Publications

Finger fractures are among the most common musculoskeletal injuries, yet conventional splints for finger are often poorly fitted, uncomfortable, and incapable of providing localized therapeutic support, which can delay healing and increase complications. This study presents a computed tomography (CT)-guided, patient-specific 3D-printed finger splint incorporating a bilayer electrospun nanofiber coating mat for localized dual delivery of hydrocortisone (HCT) and ibuprofen (IBU), providing concurrent anti-inflammatory and analgesic therapy through two distinct mechanisms. CT data were segmented to generate customized splint geometries, which were fabricated using fused deposition modeling (FDM) to produce a rigid polylactic acid outer shell and stereolithography (SLA) to create a flexible inner layer. The inner surface was sequentially coated with IBU-loaded polycaprolactone nanofibers then HCT-loaded pullulan. Comprehensive characterization by SEM, FTIR, DSC, and XRD confirmed smooth, bead-free PCL nanofibers, strong adhesion to the microtextured SLA surface, and amorphous dispersion of both drugs with entrapment efficiencies above 90%. In vitro release studies demonstrated rapid HCT liberation of 79.68 ± 0.17% within 2 h, and IBU release of 51.75 ± 4.35% within 24 h. Ex vivo porcine skin permeation studies showed significantly enhanced drug delivery compared with pure drug controls, with cumulative permeation values of 155.52 ± 19.97 µg/cm2 for ibuprofen and 74.38 ± 2.18 µg/cm2 for hydrocortisone at 24 h. These findings demonstrate the feasibility of CT-based personalized finger splints that integrate structural support with localized multidrug delivery, highlighting a promising platform for next generation, patient-tailored fracture management.

PURPOSE: To develop a localized delivery implant by integrating doxorubicin loaded spanlastic vesicles within Freeform Reversible Embedding of Suspended Hydrogels (FRESH) printed alginate constructs.

METHODS: Spanlastics composed of Sorbitan Monostearate (Span60) and an edge activator, Polyethylene sorbitol ester (Tween 80), were prepared by ethanolic injection. Plain and drug-loaded spanlastics were characterized for their physicochemical properties. Vesicles were incorporated into 3D printed sodium alginate hydrogels in 'FRESH' bioprinting process to promote the sustained drug release of doxorubicin which was assessed using dialysis membrane for drug release. In vitro uptake and cytotoxicity were evaluated in MCF7 breast cancer cells.

RESULTS: Optimized formulations produced vesicles of approximately 200 to 300 nm with moderate encapsulation efficiency (33 to 44%) and stability during hydrogel incorporation and printing. Printed depots provided sustained doxorubicin release relative to suspension and reduced MCF7 viability, with preferential intracellular and nuclear localization consistent with doxorubicin activity.

CONCLUSION: Spanlastic-loaded FRESH printed alginate implants combine vesicle-mediated cellular delivery with matrix-governed sustained release, supporting their potential as a localized chemotherapy depot for further in vivo validation.

This proof-of-concept study evaluates the ability of three-dimensional printed lung phantoms to reproduce subtle pulmonary features relevant to medical imaging. An integrated workflow was developed for the fabrication and evaluation of patient-specific lung phantoms derived from high-resolution computed tomography, with emphasis on ground-glass opacities. De-identified HRCT datasets were segmented to generate both volumetric anthropomorphic lung models and standardized slim coronal phantoms, supporting reproducible imaging evaluation while reducing reliance on repeat clinical scans. The phantoms were fabricated at reduced scale using stereolithography and fused deposition modeling. Radiographic evaluation revealed clear fabrication-dependent imaging behavior. SLA phantoms exhibited smooth, isotropic microstructures and uniform grayscale response, enabling enhanced visualization of peripheral lung regions. In contrast, FDM phantoms demonstrated layered, porous architectures that produced lung-equivalent attenuation and scatter characteristics representative of pulmonary parenchyma. Quantitative grayscale analysis identified systematic differences in attenuation between fabrication methods, reflecting variations in material density and microstructural organization. Slim phantoms provided highly reproducible platforms suitable for quality assurance and quality control applications, whereas anthropomorphic phantoms preserved patient-specific anatomical detail relevant for diagnostic validation and training. Overall, this study demonstrates that phantom geometry and fabrication strategy critically influence radiological performance and provides a flexible framework for future validation and standardized imaging research.

Pediatric neuropathy poses significant challenges in pain management due to the limited availability of approved pharmacological options. Gabapentin, commonly used for neuropathic pain, offers therapeutic potential but necessitates careful dosing due to its variable bioavailability. This study investigates the integration of Hot Melt Extrusion and Fused Deposition Modeling in the development of polycaprolactone-based implants for sustained release of Gabapentin. A preliminary screening using Vacuum Compression Molding optimized formulations for Hot Melt Extrusion, enhancing material efficiency and process streamlining. Filaments with a diameter of 1.75 mm were successfully extruded and used for 3D printing of Gabapentin implants. Several tests were undertaken to characterize the prepared filaments and implants. Energy-Dispersive X-ray spectroscopy confirmed the uniform distribution of Gabapentin within the implant matrix. Solid-state characterization techniques were employed to assess the compatibility of implant components and to verify the solid-state of Gabapentin within the implant structure. In vitro drug release studies were conducted. Filaments with varying drug loadings were examined, revealing that a 20% w/w drug loading achieved an optimal balance between rapid and sustained release. Additionally, implants with different infill densities were analyzed, demonstrating that varying infill densities allow control over the amount and percentage of drug released. The 100% infill density resulted in the most sustained release effect, achieving approximately 40% drug release by day 28. These findings underscore the feasibility of 3D printing for producing personalized implants, emphasizing the potential for tailored drug release profiles to meet specific needs of pediatric patients.

Chronopharmaceutical systems aim to synchronize drug release with the body's biological rhythms to enhance therapeutic efficacy and minimize side effects. Current oral delivery technologies largely depend on coating technologies and pH-sensitive polymers, which are limited by significant inter- and intra-patient variability, as well as technical constraints in coating reproducibility. To address these challenges, we present a novel 3D-printed Programmable Delayed-Release Container System (PDRCS) for pH-independent, time-specific pulsatile drug delivery. Hydrocortisone was selected as the model drug to demonstrate chronotherapeutic targeting for primary adrenal insufficiency (Addison's disease). The system consists of an ethyl cellulose shell manufactured via fused deposition modeling (FDM), encapsulating a layered core comprising a swelling hydrogel disc, a separating barrier, and an immediate-release hydrocortisone tablet. Upon immersion in dissolution media, water enters through engineered perforations, triggering the swelling disc to expand and build internal pressure until rupture of the shell occurs, resulting in drug release. By adjusting perforation diameters 1.0, 1.5, and 2.0 mm, lag times of 28, 20, and 12 h, respectively, were achieved. In vitro studies confirmed the system's pH-independent behavior. Solid-state characterization (PXRD, FTIR, DSC, TGA) validated formulation stability, processing integrity, and revealing an increase in crystallinity after extrusion followed by reduction upon 3D printing. SEM imaging, rupture force analysis, and hydrogel swelling test were conducted to characterize the rupture behavior. This mechanically governed, rupture-based delivery platform enables customizable and reliable time-controlled oral drug administration, supporting personalized chronotherapeutic regimens.

The commercialization of additive manufacturing (AM) in pharmaceuticals manufacturing has attracted significant attention for its potential to produce customized products. However, the process is slow and hindered by the lack of designated regulatory guidelines tailored to 3D-printed pharmaceutical products (3DPPs). The 3D-printing technology has paved the way for personalized medicine, enabled treatment of rare genetic disorders, and offered many other possibilities for patients. Despite the US Food and Drug Administration (FDA) approval of Spritam®, a clear regulatory framework for licensing 3DPPs by the FDA or EMA remains unavailable. The current practice considers all products the same, regardless of their manufacturing method and/or complexity. While this approach has been generally accepted, it frequently fails to evaluate the unique quality attributes of 3DPPs. The lack of a harmonized regulatory framework tailored to the 3DPPs presents a major barrier to the widespread adoption of AM and other innovative technologies. To bridge this gap, this review highlights the most critical parameters related to the feedstock materials and 3D-printing processes, emphasizing their impact on the quality attributes of finished 3DPPs. Numerous scenarios have been proposed to encourage regulatory authorities to establish robust regulatory guidance for the 3D-printing technology at either industrial or point-of-care (PoC) settings. Coordinated efforts between regulatory authorities, industry partners and other stakeholders are necessary to define product specifications and identify appropriate analytical techniques for evaluating finished 3DPPs. By developing a harmonized regulatory framework and establishing quality control measures, the full potential of AM can be realized. This will ultimately ensure that novel 3DPPs and personalized medicines adhere to rigorous regulatory standards of quality, safety and efficacy.

Three-dimensional printing (3DP) holds significant potential for developing personalized pharmaceutical oral dosage forms (printlets). 3D printing has the advantage of fabricating complex geometric structures for versatile drug release profiles, enhancing patient preference, palatability and swallowability, reducing the pill burden, and increasing dose accuracy. Optimizing printing parameters is crucial in determining the quality of the printlets during dosage development. The integration of machine learning (ML) can reduce production costs and time through parameter optimization based on trained datasets. This research is focused on optimizing parameters for fused deposition modeling (FDM) based batch and continuous printing methods. The algorithm was trained using a three-level full factorial design, which generated data in the form of printlets with different parameters. Both defect and defect-free printlets were analyzed using image segmentation. Machine learning tools including Gaussian Process Regressor (GPR) and Efficient Global Optimization (EGO) were used to predict and select processing parameters for a targeted percentage surface defect. The final trained algorithm predicted new parameter sets for both batch (R2-0.8783) and continuous (R2-0.9364) printing methods to achieve zero defects, and the same was confirmed through printing and characterization of printlets which showed no defects. The algorithm was later adapted successfully to a variety of materials within the temperature range of 190-220 ℃ and predicted zero-defect printlets. Scanning electron microscopy (SEM) revealed the absence of defects on the surfaces of the materials. Results showed that flow rate (110 and 120 mm3/s) had a significant impact on printlet quality withwithout defects for both batch and continuous printing, compared to print speed, print temperature, and infill density. This research provides new insights into the development of optimized FDM printlets using batch and continuous printing with adaptive machine learning for pharmaceutical dosage manufacturing.

Vitamin D3 (VD3) and iron-blend granules were blended with corn and lentil composite flour (75/25, w/w) and fed into a pilot-scale twin-screw extruder to produce ready-to-eat snacks. The morphology and microstructure of extruded snacks were examined using scanning electron microscopy with energy-dispersive X-ray (SEM-EDX), X-ray powder diffraction, and FT-IR. Differential scanning calorimetry and thermogravimetric analysis measured the melting temperature and thermal stability of the extrudates. SEM and FT-IR analysis demonstrate that micronutrients are mixed well in formulations used in extrudates at high shear and high temperatures. The SEM-EDX exhibited the presence of iron, whereas high performance liquid chromatography measurements confirmed the significant retention of VD3 in the extruded snacks. The interaction between VD3 and human osteoblast cells was studied using live imaging and the MMT assay. Overall, for the first time, VD3 and Fe2+ blend granules have been used in an extrusion platform, which has significant potential for the intervention of VD3 and iron deficiencies. PRACTICAL APPLICATION: For the first time, we reported the use of VD3/iron-blend granules in extruded products. The findings of this work demonstrated the thermal stability and capability of providing adequate quantities of VD3 and iron in corn flour/lentil flour/VD3-iron blend extruded snacks. Furthermore, the interaction of VD3 with osteoblast cells highlights the potential health benefits of the extrudates.

Recently, binder jet printed modular tablets were loaded with three anti-viral drugs via Drop on Demand (DoD) technology where drug solutions prepared in ethanol showed faster release than those prepared in water. During printing, water is used as a binding agent, whereas ethanol is added to maintain the porous structure of the tablets. Thus, the hypothesis is that the porosity would be controlled by manipulating the percentage of water and ethanol. In this study, Rhodamine 6G (R6G) was selected as a model drug due to its high solubility in water and ethanol, visualization function as a fluorescent dye, and potential therapeutic effects for cancer treatment. Approximately, 10 mg/ml R6G solutions were prepared with five different water-ethanol ratios (0-100, 75-25, 50-50, 75-25, 100-0). The ink solutions were printed onto blank binder jet 3D-printed tablets containing calcium sulphate hemihydrate using DoD technology. The tablets were dried at room temperature and then characterized using SEM-EDX, fluorescent microscope, TGA, XRD, FTIR, and DSC as well as in vitro release studies to investigate the impact of water-ethanol ratio on the release profile of R6G. Results indicated that the solution with higher ethanol ratio penetrated the tablets faster than the lower ethanol ratio, while the solution prepared with pure water was first accumulated onto the tablets' surface and then absorbed by the tablets. Moreover, tablets with more water content gained more weight and thickness. The EDX analysis and fluorescent microscope showed the uniform surface distribution of the drug. The SEM images revealed the difference in the tablet surface among the five formulations. Furthermore, the TGA data presents a notable increase in water loss, with XRD analysis suggesting the formation of gypsum in tablets containing elevated water content. The release study exhibited that the fastest release was from WE0-100, whereas the release rate decreases as the content of water increases. The WE0-100 releases more than 40 % drug within the first hour which is almost twice as high of the WE100-0 formulation. This DoD technology could distribute drugs onto the tablet's surface uniformly. The calcium sulfate would transform from hemihydrate to dihydrate form in the presence of water and therefore, those tablets treated with higher water content led to slower release. In conclusion, this study underscores the substantial impact of the water-ethanol ratio on drug release from binder jet printed tablets and highlights the potential of DoD technology for uniform drug distribution and controlled release.

Three-dimensional (3D) printing is a promising approach for the stabilization and delivery of non-living biologics. This versatile tool builds complex structures and customized resolutions, and has significant potential in various industries, especially pharmaceutics and biopharmaceutics. Biologics have become increasingly prevalent in the field of medicine due to their diverse applications and benefits. Stability is the main attribute that must be achieved during the development of biologic formulations. 3D printing could help to stabilize biologics by entrapment, support binding, or crosslinking. Furthermore, gene fragments could be transited into cells during co-printing, when the pores on the membrane are enlarged. This review provides: (i) an introduction to 3D printing technologies and biologics, covering genetic elements, therapeutic proteins, antibodies, and bacteriophages; (ii) an overview of the applications of 3D printing of biologics, including regenerative medicine, gene therapy, and personalized treatments; (iii) information on how 3D printing could help to stabilize and deliver biologics; and (iv) discussion on regulations, challenges, and future directions, including microneedle vaccines, novel 3D printing technologies and artificial-intelligence-facilitated research and product development. Overall, the 3D printing of biologics holds great promise for enhancing human health by providing extended longevity and enhanced quality of life, making it an exciting area in the rapidly evolving field of biomedicine.