<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>

Abstract

Background: Adhesion after tendon injury is a common complication in clinical practice. The lack of effective prevention mechanisms seriously affects the functional rehabilitation of patients. This research aimed to optimise the amniotic membrane and explain the mechanism of tendon-amniotic membrane by imitating the tendon sheath to construct a multilayer electrospun polycaprolactone (PCL) nanofibre membrane. Materials and Methods: Fresh amnions were subjected to freezing and vacuum drying. The two surfaces of freeze-dried amnions were coated with PCL nanofibres by electrospinning, thereby forming a multilayer composite membrane and constructing a growth factor-sustained release system conforming to the tendon-healing cycle. The new materials were characterised, and the biological effects on tenocytes and fibroblasts were evaluated. The tendon injury model of New Zealand rabbits was constructed to observe the effects on tendon adhesion and healing. Results: After freezing and vacuum drying, fresh amnions were found to effectively remove most of the cell components but retained the active components TGF-β1, bFGF, VEGF, and PDGF, as well as the fibrous reticular structure of the basement membrane. After coating with PCL nanofibres, a composite membrane mimicking the structure of the tendon sheath was constructed, thereby strengthening the tensile strength of the amnion. By up-regulating the phosphorylation of ERK1/2 and SMAD2/3, the adhesion and proliferation of tenocytes and fibroblasts were promoted, and collagen synthesis was enhanced. In the rabbit tendon repair model, the composite membrane effectively isolated the exogenous adhesion tissue and promoted endogenous tendon healing. Conclusion: The composite membrane mimicking the structure of tendon sheath effectively isolated the exogenous adhesion tissue and achieved good tendon slip. By slowly releasing the growth factors TGF-β1, bFGF, VEGF and PDGF, the ERK1/2 and SMAD2/3 pathways were regulated. Consequently, endogenous tendon healing was promoted. This strategy can alternatively address the clinical problem of tendon adhesion.

An Integrative Dual-Layer Poly-L-Lactic Acid Fibrous Membrane Prevents Peritendinous Adhesions

“…TGF-β is one of the most important cytokines involved in tendon regeneration and tissue adhesion (Liu et al, 2019). Moreover, TGF-β enhances collagen synthesis and fibroblast proliferation via the extracellular signal-regulated kinase 2/SMAD pathway (Liu C. et al, 2020), and increased collagen levels in turn stimulate tendon regeneration. Importantly, TGF-β can localize to repaired tendon sites, resulting in increased collagen synthesis and tendon healing.…”

Electrospun polycaprolactone (PCL)-amnion nanofibrous membrane prevents adhesions and promotes nerve repair in a rat model of sciatic nerve compression

“…The hydrophilic angles of freeze-dried amnion and nanofiber membrane were 51.18° ± 2.72° and 59.44° ± 4.15°, respectively. The maximum modulus of elasticity of the nanofiber membrane was higher than that of the freeze-dried amnion, and the tensile strength and toughness of the nanofiber membrane were higher than those of the freeze-dried amnion [ 25 ]. The nanofibrous membranes were sterilized with UV radiation before use [ 26 ].…”

“…The PCL-amnion nanofibrous membrane had better mechanical strength and biocompatibility. In a previous study, we found that an electrospun PCL-amnion nanofibrous membrane effectively prevented post-surgical tendon adhesion and promoted tendon healing [25]. Although there is a number of studies that report on the application of amniotic membranes in nerve repair, they are not yet widely used in the clinic [24,35].…”

Fibrous Systems as Potential Solutions for Tendon and Ligament Repair, Healing, and Regeneration

“…Lately, multilayered approaches have gained attention as novel methods for scaffold design. [ 191,192 ] Different layer‐by‐layer techniques such as simultaneous wet electrospinning and cell‐seeding, alternating layers of nanofibers and microfibers, varying polymers, or arranging electrospun layers coated with hydrogels have been developed. [ 193–195 ] Systems combining electrospun fibrous mats with woven/knitted constructs in multilayered scaffolds have been recently explored for tendon and ligament engineering.…”