Rapid and accurate visible-light photopolymerization is essential for advancing bioprinted engineered tissues. In this study, we developed a novel three-component photoinitiator system for visible light-induced crosslinking of gelatin methacryloyl (GelMA) hydrogels, designed to improve polymerization kinetics, mechanical strength, and structural integrity. Incorporation of 2-bromoacetophenone (BAP) considerably accelerated photopolymerization, with reaction rates increasing alongside BAP concentration, enabling the rapid fabrication of stable hydrogel scaffolds. Printing experiments confirmed that BAP promoted fast crosslinking of GelMA bioinks under visible light, reducing printing time while preserving high-resolution structural features. Additionally, the incorporation of BAP induced microscale structural transformations in the hydrogels during hydration, as evidenced by scanning electron microscopy imaging and swelling analyses. This unique property enabled the fabrication of multilayer constructs exhibiting time-dependent deformation, demonstrating four-dimensional (4D) printing capabilities. Moreover, biocompatibility evaluations revealed that cells maintained high viability in BAP-containing hydrogels. Overall, the BAP-based photoinitiator system offers a promising strategy for high-speed, high-resolution bioprinting, combining enhanced mechanical performance, reduced fabrication time, and dynamic structural adaptability—features that make it highly suitable for advanced biofabrication and tissue engineering applications.

Spinal cord injury (SCI) causes severe trauma to the central nervous system (CNS), involving complex pathological processes such as oxidative stress, inflammation, demyelination, and scar formation. During SCI progression, ongoing myelin degeneration leads to the release of myelin debris, which directly inhibits neural regeneration and impairs functional recovery following the injury. Moreover, bone marrow-derived macrophages (BMDMs) infiltrate the injured site and extensively phagocytose myelin debris, transforming into lipid-laden foam cells. These foam cells accumulate at the lesion core, significantly promoting fibrotic scar formation. To address these challenges, we developed a composite scaffold consisting of a foam cell membrane-coated polycaprolactone (PCL) nanofiber membrane that was integrated with a dual-matrix human acellular amniotic membrane (HAAM) hydrogel. A comprehensive evaluation combining material characterization, in vitro assays, and in vivo assessment using a Sprague–Dawley rat spinal cord defect model demonstrated that the scaffold retains the bioactive properties of HAAM, effectively clearing myelin debris and mitigating foam cell accumulation while concurrently promoting neural regeneration following SCI. The proposed novel biomaterial-based strategy offers a promising approach to addressing the persistent accumulation of myelin debris after SCI.

Abstract Chronic total occlusion (CTO) is a cardiovascular disease in which coronary arteries are completely obstructed by atherosclerotic plaques for more than three months. Percutaneous coronary intervention (PCI) treatment of calcified CTO is challenging because hardened plaques prevent the crossing and delivery of microcatheters and balloons. In this study, a two-step atherectomy method for CTO treatment using a miniature electroplated nickel (Ni)-diamond wheel is proposed. The Ni-diamond wheel first drills a hole in the CTO lesion with rotational and oscillatory translational motion along a guidewire and then grinds the lesion using orbital motion to enlarge the hole beyond the diameter of the grinding wheel. The feasibility of the proposed two-step atherectomy method, combining drilling and grinding, and the forces exerted during drilling and grinding were experimentally investigated using two types of calcified CTO plaque surrogates: gypsum cement and ex vivo bovine bone. Drilling experiments were conducted in both manual and automated feeding modes. The experimental results demonstrate that the proposed miniature wheel drills through both types of CTO surrogates in the manual and automated feeding modes with more consistent drilling forces of approximately 0.046 and 0.027 N in the rapid and slow modes under automated feeding, respectively, than under manual feeding. During grinding, the miniature wheel generates orbital motion in the hole and expands the hole diameter from 0.85 to 1.26 mm within 120 s. The proposed integrated drilling and grinding approach has promise in addressing the clinical challenges of microcatheter- and balloon-uncrossable lesions in PCI treatment of CTO.

Abstract Nerve guidance conduits (NGCs) effectively support and guide the regeneration of injured nerves. However, traditional NGCs often lack essential growth factors and fail to create a biomimetic microenvironment conducive to nerve regrowth. This study develops a highly bionic nerve guidance conduit (HB-NGC) using hybrid high-voltage electrotechnologies that integrate electrospinning with electrohydrodynamic (EHD) printing. The outer layer consists of electrospun polycaprolactone fibers loaded with carboxyl-multi-walled carbon nanotubes, while the inner layer is composed of highly aligned polycaprolactone fibers created by EHD printing. The tubular core of the HB-NGC is filled with hyaluronic acid methacryloyl (HAMA) hydrogel encapsulating bone marrow mesenchymal stem cells (BMSCs). This highly biomimetic NGC is conductive, capable of guiding axon growth, and sustainably releases growth factors, effectively mimicking the structure, function, and characteristics of natural peripheral nerves. Its distinctive architectural layers provide an exceptional bionic microenvironment by restoring physical pathways, facilitating electrical signal conduction, and supplying an extracellular matrix (ECM) environment enriched with essential growth factors. Additionally, the HB-NGC’s morphology, along with its physicochemical and mechanical properties, effectively bridges the gap between severed nerve ends. In vivo animal studies validate the HB-NGC’s effectiveness, highlighting its significant potential to enhance peripheral nerve regeneration.

Stem cell- or tissue-derived three-dimensional organ-like formations, known as organoids, are emerging as effective tools in biomedicine. Since they may be useful in developing customized therapeutic solutions and efficient drug screening protocols, organoids can deepen our understanding of novel disease mechanisms. In doing so, they can facilitate advancements in drug discovery platforms, pharmacological safety, and clinical trials. This review explores various biomedical applications of organoids, including drug development and disease modeling, and highlights specific tools and analytical techniques that can be employed to investigate organoids and their microenvironments. Finally, we review recent clinical trials and patents related to organoids that show great promise for future clinical translation.

Abstract Osteoarthritis is a common aging-related disorder that is confined mostly to the chondral layer of joints (e.g., the knee) but can spread to bony layers over time. In its early stages, osteoarthritis has minimal symptoms; however, these gradually worsen over time and include joint pain, stiffness, loss of mobility, and inflammation. The exposed subchondral bone of a Grade 4 osteoarthritic knee is highly prone to erosion if left untreated due to persistent rubbing between the bones, which can lead to painful bone spurs. However, treating osteoarthritis is especially challenging due to the poor mitotic potential and low metabolic activity of chondrocytes. Although currently available tissue-engineered products (e.g., BST-CarGel®, TruFit®, and Atelocollagen®) can achieve structural reconstruction and tissue regeneration, final clinical outcomes can still be improved. Major challenges faced during clinical studies of tissue-engineered constructs include chondrocyte hypertrophy and the development of mechanically inferior fibrous tissue, among others. These issues can be addressed by selecting suitable biomaterial combinations, mimicking the three-dimensional (3D) architecture of the tissue matrix, and better controlling inflammation. Furthermore, it is crucial to generate essential signaling molecules within the articular cartilage ecosystem. This approach must also account for the microarchitecture of the affected joint and support the chondrogenic differentiation of mesenchymal stem cells. The use of tissue-engineered constructs has the potential to overcome each of these challenges, since materials can be modified for drug/biomolecule delivery while simultaneously facilitating the regeneration of robust articular cartilage. Three-dimensional printing has been successfully used in tissue engineering to achieve bioprinting. By manipulating conventional 3D printing techniques and the types of bioink used, many different types of bioprinting have emerged. Overall, these bioprinting techniques can be used to address various challenges associated with osteoarthritis treatment.

Abstract The global demand for in vitro respiratory airway models has surged due to the coronavirus disease 2019 (COVID-19) pandemic. Current state-of-the-art models use polymer membranes to separate epithelial cells from other cell types, creating a nonphysiological barrier. In this study, we applied three-dimensional (3D) printing and bioprinting to develop an in vitro model where endothelial and epithelial cells were in direct contact, mimicking their natural arrangement. This proof-of-concept model includes a culture chamber, with an endothelial bioink printed and perfused through an epithelial channel. In silico simulations of the air velocity within the channel revealed shear stress values ranging from 0.13 to 0.39 Pa, aligning with the desired in vivo shear stress observed in the bronchi regions (0.1–0.4 Pa). Biomechanical movements during resting breathing were mimicked by incorporating a textile mesh positioned away from the cell–cell interface. The epithelial channel demonstrated a capacity for compression and expansion of up to −14.7% and +6.4%, respectively. Microscopic images showed that the epithelial cells formed a uniform monolayer within the lumen of the channel close to the bioprinted endothelial cells. Our novel model offers a valuable tool for future research into respiratory diseases and potential treatments under conditions closely mimicking those in the lung.

Bioreactors are used to dynamically condition engineered tissues to achieve the required degree of maturation before in vivo implantation. Integrating sensors and imaging capabilities into bioreactors can help us understand how the culture environment influences tissue maturation and growth. Additionally, this enables the monitoring of tissue constructs and provides critical information for quality control. This study aimed to develop a standardized, self-contained, uniaxial bioreactor module for the clinical manufacturing of tissue constructs; this system would benefit from unidirectional mechanical or electrical stimulation, or both. We achieved this goal by integrating stimulation and sensing components that provide an optimal culture environment and monitoring capabilities to improve tissue manufacturing. The uniaxial bioreactor module included integrated, user-friendly mechanical and electrical stimulations with force measurement to enhance the preconditioning of the engineered tissues. Also, a sensor loop and media exchange system were integrated to monitor the culture environment and cellular metabolites over time, and the camera system above the tissue construct enabled the macroscopic visualization of tissue maturation. Furthermore, the onboard media exchange system was programmed into the module to maintain aseptic culture conditions in the long term. Subsequently, using native skeletal muscle tissue and tissue-engineered skeletal muscle constructs, the performance of the uniaxial bioreactor module was validated for its application in preconditioning and enhancing tissue maturation.

Fast electron–hole recombination issues during titanium dioxide (TiO2) photocatalysis limit its application in preventing bacterial infection during bone defect repair. In this study, TiO2@reduced graphene oxide (rGO) composites were synthesized using a hydrothermal method in which rGO, which possesses very high electrical conductivity, promotes the separation of photoelectron–hole pairs of TiO2, thus improving the efficiency of photocatalytic production of reactive oxygen species (ROS). Subsequently, TiO2@rGO composites were introduced into poly-L-lactic acid (PLLA) to prepare bone scaffolds with photocatalytic antibacterial function via selective laser sintering. The results showed that TiO2 grew on the surface of rGO and formed a covalent bond connection (Ti–O–C) with rGO. A decreased electrochemical impedance of TiO2@rGO composites was observed, and the transient photocurrent intensity increased from 0.05 to 0.5 µA/cm2. Analysis of electron spin resonance found that the photocatalytic products of TiO2 were ·OH and ·O2−, two kinds of ROS capable of killing bacteria via disrupting the structure of the bacterial membrane in vitro. Antibacterial experiments showed that the PLLA/TiO2@rGO scaffolds had good antibacterial properties against Escherichia coli and Staphylococcus aureus. Finally, we report that these scaffolds exhibited both enhanced mechanical properties due to the addition of TiO2@rGO as a reinforcement material and good biocompatibility during cell proliferation.

Wireless millirobots engineered to infiltrate intricate vascular networks within living organisms, particularly within constricted and confined spaces, hold immense promise for the future of medical treatments. However, with their multifaceted and intricate designs, some robots often grapple with motion and functionality issues when confronted with tight spaces characterized by small cross-sectional dimensions. In this study, drawing inspiration from the high aspect ratio and undulating swimming patterns of snakes, a millimeter-scale, snake-like robot was designed and fabricated via a combination of extrusion-based four-dimensional (4D) printing and magnetic-responsive intelligent functional inks. A sophisticated motion control strategy was also developed, which enables the robots to perform various dynamic movements, such as undulating swimming, precise turns, graceful circular motions, and coordinated cluster movements, under diverse magnetic field variations. As a potential application, the snake robot can navigate and release drugs in a model coronary intervention vessel with tortuous channels and fluid filling. The novel design and promising applications of this snake robot are invaluable tools in future medical surgeries and interventions.