ABSTRACT
Peripheral nerve injuries (PNI) represent a prevalent and severe category of damage resulting from traumatic incidents. Predominantly, the deficiency in nerve regeneration can be ascribed to enduring inflammatory reactions, hence imposing substantial clinical implications for patients. Fisetin, a flavonoid derived from plants, is naturally present in an array of vegetables and fruits, including strawberries, apples, onions, and cucumbers. It exhibits immunomodulatory properties through the reduction of inflammation and oxidative stress. In the present research, a nerve defect is addressed for the first time utilizing a scaffold primed for controlled fisetin release. In this regard, fisetin-loaded chitosan hydrogels are incorporated into the lumen of polycaprolactone (PCL) nerve guide conduits (NGCs). The hydrogel maintained a steady release of an appropriate fisetin dosage. The study outcomes indicated that the fisetin/chitosan/polycaprolactone (FIS/CS/PCL) NGCs amplified Schwann cell proliferation and neural expression, curtailed oxidative stress, alleviated inflammation, and improved functions, electrophysiological properties, and morphology. This pioneering scaffold has the potential to contribute significantly to the field of neuroengineering.
Subject(s)
Chitosan , Flavonols , Hydrogels , Inflammation , Nerve Regeneration , Oxidative Stress , Polyesters , Flavonols/pharmacology , Chitosan/chemistry , Chitosan/pharmacology , Hydrogels/chemistry , Hydrogels/pharmacology , Oxidative Stress/drug effects , Animals , Nerve Regeneration/drug effects , Polyesters/chemistry , Polyesters/pharmacology , Inflammation/drug therapy , Inflammation/pathology , Schwann Cells/drug effects , Schwann Cells/metabolism , Tissue Scaffolds/chemistry , Rats , Guided Tissue Regeneration/methods , Cell Proliferation/drug effects , Flavonoids/pharmacology , Flavonoids/chemistry , Peripheral Nerve Injuries/drug therapy , Peripheral Nerve Injuries/pathology , Peripheral Nerve Injuries/therapyABSTRACT
Electrical stimulation can effectively accelerate bone healing. However, the substantial size and weight of electrical stimulation devices result in reduced patient benefits and compliance. It remains a challenge to establish a flexible and lightweight implantable microelectronic stimulator for bone regeneration. Here, we use self-powered technology to develop an electric pulse stimulator without circuits and batteries, which removes the problems of weight, volume, and necessary rigid packaging. The fully implantable bone defect electrical stimulation (BD-ES) system combines a hybrid tribo/piezoelectric nanogenerator to provide biphasic electric pulses in response to rehabilitation exercise with a conductive bioactive hydrogel. BD-ES can enhance multiple osteogenesis-related biological processes, including calcium ion import and osteogenic differentiation. In a rat model of critical-sized femoral defects, the bone defect was reversed by electrical stimulation therapy with BD-ES and subsequent bone mineralization, and the femur completely healed within 6 weeks. This work is expected to advance the development of symbiotic electrical stimulation therapy devices without batteries and circuits.