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Uday Jammalamadaka,1 Karthik Tappa,1 Jeffery A Weisman,1 James Connor Nicholson,2 David K Mills1,3 1Center for Biomedical Engineering and Rehabilitation Science, 2Nanosystems Engineering, 3The School of Biological Sciences, Louisiana Tech University, Ruston, LA, USA Abstract: Halloysite nanotubes (HNTs) were investigated as a platform for tunable nanoparticle composition and enhanced opacity in poly(methyl methacrylate) (PMMA) bone cement. Halloysite has been widely used to increase the mechanical properties of various polymer matrices, in stark contrast to other fillers such as barium sulfate that provide opacity but also decrease mechanical strength. The present work describes a dry deposition method for successively fabricating barium sulfate nanoparticles onto the exterior surface of HNTs. A sintering process was used to coat the HNTs in barium sulfate. Barium sulfate-coated HNTs were then added to PMMA bone cement and the samples were tested for mechanical strength and tailored opacity correlated with the fabrication ratio and the amount of barium sulfate-coated HNTs added. The potential cytotoxic effect of barium-coated HNTs in PMMA cement was also tested on osteosarcoma cells. Barium-coated HNTs were found to be completely cytocompatible, and cell proliferation was not inhibited after exposure to the barium-coated HNTs embedded in PMMA cement. We demonstrate a simple method for the creation of barium-coated nanoparticles that imparted improved contrast and material properties to native PMMA. An easy and efficient method for coating clay nanotubes offers the potential for enhanced imaging by radiologists or orthopedic surgeons. Keywords: barium, bone cement, halloysite, imaging, PMMA, sintering

Jeffery A Weisman,1 James C Nicholson,2 Karthik Tappa,1 UdayaBhanu Jammalamadaka,1 Chester G Wilson,2 David K Mills1,3 1Center for Biomedical Engineering and Rehabilitation Science, 2Nanosystems Engineering, 3School of Biological Sciences, Louisiana Technical University, Ruston, LA, USAAbstract: Three-dimensional (3D) printing and additive manufacturing holds potential for highly personalized medicine, and its introduction into clinical medicine will have many implications for patient care. This paper demonstrates the first application of 3D printing as a method for the potential sustained delivery of antibiotic and chemotherapeutic drugs from constructs for patient treatment. Our design is focused on the on-demand production of anti-infective and chemotherapeutic filaments that can be used to create discs, beads, catheters, or any medical construct using a 3D printing system. The design parameters for this project were to create a system that could be modularly loaded with bioactive agents. All 3D-printed constructs were loaded with either gentamicin or methotrexate and were optimized for efficient and extended antibacterial and cancer growth-inhibiting cytostatic activity. Preliminary results demonstrate that combining gentamicin and methotrexate with polylactic acid forms a composite possessing a superior combination of strength, versatility, and enhanced drug delivery. Antibacterial effects and a reduction in proliferation of osteosarcoma cells were observed with all constructs, attesting to the technical and clinical viability of our composites. In this study, 3D constructs were loaded with gentamicin and methotrexate, but the method can be extended to many other drugs. This method could permit clinicians to provide customized and tailored treatment that allows patient-specific treatment of disease and has significant potential for use as a tunable drug delivery system with sustained-release capacity for an array of biomedical applications. Keywords: three-dimensional printing, polymers, antibacterial, drug delivery, medical device

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.

Single-photon emission-computed tomography (SPECT) provides a mechanism to estimate regional isotope uptake in lesions and at-risk organs after administration of α -particle-emitting radiopharmaceutical therapies ( α -RPTs). However, this estimation task is challenging due to the complex emission spectra, the very low number of detected counts (~20 times lower than in conventional SPECT), the impact of stray-radiation-related noise at these low counts, and the multiple image-degrading processes in SPECT. The conventional reconstruction-based quantification methods are observed to be erroneous for α -RPT SPECT. To address these challenges, we developed a low-count quantitative SPECT (LC-QSPECT) method that directly estimates the regional activity uptake from the projection data (obviating the reconstruction step), compensates for stray-radiation-related noise, and accounts for the radioisotope and SPECT physics, including the isotope spectra, scatter, attenuation, and collimator-detector response, using a Monte Carlo-based approach. The method was validated in the context of 3-D SPECT with 223 Ra, a commonly used radionuclide for α -RPT. Validation was performed using both realistic simulation studies, including a virtual clinical trial, and synthetic and 3-D-printed anthropomorphic physical-phantom studies. Across all studies, the LC-QSPECT method yielded reliable regional-uptake estimates and outperformed the conventional ordered subset expectation-maximization (OSEM)-based reconstruction and geometric transfer matrix (GTM)-based post-reconstruction partial-volume compensation methods. Furthermore, the method yielded reliable uptake across different lesion sizes, contrasts, and different levels of intralesion heterogeneity. Additionally, the variance of the estimated uptake approached the Cramér-Rao bound-defined theoretical limit. In conclusion, the proposed LC-QSPECT method demonstrated the ability to perform reliable quantification for α -RPT SPECT.

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., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: David Ballard reports financial support was provided by National Institutes of Health. ., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: Head trauma is the most common indication for a CT scan. In this pilot study, the authors assess the feasibility of a 5-minute high-resolution 3D golden-angle (GA) stack-of-stars radial volumetric interpolated breath-hold examination (VIBE) MRI sequence (GA-VIBE) to obtain clinically acceptable cranial bone images and identify cranial vault fractures compared to CT., Methods: Patients younger than 18 years of age presenting after head trauma were eligible for the study. Three clinicians reviewed and assessed 1) slice-by-slice volumetric CT and inverted MR images, and 2) 3D reconstructions obtained from inverted MR images and the gold standard (CT). For each image set, reviewers noted on 5-point Likert scales whether they recommended that a repeat scan be performed and the presence or absence of cranial vault fractures., Results: Thirty-one patients completed MRI after a clinical head CT scan was performed. Based on CT imaging, 8 of 31 patients had cranial fractures. Two of 31 patients were sedated as part of their clinical MRI scan. In 30 (97%) of 31 MRI reviews, clinicians agreed (or strongly agreed) that the image quality was acceptable for clinical diagnosis. Overall, comparing MRI to acceptable gold-standard CT, sensitivity and specificity of fracture detection were 100%. Furthermore, there were no discrepancies between CT and MRI in classification of fracture type or location., Conclusions: When compared with the gold standard (CT), the volumetric and 3D reconstructed images using the GA-VIBE sequence were able to produce clinically acceptable cranial images with excellent ability to detect cranial vault fractures.

Rationale: Alpha particle emitting radiopharmaceuticals are generating considerable interest for the treatment of disseminated metastatic disease. Molecular imaging of the distribution of these agents is critical to safely and effectively maximize the clinical potential of this emerging drug class. The present studies aim to investigate the feasibility and limitations of quantitative SPECT for 223 Ra, 225 Ac and 227 Th. Methods: Three state-of-the-art SPECT/CT systems were investigated: the GE Discovery NM/CT 670, the GE Optima NM/CT 640, and the Siemens Symbia T6. A series of phantoms, including the NEMA IEC Body phantom, were used to compare and calibrate each camera. Additionally, anthropomorphic physical tumor and vertebrae phantoms were developed and imaged to evaluate the quantitative imaging protocol. Results: This work describes and validates a methodology to calibrate each clinical system. The efficiency of each gamma camera was analyzed and compared. Using the calibration factors obtained with the NEMA phantom, we were able to quantify the activity in 3D-printed tissue phantoms with an error of 2.1%, 3.5% and 11.8% for 223 Ra, 225 Ac, and 227 Th, respectively. Conclusion: The present study validates that quantitative SPECT/CT imaging of 223 Ra, 225 Ac, and 227 Th is achievable but that careful considerations for camera configuration are required. These results will aid in future implementation of SPECT-based patient studies and will help to identify the limiting factors for accurate image-based quantification with alpha particle emitting radionuclides., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objective: The COVID-19 pandemic has precipitated widespread shortages of filtering facepiece respirators (FFRs) and the creation and sharing of proposed substitutes (novel designs, repurposed materials) with limited testing against regulatory standards. We aimed to categorically test the efficacy and fit of potential N95 respirator substitutes using protocols that can be replicated in university laboratories., Setting: Academic medical centre with occupational health-supervised fit testing along with laboratory studies., Participants: Seven adult volunteers who passed quantitative fit testing for small-sized (n=2) and regular-sized (n=5) commercial N95 respirators., Methods: Five open-source potential N95 respirator substitutes were evaluated and compared with commercial National Institute for Occupational Safety and Health (NIOSH)-approved N95 respirators as controls. Fit testing using the 7-minute standardised Occupational Safety and Health Administration fit test was performed. In addition, protocols that can be performed in university laboratories for materials testing (filtration efficiency, air resistance and fluid resistance) were developed to evaluate alternate filtration materials., Results: Among five open-source, improvised substitutes evaluated in this study, only one (which included a commercial elastomeric mask and commercial HEPA filter) passed a standard quantitative fit test. The four alternative materials evaluated for filtration efficiency (67%-89%) failed to meet the 95% threshold at a face velocity (7.6 cm/s) equivalent to that of a NIOSH particle filtration test for the control N95 FFR. In addition, for all but one material, the small surface area of two 3D-printed substitutes resulted in air resistance that was above the maximum in the NIOSH standard., Conclusions: Testing protocols such as those described here are essential to evaluate proposed improvised respiratory protection substitutes, and our testing platform could be replicated by teams with similar cross-disciplinary research capacity. Healthcare professionals should be cautious of claims associated with improvised respirators when suggested as FFR substitutes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The use of facemasks is proven to mitigate the spread of the coronavirus and other biological agents that cause disease. Various forms of facemasks, made using different materials, are being used extensively, and it is important to determine their performance characteristics. The size-dependent filtration efficiency and breathing resistance of household sterilization wrap fabrics, and isolation media (American Society for Testing and Materials (ASTM)- and non-ASTM-rated), were measured in filter-holder- and mannequin-in-chamber-based systems, focusing on particles sizes between 20 nm and 2 μm. Double-layer MERV-14 (Minimum Efficiency Reporting Values with rating 14) showed the highest filtration efficiency (94.9-73.3%) amongst household filter media, whereas ASTM-rated isolation masks showed the highest filtration efficiencies (95.6-88.7) amongst all the masks considered. Filtration efficiency of 3D-printed masks with replaceable filter media was found to depend on the degree of sealing around the media holder, which depended on the material's compressibility. Filtration efficiencies of triple-layer combinations (95.8-85.3%) follow a profile similar to single layers but with improved filtration efficiencies.

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., (Copyright © 2020 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Objective: There is an unmet need to perform imaging in young children and obtain CT-equivalent cranial bone images without subjecting the patients to radiation. In this study, the authors propose using a high-resolution fast low-angle shot golden-angle 3D stack-of-stars radial volumetric interpolated breath-hold examination (GA-VIBE) MRI sequence that is intrinsically robust to motion and has enhanced bone versus soft-tissue contrast., Methods: Patients younger than 11 years of age, who underwent clinical head CT scanning for craniosynostosis or other cranial malformations, were eligible for the study. 3D reconstructed images created from the GA-VIBE MRI sequence and the gold-standard CT scan were randomized and presented to 3 blinded reviewers. For all image sets, each reviewer noted the presence or absence of the 6 primary cranial sutures and recorded on 5-point Likert scales whether they recommended a second scan be performed., Results: Eleven patients (median age 1.8 years) underwent MRI after clinical head CT scanning was performed. Five of the 11 patients were sedated. Three clinicians reviewed the images, and there were no cases, either with CT scans or MR images, in which a reviewer agreed a repeat scan was required for diagnosis or surgical planning. The reviewers reported clear imaging of the regions of interest on 99% of the CT reviews and 96% of the MRI reviews. With CT as the standard, the sensitivity and specificity of the GA-VIBE MRI sequence to detect suture closure were 97% and 96%, respectively (n = 198 sutures read)., Conclusions: The 3D reconstructed images using the GA-VIBE sequence in comparison to the CT scans created clinically acceptable cranial images capable of detecting cranial sutures. Future directions include reducing the scan time, improving motion correction, and automating postprocessing for clinical utility.

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., Competing Interests: Financial & competing interests disclosure DH Ballard receives salary support from NIH TOP-TIER grant T32-EB021955. JA Weisman and DK Mills are co-inventors on a patent application that related to methods described in this paper: ‘Methods and Devices for Three-Dimensional Printing or Additive Manufacturing of Bioactive Medical Devices’, application number US14822275. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

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.

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.

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 mm 2 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., (Copyright © 2018. Published by Elsevier Inc.)

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 (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.

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., Competing Interests: No conflict of interests is declared.

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., Competing Interests: The authors declare no conflict of interest.

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.

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., Competing Interests: The authors declare no conflicts of interest.

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., Competing Interests: US Patent No. 9,192,912, Ceramic Nanotube Composite with Sustained Drug Release Capability for Implants, Bone Repair, and Regeneration held by David K. Mills.

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.

The use of nanomaterials for improving drug delivery methods has been shown to be advantageous technically and viable economically. This study employed the use of halloysite nanotubes (HNTs) as nanocontainers, as well as enhancers of structural integrity in electrospun poly- e -caprolactone (PCL) scaffolds. HNTs were loaded with amoxicillin, Brilliant Green, chlorhexidine, doxycycline, gentamicin sulfate, iodine, and potassium calvulanate and release profiles assessed. Selected doped halloysite nanotubes (containing either Brilliant Green, amoxicillin and potassium calvulanate) were then mixed with poly- e -caprolactone (PLC) using the electrospinning method and woven into random and oriented-fibered nanocomposite mats. The rate of drug release from HNTs, HNTs/PCL nanocomposites, and their effect on inhibiting bacterial growth was investigated. Release profiles from nanocomposite mats showed a pattern of sustained release for all bacterial agents. Nanocomposites were able to inhibit bacterial growth for up to one-month with only a slight decrease in bacterial growth inhibition. We propose that halloysite doped nanotubes have the potential for use in a variety of medical applications including sutures and surgical dressings, without compromising material properties.

Calcium phosphate cements (CPCs) with osteoconductive properties are limited in their applications because of their poor mechanical properties. This study investigated the additive effect of Dexamethasone-doped Halloysite Nanotubes (HNTs on the mechanical properties of CPCs. HNTs are nanosized tubes with alumino-silicate composition. Physico-chemical properties, cytocompatability and cellular functionality of the nanocomposites were assayed. Results suggest that these nanoenhanced composites have a huge potential to broaden the applications of CPCs.