Recombinant Human Amelogenin Protein Enhances Tendon-To-Bone Healing in a Rat Rotator Cuff Tear Model

Rotator cuff tears (RCTs) often require surgical intervention; however, surgical outcome is frequently insufficient due to poor healing of the tendon-bone enthesis, leading to high retear rates. Previously, the recombinant human amelogenin protein (rHAM⁺) regenerated injured or diseased musculoskeletal tissues including ligaments and osteochondral injuries. We therefore hypothesized that rHAM⁺ can also induce regeneration of the biomechanical and structural properties of the enthesis. The right shoulder infraspinatus tendon of 75 rats was fully-transected, and treated either with 0.5 mg/mL rHAM⁺ dissolved in propylene glycol alginate (PGA) carrier (n = 30), or with PGA carrier alone (n = 30). Fifteen unoperated rats were additionally evaluated. Four- and eight-weeks posttreatment, the degree of regeneration was evaluated using biomechanical and histological analyses. rHAM⁺ induced full recovery of biomechanical properties 8 weeks posttreatment, with the transected tendon demonstrating similar averaged tensile strength as the unoperated contralateral tendon, while PGA brought about substantially inferior biomechanical outcome. Eight weeks after treatment with rHAM⁺, progressive structural improvement was observed, including parallel type I collagen fibers with orientation and width similar to the uninjured group, restoration of the fibrocartilage zone, bone ingrowth, and a detectable tidemark, contrary to poor tissue maturation of the PGA-treated tendons. Furthermore, rHAM⁺ led to significantly less fatty degeneration of the infraspinatus muscle compared to PGA. rHAM⁺ induced regeneration of biomechanical strength and promoted maturation of the enthesis of fully transected rat RCT. Therefore, we recommend further evaluation of amelogenin as possible adjunct therapeutic strategy to improve the healing and reduce retears in clinical RC repair.