al show significantly worse clinical scores (ASES, UCLA) in smokers at 6 months and 1 year post-op

In contrast Prasad showed no difference

• structural integrity (MRI/USS)

4 studies

Neyton significantly reduced healing on MRI at 16 months

Thashijan et al and Dhanjari et al showed trend to inferior outcomes in smokers on USS

Nho et al, no difference on USS

Diabetic control• Cho et al, AJSM 2015

• Cohort study

• Diabetic patients with post-operative Hba1c more than 7% greater than pre-op value classified as poor control

• Cuff re-tear rate defined by MRI significantly higher (43%) in poorly controlled diabetics than in good control (26%) p<0.001

Vitamin DRyu, AJSM 2015

• Cohort study

• 91 patients

• No association between Vitamin D levels, clinical scores and structural outcomes

PRP: Systematic Review of Meta AnalysesSaltzman et al, Arthroscopy 2016

• The current highest level of evidence suggests that PRP use at the time of arthroscopic rotator cuff repair does not universally improve re-tear rates or affect clinical outcome scores.

• However, the effects of PRP use on re-tear rates trend toward beneficial outcomes if evaluated in the context of the following specific variables:

use of a solid PRP matrix

application of PRP at the tendon-bone interface

in double-row repairs

and with small- and/or medium-sized rotator cuff tears.

Stem cells in tendon disordersSystematic Review: Pas et al BJSM 2017

• No high quality evidence found for the therapeutic use of stem cells for tendon disorders (including cuff repair).

• The use of stem cell therapy for tendon disorders in clinical practice is currently not advised.

• Kim et al AJSM 2017

MSCs loaded in fibrin glue

Cohort study

No clinical differences at 28 months

MRI retear rate 28% vs 14% p<0.001

Human Dermal Matrix AugmentationRCT, Barber et al, Arthroscopy 2012

Augmentation associated with better scores at mean f/up 24 months

• The ASES score improved from 48.5 to 98.9 in group 1 and from 46.0 to 94.8 in group 2. (P = .035).

• The Constant score improved from 41.0 to 91.9 in group 1 and from 45.8 to 85.3 in group 2. (P = .008).

• No difference in UCLA score

Outcomes after patch useSR: Steinhaus, Arthroscopy 2016• 24 included studies (19 level IV)

• When categorized by graft type, the rates of complete re-tears were synthetic: 15.0% (33 of 220), xenograft: 42.0% (50 of 119), and allograft: 9.9% (7 of 71)

• Overall, the complication rate was 3.5% (12 of 340) including 1 severe inflamm reaction, 2 x cystic change HH, 1 deep infection

• Failure rates seem low compared to previously reported rates for large tears but broad inclusion criteria and predominantly cohort series

Some studies included smaller tears

Differing lengths of follow up

Broad inclusion criteria

Weak evidence

Future directions• MSC/biomolecule (BMP-7) loaded hydrogels and synthetic scaffolds have

shown promise in animal studies

• However, a cautious approach must be adopted as animal models have limitations. Eg. Rat model – much higher healing rates, limited fatty degeneration, different morphology and loading

Summary• Avoid steroid injections

• Counsel diabetics and smokers

• Some evidence for footprint preparation but avoid compromising fixation

• PRP/MSCs insufficient evidence to currently support a role

• Patch augmentation – some evidence but mainly Level IV only. More comparative studies required

• Animal studies should be interpreted with caution (as learned from PRP)