Three-dimensional (3D) and Four-dimensional (4D) printing emerged as the next generation of fabrication techniques, spanning across various research areas, such as engineering, chemistry, biology, computer science, and materials science. Three-dimensional printing enables the fabrication of complex forms with high precision, through a layer-by-layer addition of different materials. Use of intelligent materials which change shape or color, produce an electrical current, become bioactive, or perform an intended function in response to an external stimulus, paves the way for the production of dynamic 3D structures, which is now called 4D printing. 3D and 4D printing techniques have great potential in the production of scaffolds to be applied in tissue engineering, especially in constructing patient specific scaffolds. Furthermore, physical and chemical guidance cues can be printed with these methods to improve the extent and rate of targeted tissue regeneration. This review presents a comprehensive survey of 3D and 4D printing methods, and the advantage of their use in tissue regeneration over other scaffold production approaches.

Cell-substrate interactions play a crucial role in the design of better biomaterials and integration of implants with the tissues. Adhesion is the binding process of the cells to the substrate through interactions between the surface molecules of the cell membrane and the substrate. There are several factors that affect cell adhesion including substrate surface chemistry, topography, and stiffness. These factors physically and chemically guide and influence the adhesion strength, spreading, shape and fate of the cell. Recently, technological advances enabled us to precisely engineer the geometry and chemistry of substrate surfaces enabling the control of the interaction cells with the substrate. Some of the most commonly used surface engineering methods for eliciting the desired cellular responses on biomaterials are photolithography, electron beam lithography, microcontact printing, and microfluidics. These methods allow production of nano- and micron level substrate features that can control cell adhesion, migration, differentiation, shape of the cells and the nuclei as well as measurement of the forces involved in such activities. This review aims to summarize the current techniques and associate these techniques with cellular responses in order to emphasize the effect of chemistry, dimensions, density and design of surface patterns on cell-substrate interactions. We conclude with future projections in the field of cell-substrate interactions in the hope of providing an outlook for the future studies.

Peripheral nerve injury is a worldwide clinical problem which could lead to loss of neuronal communication along sensory and motor nerves between the central nervous system (CNS) and the peripheral organs and impairs the quality of life of a patient. The primary requirement for the treatment of complete lesions is a tension-free, end-to-end repair. When end-to-end repair is not possible, peripheral nerve grafts or nerve conduits are used. The limited availability of autografts, and drawbacks of the allografts and xenografts like immunological reactions, forced the researchers to investigate and develop alternative approaches, mainly nerve conduits. In this review, recent information on the various types of conduit materials (made of biological and synthetic polymers) and designs (tubular, fibrous, and matrix type) are being presented.

Tissue engineering aims to replace missing or damaged tissues and restore their functions. Three-dimensional (3D) printing has been gaining more attention because it enables the researchers to design and produce cell loaded constructs with predetermined shapes, sizes, and interior architecture. In the present study, a 3D bioprinted corneal stroma equivalent was designed to substitute for the native tissue. Reproducible outer and inner organization of the stroma was obtained by optimizing printing conditions such as the nozzle speed in the x–y direction and the spindle speed. 3D printed GelMA hydrogels were highly stable in PBS during three weeks of incubation (8% weight loss). Live–Dead cell viability assay showed 98% cell viability on day 21 indicating that printing conditions were suitable for keratocyte printing. Mechanical properties of the cell loaded 3D printed hydrogels increased 2-fold during this incubation period and approached those of the native cornea (ca. 20 kPa vs. 27 kPa, respectively). Expression of collagens types I and V, and proteoglycan (decorin) in keratocytes indicates maintenance of the phenotype in the hydrogels. Transparency of cell-loaded and cell-free hydrogels was over 80% (at 700 nm) during the three week culture period and comparable to that of the native cornea (85%) at the same wavelength. Thus, GelMA hydrogels bioprinted with keratocytes mimic the biological and physical properties of the corneal stroma with their excellent transparency, adequate mechanical strength, and high cell viability.