Abstract
A desirable multi-functional nanofibrous membrane (NFM) for prevention of postoperative tendon adhesion should be endowed with abilities to prevent fibroblast attachment and penetration and exert anti-inflammation effects. To meet this need, hyaluronic acid (HA)/ibuprofen (IBU) (HAI) NFMs were prepared by electrospinning, followed by dual ionic crosslinking with FeCl3 (HAIF NFMs) and covalent crosslinking with 1,4-butanediol diglycidyl ether (BDDE) to produce HAIFB NFMs. It is expected that the multi-functional NFMs will act as a physical barrier to prevent fibroblast penetration, HA will reduce fibroblast attachment and impart a lubrication effect for tendon gliding, while IBU will function as an anti-inflammation drug. For this purpose, we successfully fabricated HAIFB NFMs containing 20% (HAI20FB), 30% (HAI30FB), and 40% (HAI40FB) IBU and characterized their physico-chemical properties by scanning electron microscopy, Fourier transformed infrared spectroscopy, thermal gravimetric analysis, and mechanical testing. In vitro cell culture studies revealed that all NFMs except HAI40FB possessed excellent effects in preventing fibroblast attachment and penetration while preserving high biocompatibility without influencing cell proliferation. Although showing significant improvement in mechanical properties over other NFMs, the HAI40FB NFM exhibited cytotoxicity towards fibroblasts due to the higher percentage and concentration of IBU released form the membrane. In vivo studies in a rabbit flexor tendon rupture model demonstrated the efficacy of IBU-loaded NFMs (HAI30FB) over Seprafilm® and NFMs without IBU (HAFB) in reducing local inflammation and preventing tendon adhesion based on gross observation, histological analyses, and biomechanical functional assays. We concluded that an HAI30FB NFM will act as a multi-functional barrier membrane to prevent peritendinous adhesion after tendon surgery.
Highlights
The limitation of hand function caused by postoperative tendon adhesion is mainly attributed to tendons adhering to surrounding tissues during the healing process, thereby limiting joint mobility [1]
The microporous structure and excellent mechanical properties of the nanofibrous membrane (NFM) enables proper tendon healing while providing a powerful physical barrier to prevent postoperative fibroblastic penetration, which leads to tissue adhesion
The different loading content of IBU did not change the macroporous nature of the NFMs, which contained nanofibers with similar fiber diameter and physico-chemical properties
Summary
The limitation of hand function caused by postoperative tendon adhesion is mainly attributed to tendons adhering to surrounding tissues during the healing process, thereby limiting joint mobility [1]. Seprafilm® is an anti-adhesion membrane comprising hydrophilic hyaluronic acid (HA) and carboxymethyl cellulose. SurgiWrap® is a membrane that mainly comprises polylactic acid (PLA), which does not curl over to cover the whole surgical site. SurgiWrap® is brittle due to the fact of its hydrophobic and nonporous natures, which hinders nutrient exchanges in a surgical site with limited blood supply, such as during tendon repair operation, affecting postoperative healing [4]. Considering that an ideal anti-adhesion device requires properties such as mimicking the native tendon sheath, a nanofibrous membrane (NFM) obtained through electrospinning is expected to structurally serve as a tendon sheath to effectively separate damaged tendon tissue from surrounding tissues [5]. Suitable pore size, and excellent permeability associated with an NFM, it can effectively prevent the penetration of fibroblasts without simultaneously compromising nutrient/waste exchanges [6]
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