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Trends in 3D Printing Processes for Biomedical Field: Opportunities and...
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Trends in 3D Printing Processes for Biomedical Field: Opportunities and Challenges

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Biomedical Engineering and Materials".

Deadline for manuscript submissions: closed (29 February 2024) | Viewed by 8131

Special Issue Editor

Prof. Dr. M. R. Mozafari

E-Mail Website
Guest Editor
Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Australia
Interests: nanobiotechnology; drug delivery; pharmaceutics; molecular biology; liposomes; drug targeting; cancer; pharmaceutical nanotechnology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The field of three-dimensional bioprinting has evolved impressively in the past few years. In fact, this field is considered the latest technology that creates breakthrough innovations and addresses complex medical problems. During this time, 3D bioprinting has successfully served as a potent technology for the processing of biomaterials and living materials into advanced biosystems for in vitro and in vivo applications. Researchers have never had more materials at their disposal, with significant advances in polymers, metals, ceramics, and composites. 3D bioprinting provides the ability to construct these materials in any desired shape and size, and with increasingly high resolution as fabrication processes are improved. Trends in the progress of this technology has been indicating that within the next few years, 3D bioprinting is set to become an important component in patient-specific medical technologies. In this special issue, it is aimed to highlight the most recent advances in the 3D bioprinting and advanced fabrication of biomaterials for medical and biological applications. Topics will include, but are not limited to, the following:

  • Development and optimization of 3D bioprinting techniques;
  • The latest improvements in functional biomaterials for 3D bioprinting processes;
  • Novel fabrication techniques based on mechanical, acoustic, light, magnetic, electrical and other driving mechanisms;
  • Bio-inks and hydrogels for the engineering of 3D cellular microenvironment;
  • Biomaterial inks for the fabrication of bio-functional scaffolds and substrates;
  • Novel 3D/4D bioprinting techniques and technologies for the fabrication of high-quality biobased products;
  • 3D bioprinting and fabrication for tissue engineering, disease modelling, drug delivery, drug testing and other biological applications.

Prof. Dr. M. R. Mozafari
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (7 papers)

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Research

13 pages, 6267 KiB  
Article
Advancing Surgical Arrhythmia Ablation: Novel Insights on 3D Printing Applications and Two Biocompatible Materials
by Cinzia Monaco, Rani Kronenberger, Giacomo Talevi, Luigi Pannone, Ida Anna Cappello, Mara Candelari, Robbert Ramak, Domenico Giovanni Della Rocca, Edoardo Bori, Herman Terryn, Kitty Baert, Priya Laha, Ahmet Krasniqi, Ali Gharaviri, Gezim Bala, Gian Battista Chierchia, Mark La Meir, Bernardo Innocenti and Carlo de Asmundis
Biomedicines 2024, 12(4), 869; https://doi.org/10.3390/biomedicines12040869 - 15 Apr 2024
Viewed by 447
Abstract
To date, studies assessing the safety profile of 3D printing materials for application in cardiac ablation are sparse. Our aim is to evaluate the safety and feasibility of two biocompatible 3D printing materials, investigating their potential use for intra-procedural guides to navigate surgical [...] Read more.
To date, studies assessing the safety profile of 3D printing materials for application in cardiac ablation are sparse. Our aim is to evaluate the safety and feasibility of two biocompatible 3D printing materials, investigating their potential use for intra-procedural guides to navigate surgical cardiac arrhythmia ablation. Herein, we 3D printed various prototypes in varying thicknesses (0.8 mm–3 mm) using a resin (MED625FLX) and a thermoplastic polyurethane elastomer (TPU95A). Geometrical testing was performed to assess the material properties pre- and post-sterilization. Furthermore, we investigated the thermal propagation behavior beneath the 3D printing materials during cryo-energy and radiofrequency ablation using an in vitro wet-lab setup. Moreover, electron microscopy and Raman spectroscopy were performed on biological tissue that had been exposed to the 3D printing materials to assess microparticle release. Post-sterilization assessments revealed that MED625FLX at thicknesses of 1 mm, 2.5 mm, and 3 mm, along with TPU95A at 1 mm and 2.5 mm, maintained geometrical integrity. Thermal analysis revealed that material type, energy source, and their factorial combination with distance from the energy source significantly influenced the temperatures beneath the 3D-printed material. Electron microscopy revealed traces of nitrogen and sulfur underneath the MED625FLX prints (1 mm, 2.5 mm) after cryo-ablation exposure. The other samples were uncontaminated. While Raman spectroscopy did not detect material release, further research is warranted to better understand these findings for application in clinical settings. Full article
(This article belongs to the Special Issue Trends in 3D Printing Processes for Biomedical Field: Opportunities and Challenges)
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20 pages, 3533 KiB  
Article
Engineering Precise Interconnected Porosity in β-Tricalcium Phosphate (β-TCP) Matrices by Means of Top–Down Digital Light Processing
by Thomas Wojcik, Feng Chai, Vincent Hornez, Gwenael Raoul and Jean-Christophe Hornez
Biomedicines 2024, 12(4), 736; https://doi.org/10.3390/biomedicines12040736 - 26 Mar 2024
Viewed by 519
Abstract
This study evaluated the biocompatibility and accuracy of 3D-printed β-tricalcium phosphate (β-TCP) pure ceramic scaffolds. A specific shaping process associating a digital light processing (DLP) 3D printer and a heat treatment was developed to produce pure β-TCP scaffolds leaving no polymer binder residue. [...] Read more.
This study evaluated the biocompatibility and accuracy of 3D-printed β-tricalcium phosphate (β-TCP) pure ceramic scaffolds. A specific shaping process associating a digital light processing (DLP) 3D printer and a heat treatment was developed to produce pure β-TCP scaffolds leaving no polymer binder residue. The β-TCP was characterised using X-ray diffraction, infrared spectroscopy and the detection of pollutants. The open porosity of produced matrices and their resorption were studied by hydrostatic weighing and calcium release measures. The biocompatibility of the printed matrices was evaluated by mean of osteoblast cultures. Finally, macroporous cubic matrices were produced. They were scanned using a micro-Computed Tomography scanner (micro-CT scan) and compared to their numeric models. The results demonstrated that DLP 3D printing with heat treatment produces pure β-TCP matrices with enhanced biocompatibility. They also demonstrated the printing accuracy of our technique, associating top-down DLP with the sintering of green parts. Thus, this production process is promising and will enable us to explore complex phosphocalcic matrices with a special focus on the development of a functional vascular network. Full article
(This article belongs to the Special Issue Trends in 3D Printing Processes for Biomedical Field: Opportunities and Challenges)
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16 pages, 3038 KiB  
Article
In Vivo Osteogenic and Angiogenic Properties of a 3D-Printed Isosorbide-Based Gyroid Scaffold Manufactured via Digital Light Processing
by Fiona Verisqa, Jeong-Hui Park, Nandin Mandakhbayar, Jae-Ryung Cha, Linh Nguyen, Hae-Won Kim and Jonathan C. Knowles
Biomedicines 2024, 12(3), 609; https://doi.org/10.3390/biomedicines12030609 - 7 Mar 2024
Viewed by 769
Abstract
Introduction: Osteogenic and angiogenic properties of synthetic bone grafts play a crucial role in the restoration of bone defects. Angiogenesis is recognised for its support in bone regeneration, particularly in larger defects. The objective of this study is to evaluate the new bone [...] Read more.
Introduction: Osteogenic and angiogenic properties of synthetic bone grafts play a crucial role in the restoration of bone defects. Angiogenesis is recognised for its support in bone regeneration, particularly in larger defects. The objective of this study is to evaluate the new bone formation and neovascularisation of a 3D-printed isosorbide-based novel CSMA-2 polymer in biomimetic gyroid structures. Methods: The gyroid scaffolds were fabricated by 3D printing CSMA-2 polymers with different hydroxyapatite (HA) filler concentrations using the digital light processing (DLP) method. A small animal subcutaneous model and a rat calvaria critical-size defect model were performed to analyse tissue compatibility, angiogenesis, and new bone formation. Results: The in vivo results showed good biocompatibility of the 3D-printed gyroid scaffolds with no visible prolonged inflammatory reaction. Blood vessels were found to infiltrate the pores from day 7 of the implantation. New bone formation was confirmed with positive MT staining and BMP-2 expression, particularly on scaffolds with 10% HA. Bone volume was significantly higher in the CSMA-2 10HA group compared to the sham control group. Discussion and Conclusions: The results of the subcutaneous model demonstrated a favourable tissue response, including angiogenesis and fibrous tissue, indicative of the early wound healing process. The results from the critical-size defect model showcased new bone formation, as confirmed by micro-CT imaging and immunohistochemistry. The combination of CSMA-2 as the 3D printing material and the gyroid as the 3D structure was found to support essential events in bone healing, specifically angiogenesis and osteogenesis. Full article
(This article belongs to the Special Issue Trends in 3D Printing Processes for Biomedical Field: Opportunities and Challenges)
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16 pages, 28211 KiB  
Article
A Combined Computational and Experimental Analysis of PLA and PCL Hybrid Nanocomposites 3D Printed Scaffolds for Bone Regeneration
by Spyros V. Kallivokas, Lykourgos C. Kontaxis, Spyridon Psarras, Maria Roumpi, Ourania Ntousi, Iοannis Kakkos, Despina Deligianni, George K. Matsopoulos, Dimitrios I. Fotiadis and Vassilis Kostopoulos
Biomedicines 2024, 12(2), 261; https://doi.org/10.3390/biomedicines12020261 - 24 Jan 2024
Cited by 2 | Viewed by 1114
Abstract
A combined computational and experimental study of 3D-printed scaffolds made from hybrid nanocomposite materials for potential applications in bone tissue engineering is presented. Polycaprolactone (PCL) and polylactic acid (PLA), enhanced with chitosan (CS) and multiwalled carbon nanotubes (MWCNTs), were investigated in respect of [...] Read more.
A combined computational and experimental study of 3D-printed scaffolds made from hybrid nanocomposite materials for potential applications in bone tissue engineering is presented. Polycaprolactone (PCL) and polylactic acid (PLA), enhanced with chitosan (CS) and multiwalled carbon nanotubes (MWCNTs), were investigated in respect of their mechanical characteristics and responses in fluidic environments. A novel scaffold geometry was designed, considering the requirements of cellular proliferation and mechanical properties. Specimens with the same dimensions and porosity of 45% were studied to fully describe and understand the yielding behavior. Mechanical testing indicated higher apparent moduli in the PLA-based scaffolds, while compressive strength decreased with CS/MWCNTs reinforcement due to nanoscale challenges in 3D printing. Mechanical modeling revealed lower stresses in the PLA scaffolds, attributed to the molecular mass of the filler. Despite modeling challenges, adjustments improved simulation accuracy, aligning well with experimental values. Material and reinforcement choices significantly influenced responses to mechanical loads, emphasizing optimal structural robustness. Computational fluid dynamics emphasized the significance of scaffold permeability and wall shear stress in influencing bone tissue growth. For an inlet velocity of 0.1 mm/s, the permeability value was estimated at 4.41 × 10−9 m2, which is in the acceptable range close to human natural bone permeability. The average wall shear stress (WSS) value that indicates the mechanical stimuli produced by cells was calculated to be 2.48 mPa, which is within the range of the reported literature values for promoting a higher proliferation rate and improving osteogenic differentiation. Overall, a holistic approach was utilized to achieve a delicate balance between structural robustness and optimal fluidic conditions, in order to enhance the overall performance of scaffolds in tissue engineering applications. Full article
(This article belongs to the Special Issue Trends in 3D Printing Processes for Biomedical Field: Opportunities and Challenges)
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22 pages, 4126 KiB  
Article
Enhanced Apigenin Dissolution and Effectiveness Using Glycyrrhizin Spray-Dried Solid Dispersions Filled in 3D-Printed Tablets
by Asma B. Omer, Farhat Fatima, Mohammed Muqtader Ahmed, Mohammed F. Aldawsari, Ahmed Alalaiwe, Md. Khalid Anwer and Abdul Aleem Mohammed
Biomedicines 2023, 11(12), 3341; https://doi.org/10.3390/biomedicines11123341 - 18 Dec 2023
Viewed by 833
Abstract
This study aimed to prepare glycyrrhizin–apigenin spray-dried solid dispersions and develop PVA filament-based 3D printlets to enhance the dissolution and therapeutic effects of apigenin (APN); three formulations (APN1–APN3) were proportioned from 1:1 to 1:3. A physicochemical analysis was conducted, which revealed process yields [...] Read more.
This study aimed to prepare glycyrrhizin–apigenin spray-dried solid dispersions and develop PVA filament-based 3D printlets to enhance the dissolution and therapeutic effects of apigenin (APN); three formulations (APN1–APN3) were proportioned from 1:1 to 1:3. A physicochemical analysis was conducted, which revealed process yields of 80.5–91% and APN content within 98.0–102.0%. FTIR spectroscopy confirmed the structural preservation of APN, while Powder-XRD analysis and Differential Scanning Calorimetry indicated its transformation from a crystalline to an amorphous form. APN2 exhibited improved flow properties, a lower Angle of Repose, and Carr’s Index, enhancing compressibility, with the Hausner Ratio confirming favorable flow properties for pharmaceutical applications. In vitro dissolution studies demonstrated superior performance with APN2, releasing up to 94.65% of the drug and revealing controlled release mechanisms with a lower mean dissolution time of 71.80 min and a higher dissolution efficiency of 19.2% compared to the marketed APN formulation. This signified enhanced dissolution and improved therapeutic onset. APN2 exhibited enhanced antioxidant activity; superior cytotoxicity against colon cancer cells (HCT-116), with a lower IC50 than APN pure; and increased antimicrobial activity. A stability study confirmed the consistency of APN2 after 90 days, as per ICH, with an f2 value of 70.59 for both test and reference formulations, ensuring reliable pharmaceutical development. This research underscores the potential of glycyrrhizin–apigenin solid dispersions for pharmaceutical and therapeutic applications, particularly highlighting the superior physicochemical properties, dissolution behavior, biological activities, and stability of APN2, while the development of a 3D printlet shell offers promise for enhanced drug delivery and therapeutic outcomes in colon cancer treatment, displaying advanced formulation and processing techniques. Full article
(This article belongs to the Special Issue Trends in 3D Printing Processes for Biomedical Field: Opportunities and Challenges)
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17 pages, 1513 KiB  
Article
Effect of pH, Ionic Strength and Agitation Rate on Dissolution Behaviour of 3D-Printed Tablets, Tablets Prepared from Ground Hot-Melt Extruded Filaments and Physical Mixtures
by Nour Nashed, Stephanie Chan, Matthew Lam, Taravat Ghafourian and Ali Nokhodchi
Biomedicines 2023, 11(2), 375; https://doi.org/10.3390/biomedicines11020375 - 27 Jan 2023
Cited by 4 | Viewed by 1566
Abstract
With the current focus on 3D-printing technologies, it is essential to understand the processes involved in such printing methods and approaches to minimize the variability in dissolution behaviour to achieve better quality control outcomes. For this purpose, two formulations of theophylline tablets were [...] Read more.
With the current focus on 3D-printing technologies, it is essential to understand the processes involved in such printing methods and approaches to minimize the variability in dissolution behaviour to achieve better quality control outcomes. For this purpose, two formulations of theophylline tablets were prepared using hydroxypropyl cellulose (HPC) and ethyl cellulose (EC). Among the two types of tablets, three different methods (physical mixture (PM), hot-melt extrusion (HME) and 3D-printing fused deposition modelling (FDM)) were applied and their dissolution behaviours were studied under various conditions using a biodissolution tester. This was carried out at pH values of 1.2, 2.2, 5.8, 6.8, 7.2 and 7.5, mimicking the medium in the gastrointestinal tract. Dissolution tests under two dipping rates (10 dpm and 20 dpm) and two ionic strengths (0.2 M and 0.4 M) were conducted to mimic fed and fasting conditions. The dissolution efficiency (DE%), release rate, similarity factor (f2) and difference factor (f1) were calculated. When comparing the DE%, the formulation containing EC showed less sensitivity to changes in the dipping rate and ionic strength compared to the HPC formulation. As for the manufacturing method, 3D-printing FDM could improve the robustness of the dissolution behaviour of both formulations to dipping rate changes. However, for ionic strength changes, the effect of the manufacturing method was dependent on the formulation composition. For example, the 3D-printed tablets of the HPC formulation were more sensitive to changes in ionic strength compared to the EC-containing formulation. The release mechanism also changed after the thermal process, where n values in the Korsmeyer–Peppas model were much higher in the printing and HME methods compared to the PM. Based on the formulation composition, the 3D-printing method could be a good candidate method for tablets with a robust dissolution behaviour in the GI tract. Compared to HPC polymers, using hydrophobic EC polymers in printable formulations can result in a more robust dissolution behaviour in fed and fasting states. Full article
(This article belongs to the Special Issue Trends in 3D Printing Processes for Biomedical Field: Opportunities and Challenges)
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10 pages, 3071 KiB  
Article
Development of a 3D Printed Brain Model with Vasculature for Neurosurgical Procedure Visualisation and Training
by Manuel Encarnacion Ramirez, Issael Ramirez Pena, Rossi E. Barrientos Castillo, Albert Sufianov, Evgeniy Goncharov, Jose A. Soriano Sanchez, Manuel Colome-Hidalgo, Renat Nurmukhametov, José Rafael Cerda Céspedes and Nicola Montemurro
Biomedicines 2023, 11(2), 330; https://doi.org/10.3390/biomedicines11020330 - 24 Jan 2023
Cited by 15 | Viewed by 1879
Abstract
Background: Simulation-based techniques using three-dimensional models are gaining popularity in neurosurgical training. Most pre-existing models are expensive, so we felt a need to develop a real-life model using 3D printing technology to train in endoscopic third ventriculostomy. Methods: The brain model was made [...] Read more.
Background: Simulation-based techniques using three-dimensional models are gaining popularity in neurosurgical training. Most pre-existing models are expensive, so we felt a need to develop a real-life model using 3D printing technology to train in endoscopic third ventriculostomy. Methods: The brain model was made using a 3D-printed resin mold from patient-specific MRI data. The mold was filled with silicone Ecoflex™ 00-10 and mixed with Silc Pig® pigment additives to replicate the color and consistency of brain tissue. The dura mater was made from quick-drying silicone paste admixed with gray dye. The blood vessels were made from a silicone 3D-printed mold based on magnetic resonance imaging. Liquid containing paprika oleoresin dye was used to simulate blood and was pumped through the vessels to simulate pulsatile motion. Results: Seven residents and eight senior neurosurgeons were recruited to test our model. The participants reported that the size and anatomy of the elements were very similar to real structures. The model was helpful for training neuroendoscopic 3D perception and navigation. Conclusions: We developed an endoscopic third ventriculostomy training model using 3D printing technology that provides anatomical precision and a realistic simulation. We hope our model can provide an indispensable tool for young neurosurgeons to gain operative experience without exposing patients to risk. Full article
(This article belongs to the Special Issue Trends in 3D Printing Processes for Biomedical Field: Opportunities and Challenges)
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