Gene Silencing via PDA/ERK2‐siRNA‐Mediated Electrospun Fibers for Peritendinous Antiadhesion

Abstract

Sustained delivery of small interfering RNA (siRNA) is a challenge in gene silencing for managing gene‐related disorders. Although nanoparticle‐mediated electrospun fibers enable sustainable gene silencing, low efficiency, loss of biological activity, toxicity issues, and complex electrospinning techniques are all bottlenecks of these systems. Preventing peritendinous adhesion is crucial for their successful use, which involves blocking cellular signaling via physical barriers. Here, a multifunctional, yet structurally simple, cationic 2,6‐pyridinedicarboxaldehyde‐polyethylenimine (PDA)‐mediated extracellular signal‐regulated kinase (ERK)2‐siRNA polymeric delivery system is reported, in the form of peritendinous antiadhesion electrospun poly‐l‐lactic acid/hyaluronan membranes (P/H), with the ability to perform sustained release of bioactive siRNA for long‐term prevention of adhesions and ERK2 silencing. After 4 days of culture, the cell area and proliferation rate of chicken embryonic fibroblasts on siRNA+PDA+P/H membrane are significantly less than those on P/H and siRNA+P/H membranes. The in vivo results of average optical density of collagen type III (Col III) and gene expression of ERK2 and its downstream SMAD3 in the siRNA+PDA+P/H group are less than those of P/H and siRNA+P/H groups. Consequently, siRNA+PDA+P/H electrospun membrane can protect the bioactivity of ERK2‐siRNA and release it in a sustained manner. Moreover, adhesion formation is inhibited by reducing fibroblast proliferation and Col III deposition, and downregulating ERK2 and its downstream SMAD3.

<p>Regulation of ERK1/2 and SMAD2/3 Pathways by Using Multi-Layered Electrospun PCL–Amnion Nanofibrous Membranes for the Prevention of Post-Surgical Tendon Adhesion</p>

“…The experimental results of the rabbit tendon injury model showed that the nanofibre composite membrane, which imitated the structure of natural tendon sheath, effectively isolated the exogenous adhesion tissue and achieved good tendon sliding. 41,42 PCL nanofibres completely enveloped the AM through physical action without extrusion or crosslinking and retained the biological activity of the proteins to the greatest extent. Zhou et al constructed a composite membrane containing a single layer of PCL and AM.…”

ASH2L is involved in promotion of endometrial cancer progression via upregulation of PAX2 transcription

“…Evaluation of ASH2L expression in endometrial tissue was performed using immunohistochemistry as described previously 23 . Average optical density (AOD, IOD SUM/Area SUM) of the nucleus was used to evaluate ASH2L expression 24 …”

Electrospinning for healthcare: recent advancements

“…106 The incorporation of ibuprofen or siRNA into the fibres was also found to be beneficial here. 107,108 In other work, MgO loaded ES fibres have been found to have significant promise in periodontal tissue regeneration. 109…”