Pigs, cows and rotator cuff repair - Revisiting AAOS' strong recommendation for bioinductive implants

Last month we took a critical look at "AAOS: Strong recommendation for "bioinductive tendon implants to augment rotator cuff repair". Please take a moment to review it.

Lets look at some new information, focusing on patient reported outcomes rather than MRI findings.

Recently, the authors of No Short-term Clinical Benefit to Bovine Collagen Implant Augmentation in Primary Rotator Cuff Repair: A Matched Retrospective Study used a single surgeon, minimum two year retrospective, matched, comparative study of patients who underwent primary arthroscopic repair of partial or full-thickness rotator cuff tears to determine (1) whether the proportion of patients undergoing re-operation for postoperative stiffness and inflammation differed between patients having cuff repair with a bovine collagen implant (Regeneten) and patients having cuff repair without the implant, (2) whether short-term patient-reported outcomes differed between the two groups, and (3) whether the proportion of patients receiving postoperative methylprednisolone prescriptions and corticosteroid injections differed between the two groups.

They found that a greater proportion of patients in the bovine collagen implant group (9% [4 of 47]) underwent reoperation for inflammation and stiffness than in the control group (0% [0 of 94]). At minimum 2-year follow-up, patients receiving the Regeneten implant did not have better reported outcomes:  American Shoulder and Elbow Surgeon score (81 ± 24 implant versus 85 ±19 control, SSV (79 ± 24 implant versus 85 ± 18 control), VAS score for pain (2.0 ± 2.9 implant versus 1.5 ± 2.3 control). The cohorts did not differ in the proportion who received postoperative corticosteroid injections or methylprednisolone prescriptions.

They concluded that "at minimum 2-year follow-up, patients undergoing primary arthroscopic rotator cuff repair with bovine collagen implant augmentation had a greater proportion of re-operation due to inflammation and stiffness compared with patients who did not receive the implant. Furthermore, the implant offered no benefit in patient-reported outcomes or need for postoperative corticosteroid injections or methylprednisolone prescriptions. Because of the lack of clinical benefit and potential increase in postoperative complications, we recommend against the use of these bovine collagen implants unless high-quality randomized controlled trials are able to demonstrate their clinical effectiveness, cost-effectiveness, and overall safety."

The authors of Bioinductive patch as an augmentation for rotator cuff repair, a systematic review and meta-analysis found that patient-reported outcome improvements with Regeneten (cow collagen) were not superior to improvements for standard rototor cuff repair; a similar proportion of patients achieved the minimal clinically important difference as for standard repair. The overall complication rate with the bioinductive patch was 16%, most commonly for stiffness and capsulitis.

The authors of Effect of Porcine-Derived Absorbable Patch-Type Atelocollagen for Arthroscopic Rotator Cuff Repair compared standard rotator cuff repair to repair with a type-I atelocollagen absorbable patch derived from pigs (RegenSeal) in patients having rotator cuff repair. For the atelocollagen group, before securing the lateral anchors,  porcine-derived absorbable patch-type atelocollagen was inserted between the footprint and the tendon. They found no significant differences in pre to postoperative improvement in Constant Score, pain, other functional scores, and range of motion between the groups at 1 year postoperatively.

The authors Acellular Collagen Matrix Patch Augmentation of Arthroscopic Rotator Cuff Repair Reduces Re-TearRates: A Meta-analysis of Randomized Control Trials  pooled outcomes of studies found that in 5 studies with 156 patients augmented with ACMP and 151 controls, the average final Constant score was 90 in the ACMP group and 87 in controls. This difference did not exceed the minimal clinically important difference for the Constant score (10 points).  In 3 studies with 64 patients augmented with ACMP and 61 controls, the average American Shoulder and Elbow Surgeons Score score was 87 in the ACMP group and 82 in controls.  This difference did not exceed the minimal clinically important difference for the ASES (20 points). 

See also:

AAOS: Strong recommendation for "bioinductive tendon implants to augment rotator cuff repair"

The value of the Regeneten bioinductive implant in managing rotator cuff disease: what does the literature say?

The "Secret Sauce" for Optimizing Rotator Cuff Outcomes: Biologics or nutrition?

Comment: A strong recommendation from our Academy could conceivably put patients and surgeons at risk if this recommendation were not followed. In the case of rotator cuff repair, evidence that porcine or bovine patches are of clinically significant benefit in terms of patient-reported outcomes seems to be lacking. Until more convincing data become available, it may be appropriate to consider modifying the recommendation for the use of these implants in cuff repair.

Worthy of discussion

Ravens and Red Tailed Hawk

Union Bay Natural Area

2020

Follow on twitter/X: https://x.com/RickMatsen
Follow on facebook: https://www.facebook.com/shoulder.arthritis
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Here are some videos that are of shoulder interest
Shoulder arthritis - what you need to know (see this link).
How to x-ray the shoulder (see this link).
The ream and run procedure (see this link)
The total shoulder arthroplasty (see this link)
The cuff tear arthropathy arthroplasty (see this link).
The reverse total shoulder arthroplasty (see this link).
The smooth and move procedure for irreparable rotator cuff tears (see this link)
Shoulder rehabilitation exercises (see this link).

AAOS: Strong recommendation for "bioinductive tendon implants to augment rotator cuff repair"

Recently the AAOS updated its clinical practice guidelines, including those for the management of rotator cuff injuries.The 2025 CPG contains a strong recommendation for the use of bioinductive implants during rotator cuff repair, as it may reduce the chances of retear and improve patient-reported outcomes.

Let's take a look at the two papers quoted as support for this recommendation

Augmentation of a Transosseous-Equivalent Repair in Posterosuperior Nonacute Rotator Cuff Tears With a Bioinductive Collagen Implant Decreases the Retear Rate at 1 Year: A Randomized Controlled Trial

and

An isolated bioinductive repair vs sutured repairfor full-thickness rotator cuff tears: 2-year resultsof a double blinded, randomized controlled trial 

Both of studies used Regeneten, a patch made of purified type I collagen derived from bovine (cow) Achilles Tendon marketed by Smith and Nephew. The authors of both studies acknowledged support from the company. 

The first study compared transosseous equivalent (TOE) repairs of medium to large cuff tears randomized at surgery after the TOE repair to repair alone or to TOE repair with a bovine collage patch placed over the repaired tendon, stretching 5- to 10-mm lateral to the footprint, and fixed to the tendon with 5-8 absorbable anchors and to the bone with 1 to 3 PEEK (polyether ether ketone) anchors. In the Control group, there were 16 retears in 62 subjects (25.8%); in the bovine collage patch group, there were 5 retears in 60 subjects (8.33%).While the retear rate was lower in the bovine collage patch group, up to a year after surgery there were no differences in the ASES scores between the two groups.

In the second study patients with small/medium (2.5 cm) full thickness supraspinatus tears and intact rotator cable were randomized to arthroscopic transosseous-equivalent repair or debridement after which the bovine collage patch was placed on top of the tear, overlapping the bone-tendon junction. The patch was secured with tendon anchors and 2 bone anchors. No structural tendon repair was carried out.

Measured via a 6-month biopsy, highly organized, parallel bundles of collagen, without inflammation, were present in all bovine collage patch patients, whereas poorly organized, nonparallel collagen fibers were present in 24/30 (80%) of control patients, with 28/30 having minimal to mild inflammation.  All bovine collage patch patients had 100% healing on MRI at 12 and 24 months measured as gap fill-in; the gap fill-in for the controls was not reported. The bovine collage patch group returned to work significantly faster (median 90 days vs. median 163.5 days) than the control group. 

Compared with the control group, the bovine collage patch group had higher American Shoulder and Elbow Surgeons and Constant-Murley Shoulder scores at each evaluation, less pain at 6 and 12 months, and greater satisfaction at 12 and 24 months. 

At two years after surgery, the ASES scores for the bovine collage patch and Control were 88 and 80; for the Constant Scores were 88 and 78. In each group, both measures were improved by 100% of the minimal clinically important difference (MCID).

Here are a few other recent articles relating to the use of Regenetin in rotator cuff surgery. These articles were not mentioned in the "current practice guidelines"

Economic value. Two studies attempted to assess the economic value of Regeneten, but did not evaluate patient reported clinical outcomes.

Resorbable Bioinductive Collagen Implant Is Cost Effective in the Treatment of Rotator Cuff Tears Average cost of treatment $32,213 without Regeneten, $54,459 with Regeneten (additional cost 69%). Did not assess patient reported outcomes or revision rates for patients without or with the patch. While using "healing" as the study endpoint, the authors point out that there is lack of agreement on what constitutes healing or retearing after a cuff repair based on magnetic resonance imaging, ultrasound, or arthrogram. Evidence was not presented that "healing" by imaging correlated with better clinical outcomes .

Economic Evaluation of a Bioinductive Implant for the Repair of Rotator Cuff Tears Compared with Standard Surgery in Italy. Average cost of treatment €4650 without Regeneten, €7828 with Regeneten (additional cost 68%). Study limitations the same as those for the report above.

Complications: The one study that compared clinical outcomes of repairs without and with Regeneten found an eight-fold increase in postoperative stiffness in the Regeneten group. All reoperations were in the Regeneten group.

Increased stiffness and reoperation rate in partial rotator cuff repairs treated with a bovine patch: a propensity-matched trial found that postoperative stiffness was observed in the first 12 weeks in 8 of 32 patients in the patch group compared with 1 of 32 patients in the control group. Six patients in the patch group underwent reoperations compared with no patients in the control group. All 6 reoperations in the patch group were performed to address stiffness. The authors concluded that patients in the patch group had a significantly higher rate of postoperative stiffness. In the majority of patients in whom shoulder stiffness developed, reoperation was required. It seems possible that this stiffness may be related to overstuffing the subacromial space by the graft as well as associated scarring in the humeroscapular motion interface.

A report of revision because of bursitis and rice bodies in a Regeneten-treated cuff repair.

Subacromial-Subdeltoid Bursitis With Rice Bodies After Rotator Cuff Repair With a Collagen Scaffold Implant: A Case Report. reported a case of subacromial-subdeltoid bursitis with rice bodies after rotator cuff repair with a Smith + Nephew REGENETEN bovine-derived bioinductive collagen scaffold implant. After debridement, the patient recovered well and made a full return to work and recreational activities.

Report of revisions because of reactive bursitis: Revision arthroscopic surgery after rotator cuff repair with a collagen graft: histologic evaluation of biopsy specimens from two patients.

Comment: The use of "biologics" in rotator cuff surgery is of interest clinically, scientifically, and economically. From what has been reported, bovine collagen patches can enhance the healing of certain cuff tears. However, their impact on the outcomes perceived by the patient (patient reported outcomes, PROs) appears to vary according to the type of tear being treated. The best results seem to be for small tears with an intact rotator cuff cable. The value to patients with other tear types has yet to be rigorously evaluated. 

Thus, the clearest patient-perceived value is in carefully selected small/medium tears with an intact rotator cable; the broader value proposition (medium–large repairs, partial tears) still needs longer-term PROs, complication surveillance, and transparent cost-effectiveness that includes PROs, not just imaging.

Thinking through the options

Western Bluebirds

Orcas Island

2021

Follow on twitter/X: https://x.com/RickMatsen
Follow on facebook: https://www.facebook.com/shoulder.arthritis
Follow on LinkedIn: https://www.linkedin.com/in/rick-matsen-88b1a8133/

Here are some videos that are of shoulder interest
Shoulder arthritis - what you need to know (see this link).
How to x-ray the shoulder (see this link).
The ream and run procedure (see this link).
The total shoulder arthroplasty (see this link).
The cuff tear arthropathy arthroplasty (see this link).
The reverse total shoulder arthroplasty (see this link).
The smooth and move procedure for irreparable rotator cuff tears (see this link)
Shoulder rehabilitation exercises (see this link).