Abstract
The development of nerve conduits with a three-dimensional porous structure has attracted great attention as they closely mimic the major features of the natural extracellular matrix of the nerve tissue. As low levels of reactive oxygen species (ROS) function as signaling molecules to promote cell proliferation and growth, this study aimed to fabricate protoporphyrin IX (PpIX)-immobilized cellulose (CEPP) monoliths as a means to both guide and stimulate nerve regeneration. CEPP monoliths can be fabricated via a simple thermally induced phase separation method and surface modification. The improved nerve tissue regeneration of CEPP monoliths was achieved by the activation of mitogen-activated protein kinases, such as extracellular signal-regulated kinases (ERKs). The resulting CEPP monoliths exhibited interconnected microporous structures and uniform morphology. The results of in vitro bioactivity assays demonstrated that the CEPP monoliths with under 0.54 ± 0.07 μmol/g PpIX exhibited enhanced photodynamic activity on Schwann cells via the generation of low levels of ROS. This photodynamic activation of the CEPP monoliths is a cell-safe process to stimulate cell proliferation without cytotoxic side effects. In addition, the protein expression of phospho-ERK increased considerably after the laser irradiation on the CEPP monoliths with low content of PpIX. Therefore, the CEPP monoliths have a potential application in nerve tissue regeneration as new nerve conduits.
Highlights
Peripheral nerve injuries, usually caused by traumatic lesions or tumor expiration, are always accompanied by dysfunction, movement and sensory disorders, and neuropathic pains, which seriously influence the patient’s quality of life [1,2]
The development of porous nerve conduits is an essential feature for the regeneration of nerve tissue as the pore structure prevents the infiltration of scar tissue while providing nutrients
Simple TIPS and surface modification were employed to produce the CEPP monoliths for promoting nerve tissue regeneration through the activation of MAPKs involved in cell survival and proliferation
Summary
Peripheral nerve injuries, usually caused by traumatic lesions or tumor expiration, are always accompanied by dysfunction, movement and sensory disorders, and neuropathic pains, which seriously influence the patient’s quality of life [1,2]. Peripheral nerves have an intrinsic potential to regenerate after lesions, damage involving extensive nerve tissue loss precludes the reconnection between proximal and distal nerve stumps [3]. Nerve guidance conduits are considered a substitute for autografts [2]. These conduits should provide a favorable microenvironment for nerve regeneration while guiding axonal sprouting from the proximal to the distal stump. Most of the commercially available tubular conduits provide an insufficient surface area to support the large number of cells needed to complete the functional regeneration of nerve tissue [5]. As one of the basic elements for nerve regeneration, the conduits play an important role in regulating cell growth and accelerating the formation of newborn nerve tissue through their three-dimensional porous structure [6]. An ideal conduit for peripheral nerve regeneration should closely mimic the natural microenvironment of the peripheral nerve matrix
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