Differential effects of rat ADSCs encapsulation in fibrin matrix and combination delivery of BDNF and Gold nanoparticles on peripheral nerve regeneration

Shahnaz Razavi,Elham Vatankhah,Reihaneh Seyedebrahimi,Maliheh Jahromi

doi:10.1186/s12868-021-00655-y

Shahnaz Razavi, Elham Vatankhah + Show 2 more

Open Access

https://doi.org/10.1186/s12868-021-00655-y

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Abstract

BackgroundFibrin as an extracellular matrix feature like biocompatibility, creates a favorable environment for proliferation and migration of cells and it can act as a reservoir for storage and release of growth factors in tissue engineering.MethodsIn this study, the inner surface of electrospun poly (lactic-co-glycolic acid) (PLGA) nanofibrous conduit was biofunctionalized with laminin containing brain derived neurotrophic factor (BDNF) and gold nanoparticles in chitosan nanoparticle. The rats were randomly divided into five groups, including autograft group as the positive control, PLGA conduit coated by laminin and filled with DMEM/F12, PLGA conduit coated by laminin and filled with rat-adipose derived stem cells (r-ADSCs), PLGA conduit coated by laminin containing gold-chitosan nanoparticles (AuNPs-CNPs), BDNF-chitosan nanoparticles (BDNF-CNPs) and filled with r-ADSCs or filled with r-ADSCs suspended in fibrin matrix, and they were implanted into a 10 mm rat sciatic nerve gap. Eventually, axonal regeneration and functional recovery were assessed after 12 weeks.ResultsAfter 3 months post-surgery period, the results showed that in the PLGA conduit filled with r-ADSCs without fibrin matrix group, positive effects were obtained as compared to other implanted groups by increasing the sciatic functional index significantly (p < 0.05). In addition, the diameter nerve fibers had a significant difference mean in the PLGA conduit coated by laminin and conduit filled with r-ADSCs in fibrin matrix groups relative to the autograft group (p < 0.001). However, G-ratio and amplitude (AMP) results showed that fibrin matrix might have beneficial effects on nerve regeneration but, immunohistochemistry and real-time RT-PCR outcomes indicated that the implanted conduit which filled with r-ADSCs, with or without BDNF-CNPs and AuNPs-CNPs had significantly higher expression of S100 and MBP markers than other conduit implanted groups (p < 0.05).ConclusionsIt seems, in this study differential effects of fibrin matrix, could be interfered it with other factors thereby and further studies are required to determine the distinctive effects of fibrin matrix combination with other exogenous factors in peripheral nerve regeneration.

Highlights

Fibrin as an extracellular matrix feature like biocompatibility, creates a favorable environment for proliferation and migration of cells and it can act as a reservoir for storage and release of growth factors in tissue engineering
Characterization of poly (lactic-co-glycolic) acid (PLGA) nerve conduit and injected r‐Adipose-derived stem cells (ADSCs) The schematic of fabrication of nerve conduit was illustrated in Fig. 1, the inner surfaces of PLGA nerve conduit coated with laminin containing brain derived neurotrophic factor (BDNF) and AuNPs encapsulated in chitosan nanoparticles were rolled up to form a tubular nerve conduit
Fibrin gel was loaded with isolated rat-adipose derived stem cells (r-ADSCs) and injected into the lumen of the PLGA conduit implanted into the 10 mm transected sciatic nerve rat model

Summary

Introduction

Fibrin as an extracellular matrix feature like biocompatibility, creates a favorable environment for proliferation and migration of cells and it can act as a reservoir for storage and release of growth factors in tissue engineering. It is important to improve the hydrophilic property of PLGA scaffold surfaces and modify them with an extracellular matrix like laminin [4, 5]. Laminin can be used as a natural material in the inner surface of PLGA nerve conduit to stimulate neurite outgrowth [6], it can promote cell adhesion and proliferation rate on the PLGA sheet [7]. Fibrin matrix has been used as a filler within the lumen of conduits with biodegradability, biocompatibility, nonreactiveness, lower toxicity and stability properties which may impact the tissue repair in a positive pathway [8]. Fibrin matrix as a natural polymer may be appropriate for this purpose via retaining the cells in the damage zone, providing interaction of cells with extracellular matrix and physical connection to the nerve end [12]

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