Muscle degeneration in chronic massive rotator cuff tears of the shoulder: Addressing the real problem using a graphene matrix

Abstract

Massive rotator cuff tears (MRCTs) of the shoulder cause disability and pain among the adult population. In chronic injuries, the tendon retraction and subsequently the loss of mechanical load lead to muscle atrophy, fat accumulation, and fibrosis formation over time. The intrinsic repair mechanism of muscle and the successful repair of the torn tendon cannot reverse the muscle degeneration following MRCTs. To address these limitations, we developed an electroconductive matrix by incorporating graphene nanoplatelets (GnPs) into aligned poly(l-lactic acid) (PLLA) nanofibers. This study aimed to understand 1) the effects of GnP matrices on muscle regeneration and inhibition of fat formation in vitro and 2) the ability of GnP matrices to reverse muscle degenerative changes in vivo following an MRCT. The GnP matrix significantly increased myotube formation, which can be attributed to enhanced intracellular calcium ions in myoblasts. Moreover, the GnP matrix suppressed adipogenesis in adipose-derived stem cells. These results supported the clinical effects of the GnP matrix on reducing fat accumulation and muscle atrophy. The histological evaluation showed the potential of the GnP matrix to reverse muscle atrophy, fat accumulation, and fibrosis in both supraspinatus and infraspinatus muscles at 24 and 32 wk after the chronic MRCTs of the rat shoulder. The pathological evaluation of internal organs confirmed the long-term biocompatibility of the GnP matrix. We found that reversing muscle degenerative changes improved the morphology and tensile properties of the tendon compared with current surgical techniques. The long-term biocompatibility and the ability of the GnP matrix to treat muscle degeneration are promising for the realization of MRCT healing and regeneration.

Efficacy of a Novel Electroconductive Matrix To Treat Muscle Atrophy and Fat Accumulation in Chronic Massive Rotator Cuff Tears of the Shoulder

“…Muscle Histological Analysis. The same parameter in our previous study 32 for histological analysis was used. Briefly, the crosssectional areas of muscle fibers were measured using ImageJ software (National Institutes of Health).…”

“…Rats were divided into three groups for two time-points (24 weeks and 32 weeks): (1) No repair (NR-24 and NR-32), (2) Suture (S-24 and S-32), and (3) PEDOT:PSS matrix (P-24 & P-32) (Figure A, right). All groups data were performed at the same time in a single study where Native, No Repair, and Suture groups data was recently published on a separate study . An open surgical method was performed to create the RCTs of the supraspinatus and infraspinatus tendons in the left shoulder of rats.…”

“…Subsequently, an incision was made on the deltoid-trapezius interface to reveal the RC tendons. The supraspinatus and infraspinatus tendons were marked with a 5–0 Prolene suture (Ethicon, Johnson & Johnson Medical Ltd.) and then completely detached from their insertions on the humeral head and allowed to retract as mentioned in our previous study . Following the detachment of both tendons, the deltoid-trapezius muscle and skin were closed with 5–0 Vicryl by using the interrupted suture technique.…”

“…The structural properties including tendon cross-sectional area, peak load, stiffness of the linear region, and Young’s modulus of the linear region were calculated. Results for Native, No Repair, and Suture groups from our previous study were adopted in the current study …”

“…Fibrous structures are reported to have similar muscle organization in terms of structures and mechanical properties. ,, In addition, aligned nanofibrous matrices mimic the aligned and multinucleated myotubes in skeletal muscle tissue. − Skeletal muscle is an electrically excitable tissue. Applying electroactive biomaterials into the matrix has been reported to improve interactions between materials and cells and facilitate myoblast communication, growth, and development. ,,− The intrinsic properties of electroconductive materials such as conductive polymers have shown the properties of polymers and the electrical features of metals, all of which are important properties for regulating tissue functions . Therefore, combining an electroactive biomaterial and aligned nanofibers can serve as a critical guidance cue for muscle regeneration.…”