Emerging Insights On Using Acellular Amniotic Scaffolds To Treat Periarticular Tendon Tears

Physicians have used amniotic membranes in wound healing for many years and researchers have shown a corresponding decrease in the time to healing, reduced recurrence of wounds, and increased revascularization.^1-4 While many of these properties are desirable for tendon healing, the data supporting the use of amniotic membrane for tendon healing is promising albeit limited.

Recent animal investigations employing tendon repair models have demonstrated that amniotic cells have the ability to increase the number of proliferating tendon reparative cells, reduce adhesion formation, and improve tendon strength, tensile strength and yield strength.^5-8 Furthermore, amniotic cells are reportedly capable of differentiating into a tendinous material with a highly organized architecture.^7,9

Most recently, in 2013, Zelen and colleagues conducted a prospective randomized study in humans to evaluate the use of injected micronized dehydrated human amniotic/chorionic membrane to treat chronic plantar fasciitis.¹⁰ In comparison with controls, the treatment groups demonstrated significantly greater improvements in symptoms and American Orthopaedic Foot and Ankle Society (AOFAS) scores.

Preliminary research has shown clinical promise for the use of an acellular human amniotic scaffold (Biovance, Alliqua BioMedical) to facilitate tendon healing.¹¹ Quite simply, the role of a collagen amniotic scaffold is to trick the body into using its own cells and growth factors to stimulate a healthy regenerative healing process. This differs from normal healing in that this regenerative scaffold allows the body to minimize scarring. This occurs by downregulating the M1 macrophage and upregulating the M2 macrophage.¹² By minimizing the inflammatory process (M1 macrophage) and stimulating the recruitment of vessels (M2 macrophage), the body is able to control fibrin and ultimately the final resulting scar.  

As foot and ankle surgeons, we know that periarticular tendon injuries can be both challenging and fun to treat. Accordingly, let us take a closer look at the surgical technique for using an acellular amniotic scaffold in the repair of a tendon. The technique is rather straightforward and adds little time to the case.

Pertinent Pearls On Tendon Repair
The surgical approach to tendon repairs certainly depends on the tendon and location of injury. For the sake of this column, we will assume that the tendon one is repairing is either a peroneal or posterior tibial tendon. The basic principles of applying the amniotic scaffold do not change when repairing the different tendons of the foot, ankle and leg.  

The dissection for the peroneal tendon includes a curvilinear incision over the tendon complex with the length and exact location of the incision dependent upon the location and extent of the tear. Carry blunt dissection down to the peroneal retinaculum. Sharply incise the retinacular structure, taking care to ensure the margins are healthy enough for closure.  

Once the tendon complex is visible, isolate the damaged tendon by placing a ribbon retractor behind the retinacular structure. If there is a longitudinal split tear, sharply debride the tear and remove the nonviable tendon. If there is chronic mucoid degeneration, excise the diseased tissue by making an incision in the tendon and removing nonviable tissue from the inside out.

After removing the nonviable tissue, proceed to reapproximate the tendon. Use the suture of your choice in a running, interlocking fashion. Take care to ensure that knots are not in areas of irritation. When tubularizing the tendon, it is important to purchase an adequate amount of tendon with the stitch in order to gather and repair the tendon.   

Applying The Amniotic Scaffold
After tubularizing the tendon, the next step in the repair is applying the acellular amniotic scaffold. With the ribbon retractor behind the tendon, place the scaffold on the tendon so the superior margin of the scaffold is in line with the superior margin of the tendon. Then place two simple sutures, using 4.0 Monocryl (Ethicon), in the superior proximal and superior distal border of the tendon. These simple sutures will serve as the anchors for the scaffold on the tendon. We prefer 4.0 Monocryl because of its quick loss of tensile strength and low risk of irritation to the soft tissue structures.

After anchoring the scaffold, use a bulb syringe to place a few drops of saline onto the membrane. This provides the scaffold with the ability to adhere minimally to the ribbon retractor. After irrigation, pull the ribbon retractor out from behind the tendon. Pulling the ribbon retractor away from the tendon will simultaneously pull the scaffold behind and around the tendon. Use forceps to wrap the scaffold around the tendon. As the fluid from the body hydrates the scaffold, the membrane will easily contour to the tendinous structure. No additional suture is needed to secure the scaffold to the repair.  

If the surgeon is unfamiliar with using this type of scaffold, he or she will notice that the texture and consistency will change as the scaffold comes into contact with body fluid. Initially, the scaffold will have a “tissue paper” texture and appearance. Once hydrated, the scaffold will thicken and gain some tensile strength. This will allow the scaffold to retain a suture and allow for easy handling.  

In Conclusion
As the demands of life increase, patients have the desire to return to work and activities as fast as possible. As surgeons, we want to provide our patients the ability to return to a pre-injury state. Having a firm understanding of the principles of regenerative healing can assist in the quest to return injured tissue back to the pre-injury state.  

For regenerative healing to occur, three biologic activities must occur. First, cells from the body must occupy the scaffold that one is placing on the body. Second, the body must form a blood supply that can penetrate the scaffold. Finally, the scaffold must incorporate into the tissue and become reorganized by the body. If these three things occur, this will allow the body to exit the state of repair (scar) and regenerate tissue closer to a pre-injury level.  

Acellular amniotic scaffolds are great tools for providing the body the opportunity to take advantage of the tenets of regenerative healing. After the placement of the scaffold, the body can subsequently introduce its own cells, vessels and ultimately growth factors to create an environment for healing.

Dr. Brigido is the Section Chief of Foot and Ankle Reconstruction and the Director of Fellowship for Foot and Ankle Reconstruction at Coordinated Health in Bethlehem, Pa. He is a Clinical Professor of Surgery at the Commonwealth Medical College in Scranton, Pa.

References

1. Zelen CM, Serena TE, Denoziere G, Fetterolf DE. A prospective randomised comparative parallel study of amniotic membrane wound graft in the management of diabetic foot ulcers. Int Wound J. 2013; 10(5):502-7.
2. Zelen CM, Serena TE, Snyder RJ. A prospective, randomised, comparative study of weekly versus biweekly application of dehydrated human amnion/chorion membrane allograft in the management of diabetic foot ulcers. Int Wound J. 2014; 11(2):122-8.
3. Sheikh ES, Sheikh ES, Fetterolf DE. Use of dehydrated human amniotic membrane allografts to promote healing in patients with refractory non healing wounds. Int Wound J. 2014; 11(6):711-7.
4. Koob TJ, Lim JJ, Massee M, Zabek N, Rannert R, Gurtner G, Li WW. Angiogenic properties of dehydrated human amnion/chorion allografts: therapeutic potential for soft tissue repair and regeneration. Vasc Cell. 2014 May 1; 6:10.
5. Muttini A, Mattioli M, Petrizzi L, Varasano V, Sciarrini C, Russo V, Mauro A, Cocciolone D, Turriani M, Barboni B. Experimental study on allografts of amniotic epithelial cells in calcaneal tendon lesions of sheep. Vet Res Commun. 2010; 34(Suppl 1):S117-20.
6. Ozbölük S, Ozkan Y, Oztürk A, Gül N, Ozdemir RM, Yanik K. The effects of human amniotic membrane and periosteal autograft on tendon healing: experimental study in rabbits. J Hand Surg Eur. 2010; 35(4):262-8.
7. Demirkan F, Colakoglu N, Herek O, Erkula G. The use of amniotic membrane in flexor tendon repair: an experimental model. Arch Orthop Trauma Surg. 2002; 122(7):396-9.
8. Kueckelhaus M, Philip J, Kamel RA, Canseco JA, Hackl F, Kiwanuka E, Kim MJ, Wilkie R, Caterson EJ, Junker JP, Eriksson E. Sustained release of amnion-derived cellular cytokine solution facilitates achilles tendon healing in rats. Eplasty. 2014 Aug. 4; 14:e29.
9. Barboni B, Russo V, Curini V, Mauro A, Martelli A, Muttini A, Bernabò N, Valbonetti L, Marchisio M, Di Giacinto O, Berardinelli P, Mattioli M. Achilles tendon regeneration can be improved by amniotic epithelial cell allotransplantation. Cell Transplant. 2012; 21(11):2377-95.
10. Zelen CM, Poka A, Andrews J. Prospective, randomized, blinded, comparative study of injectable micronized dehydrated amniotic/chorionic membrane allograft for plantar fasciitis -- a feasibility study. Foot Ankle Int. 2013; 34(10):1332-9.
11. Mulhern JL, Protzman N, Brigido SA. The use of a decellularized, dehydrated human amniotic membrane in tendon repair: a case series. Poster presented at the 2015 American College of Foot and Ankle Surgeons Annual Meeting, Phoenix, AZ.  
12. Data on File. Alliqua Biomedical.