Abstract
The applications of tissue engineered constructs have witnessed great advances in the last few years, as advanced fabrication techniques have enabled promising approaches to develop structures and devices for biomedical uses. (Bio-)printing, including both plain material and cell/material printing, offers remarkable advantages and versatility to produce multilateral and cell-laden tissue constructs; however, it has often revealed to be insufficient to fulfill clinical needs. Indeed, three-dimensional (3D) (bio-)printing does not provide one critical element, fundamental to mimic native live tissues, i.e., the ability to change shape/properties with time to respond to microenvironmental stimuli in a personalized manner. This capability is in charge of the so-called “smart materials”; thus, 3D (bio-)printing these biomaterials is a possible way to reach four-dimensional (4D) (bio-)printing. We present a comprehensive review on stimuli-responsive materials to produce scaffolds and constructs via additive manufacturing techniques, aiming to obtain constructs that closely mimic the dynamics of native tissues. Our work deploys the advantages and drawbacks of the mechanisms used to produce stimuli-responsive constructs, using a classification based on the target stimulus: humidity, temperature, electricity, magnetism, light, pH, among others. A deep understanding of biomaterial properties, the scaffolding technologies, and the implant site microenvironment would help the design of innovative devices suitable and valuable for many biomedical applications.
Highlights
IntroductionThe main scope of tissue engineering (TE) is defined as the set of processes to develop biological structures that are able to restore, maintain, or even improve the function of tissues and/or organs [1]
The main scope of tissue engineering (TE) is defined as the set of processes to develop biological structures that are able to restore, maintain, or even improve the function of tissues and/or organs [1].Aiming to meet this challenging goal, multidisciplinary teams are required to work together in the fields of materials engineering and life sciences [2], to successfully employ scaffolds, growth factors, and cells, which represent the widely famous three pillars of TE
A successful bioprinted hydrogel construct should have the following properties: (i) printability, which is related to proper viscosity, short response, transition time, and a suitable sol-gel transition stimulus [44,45]; (ii) biocompatibility, including biodegradability, ability to withstand cell–cell and cell–matrix connections and absence of toxicity; (iii) mechanical properties, identical to the target tissue regarding stiffness, elasticity, and strength, and (iv) shape and structure, as the print should exhibit high structural similarities to the natural tissue
Summary
The main scope of tissue engineering (TE) is defined as the set of processes to develop biological structures that are able to restore, maintain, or even improve the function of tissues and/or organs [1]. Smart biomaterials are at the basis of 4D printing, which, for biomedical applications, may include printed live cells, being defined “bio”-printing [21] Such materials can change shape or properties (e.g., stiffness, color, texture, transparency, energy transfer/conversion, volume) under the influence of external stimuli. A widely accepted definition of 4D printing is still missing, as from Moroni et al.: “Whether we are really witnessing 4D printing, a process that should be defined as a programmed temporal shape change occurring during the 3D manufacturing itself, or not, is still to be clarified in the field” [28] In this scenario, many researchers are investigating different materials and approaches enabling controllable shape/property changes upon different stimuli and timeframes, which are suggested in this review under the name of 4D (bio-)printing. We focus on smart hydrogels and their applications in 4D (bio-)printing
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