Antimicrobial resistance (AMR) represents an escalating global health crisis, demanding alternative strategies to reduce resistant pathogen burden across environments. Microbe-based biocontrol is promising, yet effectively deploying it in practical settings remains challenging. In this study, we present a 3D bioprinted core-shell construct featuring a polyethylene glycol diacrylate (PEGDA) shell with tunable nanoscale porosity, encapsulating germinable spores of the biocontrol agent Bacillus subtilis TH035. This configuration supports long-term spore viability while providing protection from common environmental stressors including UV-C irradiation, ethanol exposure, and desiccation over 4 weeks. The nanoporous PEGDA shell enables effective bacterial confinement while facilitating sufficient metabolite exchange for B. subtilis germination and growth, as well as suppression of methicillin-resistant Staphylococcus aureus (MRSA) growth by approximately one order of magnitude. This approach demonstrates the feasibility of embedding B. subtilis spores within engineered scaffolds for extended competitive functionality. The versatility and scalability of digital light processing (DLP) based bioprinting offers significant potential for tailored designs and high-throughput manufacturing. This proof-of-concept platform may find future applications in areas such as biomedical packaging, environmental sanitation, and built environment surface coatings, particularly in settings where intermittent moisture or nutrient availability can support spore germination and biocontrol activity.

In this work, we developed a collagenase-responsive hydrogel system to covalently load cancer immunotherapy candidate cowpea mosaic virus (CPMV) using 3D digital light processing bioprinting technology. CPMV was functionalized with norbornene groups (CPMV-NB), which was then bioprinted into hydrogels with 8-arm polyethylene glycol norbornene and a collagenase-cleavable peptide via photoinduced thiol-ene click chemistry. This strategy enabled stable retention of CPMV-NB within the hydrogels and achieved controlled release of CPMV-NB triggered by collagenase. Furthermore, released CPMV-NB retained its immunogenicity to stimulate immune cells.

Peripheral nerve injury remains a significant clinical challenge, with current therapeutic material limited by inadequate degradation control, insufficient oxidative stress management, and poor adaptability to patient-specific contexts. We developed a degradable poly(ethylene glycol) diacrylate-dopamine-acrylamide hydrogel platform that addresses these limitations, enabling tunable bulk degradation with concomitant dopamine release. By systematically varying the ratio of degradable crosslinker poly(ethylene glycol) diacrylate-dopamine, we generated composition-defined degradation profiles spanning 2 months with corresponding dopamine release patterns. The hydrogels exhibited mechanical properties comparable to native peripheral nerves while maintaining exceptional flexibility through multiple bending and torsional cycles. In vitro validation demonstrated that dopamine-releasing hydrogels effectively scavenged intracellular reactive oxygen species in both human Schwann cells and endothelial cells under oxidative challenge, while modulating Schwann cell gene expression in a pattern consistent with a transition from repair toward a pro-remyelination transcriptional profile, and shifting endothelial gene expression toward a pro-angiogenic transcriptional pattern. Using digital light processing bioprinting we fabricated customizable nerve wraps, tubular structures, and microarchitectures with internal channels that directed cell alignment, while controlled FITC-dextran release validated localized delivery capabilities. These findings establish a multifunctional hydrogel platform combining programmable degradation, antioxidant functionality, and cellular microenvironment control for peripheral nerve repair applications.

Current vascular grafts face limitations including inadequate mechanical strength, inability to replicate small and complex anatomical structures, ethical concerns with animal-based training models, and high costs that limit accessibility. We developed a cytocompatible vascular graft fabrication platform combining dual-network hydrogels with high-resolution digital light processing (DLP) 3D printing to address these bottlenecks. Through systematic evaluation of hydrogel formulations, we identified a polyacrylamide-alginate-calcium dual-network system achieving tensile properties comparable to native vessels while enabling exceptional suture retention and structural integrity required for microsurgical applications. Integration with DLP printing enabled fabrication of ultra-small microchannels and complex branching vascular networks with patient-specific geometries derived from magnetic resonance imaging (MRI) data. To fine-tune the material properties of the vessels, we developed a machine learning model that optimizes the bioink composition to achieve targeted mechanical properties. We further established an integrated microsurgery training platform combining 3D-printed vessels with essential surgical equipment, providing authentic haptic feedback at a significantly lower cost than commercial alternatives. Biological validation demonstrated robust endothelial cell viability and barrier formation. These studies demonstrated a comprehensive platform addressing multiple critical bottlenecks in vascular graft technology with potential for both accessible microsurgical training and future therapeutic applications in personalized vascular reconstruction.

Developing predictive human in vitro drug screening platforms requires models that capture the spatial complexity, cellular diversity, and functional maturity of a native liver tissue. Here, we present a bioprinted multi-cellular liver model that integrates induced pluripotent stem cells (iPSCs)-derived hepatocytes and endothelial cells within a matrix metalloproteinase (MMP)-degradable, YIGSR-functionalized polyethylene glycol (PEG)-norbornene (NB) hydrogel. The multi-cellular architecture recapitulates hepatic organization by spatially positioning endothelial and parenchymal compartments in physiologically relevant arrangements, enabling paracrine signaling, enhanced nutrient exchange, and stable cell-cell/matrix interactions. Integrated with a dynamic microfluidic perfusion system, the construct supports matrix remodeling, delivers physiological shear stress, and sustains a well-oxygenated microenvironment. Compared to static culture, dynamic perfusion preserved long-term albumin and urea secretion, enhanced cytochrome P450 activity, reduced oxidative stress, and maintained mitochondrial integrity over extended culture periods. Transcriptomic profiling confirmed significant enrichment of metabolic, junctional, and drug-processing pathways. Functionally, the multi-cellular platform demonstrated robust and inducible drug-metabolizing capacity, enabling accurate identification of clinically relevant hepatotoxic compounds. Drug potency metrics-including IC50 and benchmark dose values-closely matched reported human plasma concentration thresholds, underscoring the translational potential of the system. This reproducible, physiomimetic multi-cellular liver platform provides a high-content, human-iPSC based liver tissue to conventional preclinical models, bridging the gap between early-stage drug testing and clinical outcomes while offering new opportunities for predictive pharmacology and toxicity assessment.

Glioblastoma (GBM) is the most common and malignant brain tumor, characterized by its highly aggressive and rapidly proliferative behavior. In this study, we developed a high throughput GBM model with a cell density modulated hypoxic niche to investigate the important role of hypoxia in shaping GBM progression and therapeutic response. Harnessing the precise control over materials using digital light processing (DLP) bioprinting, we fabricated GBM constructs with tunable cell densities in gelatin methacrylate (GelMA), a photopolymerizable hydrogel that mimics the extracellular matrix. High cell density (HCD) constructs gave rise to a hypoxic microenvironment, allowing us to study natural hypoxia-driven adaptations, including ROS signaling, migration patterns, and altered metabolic pathways. The major hypoxia pathway, hypoxia inducible factor (HIF-1α), was significantly enriched by 15-fold in the HCD condition compared to its base condition. Following this, we explored cellular response to drug treatment using standard-of-care GBM therapies to validate the hypoxic niche. These data show HCD model provides a more robust and Temozolomide-resistant environment compared to spheroids and low density conditions. Our findings demonstrate that DLP bioprinting provides a precise and reproducible platform for modeling GBM physiology and highlight its potential for high throughput drug screening in vitro.

Advances in biofabrication, stem cell biology, and biomaterials engineering have enabled the generation of multicellular tissue constructs capable of recapitulating key aspects of biological function. Despite these advances, the transition from millimeter-scale engineered tissues to centimeter-scale solid organs remains limited by the inability to establish dense, functional vascular networks capable of sustaining metabolically active tissues. This focused review summarizes the complexities involved in generating physiological vasculature and highlights progress in several approaches developed over the past two decades. We discuss progress across several core technology categories, including organoid-based and microfluidic-based platforms to model the vasculatures, as well as the techniques feasible to construct an organ-scale tissue, including recellularization of decellularized organ scaffolds, and bottom-up biofabrication approaches for complex 3D vasculature and high-cell density compatibility. By synthesizing insights from these complementary approaches, we highlight emerging design principles for constructing hierarchical and functional vascular networks. Finally, we outline a forward-looking roadmap toward scalable vascularization strategies that may enable the realization of biofabricated, functional human organs in the coming decade.

Biofabrication and biomedical manufacturing are inherently multidisciplinary, integrating living systems with advanced manufacturing to create functional products for applications spanning regenerative engineering and medicine, in vitro disease modeling, drug discovery, and medical devices. As these technologies develop, they are emerging as core enablers of next-generation healthcare and life-science innovation. In the United States (U.S.), rapid progress across fabrication processes, material systems, physics-based modeling, and translation-oriented strategies is expanding the achievable design space and accelerating movement from laboratory demonstrations toward clinical and commercial deployment. We introduce major U.S. research frontiers and highlight representative advances in this field that support applications including organoids and other microphysiological systems for in vitro testing, engineered tissue constructs for in vivo use, and medical devices and biohybrid platforms. We further provide an outlook on advancing robust, ethical biofabrication and biomedical manufacturing in the U.S. research ecosystem.

Coral skeletal morphology and optical properties play critical roles in regulating light distribution to symbiotic dinoflagellates and shaping their growth and photosynthetic performance. However, existing experimental approaches lack precise control over skeletal microgeometry and optical scattering, limiting comprehensive studies of coral photophysiology. Here, we present a 3D bioprinted artificial coral platform integrating engineered hydrogel-based tissue with tunable skeletal structures to investigate coral-algal light interactions. Diffusion-optimized hyaluronic acid glycidyl methacrylate (HAGM) hydrogels supported robust growth and photosynthesis of encapsulated dinoflagellates. Using natural coral skeletons from shallow and mesophotic environments, we demonstrate that algal growth within the HAGM tissue layer is regulated by the underlying skeletal morphology. We further fabricated artificial coral skeletons with fine-scale corallite geometries by incorporating cellulose nanocrystals to enhance light scattering. Evaluation under varying light intensities revealed photosynthetic performance trends consistent with those observed under natural conditions. This platform provides a controllable in vitro model for studying coral-algal photophysiology.

Light-based 3D bioprinting has emerged as a transformative technology for fabrication of biomimetic tissues and artificial organs. High cell density (HCD) bioprinting aims to recapitulate the cellular density and interactions in native tissue, but faces significant challenges in achieving both high resolution and structural fidelity due to light scattering during the photopolymerization process. Refractive index (RI) tuning of the bioink mitigates light scattering to improve printing fidelity. In this study, we developed an iohexol (IHX)-based bioink for digital light processing (DLP) bioprinting. IHX effectively tuned the RI of the bioink to match cellular components to reduce light scattering while still maintaining printability. The bioink demonstrated excellent biocompatibility across multiple cell types, including epithelial, endothelial, parenchymal, and stem cells, while simultaneously supporting post-printing cellular viability, reorganization, and functionality. Using IHX-bioink, we fabricated tubular constructs with lumen diameters ranging from 400 μm to 1.1 mm and utilized strategies to minimize overpolymerization and ensure lumen fidelity. Our results underscore IHX-bioink as a promising biomaterial for scalable, RI-matching 3D bioprinting, enabling the creation of perfusable, HCD constructs for various applications in tissue engineering and regenerative medicine.

The placenta plays a vital role in pregnancy by regulating selective exchange between maternal and fetal circulations and producing essential hormonal signals. Here, we present an in vitro placenta-on-a-chip platform that leverages 3D bioprinting to replicate the structural and functional features of the human placental barrier. This microengineered system utilizes digital light processing 3D bioprinting to fabricate the microfluidic mold and to construct 3D encapsulated cell cultures within a biomimetic hydrogel scaffold, enabling co-culture of three human cell types, including two derived from primary placental tissue. We demonstrate excellent cell viability, high metabolic activity, placental hormone secretion, and native-like selective barrier transport properties within the model. This system offers a versatile platform for experimental perturbations to explore mechanisms of normal placental function and identify contributors to placental dysfunction.

Bioprinting of cell-laden hydrogels is a rapidly growing field in tissue engineering. The advent of digital light processing (DLP) three-dimensional (3D) bioprinting technique has revolutionized the fabrication of complex 3D structures. By adjusting light exposure, it becomes possible to control the mechanical properties of the structure, a critical factor in modulating cell activities. To better mimic cell densities in real tissues, recent progress has been made in achieving high-cell-density (HCD) printing with high resolution. However, regulating the stiffness in HCD constructs remains challenging. The large volume of cells greatly affects the light-based DLP bioprinting by causing light absorption, reflection, and scattering. Here, we introduce a neural network-based machine learning technique to predict the stiffness of cell-laden hydrogel scaffolds. Using comprehensive mechanical testing data from 3D bioprinted samples, the model was trained to deliver accurate predictions. To address the demand of working with precious and costly cell types, we employed various methods to ensure the generalizability of the model, even with limited datasets. We demonstrated a transfer learning method to achieve good performance for a precious cell type with a reduced amount of data. The chosen method outperformed many other machine learning techniques, offering a reliable and efficient solution for stiffness prediction in cell-laden scaffolds. This breakthrough paves the way for the next generation of precision bioprinting and more customized tissue engineering.

In vitro liver tissue models are valuable for studying liver function, understanding liver diseases, and screening candidate drugs for toxicity and efficacy. While three-dimensional (3D) bioprinting shows promise in creating various types of functional tissues, current efforts to engineer a functional liver tissue face challenges in replicating native high cell density (HCD) and maintaining long-term cell viability. HCD is crucial for establishing the cell-cell interactions necessary to mimic the liver's metabolic and detoxification functions. However, HCD bioinks exacerbate light scattering in light-based 3D bioprinting. In this study, we incorporated iodixanol into our bioink formulation to minimize light scattering, enabling the fabrication of hepatic tissue constructs with an HCD of 8 × 107 cells/mL while maintaining high cell viability (∼80 %). The printed dense hepatic tissue constructs showed enhanced cell-cell interactions, as evidenced by increased expression of E-cadherin and ZO-1. Furthermore, these constructs promoted albumin secretion, urea production, and P450 metabolic activity. Additionally, HCD hepatic tissue inactivated the YAP/TAZ pathway via cell-cell interactions, preserving primary hepatocyte functions. Further screening revealed that hepatocytes in the dense model were more sensitive to drug treatments than those in a lower-density hepatic model, highlighting the importance of HCD in recapitulating the physiological drug responses. Overall, our approach represents a significant advancement in liver tissue engineering, providing a promising platform for the development of physiologically relevant in vitro liver models for drug screening and toxicity testing.

The global decline of coral reefs calls for new strategies to rapidly restock coral populations and maintain ecosystem functions and services. Low recruitment success on degraded reefs hampers coral sexual propagation and leads to reduced genetic diversity and impaired reef resilience. Here, we introduce a Bacterial Reef Ink (Brink) to assist in coral larval settlement. Brink is a photopolymerized living material that can be rapidly applied to restoration substrates and has been formulated to cultivate two settlement-inducing bacterial strains (Cellulophaga lytica and Thalassotalea euphylliae). Settlement assays performed with broadcast spawning (Montipora capitata) and brooding (Pocillopora acuta) Indo-Pacific corals showed that Brink-coated substrates increased settlement >5-fold compared with uncoated control substrates. Brink can be applied as a flat coating or patterned using light-assisted 3D bioprinting, enabling diverse applications in reef restoration and engineering. This approach demonstrates the potential of functional living materials to enhance coral ecosystem engineering and support coral reef rehabilitation.

Wastewater treatment, particularly for persistent organic pollutants (POPs), remains a significant challenge. Although advanced oxidation processes (AOPs) currently used for treating POPs can achieve a decent efficiency, they often involve high costs and necessitate additional post-treatment processes. Here, a jellyfish-mimicking, multi-functional living material encapsulating algae cells are presented, namely Algelly, created using a multi-material digital-light processing (DLP) bioprinting technique. The Algelly construct comprises a methacrylated alginate (AlgMA) layer designed to support algae growth, and a poly(N-isopropylacrylamide) (PNIPAM) layer embedded with magnetic nanoparticles (MNs). The MNs enable the Algelly to respond to near-infrared (NIR) laser for deformation and magnetic force for steering. It is demonstrated that the DLP bioprinting technique can fabricate the heterogeneous Algelly with high spatial resolution and efficiency, which supports subsequent algae proliferation and effective photosynthesis in the Algelly matrix. Moreover, the NIR-induced thermo-responsive deformation and magnetic steering capabilities enhance Algelly's adaptability for recycling and collection. Most importantly, Algelly demonstrates a high efficiency in degrading POPs under white light illumination. Therefore, it is believed that Algelly holds a promising potential for new applications in wastewater treatment, given its efficiency in POP decomposition and flexible location control capabilities.

There is a clinical need for an effective nerve guidance conduit to treat peripheral nerve injuries. Many studies have explored different materials and active cues to guide neural regeneration, with some success. However, none have demonstrated a comparable or better functional recovery than the clinical standard autograft. Autografts are often insufficient for reconstruction of an injury to long nerves such as the sciatic or brachial plexus. Synthetic nerve guidance conduits (NGCs) have been investigated for these injuries to guide axonal regeneration and lead to functional recovery. We have designed a biologics-free hydrogel-based multi-channel conduit with defined microscale features to guide axonal outgrowth. To investigate extraneural vascular infiltration and its effects on functional recovery, we also designed a multi-microchannel conduit with defined regularly spaced micropores, orthogonal to the axon guidance channels. Using our custom-built Rapid Projection, Image-guided, Dynamic (RaPID) bioprinting system, we were able to fabricate each hydrogel conduit within minutes from a milliliter-volume prepolymer vat. With our state-of-the-art printing platform, we have achieved NGCs with a consistent channel wall width of 10 μm. We implanted the NGCs for 17 weeks in a murine sciatic nerve transection injury model. We assessed the functional recovery by dynamic gait analysis throughout the recovery period and by compound muscle action potential (CMAP) electrophysiology before NGC harvesting. Both the non-porous and micro-porous conduit groups led to functional nerve regeneration on par with the autograft group. Further, both conduit groups resulted in restoration of bulk motor function to pre-injury performance.

Anthropogenic stressors pose substantial threats to the existence of coral reefs. Achieving successful coral recruitment stands as a bottleneck in reef restoration and hybrid reef engineering efforts. Here, we enhance coral settlement through the development of biomimetic microhabitats that replicate the chemical landscape of healthy reefs. We engineered a soft biomaterial, SNAP-X, comprising silica nanoparticles (NPs), biopolymers, and algal exometabolites, to enrich reef microhabitats with bioactive molecules from crustose coralline algae (CCA). Coral settlement was enhanced over 20-fold using SNAP-X-coated substrates compared with uncoated controls. SNAP-X is designed to release chemical signals slowly (>1 month) under natural seawater conditions, and can be rapidly applied to natural reef substrates via photopolymerization, facilitating the light-assisted 3D printing of microengineered habitats. We anticipate that these biomimetic chemical microhabitats will be widely used to augment coral settlement on degraded reefs and to support ecosystem processes on hybrid reefs.

The myotendinous junction (MTJ) facilitates force transmission between muscle and tendon to produce joint movement. The complex microarchitecture and regional mechanical heterogeneity of the myotendinous junction pose major challenges in creating this interface in vitro. Engineering this junction in vitro is challenging due to substantial fabrication difficulties in creating scaffolds with intricate microarchitecture and stiffness heterogeneity to mimic the native muscle-tendon interface. To address the current challenges in creating the MTJ in vitro, digital light processing (DLP)-based 3D printing was used to fabricate poly(glycerol sebacate)acrylate (PGSA)-based muscle-tendon scaffolds with physiologically informed microstructure and mechanical properties. Local mechanical properties in various regions of the scaffold were tuned by adjusting the exposure time and light intensity used during the continuous DLP-based 3D printing process to match the mechanical properties present in distinct regions of native muscle-tendon tissue using printing parameters defined by an artificial intelligence-trained algorithm. To evaluate how the presence of zonal stiffness regions can affect the phenotype of a 3D-printed MTJ in vitro model, three 3D-printed PGSA-based scaffold conditions were investigated: (1) a scaffold with muscle-informed mechanical properties in its entirety without zonal stiffness regions, (2) a scaffold with one end possessing native muscle stiffness and the other end possessing native tendon stiffness, and (3) a scaffold with three distinct regions whose stiffness values correspond to those of muscle on one end of the scaffold, MTJ in the middle junction of the scaffold, and tendon on the other end of the scaffold. The scaffold containing regional mechanical heterogeneity most similar to the native MTJ (condition 3) was found to enhance the expression of MTJ-related markers compared to those without the presence of zonal stiffness regions. Overall, the DLP-based 3D printing platform and biomaterial system developed in this study could serve as a useful tool for mimicking the complexity of the native MTJ, which possesses inherent geometric and mechanical heterogeneity.

Controllable and long-term release remains a great challenge in current drug delivery systems. Benefiting from their efficient drug loading and painless administration, microneedles (MNs) have emerged as a promising platform for transdermal drug delivery, while they often fail to achieve long-term tissue adhesion and controllable extended drug release. Here, 3D printing of an innovative MN patch is presented with succulent-inspired responsive microstructures and light-controllable long-term release capability. The MN exhibits a reversible shrink-swell volume change behavior in response to surrounding humidity, which enables sufficient mechanical strength for skin penetration under the shrinkage conditions and efficient long-term adhesion when swollen in skin tissues. Moreover, the MN patch introduces a controllable long-term drug release system, achieved through the integration of thiolated heparin (Hep-SH) for sustained growth factor release and graphene oxide (GO) nanosheets for controlled drug release via near infrared (NIR) laser irradiation. The MN patches with growth factor loading have good biocompatibility and can promote the proliferation, migration, and proangiogenesis of endothelial cells is further demonstrated. Thus, it is believed that such flexible MN patches can be promising candidates for controllable long-term transdermal drug delivery as well as other related tissue engineering applications. 3D printing of an innovative MN patch is presented with succulent-inspired responsive microstructures for prolonged tissue adhesion. By integrating thiolated heparin (Hep-SH) and graphene oxide (GO) nanosheets, this patch can achieve light-controlled sustainable growth factor release, making it a promising candidate for controllable long-term transdermal drug delivery. image