Regeneration of Rat Sciatic Nerve Using PLGA Conduit Containing Rat ADSCs with Controlled Release of BDNF and Gold Nanop

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Regeneration of Rat Sciatic Nerve Using PLGA Conduit Containing Rat ADSCs with Controlled Release of BDNF and Gold Nanoparticles Maliheh Jahromi 1 & Shahnaz Razavi 1

&

Reihaneh Seyedebrahimi 1 & Parham Reisi 2 & Mohammad Kazemi 3

Received: 4 July 2020 / Accepted: 28 August 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract Implantation of a nerve guidance conduit (NGC) carrying neuroprotective factors is promising for repairing peripheral nerve injury. Here, we developed a novel strategy for repairing peripheral nerve injury by gold nanoparticles (AuNPs) and brainderived neurotrophic factor (BDNF)–encapsulated chitosan in laminin-coated nanofiber of Poly(l-lactide-co-glycolide) (PLGA) conduit and transplantation of rat adipose–derived stem cells (r-ADSCs) suspended in alginate. Then, the beneficial effect of AuNPs, BDNF, and r-ADSCs on nerve regeneration was evaluated in rat sciatic nerve transection model. In vivo experiments showed that the combination of AuNPs- and BDNF-encapsulated chitosan nanoparticles in laminin-coated nanofiber of PLGA conduit with r-ADSCs could synergistically facilitate nerve regeneration. Furthermore, the in vivo histology, immunohistochemistry, and behavioral results demonstrated that the AuNPs- and BDNF-encapsulated chitosan nanoparticles in NGC could significantly reinforce the repair performance of r-ADSCs, which may also contribute to the therapeutic outcome of the AuNPs, BDNF, and r-ADSCs strategies. In this study, we found that the combination of AuNPs and BDNF releases in NGC with r-ADSCs may represent a new potential strategy for peripheral nerve regeneration. Keywords Adipose-derived stem cells . Brain-derived neurotrophic factor . Controlled release . Gold nanoparticle . Poly(L-lactide-co-glycolide) . Nerve conduit

Introduction Peripheral nerve injuries can be caused by accidental lacerations, congenital defects, surgical intervention, and neuropathies such as infections, inherited problems, metabolic causes, and exposure to toxins. In addition, nerve damages can lead to symptoms of neuropathic pain, atrophy of the target skeletal muscles, and partial or even complete loss of motor and sensory functions (Baltzis et al. 2018; Faroni et al. 2015). In the most severe form of injury is a full transection of the axons and myelin sheaths wherein complete discontinuity or gap of the nerve is observed (Campbell 2008). These types of injuries

* Shahnaz Razavi [email protected] 1

Department of Anatomical Sciences, School of Medicine, Isfahan University of Medical Sciences, Isfahan 81744176, Iran

2

Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

3

Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

are very hard to treat and are still a challenging clinical problem. Autologous nerve graft represents the clinical gold standard to fill the large nerve gaps and make the junction between the distal and proximal stumps of the in