Abstract

Articular cartilage defect is a common disorder caused by sustained mechanical stress. Owing to its nature of avascular, cartilage had less reconstruction ability so there is always a need for other repair strategies. In this study, we proposed tissue-mimetic pellets composed of chondrocytes and hyaluronic acid-graft-amphiphilic gelatin microcapsules (HA-AGMCs) to serve as biomimetic chondrocyte extracellular matrix (ECM) environments. The multifunctional HA-AGMC with specific targeting on CD44 receptors provides excellent structural stability and demonstrates high cell viability even in the center of pellets after 14 days culture. Furthermore, with superparamagnetic iron oxide nanoparticles (SPIOs) in the microcapsule shell of HA-AGMCs, it not only showed sound cell guiding ability but also induced two physical stimulations of static magnetic field(S) and magnet-derived shear stress (MF) on chondrogenic regeneration. Cartilage tissue-specific gene expressions of Col II and SOX9 were upregulated in the present of HA-AGMC in the early stage, and HA-AGMC+MF+S held the highest chondrogenic commitments throughout the study. Additionally, cartilage tissue-mimetic pellets with magnetic stimulation can stimulate chondrogenesis and sGAG synthesis.

Highlights

  • Articular cartilage disorder most commonly occurs at the conjunction between bones, and the condition is progressively worsened by constant and unavoidable mechanical degeneration

  • To measure the precise amount of hyaluronic acid (HA)-AGMCs attached on chondrocytes, we examined the element content of Fe by inductively coupled plasma mass spectrometry (ICP-MS)

  • As a widely used biopolymer, gelatin is composed of a series of amino acids, serving as hydrophilic backbone and modified by hexanoic anhydride to gain amphiphilic characteristic

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Summary

Introduction

Articular cartilage disorder most commonly occurs at the conjunction between bones, and the condition is progressively worsened by constant and unavoidable mechanical degeneration. Scaffolds which allow physical supporting often combines with primary chondrocytes therapies to overcome low cell proliferation or dedifferentiation problems. These 3D networks still struggle with several challenges such as cell viability, growth factor burst release or low oxygen content. The inner hydrophilic space of microcapsules is capable of encapsulating growth factor or biomolecules for cell proliferation or repair. Such HA-AGMC approaches can be used to provide cartilage structure stability, rule biochemical and biophysical stimulations, and thereby promote faster and more complete cartilage reconstruction.

Materialsand Methods
Synthesis of Hyaluronic
Quantification of HA Grafting Rate
Characterization of HA-AGMCs
Loading Efficiency of SPIOs
Chondrocyte Isolation and Culture
Cell cytotoxicity Test
2.11. Cell proliferation and Cell Compatibility Analysis
2.12. HA-AGMCs Cellular Attachment Efficiency
2.14. Alcian Blue Staining
Synthesis and Characterization of AG-g-HA
Characterization of HA-AGMCs and Cartilage Tissue-Mimetic Pellets
Cartilage
Synthesis of Sulfated Glycosaminoglycan under Physical Stimulations
Histological Analysis
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