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.

Injectable nanocomposite analgesic delivery system for musculoskeletal pain management.

Musculoskeletal pain is a major health issue which results from surgical procedures (i.e. total knee and/or hip replacements and rotator cuff repairs), as well as from non-surgical conditions (i.e. sympathetically-mediated pain syndrome and occipital neuralgia). Local anesthetics, opioids or corticosteroids are currently used for the pain management of musculoskeletal conditions. Even though local anesthetics are highly preferred, the need for multiple administration presents significant disadvantages. Development of unique delivery systems that can deliver local anesthetics at the injection site for prolonged time could significantly enhance the therapeutic efficacy and patient comfort. The goal of the present study is to evaluate the efficacy of an injectable local anesthetic nanocomposite carrier to provide sustained analgesic effect. The nanocomposite carrier was developed by encapsulating ropivacaine, a local anesthetic, in lipid nanocapsules (LNC-Rop), and incorporating the nanocapsules in enzymatically crosslinked glycol chitosan (0.3GC) hydrogels. Cryo Scanning Electron Microscopic (Cryo SEM) images showed the ability to distribute the LNCs within the hydrogel without adversely affecting their morphology. The study demonstrated the feasibility to achieve sustained release of lipophilic molecules from the nanocomposite carrier in vitro and in vivo. A rat chronic constriction injury (CCI) pain model was used to evaluate the efficacy of the nanocomposite carrier using thermal paw withdrawal latency (TWL). The nanocomposite carriers loaded with ropivacaine and dexamethasone showed significant improvement in pain response compared to the control groups for at least 7 days. The study demonstrated the clinical potential of these nanocomposite carriers for post-operative and neuropathic pain. STATEMENT OF SIGNIFICANCE: Acute or chronic pain associated with musculoskeletal conditions is considered a major health issue, with healthcare costs totaling several billion dollars. The opioid crisis presents a pressing clinical need to develop alternative and effective approaches to treat musculoskeletal pain. The goal of this study was to develop a long-acting injectable anesthetic formulation which can sustain a local anesthetic effect for a prolonged time. This in turn could increase the quality of life and rehabilitation outcome of patients, and decrease opioid consumption. The developed injectable nanocomposite demonstrated the feasibility to achieve prolonged pain relief in a rat chronic constriction injury (CCI) model.

Regenerative Engineering for Knee Osteoarthritis Treatment: Biomaterials and Cell-Based Technologies.

Knee osteoarthritis (OA) is the most common form of arthritis worldwide. The incidence of this disease is rising and its treatment poses an economic burden. Two early targets of knee OA treatment include the predominant symptom of pain, and cartilage damage in the knee joint. Current treatments have been beneficial in treating the disease but none is as effective as total knee arthroplasty (TKA). However, while TKA is an end-stage solution of the disease, it is an invasive and expensive procedure. Therefore, innovative regenerative engineering strategies should be established as these could defer or annul the need for a TKA. Several biomaterial and cell-based therapies are currently in development and have shown early promise in both preclinical and clinical studies. The use of advanced biomaterials and stem cells independently or in conjunction to treat knee OA could potentially reduce pain and regenerate focal articular cartilage damage. In this review, we discuss the pathogenesis of pain and cartilage damage in knee OA and explore novel treatment options currently being studied, along with some of their limitations.

Poly (lactic acid)-based biomaterials for orthopaedic regenerative engineering.

Regenerative engineering converges tissue engineering, advanced materials science, stem cell science, and developmental biology to regenerate complex tissues such as whole limbs. Regenerative engineering scaffolds provide mechanical support and nanoscale control over architecture, topography, and biochemical cues to influence cellular outcome. In this regard, poly (lactic acid) (PLA)-based biomaterials may be considered as a gold standard for many orthopaedic regenerative engineering applications because of their versatility in fabrication, biodegradability, and compatibility with biomolecules and cells. Here we discuss recent developments in PLA-based biomaterials with respect to processability and current applications in the clinical and research settings for bone, ligament, meniscus, and cartilage regeneration.

Animal models of osteoarthritis: classification, update, and measurement of outcomes.

Osteoarthritis (OA) is one of the most commonly occurring forms of arthritis in the world today. It is a debilitating chronic illness causing pain and immense discomfort to the affected individual. Significant research is currently ongoing to understand its pathophysiology and develop successful treatment regimens based on this knowledge. Animal models have played a key role in achieving this goal. Animal models currently used to study osteoarthritis can be classified based on the etiology under investigation, primary osteoarthritis, and post-traumatic osteoarthritis, to better clarify the relationship between these models and the pathogenesis of the disease. Non-invasive animal models have shown significant promise in understanding early osteoarthritic changes. Imaging modalities play a pivotal role in understanding the pathogenesis of OA and the correlation with pain. These imaging studies would also allow in vivo surveillance of the disease as a function of time in the animal model. This review summarizes the current understanding of the disease pathogenesis, invasive and non-invasive animal models, imaging modalities, and pain assessment techniques in the animals.