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Ultrasonographic Imaging and Anti-inflammatory Therapy of Muscle and Tendon Injuries Using Polymer Nanoparticles.

ABSTRACT: Ultrasonography is a reliable diagnostic modality for muscle and tendon injuries, but it has been challenging to find right diagnosis of minor musculoskeletal injuries by conventional ultrasonographic imaging. A large amount of hydrogen peroxide (H₂O₂) are known to be generated during tissue damages such as mechanical injury and therefore H₂O₂ holds great potential as a diagnostic and therapeutic marker for mechanical injuries in the musculoskeletal system. We previously developed poly(vanillyl alcohol-co-oxalate) (PVAX), which rapidly scavenges H₂O₂ and exerts antioxidant and anti-inflammatory activity in H₂O₂-associated diseases. Based on the notion that PVAX nanoparticles generate CO₂ bubbles through H₂O₂-triggered hydrolysis, we postulated that PVAX nanoparticles could serve as ultrasonographic contrast agents and therapeutic agents for musculoskeletal injuries associated with overproduction of H₂O₂. In the agarose gel phantom study, PVAX nanoparticles continuously generated CO₂ bubbles to enhance ultrasonographic echogenicity significantly. Contusion injury significantly elevated the level of H₂O₂ in skeletal muscles and Achilles tendons. Upon intramuscular injection, PVAX nanoparticles significantly elevated the ultrasound contrast and suppressed inflammation and apoptosis in the contusion injury of musculoskeletal systems. We anticipate that PVAX nanoparticles hold great translational potential as theranostic agents for musculoskeletal injuries.

SUBMITTER: Kim GW

PROVIDER: S-EPMC5525750 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Ultrasonographic Imaging and Anti-inflammatory Therapy of Muscle and Tendon Injuries Using Polymer Nanoparticles.

Kim Gi-Wook GW Kang Changsun C Oh Young-Bin YB Ko Myoung-Hwan MH Seo Jeong-Hwan JH Lee Dongwon D

Theranostics 20170624 9

Ultrasonography is a reliable diagnostic modality for muscle and tendon injuries, but it has been challenging to find right diagnosis of minor musculoskeletal injuries by conventional ultrasonographic imaging. A large amount of hydrogen peroxide (H2O2) are known to be generated during tissue damages such as mechanical injury and therefore H2O2 holds great potential as a diagnostic and therapeutic marker for mechanical injuries in the musculoskeletal sy ...[more]

PMID: 28744328

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Project description:Diseases that jeopardize the musculoskeletal system and cause chronic impairment are prevalent throughout the Western world. In Germany alone, ~1.8 million patients suffer from these diseases annually, and medical expenses have been reported to reach 34.2bn Euros. Although musculoskeletal disorders are seldom fatal, they compromise quality of life and diminish functional capacity. For example, musculoskeletal disorders incur an annual loss of over 0.8 million workforce years to the German economy. Among these diseases, traumatic skeletal muscle injuries are especially problematic because they can occur owing to a variety of causes and are very challenging to treat. In contrast to chronic muscle diseases such as dystrophy, sarcopenia, or cachexia, traumatic muscle injuries inflict damage to localized muscle groups. Although minor muscle trauma heals without severe consequences, no reliable clinical strategy exists to prevent excessive fibrosis or fatty degeneration, both of which occur after severe traumatic injury and contribute to muscle degeneration and dysfunction. Of the many proposed strategies, cell-based approaches have shown the most promising results in numerous pre-clinical studies and have demonstrated success in the handful of clinical trials performed so far. A number of myogenic and non-myogenic cell types benefit muscle healing, either by directly participating in new tissue formation or by stimulating the endogenous processes of muscle repair. These cell types operate via distinct modes of action, and they demonstrate varying levels of feasibility for muscle regeneration depending, to an extent, on the muscle injury model used. While in some models the injury naturally resolves over time, other models have been developed to recapitulate the peculiarities of real-life injuries and therefore mimic the structural and functional impairment observed in humans. Existing limitations of cell therapy approaches include issues related to autologous harvesting, expansion and sorting protocols, optimal dosage, and viability after transplantation. Several clinical trials have been performed to treat skeletal muscle injuries using myogenic progenitor cells or multipotent stromal cells, with promising outcomes. Recent improvements in our understanding of cell behaviour and the mechanistic basis for their modes of action have led to a new paradigm in cell therapies where physical, chemical, and signalling cues presented through biomaterials can instruct cells and enhance their regenerative capacity. Altogether, these studies and experiences provide a positive outlook on future opportunities towards innovative cell-based solutions for treating traumatic muscle injuries-a so far unmet clinical need.

Project description:BackgroundLow-cycle fatigue damage accumulating to the point of structural failure has been recently reported at the origin of the human anterior cruciate ligament under strenuous repetitive loading. If this can occur in a ligament, low-cycle fatigue damage may also occur in the connective tissue of muscle-tendon units. To this end, we reviewed what is known about how, when, and where injuries of muscle-tendon units occur throughout the body.PurposeTo systematically review injuries in the muscle-tendon-bone complex; assess the site of injury (muscle belly, musculotendinous junction [MTJ], tendon/aponeurosis, tendon/aponeurosis-bone junction, and tendon/aponeurosis avulsion), incidence, muscles and tendons involved, mechanism of injury, and main symptoms; and consider the hypothesis that injury may often be consistent with the accumulation of multiscale material fatigue damage during repetitive submaximal loading regimens.MethodsPubMed, Web of Science, Scopus, and ProQuest were searched on July 24, 2019. Quality assessment was undertaken using ARRIVE, STROBE, and CARE (Animal Research: Reporting In Vivo Experiments, Strengthening the Reporting of Observational Studies in Epidemiology, and the Case Report Statement and Checklist, respectively).ResultsOverall, 131 studies met the inclusion criteria, including 799 specimens and 2,823 patients who sustained 3,246 injuries. Laboratory studies showed a preponderance of failures at the MTJ, a viscoelastic behavior of muscle-tendon units, and damage accumulation at the MTJ with repetitive loading. Observational studies showed that 35% of injuries occurred in the tendon midsubstance; 28%, at the MTJ; 18%, at the tendon-bone junction; 13%, within the muscle belly and that 6% were tendon avulsions including a bone fragment. The biceps femoris was the most injured muscle (25%), followed by the supraspinatus (12%) and the Achilles tendon (9%). The most common symptoms were hematoma and/or swelling, tenderness, edema and muscle/tendon retraction. The onset of injury was consistent with tissue fatigue at all injury sites except for tendon avulsions, where 63% of the injuries were caused by an evident trauma.ConclusionExcluding traumatic tendon avulsions, most injuries were consistent with the hypothesis that material fatigue damage accumulated during repetitive submaximal loading regimens. If supported by data from better imaging modalities, this has implications for improving injury detection, prevention, and training regimens.

Dataset Information

Ultrasonographic Imaging and Anti-inflammatory Therapy of Muscle and Tendon Injuries Using Polymer Nanoparticles.

Publications

Ultrasonographic Imaging and Anti-inflammatory Therapy of Muscle and Tendon Injuries Using Polymer Nanoparticles.

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