Advances in Cartilage Tissue Engineering Using Bioinks with Decellularized Cartilage and Three-Dimensional Printing

Abstract

Osteoarthritis, a chronic, debilitating, and painful disease, is one of the leading causes of disability and socioeconomic burden, with an estimated 250 million people affected worldwide. Currently, there is no cure for osteoarthritis and treatments for joint disease require improvements. To address the challenge of improving cartilage repair and regeneration, three-dimensional (3D) printing for tissue engineering purposes has been developed. In this review, emerging technologies are presented with an overview of bioprinting, cartilage structure, current treatment options, decellularization, bioinks, and recent progress in the field of decellularized extracellular matrix (dECM)-bioink composites is discussed. The optimization of tissue engineering approaches using 3D-bioprinted biological scaffolds with dECM incorporated to create novel bioinks is an innovative strategy to promote cartilage repair and regeneration. Challenges and future directions that may lead to innovative improvements to currently available treatments for cartilage regeneration are presented.

Keywords: bioinks; bioprinting; cartilage; decellularized; extracellular matrix; scaffold; tissue engineering.

Figure 1

PRISMA flow chart.

Figure 2

Articular cartilage organization. The structure of the articular cartilage is organized into three distinct zones: the superficial, middle, and the deep zones. Calcified cartilage lies between the subchondral bone and the deep zone. Created with BioRender.com.

Figure 3

Visualization of cartilage tissue by histology. (a) Nondecellularized porcine cartilage stained with H&E and (b) H&E stain on final decellularized cartilage, transverse image. (c) Hoechst stain to fluorescently visualize DNA (blue). Arrow indicates nucleus of a cell. (d) Hoechst stain shows absence of DNA after decellularization process (see absence of blue). Scale bar = 100 µm for (a,b); scale bar = 50 µm for (c,d). Adapted with permission from Ref. [49] 2021, Stone and Oxford.

Figure 4

Visualization of cartilage by scanning electron microscopy. (a) Cartilage prior to decellularization. Tissue appears visibly smooth and intact. (b) Final decellularized cartilage surface. Tissue displays increased surface area and exposed collagen network. Scale bar = 20 µm. Adapted with permission from Ref. [49] 2021, Stone and Oxford.

Figure 5

Visualization of cartilage with C28/I2 chondrocytes on decellularized scaffold by scanning electron microscopy. Cells attached to scaffold after 1 week in culture. Scale bar = 20 µm.

Figure 6

Cell viability 7 days following encapsulation in cECM-MA. Living cells are stained in green, and dead cells are stained in red (scale bars = 200 µm). Adapted under open access Creative Commons CCBY 4.0 license from Ref [56].