How is 4D Bioprinting Used for Tissue Engineering?

In a assessment recently printed in the journal Bioprinting, researchers mentioned 4-dimensional (4D) bioprinting and its potential for advanced tissue engineering programs.

Research: A overview on 4-dimensional bioprinting in pursuit of innovative tissue engineering programs. Image Credit: Microgen/


By creating exceptionally exact and intricate products, additive production (AM), also recognized as 3-dimensional printing (3DP), has remodeled the globe. The exclusive 3DP approach has captivated the biomedical sector in the last ten years, and it has been widely used in the disciplines of tissue engineering (TE), regenerative medicine, and prescribed drugs.

Tissue shots are made use of to produce laptop or computer-aided structure (CAD) data files that allow the manufacturing of 3D-printed (3DPed) patient-certain tissue structures employing electronic imaging strategies this sort of as X-ray computed tomography (CT) or magnetic resonance imaging (MRI). Engineered tissues produced with 3DBP technology, on the other hand, are static and inflexible, as opposed to organic tissues, and do not ordinarily improve condition about time, which boundaries their usage in a dynamic setting.

Because of to inadequate tissue growth or maturation, 3DPed tissue constructs are restricted in their sensible uses. With the advancement of stimuli-responsive elements (SRMs), especially form memory polymers (SMPs), a new biomedical engineering regarded as “4-dimensional (4D) bioprinting” has a short while ago acquired traction.

At present, 4DBP know-how has proven tremendous promise in the biomedical discipline, specifically in TE apps. The majority of reviews focus on the 3DP of polymeric elements yet, 4DBP technology for tissue constructs is however in its early phases and calls for substantial interest in buy to boost useful apps.

About the Review

In this study, the authors introduced a point out-of-the-artwork assessment encompassing a variety of types of SRMs and bioprinting procedures as for every the existing market place traits for 4DBP engineering. On top of that, this critique provided lots of bioactive elements employed in soft and hard tissue engineering (TE) apps. Current problems in the TE space were also highlighted, which could pave the way for potential foreseeable future developments.

The team mentioned the recent challenges and opportunity developments of 4DBP technological innovation for tender and really hard tissue constructs. The crosslinking method, printing speed, cell density, materials viscosity, mobile survival, resolution, printer charge, bio-ink elements, and significant TE applications of common bioprinting technologies were being as opposed.

The authors summarized the a lot of stimuli utilized for the 4DP of condition memory elements (SMMs). To build dynamic 3DPed scaffolds for bone, cartilage, and coronary heart, as nicely as to generate biomedical devices, the use of cell traction forces (CTFs) or various environmental improvements was shown. The stimuli that ended up applied in the tissue development course of action applying 4DP technological innovation were being also demonstrated. The preparation of a 3D microstructure employing the CTF tactic was illustrated, which could be utilized in treatment shipping and delivery programs. In addition, the shape morphing ability (inflammation and folding) of 4Dconceptualized Gel film was demonstrated.


4DBP know-how was observed to be an extension of 3DBP technological know-how that built-in time as its fourth dimension. New advances in SRMs, notably SMPs and condition memory hydrogels (SMHs) had created 4DBP technologies a highly suitable approach for clinical use. Numerous research shown that 4DBP technological know-how could be employed for smooth and hard tissue regeneration. The form modify capacity of the bioactive products displayed biomimicking functions during the article-printing stage, which facilitated tissue reworking through the maturation period.

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Various reports determined that incorporating standard industrial engineering rules into biofabrication, such as lean producing and six sigma, could decreased charges and enhance efficiency. The structural capabilities and composition of scaffolds were being observed to be vital components in deciding tissue load-bearing capacity.

It was demonstrated in some scientific tests that for mobile differentiation, proliferation, and migration to be stimulated, the make contact with among 4DPed scaffolds and cells have to be suitable. Encapsulation and releasing of biomolecules for the ideal operating of biomimetic scaffolds in bone tissue engineering (BTE) could be achievable with even more breakthroughs in nanotechnology and nanoscience.

The use of are living cells was the most significant prerequisite for 4DBP technological know-how, and 4DPed resources need to be biocompatible and non-cytotoxic. Additionally, it was noticed that rheological houses must be appropriate for enhanced printability and high mobile survival. Non-harmful crosslinkers have been uncovered to be yet another prerequisite for appropriate bio-printed architectural stabilization.


In summary, this study elucidated that the bioactive elements really should be tuned for hybrid architecture preparing. It was noticed that 4DBP has a purely natural capability to establish deformable types in response to exterior stimuli, and it could be likely employed to make vascular scaffolds. Structural style and design and substance selection are two substantial parameters to look at whilst producing vascular scaffolds. 4DBP technologies have been observed to be the most ideal procedures for vascularization enhancement.

The authors emphasised that more investigation into the biomechanical functionality and functions of indigenous tissues, the creation of multi-useful hierarchical architectures for mimicking native extracellular matrix (ECM) features, and the enhancement of price tag-effective and speedy prototyping 4DBP technologies for biomedical configurations are all vital for foreseeable future advancements in the TE area. They also believe that the 4DBP technological innovation is anticipated to essentially remodel the biomedical small business in the near potential.


Arif, Z. U., Khalid, M. Y., Ahmed, W., et al. A evaluation on 4-dimensional bioprinting in pursuit of innovative tissue engineering programs. Bioprinting e00203 (2022).

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