4D Printing Shape-Morphing Hybrid Biomaterials for Advanced Bioengineering Applications

Abstract

Four-dimensional (4D) printing is an innovative additive manufacturing technology used to fabricate structures that can evolve over time when exposed to a predefined environmental stimulus. 4D printed objects are no longer static objects but programmable active structures that accomplish their functions thanks to a change over time in their physical/chemical properties that usually displays macroscopically as a shapeshifting in response to an external stimulus. 4D printing is characterized by several entangled features (e.g., involved material(s), structure geometry, and applied stimulus entities) that need to be carefully coupled to obtain a favorable fabrication and a functioning structure. Overall, the integration of micro-/nanofabrication methods of biomaterials with nanomaterials represents a promising approach for the development of advanced materials. The ability to construct complex and multifunctional triggerable structures capable of being activated allows for the control of biomedical device activity, reducing the need for invasive interventions. Such advancements provide new tools to biomedical engineers and clinicians to design dynamically actuated implantable devices. In this context, the aim of this review is to demonstrate the potential of 4D printing as an enabling manufacturing technology to code the environmentally triggered physical evolution of structures and devices of biomedical interest.

Keywords: 4D printing; bioengineering; biomaterials; functional materials.

Figure 1

(A) 4D bioprinted trachea scaffold developed by Kim et al. [62]. (i) Chemical structure of Sil-MA used to fabricate cell-laden 4D shape morphing structures by DLP. (ii) Self-shape morphing behavior of the Sil-MA bilayer scaffold in water due to differential swelling. (iii) Masson’s trichrome staining of the native trachea and trachea treated with the 4D bioprinted constructs after 8 weeks of surgery (scale: 1 mm; 1 cm for images in small boxes), and histological staining revealing newly formed respiratory epithelium 2 weeks after the implantation (scale: 0.1 mm). The engineered trachea is marked with asterisks and dotted line. Newly formed respiratory epithelium was marked as E and short arrow. Figure reproduced with permission from [62]. (B) 4D bioprinted skeleton muscle scaffold developed by Yang et al. [63] (i) Schematic of the fabrication and actuation of the constructs. (ii) Swelling-driven self-folding ability of gelatin films. (iii) Images of the real constructs before and after actuation. Scanning emission microscopy images confirmed the bundle-like structure of the constructs. Figure reproduced with permission from [63].

Figure 2

(A) Four-dimensional-printed clips for intestinal anastomosis. (i) Rationale of the device; (ii) photo of the bilayer clips, scale bar = 1 cm. (iii) An EBB equipped with a rotating spindle is used in the work. (iv) Finite element simulation, showing the ability of the clips to contract and compress the intestine wall with an increase in temperature. (v) Validation of the device through ex vivo tests. Figure reproduced with permission from [58]. (B) Four-dimensional-printed core-shell coiled structure for intestinal distraction enterogenesis. (i) Rationale of the device; (ii) photo of the core-shell springs. (iii) An extrusion-based 3D printer equipped with a core-shell needle is used in the work. (iv) Finite element simulation, showing the ability of the springs to torque and compress with the increase in temperature. (v) Validation of the device through phantom tests. Figure reproduced with permission from [59].

Figure 3

(A) Schematic of the application of EsoCap, which is composed of a hard gelatin capsule that contains a sinker to decrease buoyancy and a mucoadhesive enrolled film and retainer thread, using the 3D printed applicator. (B) A schematic presentation of the flower-shaped esophageal drug delivery system illustrates its composition, the folded configuration prior to administration, its deployment upon reaching the esophagus, and the recovery of its original shape upon thermal triggering of nitinol wires [121].