4D printing: a cutting-edge platform for biomedical applications

Abstract

Nature's materials have evolved over time to be able to respond to environmental stimuli by generating complex structures that can change their functions in response to distance, time, and direction of stimuli. A number of technical efforts are currently being made to improve printing resolution, shape fidelity, and printing speed to mimic the structural design of natural materials with three-dimensional (3D) printing. Unfortunately, this technology is limited by the fact that printed objects are static and cannot be reshaped dynamically in response to stimuli. In recent years, several smart materials have been developed that can undergo dynamic morphing in response to a stimulus, thus resolving this issue. Four-dimensional (4D) printing refers to a manufacturing process involving additive manufacturing, smart materials, and specific geometries. It has become an essential technology for biomedical engineering and has the potential to create a wide range of useful biomedical products. This paper will discuss the concept of 4D bioprinting and the recent developments in smart matrials, which can be actuated by different stimuli and be exploited to develop biomimetic materials and structures, with significant implications for pharmaceutics and biomedical research, as well as prospects for the future.

Towards 4D printing in pharmaceutics

“…In case of tissue regeneration, for example, functional scaffolds purposely engineered to assist in remodeling and replacing diseased or injured areas represent an ongoing topic of research. In this respect, new materials showing bio-mimicking features and bio-responsiveness can greatly help the development of such technologies (Free, 2021;Naniza et al, 2022;Senatov et al, 2016;Tamay et al, 2019;Zhang et al, 2018).…”

Review on Bioinspired Design of ECM-Mimicking Scaffolds by Computer-Aided Assembly of Cell-Free and Cell Laden Micro-Modules

“…The integration of molecularly imprinted materials responding to internal (e.g., cell-secreted protein degradable hydrogels) and external stimuli (e.g., temperature, electric and magnetic fields, light-responsive systems) in 3D CAD-AM scaffolds may open new avenues to control the presentation of biomolecular signals following a cell-demanding mechanism, and to recapitulate the cell/ECM dual reciprocity interaction [ 70 ]. Loading magnetically responsive particles within scaffolds was used to trigger the release of biomolecules, such as GFs, to stimulate cells proliferation and differentiation without affecting matrix degradation [ 71 , 72 ].…”

Insights into the Safety and Versatility of 4D Printed Intravesical Drug Delivery Systems

“…In more detail, samples having different original shapes, endowed with such spatial encumbrance as to avoid rapid emptying through the sphincters of the selected organs, were produced by HME and FDM. In this respect, modifications occurring on a 3D material configuration over time, triggered by an external stimulus of a non-mechanical nature and resulting in macroscopic shape changes, has been associated with the concept of 4D printing, in which time represented the fourth dimension [ 15 , 42 , 43 , 44 ]. Indeed, the resulting PVA-based prototypes turned out able to take on, after production, a temporary collapsed shape and to quickly recover the original one in the desired environment.…”