3D Printing for Tissue Engineering

Abstract

Tissue engineering aims to fabricate functional tissue for applications in regenerative medicine and drug testing. More recently, 3D printing has shown great promise in tissue fabrication with a structural control from micro- to macro-scale by using a layer-by-layer approach. Whether through scaffold-based or scaffold-free approaches, the standard for 3D printed tissue engineering constructs is to provide a biomimetic structural environment that facilitates tissue formation and promotes host tissue integration (e.g., cellular infiltration, vascularization, and active remodeling). This review will cover several approaches that have advanced the field of 3D printing through novel fabrication methods of tissue engineering constructs. It will also discuss the applications of synthetic and natural materials for 3D printing facilitated tissue fabrication.

Figure 1

Schematic representation of 3D printing for tissue engineering applications, such as for cardiac tissue engineering. (A) Tissues are composed of multiple types of cells assembled into hierarchal structures. (B) 3D printing can be utilized to assemble functional tissue from cells and scaffold-forming materials.

Figure 2

Indirect printing of villi constructs provides another method of attaining high resolution based on a sacrificial mold that can be made from medical imaging. Reprinted with permission from reference [21].

Figure 3

3D-printed gelatin/alginate/fibrinogen hydrogel construct containing adipose-derived stromal cells with open channels. (A) The 3D structure cultured in a plate. (B) Immunostaining of the construct with cell structure in green and nuclei in red. Reprinted and adjusted with permission from reference [32].

Figure 4

3D printed hydroxyapatite scaffold with interconnecting channels. (A) The macro-structure contains interconnecting channels with (B) visible porous structures resulting from polymeric additives. Reprinted with permission from reference [36].

Figure 5

Scaffold-free approach to 3D printing using either spheroids or cylinder rods of cells as bioink. The structure is supported by agarose rods that are printed layer-by-layer. Reprinted and adjusted with permission from reference [74].

Figure 6

Variety of polymeric designs addressing cellular integration. (A) The 3D plotted construct of starch-ε-polycaprolactone (SPCL) and an electrospun nanofiber mesh of allowed for homogeneous distribution of cells and osteoblastic cell preferential adherence to the nanofiber mesh. (B) An osteochondral scaffold after chondrocyte seeding comprises a cartilage region made of D,L-PLGA/L-PLA (red upper section) and a bone portion of L-PLGA/TCP composite (lower white section) with a gradient of materials and porosity between both section that showed preferential attachment of chondrocytes to the cartilage portion. Height = 4mm. (C) A multilayered lattice of carbohydrate-glass material provides a micro-structured, perfusable, dissolvable scaffold for vascular engineering. Scale bar = 1mm. Reprinted and adjusted with permission from references [31, 20, 13], respectively.

Figure 7

A representation of the common solid freeform fabrication (SFF) method of layer-by-layer 3D printing. A powder reservoir supplies the desired material (e.g., polymer, ceramic) to the build box where the print head can apply the desired binder (e.g., organic solvent, UV) in a defined pattern to form a construct layer-by-layer. Reprinted with permission from reference [40].