Cartilage Tissue Engineering Approaches Need to Assess Fibrocartilage When Hydrogel Constructs Are Mechanically Loaded.

Xiongbiao Chen,B Frank Eames,Hamed Alizadeh Sardroud,Tasker Wanlin

doi:10.3389/fbioe.2021.787538

Abstract

Chondrocytes that are impregnated within hydrogel constructs sense applied mechanical force and can respond by expressing collagens, which are deposited into the extracellular matrix (ECM). The intention of most cartilage tissue engineering is to form hyaline cartilage, but if mechanical stimulation pushes the ratio of collagen type I (Col1) to collagen type II (Col2) in the ECM too high, then fibrocartilage can form instead. With a focus on Col1 and Col2 expression, the first part of this article reviews the latest studies on hyaline cartilage regeneration within hydrogel constructs that are subjected to compression forces (one of the major types of the forces within joints) in vitro. Since the mechanical loading conditions involving compression and other forces in joints are difficult to reproduce in vitro, implantation of hydrogel constructs in vivo is also reviewed, again with a focus on Col1 and Col2 production within the newly formed cartilage. Furthermore, mechanotransduction pathways that may be related to the expression of Col1 and Col2 within chondrocytes are reviewed and examined. Also, two recently-emerged, novel approaches of load-shielding and synchrotron radiation (SR)–based imaging techniques are discussed and highlighted for future applications to the regeneration of hyaline cartilage. Going forward, all cartilage tissue engineering experiments should assess thoroughly whether fibrocartilage or hyaline cartilage is formed.

Highlights

In osteoarthritis (OA), articular cartilage at the end of bones, such as in the knee or elbow joint, degrades by various injuries or normal wear and tear caused by aging
A major problem in current studies of chondrocyte-impregnated hydrogel constructs that were subjected to compressive force is that the formation of fibrocartilage was not analyzed, but Col1 expression and fibrocartilage-like tissue often can result from such mechanical loading
Studies employing bioreactors to simulate compression forces in joints illustrated that static compression had limited effects on cartilage regeneration, which has urged researchers to switch to dynamic compression studies

Summary

Introduction

In osteoarthritis (OA), articular cartilage at the end of bones, such as in the knee or elbow joint, degrades by various injuries or normal wear and tear caused by aging. The implantation of hydrogel constructs within the joints of various animal models needs to be investigated to see whether the resulting tissue formed is the desired hyaline cartilage or fibrocartilage. The ratio of Col1:Col2 produced in these experiments is critical, so we begin by reviewing how current in vitro and in vivo studies have analyzed specific collagen expression in determining whether hydrogel-loaded constructs produce hyaline cartilage or fibrocartilage.

Results

Conclusion