Abstract: Background: Lower limb prostheses improve functioning and quality of life after amputation. The challenges in prosthetic service provision in South Africa have been researched. However, possible solutions have not been explored. Objectives: This article presents obstacles to prosthetic services in the Eastern Cape province of South Africa, and suggests research and development, health systems and clinical care solutions to alleviate these obstacles. Method: Using a pragmatic approach, current evidence, unpublished research, grey sources and author expert opinion are presented in an integrated manner to show the barriers and recommendations for solutions in five key areas that are budget, supply chain and stock barriers, poor continuity of care, insufficient human resource numbers and skills, unrecorded demand for services, and geographical stumbling blocks. Results: Tender documents, ring fencing budgets and appointing professional procurement officers are recommended to address supply chain barriers. Conscientious record keeping and an audit of appointment practices are recommended to enhance continuity of care. Outreach clinics, compulsory community service and skill shifting should be explored in response to geographical barriers and shortage of human resources. Early screening and referral might decrease waiting times. Innovative manufacturing strategies such as 3D printing and direct socket manufacturing should be researched. A database can assist with predicting new device-repair and replacement needs. Conclusion: Prosthetic service delivery is a complex open system, and a systems approach should be followed when implementing any of the suggested solutions. Contribution: The suggested solutions might assist in alleviating the barriers experienced in prosthetic service delivery in low-resourced settings.

Three-dimensional (3D) printing technologies have revolutionized bioengineering by enabling the fabrication of complex, customized structures with high morphological compatibility for specific functions. Most advances in the materials aspect of 3D printing have focused on developing inks that provide high stability and precise deposition for specific printing techniques. A new generation of printable materials not only ensures structural and mechanical integrity, but also incorporates additional functionalities directly into the material. The integration of rational structural design with functional materials offers powerful tools for biomedical applications. In this study, we developed a platform for investigating thermoresponsiveness in cell culture. By inducing controllable, localized heating, we examined the effects of hyperthermia on cancer cells, an emerging treatment modality gaining increasing attention as a promising anticancer strategy. We demonstrate that structurally controlled 3D-printed objects composed of polymer and iron oxide (IO) can generate defined thermal gradients upon exposure to infrared irradiation, thereby inducing differential cellular responses. Using precise spatial control with Digital Light Processing (DLP) printing, we created hyperthermia models. We demonstrated that the experimental conditions can detect changes in cell sensitivity, showing that pre-exposure of cancer cells to the cryoprotective compound trehalose alters their heat resistance. Moreover, repeated thermal cycles promoted the emergence of a cell subpopulation with enhanced heat resistance and increased aggressiveness, highlighting the platform's ability to drive adaptive cell selection based on thermal tolerance. Our findings indicate that thermal conditioning via 3D-printed platforms can serve as a robust tool for studying cellular responses to hyperthermia and may contribute to optimizing hyperthermia-based cancer therapies.

This article compares the results of numerical and experimental analysis of the mechanical properties of an optimized 3D-printed beam. The samples were subjected to a four-point bending test, and corresponding numerical models were created at the same time. The beams were printed using 3D printing and their weight was reduced by using an internal spatial grid with variable thickness that gradually increases towards the outer walls. This approach allows for effective optimization of material strength while minimizing raw material consumption during production. One of the key findings is the determination of the ultimate strength between fibers, the mode of failure, and the high agreement between the experimental results and the numerical model using the finite element method. The optimized beam achieved nearly 60% weight reduction while maintaining comparable load-bearing capacity. The knowledge gained opens up new possibilities in the field of materials engineering and also makes a significant contribution to the methodology of developing and optimizing these structures using 3D printing technology.

This paper presents the design and structural analysis of a support system for a 3D printer, developed to improve resin drainage by enabling rotational movement along two axes. Three design variants were created, and after evaluating their performance, the second variant was chosen for its higher torque capacity and potential for future enhancements. This variant showed the most promise in achieving the desired functionality while allowing for further optimization. Finite element analysis (FEA) was utilized to investigate the structural behavior of the support system under loading conditions, ensuring the design remained within the elastic range. The FEA simulations were performed using Beam, Solid, and Shell element types, which provided insights into stress and strain distribution within the structure. This analysis guided the design process, allowing for refinements that improved the structural integrity and load-bearing capacity of the support. Alongside FEA, analytical calculations were performed to assess the bending stress and shear forces on the aluminum profile under three-point bending conditions. These calculations confirmed that the support structure was capable of handling the operational loads while staying within the elastic domain, ensuring reliable performance. This study demonstrates the effectiveness of combining finite element analysis with analytical methods to optimize the design of 3D printer support systems. The results highlight the potential for enhancing the performance and efficiency of additive manufacturing processes through improved structural designs.

The bioengineering of three-dimensional (3D) tissues, such as spheroids and organoids, has transformed regenerative medicine, offering in vitro platforms for transplantation and drug screening. Typically, spheroids and organoids range from 50 to 200 μm in size. Larger 3D tissues (several millimeters) with high cellular density (≥108 cells/cm3) enable the development of complex tissues containing vascular networks that closely mimic in vivo environments. However, fabricating such tissues is challenging due to oxygen and nutrient limitations. This study demonstrates the development of millimeter-sized 3D in vitro tissues with high cellular density through triculture with pericytes, 3D printing, and shaking culture. These three steps enabled the rapid formation of mature hierarchical vascular networks, integrating artificial channels and capillaries to supply oxygen and nutrients. Pericytes facilitated vasculogenesis and promoted anastomosis between artificial channels and capillaries. This work offers novel approaches to scale-up in vitro tissue models with vascularized networks for tissue engineering applications.

The reconstruction of large segmental bone defects remains a formidable challenge in orthopedic surgery. Benefiting from the rapid advancement of three-dimensional (3D) printing technology, growth factor-loaded artificial bone scaffolds have been extensively studied and have emerged as one of the pivotal strategies for bone defect repair. However, the development of an ideal scaffold system that meets comprehensive clinical requirements still requires sustained efforts. This study designed a biomimetic bone repair scaffold with bioactive properties using low-temperature 3D bioprinting technology and systematically evaluated its osteogenic capacity in large segmental radial bone defects of New Zealand White rabbits. In this study, four types of composite materials were fabricated: polycaprolactone (PCL)/xenogeneic bone powder (XBP) (PB), PCL/XBP with recombinant human bone morphogenetic protein-2 (rhBMP-2) (PBB), PCL/XBP with vascular endothelial growth factor-165 (VEGF-165) (PBV), and PCL/XBP coloaded with rhBMP-2/VEGF-165 (PBBV). Characterization of the scaffolds revealed that the fabricated scaffolds exhibited a well-interconnected porous structure with a porosity of 58.7% and compressive modulus ranging from 61.73 ± 8.11 to 78.72 ± 9.83 MPa. The controlled release profiles showed sustained BMP-2 release (23.6 ± 1.52% to 28.8 ± 2.91% cumulative release over 14 days) and biphasic VEGF-165 release (initial burst followed by sustained release reaching 67.9 ± 4.51% to 75.9 ± 9.44%). In vitro bone marrow mesenchymal stem cells (BMSCs) coculture and in vivo mouse muscle pouch implantation confirmed excellent biocompatibility and early osteogenic-angiogenic potential. Validation in the large segmental rabbit radial defect model demonstrated through multimodal assessments, including micro-CT, histomorphometry, and vascular perfusion angiography, that the PBBV scaffold group (dual-factor loaded scaffolds) exhibits significantly superior osteogenic and angiogenic performance compared to the other groups. In conclusion, the BMP/VEGF coloaded biomimetic scaffold achieves spatiotemporal coordination of vascularization and osteogenesis through innovative structural design and controlled release kinetics. This study addresses critical limitations in the repair of large segmental bone defects, offering a translatable solution combining 3D-printable customization, mechanical support, and biofunctional synergy.

Fiber-reinforced polymer composites (FRPCs) are widely used in aerospace and lightweight automotive materials, and renewable energy due to their exceptional strength-to-weight ratio. Epoxy resins, the most common matrices in FRPCs, offer excellent mechanical performance but suffer from two major drawbacks: their thermoset nature makes composites unrecyclable, preventing fiber recovery, and their petroleum-derived origin raises environmental and sustainability concerns. In this work, we developed a biobased epoxy resin which incorporated dynamic covalent bonds, synthesized from l-malic acid and sorbitol polyglycidyl ether, and applied it to the fabrication of FRPCs. The resulting resin and its composites exhibited outstanding mechanical performance, comparable to or even surpassing those of conventional petroleum-based systems. More importantly, the reinforcing fibers (carbon and basalt fibers) were fully recovered through a solution-based process and reused to fabricate next-generation FRPCs without loss in mechanical performance. Furthermore, the recovered resin solution could be directly reused for photocuring-based 3D printing without additional purification or separation steps.

Printing technology is a leading strategy for creating customized 3D matrices for tissue engineering. Our study developed an injectable nanocomposite hydrogel (bHAGel) for high-fidelity 3D extrusion printing composed of gelatin (Gel) and magnesium-doped biomimetic hydroxyapatite (bHA) particles that mimics a bone extracellular matrix. bHA particles, synthesized through a bioinspired mineralization process, acted as multifunctional additives, modulating rheology for printability, ensuring homogeneous phase distribution, enabling excellent model fidelity, and providing osteoinductive cues. The optimized hydrogel formulation enables the fabrication of porous scaffolds with interconnected macro- and microporosity via extrusion-based printing and freeze-drying. This key feature promoted cell infiltration and nutrient diffusion during tissue engineering procedures. Biological validation involves tailoring 3D scaffolds to fit a perfusion bioreactor chamber supporting seamless handling, seeding, and long-term culturing without scaffold removal or repositioning. Dynamic in vitro experiments with donor-derived human bone marrow stromal cells assessed the constructs' stability, ability to maintain geometry and perfusability, cytocompatibility and osteoconductivity, as well as robust osteogenic differentiation over 28 days. A more complex dynamic coculture model further demonstrated that the scaffold supports osteoclastogenesis under physiological, osteoblast-mediated conditions. Altogether, bHAGel scaffolds provided a customizable, bioactive platform suitable for engineering bone-mimetic organoids under dynamic conditions. Their modularity and biological relevance could be exploited in bone regeneration, disease modeling, and drug testing.

Rationale: Extrusion 3D bioprinting is an additive manufacturing tissue engineering technique that uses cell-laden viscous biomaterials known as bioinks. Manually mixing cell suspensions into viscous biomaterials can be challenging due to the high viscosity ratio between the two fluids. Static mixers are an attractive approach as they can quickly and reproducibly mix two fluids, including those with a high viscosity ratio. However, static mixers intended for viscous applications have not been comprehensively investigated for bioink preparation. This work evaluates the mixing performance, shear stress, and cell viability using four different types of static mixers intended for high viscosity mixing. Methods: Three static mixers intended for mixing viscous solutions were designed based on the Sulzer SMX, Ross ISG, and serpentine mixers and fabricated using resin 3D printing. CELLMIXER, a Kenics-style static mixer commercially available through CELLINK, was used as a comparator. Two biomaterial inks based on PEGDA and methacrylated gelatin were used to characterize each mixer's performance. Shear stress was estimated via fluid dynamics simulations using shear-thinning attributes measured experimentally through rheology. Mixing effectiveness was evaluated using fluorescent beads, from which the most effective design was chosen for live cell mixing experiments. Viability of cell lines (A549 and NIH-3T3) and primary human lung fibroblasts was evaluated postmixing. A demonstration of extrusion bioprinting was performed using the mixed bioinks. Results: The SMX-style mixer provided the most uniform mixing and yielded the lowest simulated shear stresses among the designs investigated. A549, NIH-3T3, and primary human lung fibroblasts maintained viabilities above 96% postmixing using the SMX-style mixer with a more homogeneous cell distribution compared to the CELLMIXER. The bioprinting demonstration validated our mixing system for producing viable tissue constructs with evenly distributed cells. Conclusions: We present a simple, reproducible, and flexible system for mixing cells into viscous biomaterial inks. Our approach facilitates standardized fabrication of cell-laden tissue constructs to ensure consistency in the growing field of extrusion 3D bioprinting.

In future 6G systems, terahertz (THz) waves are expected to be essential for enabling extremely high-capacity wireless communication. For such systems, efficient separation of multiple THz waves is required. A diffraction grating enables simple direct detection. Therefore, we designed a blazed grating optimized for THz beam separation. The grating was fabricated using a low-cost 3D printing process with a conductive coating, resulting in a simple structure that enables effective beam separation. Experimental results confirmed high-efficiency beam separation in the 300 GHz band, and 15 Gbit/s wireless communication was successfully demonstrated under these conditions. These results indicate that the proposed blazed grating provides a promising solution as a practical approach for THz wave receivers in future 6G wireless communication networks.

Two-photon polymerization (TPP) is a powerful technique to create microscale structures with high precision, offering significant potential in tissue engineering and drug delivery.While conventional TPP-fabricated drug carriers rely on passive encapsulation, these systems often suffer from low payload capacity and diffusion-controlled release kinetics. To address these challenges, we present the first demonstration of TPP-printed polyprodrug microstructures, where the therapeutic agent is covalently integrated into the polymer network as the repeating unit itself. Estrogen-based diacrylate monomers derived from 17β-estradiol were synthesized via one-step esterification/transesterification to create a photocurable resin. Curing under flood UV irradiation yielded a rigid thermoset (E' ∼2.5GPa at 25°C) with a glass transition temperature of about 50°C. Using TPP, we fabricated various microscale needles (100 × 100 × 400 µm, 2 µm resolution) from this resin, enabling direct printing of intrinsically therapeutic microstructures without post-processing drug loading. The cured polymer acts as both a structural matrix and a hydrolytically degradable polyprodrug, releasing estradiol through cleavage of ester bonds. By combining covalent drug-polymer integration with high-resolution 3D printing, this work establishes a platform for personalized transdermal drug delivery devices with spatially controlled release profiles determined by microstructure design and polymer degradation kinetics.

Delivery of therapeutics to the middle and inner ear for the treatment of various otological pathologies is often inefficient using conventional methods. Systemic treatments may fail to reach therapeutically effective concentrations at the target site and can result in off-target effects, while local treatments typically require invasive methods such as intratympanic injections due to low tympanic membrane (TM) permeability. In this study, a series of TM transpermeation devices for topical delivery of ototherapeutics were designed, prototyped, and characterized. The devices were generated via high-precision, 2-photon polymerization 3D printing and feature tailorable tissue residence times achieved by varying design features and materials. Type 1 devices, manufactured from hyaluronic acid, rapidly dissolve after generating an initial TM perforation and should allow for quick healing and short-term treatments (several days). Type 2 and 3 devices, two variants of the same design which were either directly printed with a biocompatible photoresin or cast from poly(lactic acid), are more stable and intended for slightly longer treatments (weeks). Finally, Type 4 and 5 feature nondegrading materials and barbed designs which should significantly increase their residence time for long-term, repeat-dosing drug treatments (months). Results show that all the devices effectively insert into TM tissue analogs with minimal force. Devices applied to in vitro TM tissue models showed no tissue toxicity and substantially increased drug permeation. Finally, in-silico modeling was used to predict minimal to no expected impact on hearing. Together, this work introduces a new concept for increasing the efficacy of topical ototherapeutic delivery which could improve patient outcomes and compliance over current methods.

In the pursuit of low-carbon 3D-printed housing, this study investigates the environmental viability of 3D-printed housing made with alkali-activated binder (AAB) mortar, in comparison to conventional ordinary Portland cement (OPC) systems. A life cycle assessment (LCA) was conducted using a BIM-integrated framework, evaluating both mortar-level (A1–A3) and full building-level (A1–A5) impacts across four categories: global warming potential (GWP), acidification potential (AP), eutrophication potential (EP), and ozone depletion potential (ODP). At the material scale, the AAB mortar demonstrated around 77% lower GWP and significant reductions in AP and EP (by ~60% and ~66%, respectively) compared to OPC. These advantages are maintained and even amplified at the building scale. A 3D-printed AAB house showed a GWP of 6.52E+06 kg CO2-eq, significantly lower than the OPC house’s 2.85E+07 kg CO2-eq, while also cutting AP and EP by over 59% and 66%, respectively. These improvements stem from replacing clinker-based OPC with CDW-derived, low-carbon binders, significantly curbing emissions from production. However, the AAB system exhibited a higher ODP (0.749 kg CFC-11-eq), over four times that of the OPC house (0.166 kg CFC-11-eq), mainly due to sodium silicate and NaOH production. Contribution analysis confirmed that over 95% of all impacts stemmed from material production, affirming the critical role of binder formulation. This study confirms that AAB-integrated 3D printing can enable rapid, circular, and significantly decarbonized construction. Still, further optimization of activator chemistry is needed to fully align AAB systems with environmental sustainability targets.

The growing demand for wearable electronics and infrared stealth technologies has highlighted the limitations of traditional electromagnetic interference (EMI) shielding materials, which often lack flexibility, lightweight design, and multifunctional integration. Although hydrogels present a promising platform due to their flexibility, adhesion, and sensing capabilities, the integration of multiple functions into a single material system through a straightforward fabrication process remains challenging. In this study, we developed a one-pot synthesized multifunctional ANE hydrogel that incorporates an ionic liquid (EBIB) as a conductive medium. Unlike conventional conductive fillers, such as silver nanowires or MXene, EBIB enhances both conductivity and interfacial polarization, achieving an EMI shielding efficiency of 34.5 dB in the X-band, surpassing many reported polymer-based shields. By combining this with vat photopolymerization 3D printing, we fabricated tailored topological structures that promote electromagnetic wave dissipation and suppress infrared thermal transmission. The hydrogel demonstrates effective infrared stealth, maintaining a low temperature increase of 24 °C on a 100 °C hot stage for 20 min, outperforming typical nonporous hydrogel coatings. Furthermore, the material exhibits strong adhesion, high strain sensitivity (gauge factor = 5.282 over 150-300% strain), fast response (165 ms), and cycling stability, exceeding the performance of many existing ionic hydrogels in motion sensing. By integration of EMI shielding, infrared camouflage, and wearable sensing in a single 3D-printable system, this study offers a competitive material solution for next-generation multifunctional sensors.

The expanding range of materials available for 3D printing is driving its widespread adoption in advanced fields. As 3D printing becomes increasingly prevalent in the manufacturing of industrial components, its advantages in accommodating complex geometries and reducing material waste are attracting significant attention. Acquiring and applying precise elastic properties of materials during structural design is crucial for ensuring part safety and consistency. However, non-destructive mechanical property assessment methods remain limited. In this paper, we propose an efficient surrogate model, built using a Bayesian model updating approach combined with a random forest algorithm, to achieve high-precision calibration of material elastic constants. In the experiment, samples were 3D printed using fused deposition modeling, and modal information was obtained using operational modal analysis with one end fixed to simulate cantilever beam boundary conditions. Parameter updating was then performed within a Bayesian Markov Chain Monte Carlo framework. The deviation between the updated calculated frequencies and the measured frequencies was significantly reduced, and the Modal Assurance Criterion value between the updated calculated mode shapes and the measured mode shapes was higher than 0.99, demonstrating the accuracy of the updated parameters. Compared to traditional destructive testing methods, the proposed method directly calibrates the structural elastic modulus at the component level without affecting the normal use of the component, providing a more practical approach for the analysis and research of material properties in 3D printing additive manufacturing. The related technology can be extended to other structural forms of 3D-printed products.

The integration of 3D technologies into education opens up new opportunities for the study and preservation of cultural artifacts, particularly in the context of studying ceramics. This study aims to assess the impact of using laser scanning and 3D printing technologies on student satisfaction with the educational process. The study had a quasi-experimental design with two groups. The theoretical part of the taught course "Ceramics of China and Southeast Asia" was the same for both groups. The Intervention group (n = 114) used 3D scanning and printing in practical classes, while the Control group (n = 114) studied using traditional methods. The course lasted 15 weeks. At the end of the course, students in both groups completed a questionnaire on the scales Tutor Guidance & Support, Satisfaction, Content & Experience, Collaboration & Activities. The results of the questionnaire of students in both groups were compared using an independent t-test. The influence of individual student characteristics (gender, age, previous experience) was determined using one-way ANOVA. The Intervention group showed significantly higher scores on Satisfaction, Content & Experience, and Collaboration & Activities than the Control group. Gender and previous experience influenced the course's perception, while the students' age was not a significant factor. The obtained results are important for the development of 3D approaches to learning in the field of cultural heritage and archaeology, as well as for the creation of more interactive and effective educational programs that use modern technologies for the preservation and study of cultural artifacts.

The expanding range of materials available for 3D printing is driving its widespread adoption in advanced fields. As 3D printing becomes increasingly prevalent in the manufacturing of industrial components, its advantages in accommodating complex geometries and reducing material waste are attracting significant attention. Acquiring and applying precise elastic properties of materials during structural design is crucial for ensuring part safety and consistency. However, non-destructive mechanical property assessment methods remain limited. In this paper, we propose an efficient surrogate model, built using a Bayesian model updating approach combined with a random forest algorithm, to achieve high-precision calibration of material elastic constants. In the experiment, samples were 3D printed using fused deposition modeling, and modal information was obtained using operational modal analysis with one end fixed to simulate cantilever beam boundary conditions. Parameter updating was then performed within a Bayesian Markov Chain Monte Carlo framework. The deviation between the updated calculated frequencies and the measured frequencies was significantly reduced, and the Modal Assurance Criterion value between the updated calculated mode shapes and the measured mode shapes was higher than 0.99, demonstrating the accuracy of the updated parameters. Compared to traditional destructive testing methods, the proposed method directly calibrates the structural elastic modulus at the component level without affecting the normal use of the component, providing a more practical approach for the analysis and research of material properties in 3D printing additive manufacturing. The related technology can be extended to other structural forms of 3D-printed products.

This systematic review on novel 3D technologies aims to discuss the current evidence on the usefulness of 3D printing, virtual reality (VR) and augmented reality (AR) simulators in the education and training of young urologists for kidney cancer surgery, highlighting the modalities employed, their educational impact, and areas for future development. We performed a comprehensive literature search limited to the last 10 years across PubMed and Embase libraries, identifying studies evaluating the use of 3D technologies as educational tools in urologist training for kidney cancer surgery. The review followed PRISMA guidelines, and two reviewers independently screened eligible studies. We extracted data on study designs and on urologists' education outcomes, through different subcategories. Seventeen studies were included, mostly small-scale validation or descriptive investigations. Twelve investigated 3D-printed models and five VR/AR platforms. Simulations focused on laparoscopic and robot-assisted partial nephrectomy, often using patient-specific models for rehearsal and skill development. Training outcomes included improved spatial anatomy understanding, increased technical performance, greater procedural confidence, and enhanced familiarity with complex surgical steps. However, considerable heterogeneity in methodology and limited sample sizes across studies underscore the need for standardized evaluation of these educational tools. 3D technologies, including 3D-printed models and VR/AR platforms, show promise in enhancing surgical training for renal cancer by improving anatomical understanding and procedural skills. These technologies demonstrate good precision and can help assess trainee surgical skill. However, evidence remains limited, and further research is needed to validate their effectiveness, cost-efficiency, and integration into standardized urological training curricula.

Introduction Simulation is a mandatory component of surgical training; the challenge remains to develop ‘close-to-real’ training. Management of paediatric elbow fractures is an obligatory competence for completion of training in Trauma and Orthopaedics. Current methods use dry bone simulation to teach wire configuration, but intra-operative radiographic interpretation is not possible. Methods This proof-of-concept study aimed to explore a novel three-dimensional (3D) printed model with real-time intra-operative radiographic feedback in the training of orthopaedic surgeons. In conjunction with Axial 3D Printing (Belfast, Northern Ireland), a child’s elbow model was produced with radiopaque ‘bone’ and flexible radiolucent ‘soft tissues’ technology to produce a high-fidelity paediatric elbow model, suitable to be used under fluoroscopic guidance, as an adjunct to teaching Kirschner wiring of a supracondylar fracture. Nineteen orthopaedic trainees participated in simulation training. During the simulation, the participants were assessed using the Objective Structured Assessment of Technical Skills in addition to completion of pre- and post-training surveys. Results Positive responses were received regarding the model’s usefulness for simulation training, particularly regarding the highly anatomical radiographic appearances. A 5-point Likert scale was used to evaluate self-confidence in performing the procedure pre- and post-simulation teaching. There was an average improvement in confidence of 1.15 for performing supracondylar K-wiring, following the simulation workshop. Discussion This new 3D printing technique demonstrates a further development in modern surgical training. Sawbones have numerous limitations, while the costs and practicalities of cadaveric training remain prohibitive. By combining realism and low risk, these 3D printed models may offer a solution to these challenges and contribute to enhanced patient care.

Transdermal Drug Delivery Systems (TDDS) offer a non-invasive route for sustained systemic or localized drug delivery. By bypassing hepatic first-pass metabolism and improving bioavailability, TDDS enhances patient compliance, especially in the management of chronic diseases. Drug permeation across the skin is mediated through pathways involving the complex skin barrier, predominantly the stratum corneum, with efficacy influenced by both drug properties and skin physiology. This review systematically integrates the fundamental mechanisms underlying TDDS, highlights cutting-edge technological advancements developed to overcome the skin barrier, and discusses their expanding clinical applications. The advanced technologies covered include permeation enhancers, vesicular systems (liposomes, transfersomes, ethosomes), microemulsions, microneedles (MNs), responsive systems (pH-, temperature-, enzyme-sensitive), and 3D printing. These innovative technologies effectively enhance drug flux, enable targeted delivery, and achieve spatiotemporal control of drug release. Clinically, FDA-approved TDDS formulations have been successfully applied to manage various conditions, including chronic pain (fentanyl, buprenorphine), neurological disorders (rotigotine, rivastigmine), cardiovascular diseases (nitroglycerin, clonidine), hormone replacement, and substance dependence (nicotine). Despite significant clinical value, TDDS still faces challenges such as limitations in delivering macromolecules, potential skin irritation, and inter-individual variability. Future directions in TDDS research focus on integrating nanotechnology, AI-driven optimization, wearable sensors, and closed-loop smart systems. These integrations aim to achieve greater precision, personalization, and efficiency in transdermal drug delivery, providing valuable insights for future research and translational development.