Cardiovascular stents are widely applied in the treatment of arterial stenosis, but conventional metallic stents present limitations such as permanent implantation, hypersensitivity reactions, and late restenosis. Biodegradable polymer stents offer a promising alternative, though their translation is restricted by structural design challenges and inadequate mechanical performance. In this study, eight representative stent architectures were computationally evaluated with respect to radial elastic recoil, foreshortening, dogboning, and radial support force. Stents were fabricated from polylactide (PLA) via fused deposition modelling (FDM), and the effects of nozzle temperature, layer height, and printing speed were systematically assessed on PLA dogbone specimens to determine optimised process parameters. Computational analysis revealed that only type B and type F stents met clinical deformation requirements, with radial elastic recoil <6 %, foreshortening <10 %, and dogboning <10 %, while other designs exhibited values exceeding these thresholds. Parallel compression tests further quantified radial support capacity at 50 % compression. Fabrication and dimensional evaluation showed that, although all stent designs could be produced using optimised FDM parameters, manufacturing-induced geometric deviations at thin struts and unit connection regions were unavoidable. As a result, the finite-element simulations should be regarded as providing idealised mechanical responses for comparative design evaluation rather than exact predictions of fabricated prototypes. Overall, these findings provide structural and process design guidelines for the development of mechanically reliable 3D-printed biodegradable PLA cardiovascular stents, while emphasising the importance of manufacturing fidelity when translating computationally optimised designs into physical devices.

Three-dimensional (3D) bioprinting integrates engineering, materials science, and biology to fabricate living tissues with precise spatial control. By enabling the layer-by-layer deposition of cells and biomaterials, it overcomes many limitations of traditional scaffold-based tissue engineering and offers new opportunities for regenerative and personalized medicine. This review presents a comprehensive overview of recent advances in 3D bioprinting. It introduces a systematic, ASTM-aligned classification of key bioprinting modalities, extrusion, jetting, and vat photopolymerization, along with their respective material and biological design requirements. It also summarizes recent progress in bio-ink development and crosslinking strategies that improve print fidelity and functional tissue maturation. In addition, the review highlights applications in both systemic disease modelling and treatment (such as cardiovascular, endocrine/metabolic, and neurodegenerative disorders) and localized tissue repair (including skin, musculoskeletal, cartilage, and bone), emphasizing their relevance to civilian healthcare and military medicine. By combining technological innovation, biological insights, and regulatory considerations, this review outlines how advances in multi-modal bioprinting and intelligent process control can accelerate the translation of laboratory research into clinically viable, patient-specific therapies, driving the next generation of regenerative medicine.

Biofabrication and biomanufacturing are rapidly transforming how materials, therapeutics, and functional biological constructs are produced. These fields integrate developments in sustainable biomaterials, precision fabrication, biological systems, and data-driven engineering to produce scalable, efficient, and environmentally aligned production pathways. This review high-lights recent scientific advances led by researchers in Singapore, focusing on three interconnected pillars: sustainable bio-derived materials, enabling fabrication and manufacturing technologies, and emerging applications. We first examine the expanding use of biomass-derived feedstocks, including human hair keratin, aquaculture side-streams, and plant-derived polysaccharides, which support circular and resource-conscious material development. We then present advances in biofabrication technologies, including electrospinning, three-dimensional bioprinting, and metal additive manufacturing, that enable improved control over the structure, function, and manufacturability of biomedical and functional constructs. Emerging applications, such as machine learning-assisted additive manufacturing, food biomanufacturing, regenerative cell therapy, microneedles, and bioelectronics, exemplify how biofabrication and biomanufacturing are increasingly interrelated across the health, materials, and technological domains. These research contributions from Singapore exemplify how sustainable feedstocks, digital and automated fabrication platforms, and biologically driven applications are shaping the evolving landscape of biofabrication and biomanufacturing. The convergence of materials science, biological engineering, and advanced manufacturing continues to enable new opportunities for innovation in biomedical, industrial, and societal contexts.

Engineered tissue constructs are typically evaluated by extensive animal studies to assess their in vivo efficacy. Histological analysis is the widely used approach. However, this technique is time-consuming and highly dependent on experienced pathologists. Moreover, it provides limited insight into how tissue continuously changes at the same tissue site over time. In this study, we propose a deep learning (DL)-based model, Bone Tissue Prediction Generative Adversarial Network (BTP-GAN), which integrates synthetic histological image generation with a biological tissue growth model to simulate bone tissue development over time. Despite a small training dataset, the generated histological images are biologically meaningful and realistic, owing to three algorithmic modules: the Analysis module, Growth module, and Generation module. Moreover, Ordinary Differential Equations (ODE)-Transformer model can learn the temporal patterns and structural characteristics of real tissue images, enabling the generation of histological images according to various specific generative conditions. The BTP-GAN successfully demonstrates the continuous histological change at the same bone tissue site, relying only on a single input histological image. This in-silico animal study may change the perception of the necessity of extensive animal studies in tissue engineering and provide a practical framework for the future advancement of in-silico tissue engineering.

Abstract Vat photopolymerization (VP)‐based bioprinting is rapidly emerging as a transformative platform for fabricating complex, cell‐laden tissue constructs with unparalleled spatial resolution and geometric precision. This review presents a comprehensive overview of recent advances in VP‐based bioprinting, organized around core themes of photopolymerization chemistry, printing modalities, bio‐ink design, and biomedical applications. We first describe the underlying crosslinking mechanisms including chain‐growth, step‐growth, redox‐mediated, and initiator‐free systems that enable spatiotemporal control over polymerization. The discussion then moves to key VP‐based bioprinting techniques such as stereolithography apparatus (SLA), digital light processing, two‐photon polymerization, and volumetric additive manufacturing, emphasizing their printing principles and suitability for bioprinting applications. A central focus is placed on the rational design of photo‐crosslinkable bio‐inks, comprising functional monomers, photo‐initiators (PIs), and photo‐absorbers (PAs). We critically examine design criteria such as cytocompatibility, rheological and optical behavior, mechanical performance, degradation profiles, and scalability, highlighting the complex trade‐offs between print fidelity and biological function. The utility of VP‐based bioprinting is further illustrated through its application in constructing advanced tissues, including bone, cardiac, cartilage, corneal, and hepatic models. Finally, we explore emerging frontiers such as multi‐material and multi‐modal bioprinting, machine learning‐guided optimization, and regulatory pathways toward clinical translation. Collectively, these insights outline a roadmap for advancing VP‐based bioprinting into a clinically viable, high‐throughput tissue engineering technology.

Bone tissue scaffolds fabricated via extrusion-based bioprinting require high dimensional accuracy to ensure functional performance in tissue regeneration. However, process fluctuations caused by material behaviour, extrusion instability, and environmental variations can lead to pore size deviations and reduced fabrication repeatability. This study proposes a real-time image-based closed-loop control framework for improving dimensional accuracy in bioprinting processes. The system integrates inline visual monitoring with adaptive flow control to continuously track pore geometry during fabrication. Image-based analysis is used to compute pore size deviations in real-time, enabling dynamic adjustment of material flow to maintain predefined geometric tolerances. Unlike conventional trial-and-error or offline calibration approaches, the proposed framework autonomously compensates for process deviations during fabrication, reducing material waste and improving process stability. Experimental results demonstrate improved pore size consistency, enhanced dimensional accuracy, and increased reproducibility under varying process conditions. The proposed framework contributes to the development of adaptive and autonomous material extrusion-type bioprinting systems for reliable scaffold fabrication.

Microstructure control and high residual stresses remain key challenges in metal additive manufacturing. A novel artificial intelligence-based framework, which considers the underpinning thermal evolution, was developed to generate laser scanning strategies that can mitigate these issues. The framework integrates a convolutional neural network (CNN) and a genetic algorithm (GA): the CNN predicts temporal and spatial temperature distributions, while the GA optimizes laser scanning sequences based on designated criteria. To validate the approach, laser scanning strategies for laser powder bed fusion of stainless steel 316 L were generated and experimentally implemented. The scanning pattern designed to maximize cooling rate produced refined microstructures. Similarly, microstructure characterization revealed reduced kernel average misorientation values in samples fabricated using the minimised temperature gradient criterion, indicating lower residual stress and local plastic strain. This preliminary experimental validation demonstrates the potential of this solidification conditions associated with deep learning based framework to control microstructure and defect formation in metal additive manufacturing, particularly for larger and more realistic component sizes.

Bone tissue supports the body, enables movement, protects organs, produces blood cells and stores minerals. In regenerative medicine, bone’s natural healing ability drives the need for engineered solutions to treat fractures, defects, and support implants. This study explores the development of poly(ethylene terephthalate glycol) (PETG) and PETG/bacterial cellulose (BC) composite scaffolds with varying BC contents (10, 15, and 20 wt%) for bone tissue engineering. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) revealed porous structures with increasing surface roughness as BC content rose. Water contact angle analysis showed enhanced hydrophilicity in PETG/BC composites, particularly at higher BC levels. Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and differential scanning calorimetry (DSC) confirmed successful BC integration and interactions with PETG, along with increased crystallinity. Mechanical testing indicated that compressive strength improved with higher BC content, with 20 wt% BC achieving optimal performance. Biological tests using human adipose-derived stem cells (hADSc) showed enhanced proliferation, differentiation, and mineralization on PETG/BC scaffolds. Among all, the 20 wt% BC scaffold demonstrated the most favorable physical, mechanical, and biological properties. Overall, PETG/BC scaffolds, especially those with 20 wt% BC, show strong potential for future bone tissue engineering applications.

Bioprinting at physiological temperature (PT) is desirable to maintain cell viability during and after printing, especially for tissue and organ scale constructs requiring a long fabrication time. Typically, bioinks show a temperature viscosity dependence and exhibit poor printability at PT, limiting construct complexity and shape fidelity. Embedded bioprinting offers opportunities to print low viscosity bioinks, however, the consideration of PT is often neglected. In this study, a dual thermoresponsive and photocrosslinkable bioink was developed comprising gelatin methacryloyl (GelMA) and either methylcellulose (MC) or methylcellulose methacrylate (MCMA). This bioink serves as both a direct extrusion bioink and as a support bath for embedded bioprinting. Both MC and gelatin show synergistic thermosensitive rheological properties which was exploited to enable bioprinting at both room temperature and PT to create a semi-interpenetrating or interconnected polymer network with tuneable properties. The bioinks show sol-gel transitions at temperatures of < 27 degrees C and > 33 degrees C, representing the contribution from GelMA and MC/MCMA, respectively, and improved thixotropic, and self-healing behaviour at PT. These rheological properties significantly improve printability at a range of temperatures (18-37 degrees C) and allows the bioink to function as a support bath at PT. Moreover, higher cell viability (>90 %) post-bioprinting was observed in PT bioprinted constructs. The cell response in bioprinted constructs was dependent on bioink composition and cell density, with low polymer concentration and increased cell densities favouring the spreading and proliferation of adipose-derived stem cells. Acting as a support bath, the bioink enabled fabrication at PT of complex cell-laden structures through embedded bioprinting. This allowed spatial patterning of a variety of cell types and perfusable channels with the support bath acting as a matrix to provide long-term support and as a reservoir of cells. The bioinks successfully expand bioprinting capability at PT for both direct and embedded bioprinting and has promising potential to fabricate large-scale tissue models for tissue engineering applications.

Piezoelectric biomaterials convert mechanical energy into electrical charges, making them promising candidates for bone tissue engineering by restoring and modulating the electrophysiological microenvironment. This review explores the development of piezoelectric biomaterials by focusing on their molecular origins, particularly dipoles, and how their type, source, and spatial arrangement influence macroscopic electromechanical coupling. Beyond intrinsic origins, the concept of pseudo-piezoelectricity driven by extrinsic factors is introduced to highlight alternative approaches for piezoelectric biomaterial design. Techniques to engineer dipoles and modulate piezoelectric properties for the regulation of osteogenesis are discussed. Particular attention is given to the correlation between piezoelectricity and osteogenesis at distinct phases of bone regeneration. Finally, current challenges in molecular understanding and biofabrication of piezoelectric bone scaffolds are highlighted, along with potential future research directions.

Bioprinting is a revolutionary technology within the field of tissue engineering that enables the precise fabrication of three-dimensional (3D) tissue constructs. It combines the principles of engineering and biology to create structures that closely mimic the complexity of native human tissues, facilitating advancements in regenerative medicine and personalized healthcare. This review paper systematically explores the challenges and design requirements in the fabrication of 3D biomimetic tissue constructs, emphasizing the need for advanced bioprinting strategies. Achieving biomimicry involves creating 3D anatomically relevant structures, biomimetic microenvironments, and vascularization. The focus is on overcoming existing bottlenecks through advancements in both fabrication techniques and bio-inks. Future directions in bioprinting are outlined, including multi-modal bioprinting systems, in-situ bioprinting, and the integration of machine learning into bioprinting processes. The critical role of bio-inks and printing methodologies in influencing cell viability is highlighted, providing insights into strategies for enhancing cellular functionality throughout the bioprinting process. Furthermore, the paper addresses post-fabrication considerations, particularly in accelerating tissue maturation, as a pivotal component for advancing the clinical applicability of bioprinted tissues. By navigating through the challenges, innovations, and prospects of advanced bioprinting strategies, this review highlights the transformative impact on tissue engineering. Pushing the boundaries of technological capabilities, these strategies hold the promise of groundbreaking advancements in regenerative medicine and personalized healthcare. Ultimately, the integration of these advanced techniques into bioprinting processes will pave the way for the development of more highly biomimetic and functional bioprinted tissues.

In this review, we propose a comprehensive overview of additive manufacturing (AM) technologies and design possibilities in manufacturing metamaterials for various applications in the biomedical field, of which many are inspired by nature itself. It describes how new AM technologies (e.g. continuous liquid interface production and multiphoton polymerization, etc) and recent developments in more mature AM technologies (e.g. powder bed fusion, stereolithography, and extrusion-based bioprinting (EBB), etc) lead to more precise, efficient, and personalized biomedical components. EBB is a revolutionary topic creating intricate models with remarkable mechanical compatibility of metamaterials, for instance, stress elimination for tissue engineering and regenerative medicine, negative or zero Poisson’s ratio. By exploiting the designs of porous structures (e.g. truss, triply periodic minimal surface, plant/animal-inspired, and functionally graded lattices, etc), AM-made bioactive bone implants, artificial tissues, and organs are made for tissue replacement. The material palette of the AM metamaterials has high diversity nowadays, ranging from alloys and metals (e.g. cobalt–chromium alloys and titanium, etc) to polymers (e.g. biodegradable polycaprolactone and polymethyl methacrylate, etc), which could be even integrated within bioactive ceramics. These advancements are driving the progress of the biomedical field, improving human health and quality of life.

As global demand for sustainable and ethical protein sources grows, cultivated meat has emerged as a promising alternative to traditional animal farming. To replicate the texture, appearance, and sensory qualities of conventional meat, 3D (bio)printing technologies are gaining attention for their ability to fabricate structured meat constructs with high spatial precision. This review presents a comprehensive overview of current 3D (bio)printing strategies in cultivated meat production. It begins with introducing key 3D printing modalities, highlighting their underlying principles, advantages, and limitations. The review then discusses the critical roles of cellular components and scaffold design, with a focus on material composition and architectural features necessary for mimicking the fibrous, anisotropic structure of muscle tissue. Recent advancements across various species are examined in detail. In cultivated beef, 3D (bio)printing has enabled the alignment of muscle fibers and controlled fat distribution, effectively replicating the marbling characteristics of premium meats like Wagyu. For cultivated fish, hydrogel-based constructs and edible porous microcarriers have been employed to recreate the layered, flaky architecture of fish fillets, while enhancing both cell viability and textural fidelity. In the case of cultivated pork, innovations include microfiber-based platforms that support unidirectional muscle alignment, along with co-printing strategies that spatially integrate adipose and muscle tissues to emulate the layered structure of pork belly. Despite these promising developments, significant challenges remain. These include the need for scalable manufacturing production, the optimization of bioactive and food-safe cell-laden bio-inks, and the navigation of complex regulatory pathways. By integrating insights from bioprinting technology, cell biology, and materials science, this review identifies key limitations and outlines strategic directions for future research. Collectively, these interdisciplinary efforts are paving the way toward scalable, customizable, and nutritionally relevant cultivated meat products which offer a transformative solution for the future of food production and global food security.

Tissue engineering scaffolds are three-dimensional, biocompatible, biodegradable, and porous structures designed to support cell attachment, proliferation, and differentiation, leading to new tissue formation. Designing optimal scaffolds is complex, requiring the optimisation of various physical, chemical, and biological properties, which are cell- or tissue-dependent. For hard tissue applications such as bone, compressive strength is a critical property and can be adjusted by modifying printing conditions. The mechanical properties of scaffolds produced using different microstructural polymers (semi-crystalline and amorphous) depend on parameters that significantly impact filament extrusion and the crystallisation process. This study investigates the effect of key process parameters (printing temperature, printing speed, and flow) on scaffold mechanical properties using the Taguchi method. Three biocompatible polymers with different microstructures-polycaprolactone, polylactic acid, and polyethylene terephthalate glycol-were examined. Results show a high correlation between process parameters and compressive strength using the Taguchi method, but prediction accuracy remained low. Therefore, four machine learning algorithms-Random Forest (RF), Support Vector Regression (SVR), K-Nearest Neighbor (K-NN), and Gradient Boosting Regression (GBR)-were applied to enhance predictive performance. Notably, the RF and GBR algorithms achieved approximately 99 % prediction accuracy when evaluated on the test dataset.

The repair of critical-sized bone defects represents significant clinical challenge. An alternative approach is the use of 3D composite scaffolds to support bone regeneration. Hydroxyapatite (HA) and tri-calcium phosphate (β-TCP), combined with polycaprolactone (PCL), offer promising mechanical resistance and biocompatibility. Bioelectrical stimulation (ES) at physiological levels is proposed to reestablishes tissue bioeletrocity and modulates cell signaling communication, such as the BMP/TGF-β and the RANK/RANK-L/OPG pathways. This study aimed to evaluate the use HA/TCP scaffolds and ES therapy for bone regeneration and their impact on the TGF-β/BMP pathway, alongside their relationship with the RANK/RANKL/OPG pathway in critical bone defects. The scaffolds were implanted at the bone defect in animal model (calvarial bone) and the area was subjected to ES application twice a week at 10 µA intensity of current for 5 min each session. Samples were collected for histomorphometry, immunohistochemistry, and molecular analysis. The TGF-β/BMP pathway study showed the HA/TCP+ES group increased BMP-7 gene expression at 30 and 60 days, and also greater endothelial vascular formation. Moreover, the HA/TCP and HA/TCP+ES groups exhibited a bone remodeling profile, indicated by RANKL/OPG ratio. HA/TCP scaffolds with ES enhanced vascular formation and mineralization initially, while modulation of the BMP/TGF pathway maintained bone homeostasis, controlling resorption via ES with HA/TCP.

Cardiovascular diseases (CVDs), the leading cause of mortality worldwide, stem from structural and functional abnormalities in the heart and blood vessels. Although advancements in treatments such as percutaneous coronary intervention and vascular stent implantation have reduced complications, challenges such as restenosis, late thrombosis, and limited customisation remain. Biodegradable polymer vascular stents (BPVSs) have emerged as promising alternatives to traditional metallic stents, offering advantages such as controlled degradation, improved biocompatibility, and reduced late-stage complications. This review examines the integration of 3D printing (3DP) techniques, including material extrusion, vat photopolymerisation, powder bed fusion, material jetting, and binder jetting into BPVS fabrication, highlighting their potential to enhance material properties, manufacturing processes, and clinical applicability. Key topics include material selection, structural design optimisation, and mechanical characterisation of 3DP BPVSs. The review also discusses preclinical evaluations and updated clinical insights, concluding with future research directions, including advanced materials development, innovative structural designs, breakthroughs in high-resolution 3DP techniques, and challenges in regulatory approval and clinical translation. These advancements underscore the potential of 3DP BPVSs to revolutionize personalised CVD treatment.

In a circular textile economy, there is a requirement to reduce the consumption of new materials and encourage ways to keep materials and apparel in use for longer while utilising waste as a raw material. Repair and reinforcement of materials are circular practices that have been applied to extend the life cycle of apparel. The digitalisation of repair tools could facilitate how the repair is adopted at scale. 3D printing has been highlighted as an important technology for future manufacturing due to its ease, speed, and ability to be locally or globally produced. Although 3D printing is an accessible tool for at-home object printing of repair parts, this tool has not been investigated to extend the life cycle of a textile material through repair or reinforcement. In this paper, we present an interdisciplinary approach explored in the Textiles Circularity Centre to investigate how 3D printing a medium consisting of bacterial cellulose and polyethylene terephthalate glycol onto textiles can reinforce a material. We characterise the printed medium and discuss the use of 3D printing as a tool for advanced repair practices in a circular textile economy. The novelty of this approach is in the deposition of a cellulose-based filament onto a textile to facilitate material longevity, namely, reinforcement for repair and reuse.

Extrusion-based 3D printing is extensively used to fabricate osteochondral (OC) constructs. However, significant challenges remain, particularly engineering constructs that can replicate the heterogeneity and structural organization of OC tissue and maintain a chondrogenic phenotype. Herein, this study introduces an integrated hybrid 3D bioprinting strategy, incorporating soft hydrogel bioinks and a bioceramic thermoplastic composite polymer, allowing the fabrication of a zone-specific construct analogous to OC tissue. The results show that the hybrid triphasic 3D bioprinted construct mimicking the full-thickness OC tissue displays a distinct layered structure with high precision and improved mechanical properties. The calcified layer fabricated by co-printing gelatin methacryloyl (GelMA) and polycaprolactone/tricalcium phosphate (PCL/TCP) enables the formation of a transition layer and provides strong bonding between the engineered PCL/TCP subchondral bone and the methacrylated methylcellulose (MCMA)/GelMA cartilage layer. The encapsulated human adipose-derived stem cells are found to be spatiotemporally released from the calcified cartilage layer and directionally attach to the subchondral bone layer of the construct. The MCMA/GelMA bioinks exhibit a stiffness and stress relaxation profile suitable for cartilage applications. Human chondrocytes (HCs) show enhanced cell viability and proliferation. Moreover, the HCs encapsulated within the MCMA/GelMA bioinks maintain their chondrogenic phenotype with high expression of collagen type II (Col2) and SOX9. At the liquid-matrix interface, they experience a loss of chondrogenic phenotype and potential chondrogenic-to-osteogenic trans-differentiation with the expression of the osteogenic marker collagen type I (Col1). This study provides a deep understanding and insightful view of chondrogenic behaviours responding to the microenvironment via extensive in-vitro studies and shed light on a promising approach for the future OC tissue regeneration.

Current clinical interventions for large peripheral nerve gap injuries are limited. Bioprinting provides opportunities to develop tissue engineered constructs that provide a biomimetic environment to guide nerve regeneration. However, hydrogels that are cell-instructive, mechanically compliant, and have an appropriate biodegradation profile for nerve guidance conduit applications are limited. In this study, a photocrosslinkable gelatin methacryloyl (GelMA) and polyethylene glycol diacrylate (PEGDA) hybrid bioink is developed. The role of PEGDA molecular weight and concentration in tuning the hydrogel physicochemical and biological properties is evaluated. PEGDA modulated the hydrogel network structure and properties in a molecular weight and concentration dependent manner. A lower molecular weight and high concentration induced high crosslinking density thus improving compressive modulus, lower swelling, and a slower degradation profile. The bioinks showed good printability and are able to fabricate multi-layer constructs with high shape fidelity and flexibility. The SH-SY5Y cells maintained high cell viability after bioprinting in all bioinks. However, cells showed limited metabolic activity and spreading in the GelMA/PEGDA hydrogels with both high concentration and molecular weight. This preliminary study provides guidance on the use of specific molecular weights and concentrations in GelMA/PEGDA bioinks for the bioprinting of SH-SY5Y cells.