Dual Network Hydrogels Incorporated with Bone Morphogenic Protein-7-Loaded Hyaluronic Acid Complex Nanoparticles for Inducing Chondrogenic Differentiation of Synovium-Derived Mesenchymal Stem Cells.

Jiliang Wu,Ying Wan,Qing Min,Jiaoyan Liu,Bin Yang,Yuchen Zhang

doi:10.3390/pharmaceutics12070613

Abstract

Alginate-poloxamer (ALG-POL) copolymer with optimal POL content was synthesized, and it was combined with silk fibroin (SF) for building ALG-POL/SF dual network hydrogels. Hyaluronic acid(HA)/chitosan-poly(dioxanone)(CH-PDO) complex nanoparticles (NPs) with optimized composition and high encapsulation efficiency were employed as a vehicle for loading bone morphogenic protein-7 (BMP-7). BMP-7-loaded HA/CH-PDO NPs were incorporated into ALG-POL/SF hydrogel for constructing composite gels to achieve controlled release of BMP-7. These gels showed thermosensitive sol-gel transitions near physiological temperature and pH; and they were tested to be elastic, tough and strong. Some gels exhibited abilities to administer the BMP-7 release in nearly linear manners for a few weeks. Synovium-derived mesenchymal stem cells (SMSCs) were seeded into optimally fabricated gels for assessing their chondrogenic differentiation potency. Real-time PCR analyses showed that the blank ALG-POL/SF gels were not able to induce the chondrogenic differentiation of SMSCs, whereas SMSCs were detected to significantly express cartilage-related genes once they were seeded in the BMP-7-loaded ALG-POL/SF gel for two weeks. The synthesis of cartilaginous matrix components further confirmed that SMSCs seeded in the BMP-7-loaded ALG-POL/SF gel differentiated toward chondrogenesis. Results suggest that BMP-7-loaded ALG-POL/SF composite gels can function as a promising biomaterial for cartilage tissue engineering applications.

Highlights

Autologous chondrocyte implantation is one of clinically usable techniques for treating articular cartilage injuries, which is usually implemented by filling cartilage defect site with high numbers of autologous chondrocytes by the aid of certain supporting materials [1,2]
Some evidence supports that synovium-derived mesenchymal stem cells (SMSCs) can retain high transplant survival rates and undergo rapid proliferation and chondrogenic differentiation when compared to bone marrow-derived mesenchymal stem cells (BMSCs) and adipose-derived stem cells (ASCs) [7,8,9,10]
It is worth pointing out that the composition for bone morphogenic protein-7 (BMP-7)-loaded HA/CH-PDO NPs was formulated as a HA/CH-PDO ratio of 4:3 in this study in order to achieve high EE while enabling the surface charge of the resulting NPs to be nearly neutral (Figure 1D)

Summary

Introduction

Autologous chondrocyte implantation is one of clinically usable techniques for treating articular cartilage injuries, which is usually implemented by filling cartilage defect site with high numbers of autologous chondrocytes by the aid of certain supporting materials [1,2]. Two-dimensional culture-expansion of chondrocytes could cause their dedifferentiation to some degree, depending on the passage of cells, and in turn, result in a loss of capacity to form stable hyaline cartilage in vivo [3,4,5]. Several types of stem cells, including bone marrow-derived mesenchymal stem cells (BMSCs), adipose-derived stem cells (ASCs) and synovium-derived mesenchymal stem cells (SMSCs), have been investigated for the usage in cartilage repair [6] Despite their applicability, some evidence supports that SMSCs can retain high transplant survival rates and undergo rapid proliferation and chondrogenic differentiation when compared to BMSCs and ASCs [7,8,9,10]

Methods

Results

Conclusion