Progress of Microfluidic Hydrogel‐Based Scaffolds and Organ‐on‐Chips for the Cartilage Tissue Engineering

Abstract

Cartilage degeneration is among the fundamental reasons behind disability and pain across the globe. Numerous approaches have been employed to treat cartilage diseases. Nevertheless, none have shown acceptable outcomes in the long run. In this regard, the convergence of tissue engineering and microfabrication principles can allow developing more advanced microfluidic technologies, thus offering attractive alternatives to current treatments and traditional constructs used in tissue engineering applications. Herein, the current developments involving microfluidic hydrogel‐based scaffolds, promising structures for cartilage regeneration, ranging from hydrogels with microfluidic channels to hydrogels prepared by the microfluidic devices, that enable therapeutic delivery of cells, drugs, and growth factors, as well as cartilage‐related organ‐on‐chips are reviewed. Thereafter, cartilage anatomy and types of damages, and present treatment options are briefly overviewed. Various hydrogels are introduced, and the advantages of microfluidic hydrogel‐based scaffolds over traditional hydrogels are thoroughly discussed. Furthermore, available technologies for fabricating microfluidic hydrogel‐based scaffolds and microfluidic chips are presented. The preclinical and clinical applications of microfluidic hydrogel‐based scaffolds in cartilage regeneration and the development of cartilage‐related microfluidic chips over time are further explained. The current developments, recent key challenges, and attractive prospects that should be considered so as to develop microfluidic systems in cartilage repair are highlighted.

Hydrogel Scaffolds with Controlled Postgelation Modulation of Structures for 3D Cell Culture and Tissue Engineering

“…In the other case, hydrophilic degradable hydrogels are employed as sacrificial components, and this method is often combined with 3D printing techniques that can prefabricate the microstructures of scaffolds. [52] Aydin et al prepared a bio-ink based on natural materials by mixing alginate and agarose to obtain a sacrificial material component, and mixing gelatin methacryloyl (GelMA), a photoinitiator (VA086), alginate, and agarose to obtain a nonsacrificial material component loaded with cells. [53] This design enables the absorbable material to build a structure suitable for cell growth within the 3D printed hydrogel, and the sacrificial bio-ink undergoes self-etching over time in the cell culture medium at 37 °C, while preserving the target shape of the bio-print.…”

Layer‐by‐layer adhesion of hydrogels for constructing heterogeneous microfluidic chips

“…To address these limitations, hydrogels have emerged as the backbone of microfluidics, offering numerous advantages over materials such as PDMS or glass. Their biocompatibility, physical stiffness, degradation, and mass transport properties make hydrogels biologically relevant 6,7 and highly promising for applications in tissue engineering, 8 biomedical research, 9 and food industry 10,11 …”

“…16,17 Recently, 3D printing has been extensively explored for complex hydrogel fabrication, including inkjet-based printing, extrusion-based printing, stereolithography printing and laser-assisted printing. 8 But these methods require specific equipment and may not be suitable for handling viscous materials, often leading to cell damage. 8 Similarly, other hydrogel-based microfluidic preparation techniques, such as hydrogel-PDMS hybrid fabrication, [18][19][20] lightcontrolled degradation, 21 and direct writing, 22 also face challenges in constructing heterogeneous and accurate structures within hydrogels due to complications in handling, low resolution, or restriction to specific materials.…”

Integrated Microwell Array-Based Microfluidic Chip with a Hand-Held Smartphone-Controlled Device for Nucleic Acid Detection

“…In the past 30 years, microfluidic chips have led to significant advances in chemistry, biology, and medicine. − As many structures and functions can be integrated into miniaturized devices, microfluidic chips have been developed as important platforms for biochemical reactions, − especially in the point-of-care testing (POCT) applications. − …”