A Controlled Release Codelivery System of MSCs Encapsulated in Dextran/Gelatin Hydrogel with TGF-β3-Loaded Nanoparticles for Nucleus Pulposus Regeneration.

Yibo Gan,Lei Luo,Xiumei Mo,Qiang Zhou,Chen Zhao,Xiangdong Luo,Liyuan Wang,Bing Tu,Sukai Li,Yuan Xu,Pei Li,Chengmin Zhang,Bin Ouyang

doi:10.1155/2016/9042019

Abstract

Mesenchymal stem cell- (MSC-) based therapy is regarded as a potential tissue engineering strategy to achieve nucleus pulposus (NP) regeneration for the treatment of intervertebral disc degeneration (IDD). However, it is still a challenge to induce MSC differentiation in NP-like cells when MSCs are implanted into the NP. The purpose of this study was to construct poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles as carriers for TGF-β3 controlled release and establish a codelivery system of a dextran/gelatin hydrogel with the nanoparticles for long-term processing of discogenesis differentiation. TGF-β3-loaded PLGA nanoparticles were prepared by the double-emulsion solvent evaporation method and seeded uniformly into the hydrogel. Morphological observations, an assessment of the release kinetics of TGF-β3, a cytotoxic assay, a cell proliferation test, a biochemical content assay, qRT-PCR, and immunohistological analyses of the codelivery system were conducted in the study. The results showed that the TGF-β3-loaded nanoparticles could release TGF-β3 gradually. The codelivery system exhibited favorable cytocompatibility, and the TGF-β3 that was released could induce MSCs to NP-like cells while promoting ECM-related biosynthesis. These results suggest this codelivery system may be employed as a promising carrier for discogenesis of MSCs in situ.

Highlights

Intervertebral disc degeneration (IDD) is a common disease that causes lower back pain, neck pain, and even disabilities [1]
The results demonstrated that PLGA nanoparticles (PLGANPs) had little cytotoxicity in the exposed concentration and good cytocompatibility when PLGANPs were loaded with the TGF-β3
The results indicate that TGF-β3-loaded PLGANPs could release active TGF-β3 in the codelivery system, and TGF-β3 could promote longterm cell metabolism

Summary

Introduction

Intervertebral disc degeneration (IDD) is a common disease that causes lower back pain, neck pain, and even disabilities [1]. The common treatments of IDD consist of bed rest, exercise, physical therapy, and surgery [2]. All of these treatments only relieve the symptoms without targeting the etiology of IDD. There is no approved therapy for IDD, and there is an urgent need for treatments that target the etiology of IDD to repair the intervertebral disc (IVD). IDD is believed to originate in NP, and improper load on IVD leads to NP dehydration and subsequently weakens IVD’s capacity to absorb compression [3].

Objectives

Methods

Discussion

Conclusion