A series of progressive 4D strategies have been proposed to address current challenges in bone tissue engineering. Over time, shape and function changes of printed structures have been the two main strategies for 4D bioprinting. Currently, most studies are focused on the shape-transforming capabilities of 4D-printed scaffolds, such as folding, lengthening, twisting, and creasing. This SMM responds to external stimuli and can change shape over time, with the result that it changes specific material properties, resulting in a fourth dimension, time. He defines 4D printing as “the use of a 3D printer to create objects that can change their form while simultaneously removing them from the 3D printer.” In other words, 4D printing is nothing new but 3D printing with the help of shape memory materials (SMM). Professor Skylar Tibbits coined the term 4D printing at an MIT conference. In order to further simulate the dynamic in vivo environment, some scholars have found that 4D printing methods can incorporate “time” into current 3D printing by using smart materials. They can recover their original shape from the temporary shape when exposed to appropriate stimuli. Various studies have used a variety of stimuli, including physical (e.g., water, temperature, light, electric and magnetic fields ), chemical (e.g., pH, and ion concentration ) or biological (e.g., glucose and enzymes ) stimulation. Because materials need to respond to external stimuli, these are also known as stimuli-responsive or “smart” materials. In recent years, shape memory material (SMM) has been proven to be a smart material and has been applied in artificial skin, bionic hands, bionic flexible joints, muscle tissue, and bionic soft tongue. ![]() Most of these dynamic functional conformational changes are caused by built-in mechanisms in response to intrinsic or/and extrinsic stimuli that cannot be mimicked by 3D bioprinting. In 3D bioprinting, only the initial state of the printed object is considered and it and assumes it is inanimate and static, but natural tissue regeneration involves complex 3D structures, microarchitecture, and extracellular matrix components, as well as the generation of tissues with unique functions through dynamic changes in tissues. However, with the deepening understanding of the dynamic biological environment and the continuous improvement of treatment precision requirements, the limitations have prevented traditional 3D printing from meeting the key requirements. In previous studies, multifunctional 3D printing (3DP) technologies based on different working principles have been applied. ![]() In the past two decades, 3D bioprinting technology for bone tissue engineering has made significant progress, and a large number of studies have combined biomaterials, cells, and bioactive factors to design bone tissue structures and promote bone regeneration through bionic structures. Tissue engineering is a promising alternative to bone-deficient or diseased tissue, allowing restoration of affected bone through engineered materials, cells, and growth factors (GFs). However, donor site morbidity and limited bone supply largely limit the efficacy of this treatment. Clinically, the gold standard treatment to resolve such large-scale bone defects consists of filling the defect with an autologous bone graft or allogeneic bone to restore structure and function. Despite the remarkable self-healing capacity of bone, large-scale irregular bone defect healing remains challenging, especially in the absence of medical intervention. In this review, we will discuss the latest research on shape memory materials and 4D printing in bone tissue repair.īone defects caused by congenital deformities, trauma, disease, and surgical resection have become major problem for clinicians. In conclusion, 4D printing is the change of the fourth dimension (time) in 3D printing, which provides unprecedented potential for bone tissue repair. Over time, 4D-printed scaffolds change their appearance or function in response to environmental stimuli (physical, chemical, and biological). It combines the concept of time with three-dimensional printing. With the emergence of stimuli-responsive materials, four-dimensional (4D) printing has become the next-generation solution for biological tissue engineering. ![]() It only takes into account the original form of the printed scaffold, which is inanimate and static, and is not suitable for dynamic organisms. The development of three-dimensional (3D) bioprinting has received considerable attention in bone tissue engineering over the past decade. ![]() The repair of severe bone defects is still a formidable clinical challenge, requiring the implantation of bone grafts or bone substitute materials.
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