Therapeutic effect of sustained release of aloe emodin via novel grafted polymer in electrospun nanofiber membranes on peritendinous adhesions

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Abstract
Introduction: Tendon injuries are prevalent musculoskeletal conditions in clinical settings, affecting various regions such as the rotator cuff tendons, forearm flexor/extensor tendons, finger flexor tendons, and Achilles tendon. While surgery is an effective treatment, it often fails to balance intrinsic and extrinsic healing processes, leading to abnormal cell activation, proliferation, and migration, resulting in collagen deposition at the injury site. This pathological fibrosis causes severe peritendinous adhesions, posing a therapeutic challenge. Traditional nonsteroidal anti-inflammatory drugs (NSAIDs) and implantable membranes have limited long-term efficacy and come with various side effects. Literature indicates that Aloe emodin(AE) can potentially inhibit multiple known pro-inflammatory pathways, including NF-κB, MAPK, p38, and ERK, directly or indirectly reducing oxidative stress. In the field of fibrosis, Aloe emodin regulates the TGFβ/Smad signaling pathway, downregulates extracellular matrix gene transcription, inhibits collagen deposition, improves cardiac function and myocardial fibrosis. Based on these findings, we hypothesize that Aloe emodin may serve as an effective therapeutic agent for improving peritendinous adhesions. Methods: This study involved grafting Aloe emodin onto polylactic acid via esterification to create a polylactic acid ‐ Aloe emodin conjugate compound. Using electrospinning technology, a novel polylactic acid-Aloe emodin conjugate electrospun nanofiber membrane (PCA) was developed and characterized, and its role in preventing peritendinous adhesions was thoroughly validated. We validated and systematically evaluated the anti-adhesive capability of the new electrospun membrane through in vitro and in vivo experiments in rats. Results: Experimental results demonstrate that the electrospun membrane of polylactic acid-Aloe emodin grafted material exhibits excellent mechanical properties and hydrophilicity, and can achieve localized targeted release of damaged tissues after treatment with lipase. Compared with polylactic acid-Aloe emodin hybrid electrospun membrane (PBA), PCA exhibits superior anti-adhesion properties and maintains longer-lasting therapeutic effects. In vitro studies showed that PCA effectively reduced fibroblast activity, inhibiting their proliferation, adhesion, and PA formation. In vivo experiments confirmed that PCA could effectively wrap around surgically treated tendons and inhibit the TGFβ1/COLIII signaling pathway, significantly reducing peritendinous adhesions in rats, offering a new approach for PA treatment. Discussion: In this study, we designed and manufactured a novel polylactic acid - Aloe emodin conjugate electrospun nanofiber membrane. We validated and systematically evaluated the anti-adhesive capability of the new electrospun membrane through in vitro and in vivo experiments in rats. In summary, our research proposed a new approach for the treatment of tendon adhesions.
Funding Information
  • National Natural Science Foundation of China (82425035)
  • National Natural Science Foundation of China (82172408)
  • National Natural Science Foundation of China (52403205)

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