The ultimate objective of manufacturing is to construct a universal tool system capable of systematically overcoming the spatiotemporal constraints facing humanity. In this context, Extreme Manufacturing (EM) has emerged. The essence of EM lies in harnessing unconventional scientific principles with the explicit goal of transcending established limits. Consequently, EM is not merely a linear extension of traditional manufacturing paradigms but a systemic revolution designed to challenge physical and engineering boundaries. Characterized by extreme environments, extreme scales, superior performance, profound interdisciplinarity, and massive data, this paradigm effectively expands human capabilities across spatial, temporal, and cognitive dimensions. Ultimately, EM will drive sustainable technological progress for human civilization and deepen our mastery over the material world.

3D (three-dimensional) printing of soft/tough hydrogels has been widely used in flexible electronics, regenerative medicine, and other fields. However, due to their loose crosslinking, strong hydration and plasticizing effect of solvent (typically water) and susceptibility to swelling, the printed hydrogels always suffer from bearing compressive stress and shear stress. Here we report a 3D photo-printable hard/soft switchable hydrogel composite which is enabled by the phase transition (liquid/solid transition) of supercooled hydrated salt solution (solvents) within hydrogel. In hard status, it achieved a hardness of 86.5 Shore D (comparable to hard plastics), a compression strength of 81.7 MPa, and Young’s modulus of 1.2 GPa. These mechanical property parameters far exceed those of any currently 3D printed hydrogels. The most interesting thing is that the soft/hard states are easily switchable and this process can be repeated for many times. In the supercooled state, the random arrangement of liquid solvent molecules within hydrogels makes it as soft as conventional hydrogels. Upon artificial seeding of the crystal nucleus, the solvent in hydrogel undergoes rapid crystallization, resulting in the in-situ formation of numerous rigids, ordered rod-like nanoscale crystals uniformly embedded within the hydrogel matrix. This hierarchical structure remarkably enhances the Young’s modulus from kPa to GPa. Furthermore, the softness of hydrogel can be restored by heating and then cooling down to recover the supercooled state of the solvent. Taking advantage of soft/hard status switching, the hydrogel can conform to complex surface morphologies in its soft state and subsequently freeze that shape through crystallization, enabling rapid mold fabrication. Moreover, a shape fixation and recyclable smart hydrogel medical plaster bandage was also developed, capable of conforming the limb shapes and providing adequate support for the bone fracture patients after 10 min of crystallization. Our work suggests a bright future for the direct use of hard hydrogel as a robust industrial material.

Neurovascularization serves as the prerequisite and assurance for fostering neurogenesis after peripheral nerve injury (PNI), not only contributing to the reconstruction of the regenerative neurovascular niche but also providing a surface and directionality for Schwann cell (SC) cords migration and axons elongation. Despite the development of nerve tissue engineering techniques has drawn increasing attention to the intervention approach for repairing nerve defects, systematic generalization summary of the efficient intervention to expedite nerve angiogenesis is still scarce. This review delves into the mechanisms by which macrophages within the nerve defect trigger angiogenesis after PNI and elucidates how the newborn vessels support nerve regeneration, and then extracts three major categories of strategies for producing vascularized nerves in vitro and in vivo from them, encompassing (1) in vitro prevascularization, (2) in vivo prevascularization, and (3) stimulation of neurovascularization in situ. Furthermore, we emphasize that the lack of accuracy for structure and spatiotemporal regulation, as well as the operational inconvenience and delayed connection to the host’s nerve stumps, have stuck the existing neurovascularization technology in the preclinical stage. The successful design of a future prospective clinical vascularized nerve scaffold should be guided by a comprehensive consideration of these aspects.

In clinical practice, the irregular shapes of traumas pose a significant challenge in rapidly manufacturing personalized scaffolds. To address these challenges, inspired by LEGO^Ⓡ bricks, this study proposed a novel concept of modular scaffolds and developed an innovative system based on machine vision for their rapid and intelligent assembly tailored to defect shapes. Trapezoidal interfaces effectively connect standardized bone units based on magnesium-doped silicate calcium, ensuring high stability of the modular scaffolds, with compressive strength up to 135 MPa and bending strength up to 17 MPa. Through self-developed defect recognition and reconstruction algorithms, defect recognition and personalized assembly schemes for bone scaffolds can be achieved autonomously. Modular scaffolds seamlessly integrate with surrounding bone tissue, promoting new bone growth, with no apparent differences compared to fully 3D printed integral scaffolds in the skull and femur repair experiments. In summary, the adoption of modular scaffolds not only integrates personalization and standardization but also satisfies the optimal treatment window.

Bioengineered organs have been seen as a promising strategy to address the shortage of transplantable organs. However, it is still difficult to achieve heterogeneous structures and complex functions similar to natural organs using current bioengineering techniques. This work introduces the methods and dilemmas in organ engineering and existing challenges. Furthermore, a new roadmap for organ engineering, which uses a modular strategy with autologous bioreactors to create organ-level bioengineered constructions, is summarized based on the latest research advances. In brief, different functional modules of natural organs are constructed in vitro, and autologous bioreactors in vivo are utilized to facilitate inter-module assembly to form a complete bioengineered organ capable of replacing natural organ functions. There are bioengineered organs, such as biomimetic tracheas, which have been successfully fabricated following this roadmap. This new roadmap for organ engineering shows prospects in addressing the shortage of transplantable organs and has broad prospects for clinical applications.

Synthetic vascular grafts suitable for small-diameter arteries (<6 mm) are in great need. However, there are still no commercially available small-diameter vascular grafts (SDVGs) in clinical practice due to thrombosis and stenosis after in vivo implantation. When designing SDVGs, many studies emphasized reendothelization but ignored the importance of reconstruction of the smooth muscle layer (SML). To facilitate rapid SML regeneration, a high-resolution 3D printing method was used to create a novel bilayer SDVG with structures and mechanical properties mimicking natural arteries. Bioinspired by the collagen alignment of SML, the inner layer of the grafts had larger pore sizes and high porosity to accelerate the infiltration of cells and their circumferential alignment, which could facilitate SML reconstruction for compliance restoration and spontaneous endothelialization. The outer layer was designed to induce fibroblast recruitment by low porosity and minor pore size and provide SDVG with sufficient mechanical strength. One month after implantation, the arteries regenerated by 3D-printed grafts exhibited better pulsatility than electrospun grafts, with a compliance (8.9%) approaching that of natural arteries (11.36%) and significantly higher than that of electrospun ones (1.9%). The 3D-printed vascular demonstrated a three-layer structure more closely resembling natural arteries while electrospun grafts showed incomplete endothelium and immature SML. Our study shows the importance of SML reconstruction during vascular graft regeneration and provides an effective strategy to reconstruct blood vessels through 3D-printed structures rapidly.

Lung diseases associated with alveoli, such as acute respiratory distress syndrome, have posed a long-term threat to human health. However, an in vitro model capable of simulating different deformations of the alveoli and a suitable material for mimicking basement membrane are currently lacking. Here, we present an innovative biomimetic controllable strain membrane (BCSM) at an air–liquid interface (ALI) to reconstruct alveolar respiration. The BCSM consists of a high-precision three-dimensional printing melt-electrowritten polycaprolactone (PCL) mesh, coated with a hydrogel substrate—to simulate the important functions (such as stiffness, porosity, wettability, and ALI) of alveolar microenvironments, and seeded pulmonary epithelial cells and vascular endothelial cells on either side, respectively. Inspired by papercutting, the BCSM was fabricated in the plane while it operated in three dimensions. A series of the topological structure of the BCSM was designed to control various local-area strain, mimicking alveolar varied deformation. Lopinavir/ritonavir could reduce Lamin A expression under over-stretch condition, which might be effective in preventing ventilator-induced lung injury. The biomimetic lung-unit model with BCSM has broader application prospects in alveoli-related research in the future, such as in drug toxicology and metabolism.

Because of the complex nerve anatomy and limited regeneration ability of natural tissue, the current treatment effect for long-distance peripheral nerve regeneration and spinal cord injury (SCI) repair is not satisfactory. As an alternative method, tissue engineering is a promising method to regenerate peripheral nerve and spinal cord, and can provide structures and functions similar to natural tissues through scaffold materials and seed cells. Recently, the rapid development of 3D printing technology enables researchers to create novel 3D constructs with sophisticated structures and diverse functions to achieve high bionics of structures and functions. In this review, we first outlined the anatomy of peripheral nerve and spinal cord, as well as the current treatment strategies for the peripheral nerve injury and SCI in clinical. After that, the design considerations of peripheral nerve and spinal cord tissue engineering were discussed, and various 3D printing technologies applicable to neural tissue engineering were elaborated, including inkjet, extrusion-based, stereolithography, projection-based, and emerging printing technologies. Finally, we focused on the application of 3D printing technology in peripheral nerve regeneration and spinal cord repair, as well as the challenges and prospects in this research field.

Inspired by natural porous architectures, numerous attempts have been made to generate porous structures. Owing to the smooth surfaces, highly interconnected porous architectures, and mathematical controllable geometry features, triply periodic minimal surface (TPMS) is emerging as an outstanding solution to constructing porous structures in recent years. However, many advantages of TPMS are not fully utilized in current research. Critical problems of the process from design, manufacturing to applications need further systematic and integrated discussions. In this work, a comprehensive overview of TPMS porous structures is provided. In order to generate the digital models of TPMS, the geometry design algorithms and performance control strategies are introduced according to diverse requirements. Based on that, precise additive manufacturing methods are summarized for fabricating physical TPMS products. Furthermore, actual multidisciplinary applications are presented to clarify the advantages and further potential of TPMS porous structures. Eventually, the existing problems and further research outlooks are discussed.