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

Peritendinous adhesion formation is one of the most common and challenging complications during the healing process following tendon injuries and tendon surgeries. Until now, approximately 30%–40% of patients suffer from peritendinous adhesion to the surrounding tissues after tendon surgeries. Pathologically, the granulation tissue invades into injury site from surrounding tissues to promote tendon healing as an exogenous repair. 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. The adhesions also increase the risk of a secondary tendon rupture because of the forceful training and mobilization. Furthermore, the decreased range of motion caused by adhesions can prolong rehabilitation and necessitate reoperation, reducing patients’ quality of life and exacerbating psycho-socioeconomic problems.

Electrospun fibrous polylactic acid (PLA) membranes are a popular anti-adhesion strategy that serve as a physical barrier. However, its wide application as anti-adhesion membrane, artificial scaffold and wound dressing may lead to foreign body reaction (FBR) after PLA membrane implantation, leading to local inflammation and thus destroying its anti-adhesion effect. On the other hand, the biodegradation and release of by-products of the PLA membrane aggravate the formation of peritendinous adhesions and impair its anti-adhesion efficiency. From these two perspectives, the degradation of PLA membrane and foreign body-induced macrophage polarization greatly weaken the anti-adhesion efficacy of PLA membrane. Therefore, modification of the PLA membrane is crucial to prevent inflammation caused by foreign bodies, delay biodegradation, and enhance anti-adhesion effects.

On April 30, 2024, Yao Xiao, Tao Zaijin of Shanghai Jiao Tong University & Ju Yufeng of Shanghai Tongji Hospital and others proposed the use of diamond-like carbon deposited on polylactic acid (PLA) film in the journal Nano-Micro Letters (impact factor 26.6) (DLC) as a biophysical mechanism of anti-adhesion barrier to encapsulate ruptured tendons in rats with tendon injury. The results showed that the PLA/DLC composite membrane showed a more effective anti-adhesion effect than the PLA membrane, with the histological score decreasing from 3.12±0.27 to 2.20±0.22, and the anti-adhesion effectiveness increasing from 21.61% to 44.72%. Mechanistically, the abundant C=O bond functional groups on the surface of DLC can effectively reduce the level of reactive oxygen species; therefore, NF-κB phosphorylation and M1 polarization of macrophages are inhibited. As a result, the excessive inflammatory response enhanced by M1 macrophage-derived cytokines, including interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor α (TNF-α), is greatly reduced . For biocompatibility evaluation, the PLA/DLC membrane absorbed slowly within tissues and exhibited a long-lasting barrier effect compared with traditional PLA membranes. Further studies showed that DLC deposition can slow down the release of the degradation product lactate and induce macrophage M2 polarization by interfering with esterase and PLA ester bonds, thereby further delaying the fibrosis process. Studies have found that PLA/DLC membrane has an effective biophysical mechanism for treating peritendinous adhesions.

Highlight 1

The anti-adhesion effect of polylactic acid (PLA) membrane with diamond-like carbon (DLC) depositing is 44.72%, enhanced by 23.11% compared to PLA.

Highlight 2

DLC deposited on PLA membranes has been shown to effectively reduce the levels of reactive oxygen species, leading to a decrease in the expression of pro-inflammatory cytokines within peritendinous adhesion tissue.

Highlight 3

DLC decelerates PLA biodegradation and lactic production, which reduces the number of CD68+CD206+ macrophages within peritendinous adhesion tissue.

Conclusion：

DLC-deposited PLA membrane displayed more effective anti-adhesion capacity than the PLA membrane. DLC displayed ROS scavenging property because of the abundant C=O dangling bonds on the surface. On the one hand, DLC reduced the production of ROS and alleviated oxidative stress following tendon injury at the inflammation stage of peritendinous adhesion formation. The ROS scavenging ability of DLC also mitigated macrophage M1 polarization-mediated inflammation through reduced NF-κB phosphorylation during the peritendinous adhesion formation after tendon injury, as well as in FBR after PLA implantation. On the other hand, DLC delayed PLA biodegradation and lactic acid release to surrounding tissue, thereby inhibiting the lactic acid-induced M2 polarization of macrophages at the proliferation stage of peritendinous adhesion formation (Fig. 9), leading to prolonged separate effects and enhanced anti-adhesion potential. Thus, DLC depositing on PLA possesses an efficient biophysical mechanism for the prevention of peritendinous adhesion.

Paper link：https://link.springer.com/article/10.1007/s40820-024-01392-7#Sec19