Review on Additives in Hydrogels for 3D Bioprinting of Regenerative Medicine: From Mechanism to Methodology

Abstract

The regeneration of biological tissues in medicine is challenging, and 3D bioprinting offers an innovative way to create functional multicellular tissues. One common way in bioprinting is bioink, which is one type of the cell-loaded hydrogel. For clinical application, however, the bioprinting still suffers from satisfactory performance, e.g., in vascularization, effective antibacterial, immunomodulation, and regulation of collagen deposition. Many studies incorporated different bioactive materials into the 3D-printed scaffolds to optimize the bioprinting. Here, we reviewed a variety of additives added to the 3D bioprinting hydrogel. The underlying mechanisms and methodology for biological regeneration are important and will provide a useful basis for future research.

Keywords: 3D bioprinting; bioink; bionic scaffold; hydrogel; tissue engineering.

Figure 1

Schematic of the preparation of the B + V scaffold [16].

Figure 2

(A–C): Digital camera photographs of PMMA-embedded blocks from longitudinal sections and 3D reconstructed μCT images of blood vessels from (D–F) side view and (G–I) top view of CPC, MS/CPC, and MS/CPC/rhBMP-2 scaffolds after 4 weeks of implantation. White arrow: newly formed blood vessels [77].

Figure 3

Schematic elucidation of the fabrication of functional 3D scaffold and 3D culture for in vitro and in vivo analysis [22].

Figure 4

Different additives incorporated in the hydrogel according to the different antimicrobial mechanisms.

Figure 5

Preparation of the AgNP-Cross-Linked Superporous Hydrogel Dressing [85].

Figure 6

Schematic of 3D printer, fabrication of 3D-printed scaffold, and application to wound dressing [30].

Figure 7

(A) Typical morphology of gram-negative E. coli captures of the tested samples for E. coli in the petri dishes after 24 h cultivation. (B) PA12/Cu₂O 0.5 wt.%, (C) PA12/Cu₂O 1.0 wt.%, (D) PA12/Cu₂O 2.0 wt.%, (E) PA12/Cu₂O 4.0 wt.%, (F) PA12/Cu₂O 6.0 wt.% [83].

Figure 8

(A) Typical morphology of Gram-positive S. aureus captures of tested samples for Gram-positive S. aureus in Petri dishes after 24 h cultivation. (B) PA12/Cu₂O 0.5 wt.%, (C) PA12/Cu₂O 1.0 wt.%, (D) PA12/Cu₂O 2.0 wt.%, (E) PA12/Cu₂O 4.0 wt.%, and (F) PA12/Cu₂O 6.0 wt.% [83].

Figure 9

Anti-inflammatory response of various surface-modified membranes based on PCL fibrous membrane. The concentration of TNF-α (a) and IL-6 (b), secreted from the RAW 264.7 cells with and without LPS treatment for 24 h, was quantified by ELISA (** p < 0.01 and *** p < 0.001) [33].

Figure 10

(a) Immunofluorescent staining of Raw264.7 cells after cultured for 4 days. (b,c) Quantitative analysis of iNOS and Arg-1. (d) The expression of Notch1 was detected by Western blotting. (e) Immunofluorescent staining of Notch1. (n = 3; # represent p < 0.05 when compared with Ti/SF, Ti/SF/MOF and Ti/SF/I, respectively; **, ## and ++ represent p < 0.01) [80].

Figure 11

In vivo collagen deposition within the mesh after 1 week. Collagen deposition (black arrow) viewed by Picro Sirius red staining within mesh area in (A) MES, (B) MES-Hydrogel and (C) MES-Hy-eMSCs and (D–F) corresponding magnified view in dashed area [122].

Figure 12

Fate of meshes after 1 week of in vivo implantation. SEM images show cross-sections of (A–C) MES (D–F) MES_Hydrogel and (G–I) MES_Hydrogel_eMSC constructs (within the red dashed area) 1 week after implantation in NSG mice; lower panels (C,F,I) show the morphology of reticular fibers (m), their interaction with the host tissue integration (white*) and the formation of new ECM [122].