The use of three-dimensional (3D) bioprinting to construct bone organoids holds significant promise in bone tissue engineering due to its potential to replicate complex structures for research and regenerative medicine. This technology enables the creation of precise 3D structures through layer-by-layer deposition of bioinks guided by digital models. However, challenges remain in achieving functional bone organoids, especially in bioink design, vascularization, and cell viability preservation. To address these issues, various printing techniques such as extrusion, inkjet, light-curing, and microfluidic printing have been explored, but further advances are needed to improve the quality and functionality of printed bone organoids. This review assesses the current state of research on the application of 3D bioprinting techniques for the construction of bone organoids, focusing on the selection of bioinks, scaffold materials, and the role of cells and growth factors. Despite notable progress, significant challenges remain in optimizing the mechanical properties of bioinks, enhancing vascularization, and mimicking the dynamic physiological environment of bone tissue. The main objective of this study is to explore the technical challenges and opportunities in the construction of functional bone organoids through 3D bioprinting, aiming to provide insights into future directions for overcoming these obstacles and improving bone tissue regeneration applications.  

Organ transplantation serves as a critical life-saving intervention. However, the persistent global shortage of donor organs continues to result in high mortality rates. This pressing clinical challenge has fueled the search for alternative therapeutic strategies. Among these strategies, three-dimensional (3D) bioprinting has emerged as a transformative technology capable of fabricating complex tissue constructs using bioinks composed of living cells and supportive biomaterials. Notably, recent advancements have highlighted the incorporation of decellularized extracellular matrix (dECM) as a bioactive component, significantly enhancing biocompatibility, structural integrity, cellular support, and the formation and maturation of vascular networks. In this review, we detail the pivotal role of the ECM as a dynamic reservoir of biochemical signals and mechanical cues that regulate cellular behavior through mechanotransduction. These processes guide essential functions including gene expression, tissue development, and remodeling, thereby ensuring tissue-specific mechanical properties such as elasticity and tensile strength. We highlight how dECM-based bioinks can retain the native structural and molecular features of the ECM, making them ideal for replicating physiologically relevant microenvironments. Representative studies demonstrate the successful application of dECM bioinks in engineering complex in vitro 3D tissue models. Furthermore, we address current challenges in tissue engineering, including the standardization of bioink formulations, the refinement of decellularization techniques, and the enhancement of the mechanical and architectural properties of scaffolds. Finally, we explore emerging solutions—such as artificial intelligence-guided optimization, in situ bioprinting, and the development of patient-specific bioinks—as promising avenues to overcome current limitations and drive the clinical translation of 3D-bioprinted tissues.

Volumetric muscle loss (VML) presents a significant clinical challenge because the intrinsic regenerative capacity of skeletal muscle is insufficient to repair extensive defects, and current therapeutic strategies remain inadequate. Bioprinting has emerged as a transformative approach, enabling the spatially controlled deposition of cells, biomaterials, and biochemical cues to create functional, biomimetic muscle tissues. This review offers a comprehensive overview of recent advancements in bioink development, bioprinting technologies, and functional reconstruction strategies for skeletal muscle regeneration. Bioinks derived from natural, synthetic, and composite materials are examined in terms of their effectiveness in supporting myogenesis, promoting cellular alignment, and facilitating neurovascular integration. We compare key bioprinting techniques—including extrusion-based, inkjet, and laser-assisted printing—highlighting their respective strengths and limitations in achieving structural fidelity and multicellular complexity. Emerging technologies such as coaxial and microfluidic-assisted printing are also discussed for their potential to fabricate aligned, anisotropic muscle constructs with hierarchical architectures. Functional outcomes are synthesized from in vitro assays (e.g., contractility, gene expression) and in vivo studies using VML models, with a focus on vascularization, innervation, and force restoration. Despite significant progress, substantial challenges remain in achieving complete neurovascular integration, long-term functionality, and clinical scalability. Moving forward, future efforts should emphasize the development of dynamic, bioresponsive materials, integration with electrical and mechanical stimulation, and the establishment of standardized preclinical protocols. By bridging material innovation, structural design, and biological functionality, bioprinting holds great promise for next-generation, clinically relevant skeletal muscle regeneration.

The blood–brain barrier (BBB), a vital defense interface of the central nervous system, selectively regulates molecular transport into the brain and maintains brain homeostasis. Disruption of BBB integrity contributes to various neurological diseases, making the BBB a key target for therapeutic compounds. However, traditional in vitro models struggle to recreate the BBB’s complex structure and dynamic functions. Recent advances in microfluidics and three-dimensional bioprinting have enabled the construction of high-fidelity in vitro BBB models that recapitulate key aspects of the brain’s vascular microenvironment. By integrating principles from materials science, microfabrication, and cell biology, these “BBB‑on‑a‑chip” platforms support physiologically relevant shear stress, cell–cell interactions, and barrier properties, making them powerful tools for compound screening and mechanistic research. This review summarizes the advances in in vitro BBB models and the application of bioprinting and microfluidic technology for compound evaluation.  

Advancements in three-dimensional (3D) printing have expanded design freedom across various fields, including footwear. Driven by recent progress in biomechanics, footwear has increasingly adopted complex structural designs to meet diverse functional demands, ranging from personal activity to competitive athletics and medical rehabilitation. Accordingly, the role of 3D printing in footwear development has become increasingly significant. This review categorizes the functions of footwear into protection, performance enhancement, and therapeutic applications, and systematically explores the impact of 3D printing on each of these primary functions. 3D printing technology enables the fabrication of complex but mechanically efficient structures, while the 3D scanning method facilitates the application of optimal, personalized designs tailored to individual biomechanics, which significantly impact all three functional areas of footwear. Such design advantages offered by 3D printing have been demonstrated across various fields, with both commercial and academic examples presented to support these findings. This review highlights interdisciplinary insights from biomechanics, ergonomics, and clinical studies to discuss the current status, limitations, and future potential of 3D-printed footwear. We conclude that continuous advancements in design methodology, material science, and printing technology will accelerate the adoption of 3D printing in next-generation footwear.  

Nanomanufacturing technology is crucial in advancing sophisticated biomedical devices, biochips, tissue engineering, and advanced biomedical materials. Two-photon polymerization (TPP) offers nanoscale fabrication precision, eliminates the need for masks, and allows the creation of arbitrary three-dimensional structures, providing technical advantages unparalleled by traditional methods. Applying TPP technology in the biomedical field presents new challenges related to materials and systems. Although there has been significant discussion regarding biomaterials, comparatively little attention has been given to the limitations of manufacturing systems for biomedical functional devices. Commercial TPP systems predominantly rely on point-by-point scanning for fabrication, which leads to low throughput. From a biomedical perspective, the goal is to achieve manufacturing precision at the single-cell level while scaling production throughput to the organ level. Advancements in precision and throughput are critical to expanding the applications of TPP in biomedical engineering. This review introduces the fundamental principles of TPP and summarizes recent advancements in TPP applications within tissue engineering, medical devices, and microfluidics. It then delves into the technological progress of TPP in recent years, focusing on aspects such as system design, manufacturing processes, and fabrication principles. The review highlights advancements in areas including the kinetics of light–matter interactions and the development of cutting-edge techniques such as spatiotemporal focusing. Finally, it discusses future development directions of TPP technology in biomedical applications

Remyelination is critical for functional recovery following peripheral nerve injury. Although autologous Schwann cell transplantation promotes effective myelin repair, its clinical translation remains limited due to donor scarcity and associated morbidity. Bone marrow-derived Schwann-like cells (B-dSCs) offer a promising alternative; however, their limited dedifferentiation capacity significantly constrains therapeutic outcomes. Neuregulin-1 (NRG1), a key axonal signal, effectively induces Schwann cell dedifferentiation but requires precise, sustained delivery to exert optimal effects. Here, we developed a three-dimensional (3D)-printed hydrogel scaffold incorporating NRG1-loaded sustained-release microspheres to achieve localized, prolonged NRG1 delivery. In vitro studies demonstrated that NRG1 significantly enhanced the dedifferentiation and remyelination capacity of B-dSCs in a dorsal root ganglion co-culture system. Mechanistically, NRG1 promoted dedifferentiation by activating the c-Jun N-terminal kinase (JNK) signaling pathway—a pivotal regulator of Schwann cell plasticity. Pharmacological inhibition of JNK markedly suppressed NRG1-induced dedifferentiation and downregulated myelin-associated gene expression, confirming pathway specificity. Furthermore, the 3D-printed scaffold effectively maintained uniform NRG1 distribution, facilitating enhanced axonal regeneration and improved myelin integrity. Collectively, these findings highlight the essential role of JNK signaling in NRG1-driven Schwann cell dedifferentiation and underscore the therapeutic promise of combining sustained-release systems with engineered cell therapies to advance peripheral nerve repair.

The placenta plays a vital role in pregnancy by regulating selective exchange between the maternal and fetal circulations and producing essential hormonal signals. In this study, 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-based 3D bioprinting to fabricate the microfluidic mold and 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. The system demonstrated excellent cell viability, high metabolic activity, placental hormone secretion, and native-like selective barrier transport properties. This system offers a versatile platform for experimental perturbations to explore mechanisms of normal placental function and identify contributors to placental dysfunction.

The concentration of the binder is a key factor affecting the quality of 3D-printed bone scaffolds. In this study, a macro–micro analysis was conducted to evaluate the effects of varying concentrations of polyvinyl alcohol (PVA) aqueous solution on the physical and biological properties of hydroxyapatite/β-tricalcium phosphate bone scaffolds. Both molecular dynamics (MD) simulations and experimental approaches were employed. The MD simulations analyzed microscopic interactions between PVA and ceramic powders by assessing changes in chain length at different concentrations. Experimentally, slurries containing 5–15% wt% PVA were characterized in terms of solid content, zeta potential, and extrusion rheology. Bone scaffolds were fabricated via 3D printing followed by freeze-drying, and their porosity, mechanical properties, dimensional shrinkage, and swelling behavior were examined. In vitro tests were conducted to assess biological performance. The results indicated that hydrogen and ionic bonding between PVA and ceramic powders were the primary mechanisms of adhesion. Increased chain length led to higher Cauchy pressure, thereby enhancing the mechanical properties of the material. Higher PVA concentrations produced slurries with increased solid content and shear-thinning capabilities, improving printability. The resulting bone scaffolds exhibited higher mechanical properties and shrinkage during drying but showed reduced porosity and swelling capability. In vitro experiments revealed that increasing PVA concentration decreased both the porosity and ion concentration of the bone scaffolds, thereby reducing their bioactivity. These findings provide a theoretical basis for optimizing binder concentration in 3D-printed bone scaffolds by linking slurry characteristics to scaffold performance.

During inkjet bioprinting, cells are subjected to direct shear stress as they pass through the nozzles, causing reversible deformation of the cell membranes and potentially triggering subcellular changes, such as activation of molecular pathways, leading to beneficial o utcomes. I n t his s tudy, n eural p rogenitor NE-4C c ells were printed through 30μm thermal inkjet nozzles. Compared to manually pipetted cells (control group), bioprinted cells (inkjet group) exhibited several distinct changes, such as reduced cell proliferation during the first four days after bioprinting, increased tolerance to high-concentration retinoic acid, and significantly elevated expression of the early neuronal marker class III β-tubulin, indicating enhanced neuronal differentiation. Furthermore, RNA sequencing and enrichment analysis further revealed upregulation of cell metabolism pathways in the bioprinted group. Collectively, these findings suggest that inkjet bioprinting may be a promising strategy to accelerate neural tissue formation, warranting further studies.

Multi-material bioprinting is a promising technique for fabricating complex, heterogeneous constructs with tailored mechanical and biological properties for tissue engineering applications. Recently, the use of a helical static mixer in bioprinting has shown feasibility for producing fibers from multiple biomaterials. However, the underlying mechanisms of transient stream mixing and the control of composition gradients during the printing process remain insufficiently understood. This study investigates biomaterial mixing with the objective of improving the spatial resolution of composition gradients along the longitudinal axis of printed fibers. Computational fluid dynamics (CFD) simulations were utilized to investigate the flow and mixing behavior of precursor streams, and the insights obtained were used to redesign the bioprinting head for improved performance. Rheological studies were performed to characterize the flow behavior of the biomaterials. The results were used, in conjunction with CFD, to examine the mixing performance and to estimate the transition time—defined as the delay between flow rate changes at the inlets and the corresponding change in fiber composition. Our results demonstrate that the redesigned bioprinting head achieved complete mixing of biomaterials and that transition time can be effectively regulated or reduced by preemptively adjusting inlet flow rates. This advancement enhanced the spatial resolution of composition gradients by 17–30%, as confirmed through a case study presented in this article. Additionally, adjustments to the toolpath further improved gradient resolution. Overall, this study elucidates key principles underlying multi-material bioprinting and provides strategies for improving bioprinting head design to achieve finer spatial control of composition gradients.

Graphene oxide quantum dots (GOQDs) possess excellent biocompatibility and have demonstrated potential to enhance osteogenesis and angiogenesis. The objective of this work was to construct Ti6Al4V porous scaffolds modified with different GOQD concentrations and investigate their influence on osteogenesis and angiogenesis. Porous Ti6Al4V scaffolds were coated with GOQDs at concentrations of 0.1, 1, and 10 μg/mL. The proliferation and adhesion of bone marrow mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs) on these scaffolds were evaluated using CCK-8 assay, immunofluorescence staining, and real time-polymerase chain reaction (RT-PCR). In vivo bone regeneration and angiogenesis were assessed through micro-computed tomography imaging and tissue section staining analysis. The results demonstrated successful deposition of GOQDs and the presence of characteristic functional groups. In vitro assays demonstrated that scaffolds coated with 0.1 μg/mL GOQDs significantly promoted the osteogenic/ angiogenic differentiation of BMSCs and HUVECs. In vivo experiments revealed that the 0.1 μg/mL GOQDs-coated scaffold (GQ@TC4) significantly enhanced bone formation and vascularization after 12 weeks. These findings suggest that Ti6Al4V biomimetic porous scaffolds functionalized with an optimal concentration (0.1 μg/ mL) of GOQDs can effectively promote both osteogenesis and angiogenesis, offering a promising strategy for bone defect repair.

The treatment of large-area bone defects has the risk of poor healing, and the development of implantable materials with mechanical adaptability, biological activity, and degradability is a clinical challenge. In this study, we prepared a 3D-printed porous tantalum (Ta) scaffold with an elastic modulus comparable to human bone, combined with biologically active magnesium (Mg) using a pressure-free impregnation process. We then conducted a comprehensive evaluation of the material’s characteristics, mechanical properties, degradation process, and its impact on MC3T3 cells. Scanning Electron Microscope (SEM) and Energy Dispersive X-ray Spectrometer (EDS) results indicated that the composite scaffold consisted of Ta and Mg phases. Through compression testing, the Ta–Mg composite scaffold displayed higher strength compared to porous Ta scaffolds. In vitro experiments revealed good biological activity of the composite material. The degradation results demonstrated that the Mg concentration within the composite material was favorable for cell growth, while the Ta scaffold maintained the integrity of the substrate throughout the degradation process. Likewise, in vivo results revealed that the Ta–Mg composite scaffold has stronger biological activity. Taken together, the excellent in vitro and ex vivo osteogenic properties and favorable degradation characteristics suggest that the Ta–Mg composite could provide new strategies and methods for developing next-generation customizable bone repair implant materials.

The advancement of bioinks capable of enabling multifunctional, skin-conformal sensing platforms is essential for the next generation of wearable health monitoring systems. In this study, we present a 3D-printed, dual-mode biosensor fabricated using a composite hydrogel ink comprising sodium alginate, exfoliated molybdenum disulfide nanosheets (MoS₂NSs), silver nanowires (AgNWs), and Ca²+ crosslinkers. This bioink enables reliable extrusion-based printing on flexible substrates, forming wearable, conductive, and mechanically robust sensor architectures. The resulting soft sensor exhibits high-sensitivity capacitive touch sensing with fast response times and excellent mechanical repeatability under dynamic loading conditions. Furthermore, the device allows for real-time monitoring of sweat rate in response to constant humidity and perspiration levels. The synergistic integration of 2D MoS₂NSs and 1D AgNWs significantly improves electrical conductivity and mechanical durability, without compromising printability or hydration compatibility. The demonstrated dual-sensing functionality and scalable fabrication strategy underscore the potential of this platform for low-cost, customizable applications in wearable healthcare, fitness tracking, and human-machine interfaces.  

The increasing demand for biomaterial safety in precision medical device manufacturing and electronic packaging highlights the critical need for the rapid development of 3D-printable photosensitive resins that offer high mechanical strength, durable antibacterial effectiveness, and consistent antistatic properties. Traditional approaches involving multiple additives often result in poor compatibility, low success rates in 3D printing, compromised functionality or mechanical properties, and insufficient functional stability and longevity. To address this challenge, we introduce a new category of pyridinium-based acrylate photosensitive additives. By adjusting the quantity of pyridinium functional groups within a single additive, we have successfully achieved multifunctionalization of the 3D printing resin. The findings indicated that the pyridinium-based acrylate additive endows the 3D-printed photosensitive resin with exceptional antibacterial efficacy (>99.99% against Escherichia coli and Staphylococcus aureus), strong antistatic performance (resistance: 10⁹ Ω), and high tensile strength (40.86 MPa). Furthermore, the resin demonstrated enduring and consistent antibacterial and antistatic properties. The study suggests that the novel pyridinium-based acrylate photosensitive additive can achieve a breakthrough in enhancing multifunctional 3D printing resin performance.  

Large, complex bone defects pose a significant clinical challenge. Conventional bone grafting approaches cannot simultaneously achieve tissue regeneration and infection prevention, resulting in impaired healing outcomes and prolonged treatment cycles. Existing therapeutic strategies lack integrated solutions capable of concurrently providing infection prevention and osteogenesis promotion within a single platform. This study developed a novel multifunctional composite scaffold using dual-nozzle three-dimensional printing technology to simultaneously achieve infection prevention and accelerated bone regeneration. Linezolid-loaded polylactic-co-glycolic acid microspheres (LMS) were uniformly dispersed within the pores of calcium sulfate/polylactic acid (CS/PLA) scaffolds to successfully construct the composite scaffold. In vitro characterization revealed uniform distribution of microspheres within the scaffold pores, with the fabricated CS/PLA-LMS demonstrating excellent biocompatibility and mechanical properties, achieving an elastic modulus of 87 MPa. Furthermore, the composite scaffold effectively inhibited Staphylococcus aureus activity in vitro. In vivo rat femoral condyle defect model revealed that the composite scaffold significantly enhanced bone formation compared to blank controls. Additionally, bone volume fraction increased by 3.2 times, and trabecular spacing decreased by 50%, with mechanistic analysis indicating activation of the phosphoinositide 3-kinase-protein kinase B signaling pathway. The integrated design successfully prevented infection-related complications while promoting robust osteogenesis, offering a clinically relevant solution for treating complex bone defects where infection prevention and regenerative capacity are primary therapeutic concerns.  

Three-dimensional (3D) printing enables precise, patient-tailored drug delivery, but its broader potential is limited by the lack of polymers that combine low processing temperatures with tunable biodegradability. This study presents the rational design, synthesis, and characterization of poly(ε-caprolactone-ran-lactide) (CL) polymer inks with tunable printability and controllable biodegradability for 3D-printed implantable drug delivery applications. By varying the poly(lactide) (PLA) content (1–20 mol%) within the poly(ε-caprolactone) backbone, the thermal and mechanical properties of the CL copolymers were precisely adjusted to meet both printing and biological performance criteria. Differential scanning calorimetry revealed that increasing PLA content systematically reduced the melting temperature (from 57 to 40°C), enabling thermal modulation of printability and depot shape retention. Rheological and printability assessments, conducted under optimized chamber temperature, feed rate, and extrusion pressure, demonstrated excellent filament continuity, layer stacking fidelity, and shape preservation. Among the synthesized variants, CL1–CL3 maintained structural stability above 40°C and were selected for detailed evaluation. The polymer inks were further validated through the fabrication of dexamethasone (Dex)-loaded CL (Dex-CL) depots, which achieved high encapsulation efficiency (>90%) and exhibited sustained drug release over 30 days in both in vitro and in vivo models. Notably, the lower melting point of Dex-CL3 contributed to accelerated release kinetics, confirming the utility of PLA content as a tunable parameter for degradation control. In vivo studies demonstrated prolonged Dex retention with minimal local inflammation, as confirmed by histological analysis. The CL polymer inks showed excellent biocompatibility and tissue integration, underscoring their potential for biomedical implantation. Collectively, these findings demonstrate that CL polymer inks provide a robust platform for 3D printing implantable drug depots with customizable degradation profiles, reliable structural performance, and immunological safety, supporting their use in sustained and responsive therapeutic delivery systems.  

The functional reconstruction of complex pelvic defects remains a global challenge. To address this, a personalized 3D-printed tantalum-coated titanium alloy pelvic reconstruction prosthesis was independently developed to enhance the osteogenic activity of existing titanium alloy prostheses. This prospective randomized controlled trial evaluated its efficacy, safety, and early clinical outcomes in 21 patients with complex pelvic defects. The patients were randomly assigned to an experimental group (11 cases of tantalum-coated prostheses) or a control group (10 cases of uncoated prostheses). The coated prostheses were designed using preoperative imaging data and coated with an approximately 15-μm tantalum coating through plasma immersion ion implantation. After post-treatment and sterilization, the prostheses were implanted during surgery. Operation time, intraoperative blood loss, and laboratory indices were recorded and compared between groups. Postoperative follow-up assessments included imaging assessments, complication monitoring, bone ingrowth analysis at the prosthesis–bone interface, and functional evaluation with the Harris Hip Score. All 21 surgeries achieved primary wound healing without early complications. Mean follow-up time was 15.1 ± 7.1 months. There was no significant difference in operation time, intraoperative blood loss, and abnormal laboratory indices. The prosthesis shape matched well with the bone defects, ensuring good stability. In the experimental group, one periprosthetic infection and one artificial femoral head dislocation occurred, compared to two periprosthetic infections and one dislocation in the control group. At final follow-up, the experimental group demonstrated significantly higher Harris Hip Scores (p < 0.01) and bone ingrowth rates (90.9% vs. 30.0% in control; p < 0.001). In conclusion, the personalized 3D-printed tantalum-coated titanium alloy pelvic reconstruction prosthesis effectively promotes bone ingrowth, enhances prosthesis stability, and improves lower limb function, representing an effective approach for reconstructing complex pelvic defects.

Three-dimensional (3D) bioprinting offers transformative potential for cardiac tissue engineering by enabling the fabrication of cell-laden constructs. However, key challenges remain, including maintaining cell viability within bioprinted constructs and understanding how embedded cells affect their physical and mechanical properties. This study addresses these challenges by incorporating human umbilical vein endothelial cells (HUVECs) into alginate–gelatin hydrogels and evaluating their impact on mechanical, physical, and rheological properties. Bioinks or hydrogels were prepared with or without HUVECs, and their rheological properties were assessed. Computational fluid dynamics (CFD) simulation was employed to determine the appropriate bioprinting pressure while minimizing cell damage. Constructs were designed and 3D-printed with an angular pattern to replicate the orientation of cardiac myofibrils and were characterized over a 21-day period for viscoelasticity, elastic modulus, swelling, mass loss, morphology, and cell viability. The incorporation of cells increased the storage and loss moduli of the bioink, demonstrating shear-thinning behavior as described by the Cross model. CFD simulation combined with preliminary cell viability assays identified 25 kPa as a suitable 3D-printing pressure, effectively preserving cell viability. Both cell-free and cell-laden constructs exhibited viscoelastic properties; however, cell-laden constructs displayed a lower elastic modulus under linear compression, reduced swelling, and greater mass retention. High cell viability was observed immediately post-bioprinting and was maintained for more than 1 week. These findings provide a framework for developing structurally robust, cell-laden constructs with enhanced functional fidelity, supporting their application in cardiac tissue engineering.

Uncontrollable local drug release from drug-loaded scaffolds is a critical challenge in treating bone tuberculosis (BTB), often leading to bacterial resistance and treatment failure. This study proposes an intelligent composite aerogel scaffold that integrates external stimulus response, sustained-release, and structural design. Using direct ink writing and freeze-drying, we integrated sodium para-aminosalicylate-encapsulated liposomes and silk fibroin-modified superparamagnetic iron oxide nanoparticles into a hydroxyapatite scaffold, thereby constructing an aerogel scaffold with an extracellular matrix-like structure and controlled-release capacity. The incorporation of liposomes significantly suppressed drug burst release and extended the effective drug release period to 336 h. Furthermore, under remote, non-invasive triggering by an external alternating magnetic field, the scaffold maintained a stable local temperature at 42°C. This enabled an accelerated, on-demand release of the drug, overcoming the limitations of uncontrolled delivery. By combining precise three-dimensional printing, liposome-based sustained release, and dynamic magnetic regulation, the intelligent scaffold offers a promising new strategy for personalized treatment of BTB.  

Reconstruction of severe mandibular defects remains a significant clinical challenge due to high recurrence rates, inadequate anatomical restoration, and the limited efficacy of systemic chemotherapy. To address these limitations, a patient-specific, 3D-printed titanium mandibular implant was developed with an integrated refillable drug storage tank for localized cisplatin release. The tank surface geometry and the hydrogel formulation were optimized using the Taguchi method and incorporated into anatomically matched implants. In vivo evaluation in six porcine mandibular defect models demonstrated systemic safety over 12 weeks, with plasma platinum levels reduced by more than 60% compared to systemic administration. Hematological and biochemical indicators—including white blood cell count, liver enzymes, and renal function markers—remained within normal ranges throughout the observation period, confirming physiological stability and biocompatibility. No significant complications or implant loosening were observed. Functional validation was further performed on three representative human mandibular large-defect models. Finite element analysis revealed implant stresses well below the yield strength of Ti6Al4V (<40%), and four-point bending fatigue tests confirmed structural endurance beyond one million loading cycles. This study presents the first functional and biocompatible patient-specific mandibular implant with integrated, refillable drug delivery, offering a clinically translatable strategy for simultaneous reconstruction and localized chemotherapy in head and neck oncology.  

Composite knee tissue defects involving bone, meniscus, and ligaments caused by high-energy trauma are rare and present significant reconstructive challenges. Herein, we report a case of a 50-year-old woman with bilateral asymmetric knee injuries arising from a traffic accident, including right medial femoral condyle loss with medial collateral ligament (MCL) deficiency, and complex defect involving left-sided bone, meniscus, and MCL, accompanied by degloving injury involving 20% total body surface area. Treatment was performed in the following three stages: debridement, soft tissue coverage, and final reconstruction using data-driven mirror modeling to design patient-specific 3D-printed titanium implants. The right MCL was reconstructed using a LARS artificial ligament. At 12-month follow-up, stable bone– implant integration, flap viability, and functional recovery were observed, with knee flexion of 120° (left) and 80° (right), and Knee Society Scores of 65 and 70. This case highlights the feasibility of personalized 3D-printed implants in complex bilateral knee reconstruction. 

Bone defects require simultaneous vascularization and sustained osteoinductive signaling to achieve functional repair—two goals that conventional grafts frequently fail to meet. The study under discussion explores the use of platelet-rich plasma (PRP) as a natural, multi-factor source, embedded in a methacrylated gelatin/methacrylated alginate (GA) hydrogel and modified with laponite (Lap) to regulate growth factor release. The resulting PRP–GA@Lap bioink is co-printed with polycaprolactone to create structurally reinforced scaffolds. In vitro, PRP–GA@ Lap stimulated bone marrow mesenchymal stem cell proliferation, migration, and osteogenic differentiation, enhanced endothelial tube formation, and polarized macrophages toward a pro-regenerative M2 phenotype. In vivo, hybrid scaffolds accelerated vascular ingrowth and improved bone volume, mineral density, and defect integration in rat femoral condyles. By coupling biologically broad PRP signaling with engineered release kinetics and mechanical stability, this approach offers a clinically adaptable, patient-specific strategy for complex bone repair, with strong potential for personalized regenerative therapy.