An Overview of Extracellular Matrix-Based Bioinks for 3D Bioprinting

Abstract

As a microenvironment where cells reside, the extracellular matrix (ECM) has a complex network structure and appropriate mechanical properties to provide structural and biochemical support for the surrounding cells. In tissue engineering, the ECM and its derivatives can mitigate foreign body responses by presenting ECM molecules at the interface between materials and tissues. With the widespread application of three-dimensional (3D) bioprinting, the use of the ECM and its derivative bioinks for 3D bioprinting to replicate biomimetic and complex tissue structures has become an innovative and successful strategy in medical fields. In this review, we summarize the significance and recent progress of ECM-based biomaterials in 3D bioprinting. Then, we discuss the most relevant applications of ECM-based biomaterials in 3D bioprinting, such as tissue regeneration and cancer research. Furthermore, we present the status of ECM-based biomaterials in current research and discuss future development prospects.

Keywords: 3D bioprinting; bioink; biomaterial; extracellular matrix; tissue engineering; tissue regeneration.

FIGURE 1

Illustrations of the seven types of 3D printing technologies. Adapted with permission from (Carew and Errickson, 2020).

FIGURE 2

The schematic of 3D bioprinting.

FIGURE 3

The 3D structure model of the natural ECM. Reprinted with permission from (Aghmiuni and Khiavi, 2017).

FIGURE 4

Different ECM-based biomaterial types and resulted constructs. (A) Tube construct printed with collagen. Adapted with permission from (Lee et al., 2019). (B) Scaffold printed with collagen/heparin sulfate. Adapted with permission from (Jiang et al., 2020). (C) The non-porous human L3 vertebrae printed with MeHA. Adapted with permission from (Poldervaart et al., 2017). (D) The scaffolds printed with gelatin-alginate-hyaluronic acid. Adapted with permission from (Bertuola et al., 2021). (E) The nerve guidance conduits printed with GelMA. Adapted with permission from (Ye et al., 2020). (F) The scaffold printed with gelMA and hydroxyapatite (Das and Basu, 2022). (G) The scaffold printed with skin-derived dECM bioink. Adapted with permission from (Kim et al., 2018). (H) The scaffold printed with liver-derived dECM/PCL bioink. Adapted with permission from (Elomaa et al., 2020). (I) The dual cross-linked constructs printed with oxidized hyaluronate (OHA)/glycol chitosan (GC)/adipic acid dihydrazide (ADH)/hyaluronate-alginate hybrid (HAH). The gel constructs maintained their original dimension after 3 weeks at 37°. Adapted with permission from (Kim et al., 2022). (J) Nose-shaped construct printed with PU-gelatin. Adapted with permission from (Hsieh and Hsu, 2019). Copyright (2019) American Chemical Society. (K) The scaffold printed with tetrameric peptides as bioinks. Adapted with permission from (Rauf et al., 2021).

FIGURE 5

The applications of ECM-based bioinks. (A) (I) A clavicle bone scaffold bioprinted with BPs GelMA-based bioink. (II) The scaffold stained for H&Eafter 28 days, the number of cells increased. Adapted with permission from (Ratheesh et al., 2020). (B) The aortic valve conduit bioprinted with bioink containing alginate/gelatin hydrogel and aortic root sinus smooth muscle cells and aortic valve leaflet interstitial cells. Adapted with permission from (Duan et al., 2013). (C) Adult size ears (8 cm) printed with bioink containing bovine gelatin/alginate/fibrinogen and human fibroblasts. Adapted with permission from (Pourchet et al., 2017). (D) A heart printed with bioink containing dECM and iPSCs-derived cardoimyocytes and ECs. Adapted with permission from (Noor et al., 2019). (E) The curved cornea based on the eyeball printed with dECM-based bioink. Adapted with permission from (Kim H. et al., 2021). (F) The multilevel vascular structures, and (G) multibranch vascular channels printed with bioink containing dECM/Pluronic F127 and endothelial cells. Adapted with permission from © 2018 by the (Xu et al., 2018). Licensee MDPI, Basel, Switzerland.