The Treatment of Muscle Atrophy after Rotator Cuff Tears Using Electroconductive Nanofibrous Matrices

Abstract

Rotator cuff tears (RCTs) are a common cause of disability and pain in the adult population. Despite the successful repair of the torn tendon, the delay between the time of injury and time of repair can cause muscle atrophy. The goal of the study was to engineer an electroconductive nanofibrous matrix with an aligned orientation to enhance muscle regeneration after rotator cuff (RC) repair. The electroconductive nanofibrous matrix was fabricated by coating Poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT:PSS) nanoparticles onto the aligned poly(ε-caprolactone) (PCL) electrospun nanofibers. The regenerative potential of the matrix was evaluated using two repair models of RCTs include acute and sub-acute. Sprague-Dawley rats (n=39) were randomly assigned to 1 of 8 groups. For the acute model, the matrix was implanted on supraspinatus muscle immediately after the injury. The repair surgery for the sub-acute model was conducted 6 weeks after injury. The supraspinatus muscle was harvested for histological analysis two and six weeks after repair. The results demonstrated the efficacy of electrical and topographical cues on the treatment of muscle atrophy in vivo. In both acute and sub-acute models, the stimulus effects of topographical and electrical cues reduced the gap area between muscle fibers. This study showed that muscle atrophy can be alleviated by successful surgical repair using an electroconductive nanofibrous matrix in a rat RC model.

Keywords: Rotator cuff; electroconductive matrix; muscle atrophy; nanofibers.

Figure 1.

A) Diagram of experimental groups. For sub-acute groups, 4 and 6 rats were sacrificed two- and six- weeks after repair respectively; B) Schematic illustration of the rotator cuff surgery model. The aligned PCL nanofibers were fabricated by electrospinning technique. Following the electrospinning, dopamine was applied onto the PCL fibers to polymerize and form a polydopamine coating. DOPA/PCL surfaces were washed, dried, and coated with 10% PEDOT:PSS. Following the surgical repair of the torn supraspinatus tendon, the matrix was implanted on top of the supraspinatus muscle in both acute and sub-acute models.

Figure 2.

Supraspinatus weight loss in A) acute and B) Sub-acute repair groups two and six weeks after surgery. (ns = P > 0.05, * = P ≤ 0.05, ** = P ≤ 0.01, *** = P ≤ 0.001, **** = P ≤ 0.0001).

Figure 3.

Histology images of the Supraspinatus muscle for both acute and sub-acute groups, A) H&E, B) Masson Trichrome staining, and C) Immunohistochemistry of myosin heavy chain.

Figure 4.

Cell infiltration into the matrix after repair A) Fast muscle fiber staining of acute and sub-acute groups two- and six- weeks post-repair B) H&E staining and Masson Trichrome staining of acute group six weeks after repair C) CD31 staining of acute and sub-acute groups six weeks post-repair.

Figure 5.

A) MHC II muscle fiber cross-sectional area of acute and sub-acute groups two and six weeks after repair B) Gap area between muscle fascicles of acute and sub-acute groups six weeks post-surgery. (ns = P > 0.05, * = P ≤ 0.05, ** = P ≤ 0.01, *** = P ≤ 0.001, **** = P ≤ 0.0001; ★ = denote **** = P ≤ 0.0001 significant difference compared with acute and sub-acute/6w).