Emerging 4D Printing Strategies for Next‐Generation Tissue Regeneration and Medical Devices

Abstract

printing. First introduced by Massachusetts Institute of Technology researcher Skylar Tibbits during a Technology, Entertainment, Design (TED) talk in 2013, and then subsequently expanded upon in published research, [2] 4D printing has gained substantial research attention in recent years and has become the subject matter of a substantial number of recent publications (Figure 1).The additional dimension over 3D printing, namely, the 4th dimension, is a time component. [3] Therein, 4D printing can be defined as a 3D printed structure that can self-transform in shape, properties, and/or functionality when exposed to predetermined stimuli, such as light, [4] heat, applied magnetic field (MF), [5] or electrical field (EF), [6] changes in pH, [7] and/or various combinations thereof postprinting. [8] Since its invention, the 4D printing approach has been utilized for multitudinous applications, such as the fabrication of sensors, [9] actuators, [10] soft robotics, [11] biomedical scaffolds/devices, drug delivery systems, [12] and others. [13] Presently, 4D printing, which is still in its infancy, has become an exciting branch of AM and has spurred great interest from both academia and industry alike. [14] In this review article, we present a general overview of the 4D printing field and recent achievements. Our review includes the discussion on the structural design of 4D printing,The rapid development of 3D printing has led to considerable progress in the field of biomedical engineering. Notably, 4D printing provides a potential strategy to achieve a time-dependent physical change within tissue scaffolds or replicate the dynamic biological behaviors of native tissues for smart tissue regeneration and the fabrication of medical devices. The fabricated stimulusresponsive structures can offer dynamic, reprogrammable deformation or actuation to mimic complex physical, biochemical, and mechanical processes of native tissues. Although there is notable progress made in the development of the 4D printing approach for various biomedical applications, its more broad-scale adoption for clinical use and tissue engineering purposes is complicated by a notable limitation of printable smart materials and the simplistic nature of achievable responses possible with current sources of stimulation. In this review, the recent progress made in the field of 4D printing by discussing the various printing mechanisms that are achieved with great emphasis on smart ink mechanisms of 4D actuation, construct structural design, and printing technologies, is highlighted. Recent 4D printing studies which focus on the applications of tissue/organ regeneration and medical devices are then summarized. Finally, the current challenges and future perspectives of 4D printing are also discussed.The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adma.202109198.

Electrospun nanofibers for bone regeneration: from biomimetic composition, structure to function

“…, which makes 3D printing alive. 273 For instance, Wang et al recently prepared a multi-responsive bilayer morphing membrane consisting of a 4D printing hydrogel layer and a shape memory polymer layer, which could achieve temporal control of multi-scale structural morphing for bone healing in vivo . As depicted in Fig.…”

“…271 With the rapid development of 3D printing and smart materials, an emerging 4D printing technology has been proposed to allow a 3D printing scaffold to change its shape, function, or property with time when exposed to external stimuli such as water, light, temperature, etc., which makes 3D printing alive. 273 For instance, Wang et al recently prepared a multi-responsive bilayer morphing membrane consisting of a 4D printing hydrogel layer and a shape memory polymer layer, which could achieve temporal control of multi-scale structural morphing for bone healing in vivo. As depicted in Fig.…”

4D Printing Applications in the Development of Smart Cardiovascular Implants

“…This property is due to loss of hysteresis and magnetic relaxation ( Kobayashi et al, 2010 ; Nakamura et al, 2012 ). According to the Néel-Brown model, the applied magnetic energy is converted into heat, also called self-heating, which allows the adaptation of the used material ( Wang et al, 2021a ). This approach has been used for the construction of biodegradable patient-specific left atrial appendage occluders (LAAO).…”

“…Between these states, a large reversible change of elastic modulus is observable ( Pei and Loh, 2018 ). Therefore, 4D printed materials can work to reversibly respond to environmental stimuli ( Agarwal et al, 2021a ; Wang et al, 2021a ). Currently, 4D printed cardiovascular implants are tested in vitro and in animal models.…”

Multi-material and Multi-dimensional 3D Printing for Biomedical Materials and Devices

“…Cartilage construct with combined mechanical and biological properties [55] Hybrid AM -Embryoid body-laden GelMA -PCL Tubular scaffold directing neural differentiation for spinal cord repair [56] path along the time dimension of the 'spacetime continuum' upon a stimulation from an external energy. Smart material is just one implementation of the 4D printing concept, even though many smart material-based biomedical devices have been 4D printed as extensively discussed in several reviews [62][63][64][65][66][67][68].…”