Sustained Release of Dicumarol via Novel Grafted Polymer in Electrospun Nanofiber Membrane for Treatment of Peritendinous Adhesion

Abstract

The prevention and treatment of post-traumatic peritendinous adhesion (PA) have always been a great difficulty for orthopedic surgeons. Current treatments include resecting surgery, non-steroidal anti-inflammatory drugs (NSAIDs) usage and implantable membranes, often target single disease pathogenic processes, resulting in unfavorable therapeutic outcomes. Here a polylactic acid (PLA)-dicumarol conjugates-electrospun nanofiber membrane (ENM) (PCD) is generated, which can achieve spatial accuracy and temporal sustainability in drug release. It is further demonstrated that PCD possesses a significantly higher and more sustainable drug release profile than traditional drug-loading ENM. By providing a physical barrier and continuous releasing of dicumarol, PCD implantation significantly reduces tissue adhesion by 25%, decreases fibroblasts activity and inhibits key fibrogenic cytokine transforming growth factor beta (TGF𝜷) production by 30%, and improves the biomechanical tendon property by 14.69%. Mechanistically, PCD potently inhibits the connexin43 (Cx43) and thereby tunes down the fibroblastic TGF𝜷/Smad3 signaling pathway. Thus, this approach leverages the anti-adhesion effect of dicumarol and drug release properties of grafted copolymer ENM by esters to provide a promising therapeutic strategy for patients who suffer from PA.

Diamond-Like Carbon Depositing on the Surface of Polylactide Membrane for Prevention of Adhesion Formation During Tendon Repair

“…The inflammatory and infective ulcers of the tendon were observed, and images were captured. The degree of peritendinous adhesion was evaluated using an adhesion scoring system described in our previous study [ 4 , 11 ]. The adhesion scoring was classified into 5 grades: 1, no obvious adhesion at the surgical site; 2, limited adhesion tissue but can be bluntly separated; 3, less than 50% of the adhesion tissue that needed sharp separation; 4, nearly 51%–97.5% of the adhesion tissue which needed sharp separation; 5, more than 97.5% severe adhesion tissue that required sharp separation.…”

“…The sections were subjected to hematoxylin & eosin (H&E) staining, Masson’s staining, and immunohistochemical staining of Collagen III (1:300 dilution, sc-271249, Santa Cruz, USA) and IL-1 β (1:400 dilution, ab283818, Abcam, UK). The degree of adhesion of the injured tendon was assessed using a 1–5 grade histological scoring system [ 4 ]. The sections were also subjected to immunofluorescence assay with rat anti-CD68 antibody (1:200 dilution, ab283654, Abcam, UK), anti-iNOS (1:200 dilution, ab178945, Abcam, UK), and anti-CD206 (1:200 dilution, ab64693, Abcam, UK).…”

“…Until now, approximately 30%–40% of patients suffer from peritendinous adhesion to the surrounding tissues after tendon surgeries [ 3 ]. Pathologically, the granulation tissue invades into injury site from surrounding tissues to promote tendon healing as an exogenous repair [ 4 ]. However, the excessive exogenous repair leads to abnormal adhesions to the surrounding tissue that limits tendon sliding, excursion, and range of motion, eventually restricting joint motion [ 5 ].…”

Nanofiber Hydrogel Drug Delivery System for Prevention of Postsurgical Intestinal Adhesion

“…Consequently, a significant amount of money has been spent on repetitive surgical treatments, such as adhesiolysis, to overcome PIA with limited success. The recurrence rate during a 41 month period following surgery is 12%, and the risk of recurrence remains significant even after 20 years of surgery. − In addition, further damage to the neighboring intestines or other organs can occur, causing intestinal perforation and septicemia. − Currently, various antiadhesion biomaterials (such as nanofibers, hydrogels, and so on) were used to prevent formation of PIA. , However, the efficacy of treatments for the prevention of PIA is inconsistent.…”