Harnessing 4D Printing Bioscaffolds for Advanced Orthopedics

Abstract

The development of programmable functional biomaterials makes 4D printing add a new dimension, time (t), based on 3D structures (x, y, z), therefore, 4D printed constructs could transform their morphology or function over time in response to environmental stimuli. Nowadays, highly efficient bone defect repair remains challenging in clinics. Combining programmable biomaterials, living cells, and bioactive factors, 4D bioprinting provides greater potential for constructing dynamic, personalized, and precise bone tissue engineering scaffolds by complex structure formation and functional maturation. Therefore, 4D bioprinting has been regarded as the next generation of bone repair technology. This review focuses on 4D printing and its advantages in orthopedics. The applications of different smart biomaterials and 4D printing strategies are briefly introduced. Furthermore, one summarizes the recent advancements of 4D printing in bone tissue engineering, uncovering the addressed and unaddressed medical requirements. In addition, current challenges and future perspectives are further discussed, which will offer more inspiration about the clinical transformation of this emerging 4D bioprinting technology in bone regeneration.

Artificial Intelligence-Empowered 3D and 4D Printing Technologies toward Smarter Biomedical Materials and Approaches

“…Such stimuli that are strictly connected with the changes in shape, properties, and functionality of 4D printed structures can be both physical (temperature, humidity, light, electromagnetism, and mechanical force) and chemical (pH, chemical reactions, ion concentration, cross-linking, redox state of metal ions) and can be applied sequentially or simultaneously to trigger a permanent or temporary change in the 4D printed objects ( Figure 3 ). In addition, such stimuli can also be of a biological nature (e.g., biomolecules, enzymes, and cell traction force), which are of particular interest for the fabrication of 4D-bioprinted engineered living scaffolds that allow tissue repair and regeneration or a replicating cell population of living organisms [ 62 , 63 , 64 ].…”

“…Through 4D-printing, self-organizing structures can be obtained using materials that mimic DNA strands with complementarity sequence that couple under appropriate physical conditions. By doing so, the building blocks of specially programmable biomaterials can be induced to self-organize on multiple length scales to recapitulate the desired tissue architectures, or to precisely control the composition and spatial distribution of cells in manufactured tissues that must mimic those natives [64].…”

Three-Dimensional Bioprinting for Cartilage Tissue Engineering: Insights into Naturally-Derived Bioinks from Land and Marine Sources

“…Recently, 3D bioprinting has evolved towards the next generation of this technology, namely, four-dimensional (4D) bioprinting, even though important limitations of the latter should still be properly addressed. Four-dimensional bioprinted scaffolds are 3D biofabricated structures, in which the shape, properties and functions can change over time when exposed to a determined external stimulus (i.e., temperature, electric/magnetic field, light, pH and ions) [ 151 ]. In this context, stimuli-responsive hydrogels are attracting research attention.…”

3D Printing GelMA/PVA Interpenetrating Polymer Networks Scaffolds Mediated with CuO Nanoparticles for Angiogenesis

“…[20,21] As a typically modified gelatin, GelMA contains many arginine-glycine-aspartic acid (RGD) and matrix metalloproteinase sequences, which conduce to promote cell adhesion and proliferation. [22][23][24] Furthermore, GelMA hydrogels with strain-responsive and light crosslinking properties can be applied to 3D printing to conveniently construct tissue scaffolds. [25] However, the application of pure GelMA in tissue engineering was still limited due to its poor mechanical properties and rapid degradation.…”