Multimodality Imaging for 3D Printing and Surgical Rehearsal in Complex Spine Surgery.

Surgery is the mainstay treatment of symptomatic spinal tumors. It aids in restoring functionality, managing pain and tumor growth, and improving overall quality of life. Over the past decade, advancements in medical imaging techniques combined with the use of three-dimensional (3D) printing technology have enabled improvements in the surgical management of spine tumors by significantly increasing the precision, accuracy, and safety of the surgical procedures. For complex spine surgical cases, the use of multimodality imaging is necessary to fully visualize the extent of disease, including both soft-tissue and bone involvement. Integrating the information provided by these examinations in a cohesive manner to facilitate surgical planning can be challenging, particularly when multiple surgical specialties work in concert. The digital 3-dimensional (3D) model or 3D rendering and the 3D printed model created from imaging examinations such as CT and MRI not only facilitate surgical planning but also allow the placement of virtual and physical surgical or osteotomy planes, further enhancing surgical planning and rehearsal. The authors provide practical information about the 3D printing workflow, from image acquisition to postprocessing of a 3D printed model, as well as optimal material selection and incorporation of quality management systems, to help surgeons utilize 3D printing for surgical planning. The authors also highlight the process of surgical rehearsal, how to prescribe digital osteotomy planes, and integration with intraoperative surgical navigation systems through a case-based discussion. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Advances in Virtual Cutting Guide and Stereotactic Navigation for Complex Tumor Resections of the Sacrum and Pelvis: Case Series with Short-Term Follow-Up.

Primary malignancies of the sacrum and pelvis are aggressive in nature, and achieving negative margins is essential for preventing recurrence and improving survival after en bloc resections. However, these are particularly challenging interventions due to the complex anatomy and proximity to vital structures. Using virtual cutting guides to perform navigated osteotomies may be a reliable method for safely obtaining negative margins in complex tumor resections of the sacrum and pelvis. This study details the technique and presents short-term outcomes. Patients who underwent an en bloc tumor resection of the sacrum and/or pelvis using virtual cutting guides with a minimum follow-up of two years were retrospectively analyzed and included in this study. Preoperative computer-assisted design (CAD) was used to design osteotomies in each case. Segmentation, delineating the tumor from normal tissue, was performed by the senior author using preoperative CT scans and MRI. Working with a team of biomedical engineers, virtual surgical planning was performed to create osteotomy lines on the preoperative CT and overlaid onto the intraoperative CT. The pre-planned osteotomy lines were visualized as "virtual cutting guides" providing real-time stereotactic navigation. A precision ultrasound-powered cutting tool was then integrated into the navigation system and used to perform the osteotomies in each case. Six patients (mean age 52.2 ± 17.7 years, 2 males, 4 females) were included in this study. Negative margins were achieved in all patients with no intraoperative complications. Mean follow-up was 38.0 ± 6.5 months (range, 24.8-42.2). Mean operative time was 1229 min (range, 522-2063). Mean length of stay (LOS) was 18.7 ± 14.5 days. There were no cases of 30-day readmissions, 30-day reoperations, or 2-year mortality. One patient was complicated by flap necrosis, which was successfully treated with irrigation and debridement and primary closure. One patient had local tumor recurrence at final follow-up and two patients are currently undergoing treatment for metastatic disease. Using virtual cutting guides to perform navigated osteotomies is a safe technique that can facilitate complex tumor resections of the sacrum and pelvis.

Reverse Engineering and 3D Printing of Medical Devices for Drug Delivery and Drug-Embedded Anatomic Implants.

In recent years, 3D printing (3DP) has advanced traditional medical treatments. This review explores the fusion of reverse engineering and 3D printing of medical implants, with a specific focus on drug delivery applications. The potential for 3D printing technology to create patient-specific implants and intricate anatomical models is discussed, along with its ability to address challenges in medical treatment. The article summarizes the current landscape, challenges, benefits, and emerging trends of using 3D-printed formulations for medical implantation and drug delivery purposes.

Incidence of resting-state functional connectivity to secondary language areas and contralateral language areas in patients with brain tumors.

PURPOSE: Secondary language areas, including the pre-supplementary motor area (pre-SMA), dorsolateral prefrontal cortex (DLPFC), and the visual word form area (VWFA) play important roles in speech, but have been under-evaluated in the realm of resting-state (rs)-fMRI. The purpose of this study is to determine the incidence that secondary language areas and contralateral language areas can be localized using seed-based correlation (SBC) rs-fMRI. METHODS: We retrospectively reviewed 40 rs-fMRIs for functional connectivity (FC) to secondary language areas in cases where FC to Broca's or Wernicke's area near tumor in the left hemisphere were successfully generated using SBC analysis. Logistical regression was used for statistical analysis. RESULTS: SBC rs-fMRI with a seed in the left Broca's or Wernicke's area ipsilateral to the tumor was performed in the 40 patients. 72.5% of cases showed FC to the left DLPFC, 67.5% to left pre-SMA, and 52.5% of cases had FC to right Broca's area. In addition to other correlations, we found older patients have a lower incidence of FC to the right Wernicke's area when seeded from both left Broca's and left Wernicke's area (p-value = .016, odds ratio = 0.94). CONCLUSION: SBC rs-fMRI can detect left hemispheric secondary language areas as well as right hemispheric primary and secondary language areas. The left DLPFC showed the highest incidence of FC, followed by the left pre-SMA when seeded from both left Broca's and Wernicke's area. Logistics regression also showed in some instances, differences in the incidence of FC to language areas was dependent on age, seed location, and gender.

Medical 3D Printing Using Desktop Inverted Vat Photopolymerization: Background, Clinical Applications, and Challenges.

Medical 3D printing is a complex, highly interdisciplinary, and revolutionary technology that is positively transforming the care of patients. The technology is being increasingly adopted at the Point of Care (PoC) as a consequence of the strong value offered to medical practitioners. One of the key technologies within the medical 3D printing portfolio enabling this transition is desktop inverted Vat Photopolymerization (VP) owing to its accessibility, high quality, and versatility of materials. Several reports in the peer-reviewed literature have detailed the medical impact of 3D printing technologies as a whole. This review focuses on the multitude of clinical applications of desktop inverted VP 3D printing which have grown substantially in the last decade. The principles, advantages, and challenges of this technology are reviewed from a medical standpoint. This review serves as a primer for the continually growing exciting applications of desktop-inverted VP 3D printing in healthcare.

Current Biomedical Applications of 3D-Printed Hydrogels.

Three-dimensional (3D) printing, also known as additive manufacturing, has revolutionized the production of physical 3D objects by transforming computer-aided design models into layered structures, eliminating the need for traditional molding or machining techniques. In recent years, hydrogels have emerged as an ideal 3D printing feedstock material for the fabrication of hydrated constructs that replicate the extracellular matrix found in endogenous tissues. Hydrogels have seen significant advancements since their first use as contact lenses in the biomedical field. These advancements have led to the development of complex 3D-printed structures that include a wide variety of organic and inorganic materials, cells, and bioactive substances. The most commonly used 3D printing techniques to fabricate hydrogel scaffolds are material extrusion, material jetting, and vat photopolymerization, but novel methods that can enhance the resolution and structural complexity of printed constructs have also emerged. The biomedical applications of hydrogels can be broadly classified into four categories-tissue engineering and regenerative medicine, 3D cell culture and disease modeling, drug screening and toxicity testing, and novel devices and drug delivery systems. Despite the recent advancements in their biomedical applications, a number of challenges still need to be addressed to maximize the use of hydrogels for 3D printing. These challenges include improving resolution and structural complexity, optimizing cell viability and function, improving cost efficiency and accessibility, and addressing ethical and regulatory concerns for clinical translation.

Guide for starting or optimizing a 3D printing clinical service.

Three-dimensional (3D) printing has applications in many fields and has gained substantial traction in medicine as a modality to transform two-dimensional scans into three-dimensional renderings. Patient-specific 3D printed models have direct patient care uses in surgical and procedural specialties, allowing for increased precision and accuracy in developing treatment plans and guiding surgeries. Medical applications include surgical planning, surgical guides, patient and trainee education, and implant fabrication. 3D printing workflow for a laboratory or clinical service that produces anatomic models and guides includes optimizing imaging acquisition and post-processing, segmenting the imaging, and printing the model. Quality assurance considerations include supervising medical imaging expert radiologists' guidance and self-implementing in-house quality control programs. The purpose of this review is to provide a workflow and guide for starting or optimizing laboratories and clinical services that 3D-print anatomic models or guides for clinical use.

Quantitative Fit Tested N95 Respirator-Alternatives Generated With CT Imaging and 3D Printing: A Response to Potential Shortages During the COVID-19 Pandemic.

RATIONALE AND OBJECTIVE: Three-dimensional (3D) printing allows innovative solutions for personal protective equipment, particularly in times of crisis. Our goal was to generate an N95-alternative 3D-printed respirator that passed Occupational Safety and Health Administration (OSHA)-certified quantitative fit testing during the COVID-19 pandemic. MATERIALS AND METHODS: 3D printed prototypes for N95 solutions were created based on the design of commercial N95 respirators. Computed tomography imaging was performed on an anthropomorphic head phantom wearing a commercially available N95 respirator and these facial contour data was used in mask prototyping. Prototypes were generated using rigid and flexible polymers. According to OSHA standards, prototypes underwent subsequent quantitative respirator fit testing on volunteers who passed fit tests on commercial N95 respirators. RESULTS: A total of 10 prototypes were 3D printed using both rigid (n = 5 designs) and flexible materials (n = 5 designs), Prototypes generated with rigid printing materials (n = 5 designs) did not pass quantitative respirator fit testing. Three of the five prototypes with flexible materials failed quantitative fit testing. The final two prototypes designs passed OSHA-certified quantitative fit tests with an overall mean fit factor of 138 (passing is over 100). CONCLUSION: Through rapid prototyping, 3D printed N95 alternative masks were designed with topographical facial computed tomography data to create mask facial contour and passed OSHA-certified quantitative respiratory testing when flexible polymer was used. This mask design may provide an alternative to disposable N95 respirators in case of pandemic-related shortages. Furthermore, this approach may allow customization for those that would otherwise fail fit testing on standard commercial respirators.

Antibiotics in 3D-printed implants, instruments and materials: benefits, challenges and future directions.

3D printing is an additive manufacturing technology, which permits innovative approaches for incorporating antibiotics into 3D printed constructs. Antibiotic-incorporating applications in medicine have included medical implants, prostheses, along with procedural and surgical instruments. 3D-printed antibiotic-impregnated devices offer the advantages of increased surface area for drug distribution, sequential layers of antibiotics produced through layer-by-layer fabrication, and the ability to rapidly fabricate constructs based on patient-specific anatomies. To date, fused deposition modeling has been the main 3D printing method used to incorporate antibiotics, although inkjet and stereolithography techniques have also been described. This review offers a state-of-the-art summary of studies that incorporate antibiotics into 3D-printed constructs and summarizes the rationale, challenges, and future directions for the potential use of this technology in patient care.

3D Printing Custom Bioactive and Absorbable Surgical Screws, Pins, and Bone Plates for Localized Drug Delivery.

Additive manufacturing has great potential for personalized medicine in osseous fixation surgery, including maxillofacial and orthopedic applications. The purpose of this study was to demonstrate 3D printing methods for the fabrication of patient-specific fixation implants that allow for localized drug delivery. 3D printing was used to fabricate gentamicin (GS) and methotrexate (MTX)-loaded fixation devices, including screws, pins, and bone plates. Scaffolds with different infill ratios of polylactic acid (PLA), both without drugs and impregnated with GS and MTX, were printed into cylindrical and rectangular-shaped constructs for compressive and flexural strength mechanical testing, respectively. Bland PLA constructs showed significantly higher flexural strength when printed in a Y axis at 100% infill compared to other axes and infill ratios; however, there was no significant difference in flexural strength between other axes and infill ratios. GS and MTX-impregnated constructs had significantly lower flexural and compressive strength as compared to the bland PLA constructs. GS-impregnated implants demonstrated bacterial inhibition in plate cultures. Similarly, MTX-impregnated implants demonstrated a cytotoxic effect in osteosarcoma assays. This proof of concept work shows the potential of developing 3D printed screws and plating materials with the requisite mechanical properties and orientations. Drug-impregnated implants were technically successful and had an anti-bacterial and chemotherapeutic effect, but drug addition significantly decreased the flexural and compressive strengths of the custom implants.

3D Printing of Poloxamer 407 Nanogel Discs and Their Applications in Adjuvant Ovarian Cancer Therapy.

Nanogels are attractive biocompatible materials that enable local delivery of multiple drugs. In this study, we demonstrated that 3D printing technology could be used to precisely construct nanogel discs carrying paclitaxel and rapamycin. 3D-printed nanogel disc rounds (12 mm diameter × 1 mm thickness) carrying paclitaxel and rapamycin evaded premature gelation during storage and the initial burst release of the drugs in the dissolution medium. In vivo 3D-printed nanogel discs permitted successful intraperitoneal delivery of paclitaxel and rapamycin in ES-2-luc ovarian-cancer-bearing xenograft mice. They were also shown to be therapeutically effective and capable of preventing postsurgical peritoneal adhesions in the treated xenograft mice.

3D Printed Antibiotic and Chemotherapeutic Eluting Catheters for Potential Use in Interventional Radiology: In Vitro Proof of Concept Study.

RATIONALE AND OBJECTIVES: Additive manufacturing may be used as a form of personalized medicine in interventional radiology by allowing for the creation of customized bioactive constructs such as catheters that can act as a form of localized drug delivery. The purpose of the present in vitro study was to use three-dimensional (3D) printing to construct bioactive-laden bioabsorbable catheters impregnated with antibiotics and chemotherapeutics. MATERIALS AND METHODS: Polylactic acid bioplastic pellets were coated with the powdered bioactive compounds gentamicin sulfate (GS) or methotrexate (MTX) to incorporate these drugs into the 3D printed constructs. The pellets were then extruded into drug-impregnated filament for fused deposition modeling 3D printing. Computer-aided design files were generated in the shapes of 14-F catheters. Scanning electron microscope imaging was used to visualize the presence of the additive powders on the surface of the printed constructs. Elution profiles were run on the antibiotic-laden catheter and MTX-laden catheters. Antibiotic-laden catheters were tested on bacterial broth and plate cultures. RESULTS: Both GS and MTX catheter constructs had sustained drug release up to the 5-day limit of testing. The 3D printed GS-enhanced catheters inhibited all bacterial growth in broth cultures and had an average zone of inhibition of 858 ± 118 mm2 on bacterial plates, whereas control catheters had no effect. CONCLUSION: The 3D printing manufacturing method to create instruments in percutaneous procedures is feasible. Further in vivo studies will substantiate these findings.

Studies on the cytocompatibility, mechanical and antimicrobial properties of 3D printed poly(methyl methacrylate) beads.

Osteomyelitis is typically a bacterial infection (usually from Staphylococcus) or, more rarely, a fungal infection of the bone. It can occur in any bone in the body, but it most often affects the long bones (leg and arm), vertebral (spine), and bones of the foot. Microbial success in osteomyelitis is due to their ability to form biofilms which inhibit the wound healing process and increases resistance to anti-infective agents. Also, biofilms do not allow easy penetration of antibiotics into their matrix making clinical treatment a challenge. The development of local antibiotic delivery systems that deliver high concentrations of antibiotics to the affected site is an emerging area of research with great potential. Standard treatment includes antibiotic therapy, either locally or systemically and refractory cases of osteomyelitis may lead to surgical intervention and a prolonged course of antibiotic treatment involving placement of antibiotic-doped beads or spacers within the wound site. There are disadvantages with this treatment modality including insufficient mixing of the antibiotic, lack of uniform bead size, resulting in lower antibiotic availability, and limitations on the antibiotics employed. Thus, a method is needed to address biofilm formations in the wound and on the surface of the surgical implants to prevent osteomyelitis. In this study, we show that all antibiotics studied were successfully doped into PMMA and antibiotic-doped 3D printed beads, disks, and filaments were easily printed. The growth inhibition capacity of the antibiotic-loaded PMMA 3D printed constructs was also demonstrated.

Recent Advances in Biomaterials for 3D Printing and Tissue Engineering.

Three-dimensional printing has significant potential as a fabrication method in creating scaffolds for tissue engineering. The applications of 3D printing in the field of regenerative medicine and tissue engineering are limited by the variety of biomaterials that can be used in this technology. Many researchers have developed novel biomaterials and compositions to enable their use in 3D printing methods. The advantages of fabricating scaffolds using 3D printing are numerous, including the ability to create complex geometries, porosities, co-culture of multiple cells, and incorporate growth factors. In this review, recently-developed biomaterials for different tissues are discussed. Biomaterials used in 3D printing are categorized into ceramics, polymers, and composites. Due to the nature of 3D printing methods, most of the ceramics are combined with polymers to enhance their printability. Polymer-based biomaterials are 3D printed mostly using extrusion-based printing and have a broader range of applications in regenerative medicine. The goal of tissue engineering is to fabricate functional and viable organs and, to achieve this, multiple biomaterials and fabrication methods need to be researched.

Nanogels for Pharmaceutical and Biomedical Applications and Their Fabrication Using 3D Printing Technologies.

Nanogels are hydrogels formed by connecting nanoscopic micelles dispersed in an aqueous medium, which give an opportunity for incorporating hydrophilic payloads to the exterior of the micellar networks and hydrophobic payloads in the core of the micelles. Biomedical and pharmaceutical applications of nanogels have been explored for tissue regeneration, wound healing, surgical device, implantation, and peroral, rectal, vaginal, ocular, and transdermal drug delivery. Although it is still in the early stages of development, due to the increasing demands of precise nanogel production to be utilized for personalized medicine, biomedical applications, and specialized drug delivery, 3D printing has been explored in the past few years and is believed to be one of the most precise, efficient, inexpensive, customizable, and convenient manufacturing techniques for nanogel production.

Novel Biomaterials Used in Medical 3D Printing Techniques.

The success of an implant depends on the type of biomaterial used for its fabrication. An ideal implant material should be biocompatible, inert, mechanically durable, and easily moldable. The ability to build patient specific implants incorporated with bioactive drugs, cells, and proteins has made 3D printing technology revolutionary in medical and pharmaceutical fields. A vast variety of biomaterials are currently being used in medical 3D printing, including metals, ceramics, polymers, and composites. With continuous research and progress in biomaterials used in 3D printing, there has been a rapid growth in applications of 3D printing in manufacturing customized implants, prostheses, drug delivery devices, and 3D scaffolds for tissue engineering and regenerative medicine. The current review focuses on the novel biomaterials used in variety of 3D printing technologies for clinical applications. Most common types of medical 3D printing technologies, including fused deposition modeling, extrusion based bioprinting, inkjet, and polyjet printing techniques, their clinical applications, different types of biomaterials currently used by researchers, and key limitations are discussed in detail.

3D printing of surgical hernia meshes impregnated with contrast agents: in vitro proof of concept with imaging characteristics on computed tomography.

BACKGROUND: Selected medical implants and other 3D printed constructs could potentially benefit from the ability to incorporate contrast agents into their structure. The purpose of the present study is to create 3D printed surgical meshes impregnated with iodinated, gadolinium, and barium contrast agents and characterize their computed tomography (CT) imaging characteristics. Commercial fused deposition layering 3D printing was used to construct surgical meshes impregnated with imaging contrast agents in an in vitro model. Polycaprolactone (PCL) meshes were printed containing iodinated, gadolinium, or barium contrast; control PCL meshes without contrast were also fabricated. The three different contrast agents were mixed with PCL powder and directly loaded into the 3D printer. CT images of the three contrast-containing meshes and the control meshes were acquired and analyzed using small elliptical regions of interest to record the Hounsfield units (HU) of each mesh. Subsequently, to test their solubility and sustainability, the contrast-containing meshes were placed in a 37 °C agar solution for 7 days and imaged by CT at days 1, 3 and 7. RESULTS: All 3D printed meshes were visible on CT. Iodinated contrast meshes had the highest attenuation (2528 mean HU), significantly higher than both and gadolinium (1178 mean HU) and barium (592 mean HU) containing meshes. Only barium meshes sustained their visibility in the agar solution; the iodine and gadolinium meshes were poorly perceptible and had significantly lower mean HU compared to their pre-agar solution imaging, with iodine and gadolinium present in the adjacent agar at day 7 CT. CONCLUSION: 3D prints embedded with contrast materials through this method displayed excellent visibility on CT; however, only barium mesh maintained visibility after 7 days incubation on agar at human body temperature. This method of 3D printing with barium may have potential applications in a variety of highly personalized and CT visible medical devices.

Three-Dimensional Printing Antimicrobial and Radiopaque Constructs.

Three-dimensional (3D) printing holds tremendous potential as a tool for patient-specific devices. This proof-of- concept study demonstrated the feasibility, antimicrobial properties, and computed tomography(CT) imaging characteristics of iodine/polyvinyl alcohol (PVA) 3D meshes and stents. Under scanning electron microscopy, cross-linked PVA displays smoother and more compacted filament arrangements. X-ray and transaxial CT images of iodized PVA vascular stents show excellent visibility and significantly higher Hounsfield units of radiopacity than control prints. Three-dimensional PVA prints stabilized by glutaraldehyde cross-linking and loaded with iodine through sublimation significantly suppressed Escherichia coli and Staphylococcus aureus growth in human blood agar disk diffusion assays. It is suggested that PVA 3D printing with iodine represents an important new synthetic platform for generating a wide variety of antimicrobial and high-visibility devices.

Doped Halloysite Nanotubes for Use in the 3D Printing of Medical Devices.

Previous studies have established halloysite nanotubes (HNTs) as viable nanocontainers capable of sustained release of a variety of antibiotics, corrosion agents, chemotherapeutics and growth factors either from their lumen or in outer surface coatings. Accordingly, halloysite nanotubes (HNTs) hold great promise as drug delivery carriers in the fields of pharmaceutical science and regenerative medicine. This study explored the potential of 3D printing drug doped HNT constructs. We used a model drug, gentamicin (GS) and polylactic acid (PLA) to fabricate GS releasing disks, beads, and pellets. Gentamicin was released from 3D printed constructs in a sustained manner and had a superior anti-bacterial growth inhibition effect that was dependent on GS doping concentration. While this study focused on a model drug, gentamicin, combination therapy is possible through the fabrication of medical devices containing HNTs doped with a suite of antibiotics or antifungals. Furthermore, tailored dosage levels, suites of antimicrobials, delivered locally would reduce the toxicity of individual agents, prevent the emergence of resistant strains, and enable the treatment of mixed infections.

Medication eluting devices for the field of OBGYN (MEDOBGYN): 3D printed biodegradable hormone eluting constructs, a proof of concept study.

3D printing has the potential to deliver personalized implants and devices for obstetric and gynecologic applications. The aim of this study is to engineer customizable and biodegradable 3D printed implant materials that can elute estrogen and/or progesterone. All 3D constructs were printed using polycaprolactone (PCL) biodegradable polymer laden with estrogen or progesterone and were subjected to hormone-release profile studies using ELISA kits. Material thermal properties were tested using thermogravimetric analysis and differential scanning calorimetry. The 3D printed constructs showed extended hormonal release over a one week period. Cytocompatibility and bioactivity were assessed using a luciferase assay. The hormone-laden 3D printed constructs demonstrated an increase in luciferase activity and without any deleterious effects. Thermal properties of the PCL and hormones showed degradation temperatures above that of the temperature used in the additive manufacturing process-suggesting that 3D printing can be achieved below the degradation temperatures of the hormones. Sample constructs in the shape of surgical meshes, subdermal rods, intrauterine devices and pessaries were designed and printed. 3D printing of estrogen and progesterone-eluting constructs was feasible in this proof of concept study. These custom designs have the potential to act as a form of personalized medicine for drug delivery and optimized fit based on patient-specific anatomy.