Four-dimensional (4D) printing is a novel emerging technology, which can be defined as the ability of 3D printed materials to change their form and functions. The term ‘time’ is added to 3D printing as the fourth dimension, in which materials can respond to a stimulus after finishing the manufacturing process. 4D printing provides more versatility in terms of size, shape, and structure after printing the construct. Complex material programmability, multi-material printing, and precise structure design are the essential requirements of 4D printing systems. The utilization of stimuli-responsive polymers has increasingly taken the place of cell traction force-dependent methods and manual folding, offering a more advanced technique to affect a construct's adjusted shape transformation. The present review highlights the concept of 4D printing and the responsive bioinks used in 4D printing, such as water-responsive, pH-responsive, thermo-responsive, and light-responsive materials used in tissue regeneration. Cell traction force methods are described as well. Finally, this paper aims to introduce the limitations and future trends of 4D printing in biomedical applications based on selected key references from the last decade.

Ultrashort pulsed direct laser interference patterning (DLIP) is used to generate hierarchical line‐like patterns on titanium surfaces to control cell adhesion and spreading on dental implants, thereby improving osseointegration. The DLIP structures have spatial periods of 3, 5, 10, and 17 μm. They are produced using a laser source with a pulse duration of 10 ps and cumulated energy densities between 0.1 and 78.9 J cm⁻². Laser‐induced periodic surface structures (LIPSS) and submicron features are obtained on the treated samples. The DLIP treatment leads to the development of a thick titanium oxide layer, which is imaged and quantified using time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS). Several days (30–56) after the laser treatment, specimens with larger spatial periods are hydrophilic, whereas samples with spatial periods of 3 μm are hydrophobic. Seeded human osteoblasts on the laser‐structured samples show 2.5 times higher cell numbers after 7 days in vitro culture compared with osteoblasts on a grit‐blasted and etched reference sample. Finally, cell adhesion to a structured 3D dental implant is demonstrated.

As a glycerol-based polyester, poly(glycerol azelaic acid) (PGAz) has shown great potential for biomedical applications, such as tissue engineering. However, it tends to show low mechanical strength and a relatively fast biodegradation rate, limiting its capability of mimicking and supporting a broad range of hard tissues such as bone. Moreover, the typical thermal curing process of poly(glycerol-co-diacids) is one of their drawbacks. To overcome these limitations, glycidyl methacrylate (GMA) moieties were first grafted on the backbone of PGAz herein to achieve a UV-curable PGAz-g-GMA (PGAG) resin. Then polyvinylidene fluoride (PVDF), nano-hydroxyapatite, and Cloisite Na⁺ nanoclay were used to fabricate photo-crosslinked PGAG/PVDF nanocomposites with efficient properties to mimic various hard tissues. Our results demonstrated that all nanocomposites possessed a semi-crystalline structure with noticeable PVDF β-phase fraction. The scaffolds yielded Young's modulus, ultimate tensile strength, and elongation at break of 15–24 MPa, 13–15 MPa, and 50–65%, respectively that could meet the requirements for supporting cancellous bone tissue. The presence of nanofillers improved the hydrophilicity and slightly accelerated the biodegradation rate of the scaffolds. Additionally, it was illustrated that the scaffolds had no noticeable in vitro cytotoxicity, and mouse fibroblast L929 cells and osteoblast MG-63 cells attached to and proliferated on their surface desirably. Our findings indicate that the PGAG/PVDF blend and its nanocomposites could be high-potential candidates for a range of hard tissues, specifically cancellous bones.