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

The high retear rate after a successful repair of the rotator cuff (RC) is a major clinical challenge. Muscle atrophy and fat accumulation of RC muscles over time adversely affect the rate of retear. Since current surgical techniques do not improve muscle degenerative conditions, new treatments are being developed to reduce muscle atrophy and fat accumulation. In the previous study, we have shown the efficacy of aligned electroconductive nanofibrous fabricated by coating poly(3,4-ethylene dioxythiophene): poly(styrenesulfonate) (PEDOT:PSS) nanoparticles onto aligned poly(ε-caprolactone) (PCL) electrospun nanofibers (PEDOT:PSS matrix) to reduce muscle atrophy in acute and subacute models of RC tears (RCTs). In this study, we further evaluated the efficacy of the PEDOT:PSS matrix to reduce muscle atrophy and fat accumulation in a rat model of chronic massive full-thickness RCTs (MRCTs). The matrices were transplanted on the myotendinous junction to the belly of the supraspinatus and infraspinatus muscles at 16 weeks after MRCTs. The biomechanics and histological assessments showed the potential of the PEDOT:PSS matrix to suppress the progression of muscle atrophy, fat accumulation, and fibrosis in both supraspinatus and infraspinatus muscles at 24 and 32 weeks after MRCTs. We also demonstrated that the PEDOT:PSS matrix implantation significantly improved the tendon morphology and tensile properties compared with current surgical techniques.

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

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.

The Role of Nanomaterials and Biological Agents on Rotator Cuff Regeneration.

The rotator cuff is a musculotendon unit responsible for movement in the shoulder. Rotator cuff tears represent a significant number of musculoskeletal injuries in the adult population. In addition, there is a high incidence of retear rates due to various complications within the complex anatomical structure and the lack of proper healing. Current clinical strategies for rotator cuff augmentation include surgical intervention with autograft tissue grafts and beneficial impacts have been shown, but challenges still exist because of limited supply. For decades, nanomaterials have been engineered for the repair of various tissue and organ systems. This review article provides a thorough summary of the role nanomaterials, stem cells and biological agents have played in rotator cuff repair to date and offers input on next generation approaches for regenerating this tissue.

Mechanically superior matrices promote osteointegration and regeneration of anterior cruciate ligament tissue in rabbits.

The gold standard treatment for anterior cruciate ligament (ACL) reconstruction is the use of tendon autografts and allografts. Limiting factors for this treatment include donor site morbidity, potential disease transmission, and variable graft quality. To address these limitations, we previously developed an off-the-shelf alternative, a poly(l-lactic) acid (PLLA) bioengineered ACL matrix, and demonstrated its feasibility to regenerate ACL tissue. This study aims to 1) accelerate the rate of regeneration using the bioengineered ACL matrix by supplementation with bone marrow aspirate concentrate (BMAC) and growth factors (BMP-2, FGF-2, and FGF-8) and 2) increase matrix strength retention. Histological evaluation showed robust tissue regeneration in all groups. The presence of cuboidal cells reminiscent of ACL fibroblasts and chondrocytes surrounded by an extracellular matrix rich in anionic macromolecules was up-regulated in the BMAC group. This was not observed in previous studies and is indicative of enhanced regeneration. Additionally, intraarticular treatment with FGF-2 and FGF-8 was found to suppress joint inflammation. To increase matrix strength retention, we incorporated nondegradable fibers, polyethylene terephthalate (PET), into the PLLA bioengineered ACL matrix to fabricate a "tiger graft." The tiger graft demonstrated the greatest peak loads among the experimental groups and the highest to date in a rabbit model. Moreover, the tiger graft showed superior osteointegration, making it an ideal bioengineered ACL matrix. The results of this study illustrate the beneficial effect bioactive factors and PET incorporation have on ACL regeneration and signal a promising step toward the clinical translation of a functional bioengineered ACL matrix.