Bioprinting provides an unparalleled tool for engineering living tissue constructs that mimic the structural organization of native skeletal muscles. However, it remains a challenge for existing bioprinting strategies to recapitulate the highly aligned cellular architectures inside skeletal muscles, primarily due to low printing resolution and limited capability for in situ microenvironmental regulation. Here, we propose to employ the electrical force during the electrohydrodynamic (EHD) bioprinting process to induce the in situ orientation of cell-laden fibrin-alginate hydrogel, which provides nanostructural guidance to the encapsulated cells for the formation of highly aligned skeletal muscle constructs. It was observed that the randomly distributed fibrin protofibril aggregates gradually elongated into uniformly aligned nanofibers at the Taylor cone stage as the applied voltage increased to 3 kV. The oriented fibrin nanofibers further direct in situ cellular alignment along the EHD bioprinting trajectory, facilitating the freeform fabrication of parallelly or circumferentially aligned muscle tissue constructs in vitro. The addition of conductive polymers into the fibrin-alginate hydrogel endows the EHD-bioprinted living constructs with muscle-specific conductivity and cellular organization, which promote myotube differentiation and maturation. The resultant aligned and conductive muscle constructs promoted in situ muscle regeneration and restored lost muscle functions at the defect regions in vivo. The presented EHD bioprinting strategy for fibrin-alginate hydrogel provides a versatile and simple platform to freely fabricate conductive, living tissue constructs with designer cellular alignments.

The inherent complexities of excitable cardiac, nervous, and skeletal muscle tissues pose great challenges in constructing artificial counterparts that closely resemble their natural bioelectrical, structural, and mechanical properties. Recent advances have increasingly revealed the beneficial impact of bioelectrical microenvironments on cellular behaviors, tissue regeneration, and therapeutic efficacy for excitable tissues. This review aims to unveil the mechanisms by which electrical microenvironments enhance the regeneration and functionality of excitable cells and tissues, considering both endogenous electrical cues from electroactive biomaterials and exogenous electrical stimuli from external electronic systems. We explore the synergistic effects of these electrical microenvironments, combined with structural and mechanical guidance, on the regeneration of excitable tissues using tissue engineering scaffolds. Additionally, the emergence of micro/nanoscale bioelectronics has significantly broadened this field, facilitating intimate interactions between implantable bioelectronics and excitable tissues across cellular, tissue, and organ levels. These interactions enable precise data acquisition and localized modulation of cell and tissue functionalities through intricately designed electronic components according to physiological needs. The integration of tissue engineering and bioelectronics promises optimal outcomes, highlighting a growing trend in developing living tissue construct-bioelectronic hybrids for restoring and monitoring damaged excitable tissues. Furthermore, we envision critical challenges in engineering the next-generation hybrids, focusing on integrated fabrication strategies, the development of ionic conductive biomaterials, and their convergence with biosensors.

The rotator cuff tear has emerged as a significant global health concern. However, existing therapies fail to fully restore the intricate bone-to-tendon gradients, resulting in compromised biomechanical functionalities of the reconstructed enthesis tissues. Herein, a tri-layered core–shell microfibrous scaffold with layer-specific growth factors (GFs) release is developed using coaxial electrohydrodynamic (EHD) printing for in situ cell recruitment and differentiation to facilitate gradient enthesis tissue repair. Stromal cell-derived factor-1 (SDF-1) is loaded in the shell, while basic fibroblast GF, transforming GF-beta, and bone morphogenetic protein-2 are loaded in the core of the EHD-printed microfibrous scaffolds in a layer-specific manner. Correspondingly, the tri-layered microfibrous scaffolds have a core–shell fiber size of (25.7 ± 5.1) μm, with a pore size sequentially increasing from (81.5 ± 4.6) μm to (173.3 ± 6.9) μm, and to (388.9 ± 6.9 μm) for the tenogenic, chondrogenic, and osteogenic instructive layers. A rapid release of embedded GFs is observed within the first 2 d, followed by a faster release of SDF-1 and a slightly slower release of differentiation GFs for approximately four weeks. The coaxial EHD-printed microfibrous scaffolds significantly promote stem cell recruitment and direct their differentiation toward tenocyte, chondrocyte, and osteocyte phenotypes in vitro. When implanted in vivo, the tri-layered core–shell microfibrous scaffolds rapidly restored the biomechanical functions and promoted enthesis tissue regeneration with native-like bone-to-tendon gradients. Our findings suggest that the microfibrous scaffolds with layer-specific GFs release may offer a promising clinical solution for enthesis regeneration.

3D printing stands at the forefront of transforming space exploration, offering unprecedented on-demand and rapid manufacturing capabilities. It adeptly addresses challenges such as mass reduction, intricate component fabrication, and resource constraints. Despite the obstacles posed by microgravity and extreme environments, continual advancements underscore the pivotal role of 3D printing in aerospace science. Beyond its primary function of producing space structures, 3D printing contributes significantly to progress in electronics, biomedicine, and resource optimization. This perspective delves into the technological advantages, environmental challenges, development status, and opportunities of 3D printing in space. Envisioning its crucial impact, we anticipate that 3D printing will unlock innovative solutions, reshape manufacturing practices, and foster self-sufficiency in future space endeavors.

Three-dimensional (3D) printing technology has opened a new paradigm to controllably and reproducibly fabricate bioengineered neural constructs for potential applications in repairing injured nervous tissues or producing in vitro nervous tissue models. However, the complexity of nervous tissues poses great challenges to 3D-printed bioengineered analogues, which should possess diverse architectural/chemical/electrical functionalities to resemble the native growth microenvironments for functional neural regeneration. In this work, we provide a state-of-the-art review of the latest development of 3D printing for bioengineered neural constructs. Various 3D printing techniques for neural tissue-engineered scaffolds or living cell-laden constructs are summarized and compared in terms of their unique advantages. We highlight the advanced strategies by integrating topographical, biochemical and electroactive cues inside 3D-printed neural constructs to replicate in vivo-like microenvironment for functional neural regeneration. The typical applications of 3D-printed bioengineered constructs for in vivo repair of injured nervous tissues, bio-electronics interfacing with native nervous system, neural-on-chips as well as brain-like tissue models are demonstrated. The challenges and future outlook associated with 3D printing for functional neural constructs in various categories are discussed.

Three-dimensional (3D) printing provides a promising way to fabricate biodegradable scaffolds with designer architectures for the regeneration of various tissues. However, the existing 3D-printed scaffolds commonly suffer from weak cell-scaffold interactions and insufficient cell organizations due to the limited resolution of the 3D-printed features. Here, composite scaffolds with mechanically-robust frameworks and aligned nanofibrous architectures are presented and hybrid manufactured by combining techniques of 3D printing, electrospinning, and unidirectional freeze-casting. It was found that the composite scaffolds provided volume-stable environments and enabled directed cellular infiltration for tissue regeneration. In particular, the nanofibrous architectures with aligned micropores served as artificial extracellular matrix materials and improved the attachment, proliferation, and infiltration of cells. The proposed scaffolds can also support the adipogenic maturation of adipose-derived stem cells (ADSCs) in vitro. Moreover, the composite scaffolds were found to guide directed tissue infiltration and promote nearby neovascularization when implanted into a subcutaneous model of rats, and the addition of ADSCs further enhanced their adipogenic potential. The presented hybrid manufacturing strategy might provide a promising way to produce additional topological cues within 3D-printed scaffolds for better tissue regeneration.