Losartan in Combination with Bone Marrow Stimulation Demonstrated Synergistic Effects on Load to Failure and Tendon Matrix Organization in a Rabbit Model

Authors:

Lacheta L, Miles JW, Gao X, Murata Y, Fukase N, Utsunomiya H, Dornan GJ, Tashmen S, Kashyap R, Altintas B, Ravuri S, Philippon MJ, Huard J, Millett PJ

Abstract:

Purpose:

To investigate the effects of combining bone marrow stimulation (BMS) with oral losartan to block transforming growth factor β1 (TGF-β1) on biomechanical repair strength in a rabbit chronic injury model.

Methods:

Forty rabbits were randomly allocated into 4 groups (10 in each group). The supraspinatus tendon was detached and left alone for 6 weeks to establish a rabbit chronic injury model and was then repaired in a surgical procedure using a transosseous, linked, crossing repair construct. The animals were divided into the following groups: control group (group C), surgical repair only; BMS group (group B), surgical repair with BMS of the tuberosity; losartan group (group L), surgical repair plus oral losartan (TGF-β1 blocker) for 8 weeks; and BMS-plus-losartan group (group BL), surgical repair plus BMS plus oral losartan for 8 weeks. At 8 weeks after repair, biomechanical and histologic evaluations were performed.

Results:

The biomechanical testing results showed significantly higher ultimate load to failure in group BL than in group B (P = .029) but not compared with group C or group L. A 2 × 2 analysis-of-variance model found that the effect of losartan on ultimate load significantly depended on whether BMS was performed (interaction term F1,28 = 5.78, P = .018). No difference was found between the other groups. No difference in stiffness was found between any groups. On histologic assessment, groups B, L, and BL showed improved tendon morphology and an organized type I collagen matrix with less type III collagen compared with group C. Group BL showed the most highly organized tendon matrix with more type I collagen and less type III collagen, which indicates less fibrosis. Similar results were found at the bone-tendon interface.

Conclusions:

Rotator cuff repair combined with oral losartan and BMS of the greater tuberosity showed improved pullout strength and a highly organized tendon matrix in this rabbit chronic injury model.

Clinical relevance:

Tendon healing or scarring is accompanied by the formation of fibrosis, which has been shown to result in compromised biomechanical properties, and is therefore a potential limiting factor in healing after rotator cuff repair. TGF-β1 expression has been shown to play an important role in the formation of fibrosis. Recent studies focusing on muscle healing and cartilage repair have found that the downregulation of TGF-β1 by losartan intake can reduce fibrosis and improve tissue regeneration in animal models.

You may request the complete study: Losartan in Combination with Bone Marrow Stimulation Demonstrated Synergistic Effects on Load to Failure and Tendon Matrix Organization in a Rabbit Model

Peter Millett, MD

Average rating:

39 reviews

Alexandra Thompson

Mar 23, 2024

by Alexandra Thompson on Peter Millett, MD

110%

Dr. Millett and his team did a SLAP tear repair and bicep tenodesis on my left shoulder. I use my arms as an artist, and love to swim in the ocean, surf, paddle, and telemark ski. So regaining full use of my shoulder and keeping my bicep attached was very important to me. Now, over two years later, my shoulder has the equivalent range of motion as my other arm and as before the injury, and no pain. After the first three months it felt so good and was so strong that - to my horror - I completely forgot my six-month follow-up.

Not only did Dr. Millett and his team make my arm as good as new, but having had the experience of such kindness and expertise throughout the process of surgery and recovery is like an added shoulder superpower.

Thank you Rita, Brooke, Jason, Sarah, Camille, Olivia, Dr. Millett and everyone! And see you soon when my husband comes in for his knee...

Jeff Chandler

Jan 31, 2022

by Jeff Chandler on Peter Millett, MD

Flawless procedure, Easy recovery

Dr. Millet's repaired my knee and tibia, following a botched operation by a different surgeon. That procedure was virtually pain free and I was weight bearing within a few days. That was 18 years ago and the knee is still strong. A few years after the knee incident, Dr Millet repaired my shoulder. My insurance company approved me for 3 months of disability following that surgery. I was off pain medication in 2 days and had 90% range of motion within a week. I withdrew my disability claim and returned to work within two weeks of surgery. I’m not a famous athlete—just a regular guy. Nonetheless, I was treated like an NFL at the Steadman clinic. Most notable was the time for recovery. Other surgeons perform their hour-long task in the OR and don’t involve themselves in the other functions. Peter and his team manages the entire process from diagnosis, anesthesia, nursing care, and therapy. He takes a holistic approach to patient care and doesn’t skip any steps.

Jenn West

Jul 2, 2021

by Jenn West on Peter Millett, MD

Saved My Life

I went to Dr. Millett after 7 knee surgeries (6 on my right and 1 on my left) and had seen 11 different surgeons who all refused to remove femur metal from my right leg. I am highly allergic to metal and the chronic pain was leaving me bedridden for 3.5wks out of a month. He personally wrote me back on my inquiry, listened to my concerns, scheduled my surgery within a week (due to insurance issues) and personally followed up with my recovery. The level of patient care from Dr. Millett and his ENTIRE team is above any care I have ever received in my 20 years of dealing with orthopedic surgeons. There are not enough words to describe the level of care, dedication and professionalism you receive from Dr. Millett and his staff.
My only disappointment is that I did not find him sooner!!!