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3D Printing and Nanotechnology in Biology and Medical Applications

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A special issue of Nanomaterials (ISSN 2079-4991). This special issue belongs to the section "Biology and Medicines".

Deadline for manuscript submissions: closed (30 November 2020) | Viewed by 39312

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Special Issue Editors

Dr. Ignazio Roppolo

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Guest Editor

Departement of Applied Science and Technology, Politecnico di Torino, Turin, Italy
Interests: 3D printing; photopolymerization; nanocomposite; functional materials; light driven reactions

Dr. Annalisa Chiappone

E-Mail Website
Guest Editor

Departement of Applied Science and Technology, Politecnico di Torino, Turin, Italy
Interests: 3D printing; photopolymerization; nanocomposite; biomaterials; natural polymers

Special Issue Information

Dear Colleagues,

3D Printing and nanotechnology present manifold advantages and unique properties that make them extremely attractive. In particular, in recent years, nanotechnology has opened a variety of routes scaling down the dimensions of materials and devices, while 3D printing has allowed the production of objects with shapes impossible to achieve by classical subtractive manufacturing techniques. The eventual combination of the two fields can bring forth unique results that are surely of great interest both at the scientific and industrial level. 3D printing and nanotechnology are exploding in myriad applications and, in particular, they are attracting strong attraction in the biomedical field.

This Special Issue of Nanomaterials aims to publish original high-quality research papers covering the most recent advances as well as comprehensive reviews addressing state-of-the-art topics in the field of materials and devices related to 3D printing and nanotechnology in biology and medical applications.

Further, opinions and papers on open questions that could give critical assessments and future directions in this research field are welcome.

This Special Issue will cover the synthesis, preparation, and characterization of both nanomaterials and new materials for 3D printing, focusing on their application in biology and medicine. New biocompatible, bioinert, and biodegradable materials to be used as 3D scaffold, antimicrobial nanomaterials, surface functionalization processes, and the development of devices for biomedical nanoreactions and medical applications will be of interest. Topics to be covered by this Special Issue include but are not limited to the following:

3D printable nanomaterials and nanocomposites preparation and characterization;
Biocompatibility of 3D printable materials;
Antimicrobial nanomaterials for 3D structures;
Advances in bioplotting materials and 3D structures;
SL–DLP printable materials and 3D structures for the biomedical field;
FFF and SLS printable materials and 3D structures for the biomedical field;
2 photons resins and nanodevices;
Electrospinnable materials for 3D scaffolds or porous substrates;
Surface functionalization processes for molecules immobilization and detection in 3D devices;
Microfluidic devices for nanoreactors.

We would like to gratefully acknowledge in advance the authors and reviewers who will participate to the elaboration of this Special Issue.

Dr. Ignazio Roppolo
Dr. Annalisa Chiappone
Guest Editors

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. Nanomaterials is an international peer-reviewed open access semimonthly 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 2900 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.

Keywords

3D printing
Biology and medical implants
nanomaterials
surface functionalization
device design and fabrication

Published Papers (9 papers)

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Research

17 pages, 2679 KiB

Open AccessArticle

Three-Dimensional Technology Applications in Maxillofacial Reconstructive Surgery: Current Surgical Implications

by Yasmin Ghantous, Aysar Nashef, Aladdin Mohanna and Imad Abu-El-naaj

Nanomaterials 2020, 10(12), 2523; https://0-doi-org.brum.beds.ac.uk/10.3390/nano10122523 - 16 Dec 2020

Cited by 17 | Viewed by 2775

Abstract

Defects in the oral and maxillofacial (OMF) complex may lead to functional and esthetic impairment, aspiration, speech difficulty, and reduced quality of life. Reconstruction of such defects is considered one of the most challenging procedures in head and neck surgery. Transfer of different auto-grafts is still considered as the “gold standard” of regenerative and reconstructive procedures for OMF defects. However, harvesting of these grafts can lead to many complications including donor-site morbidity, extending of surgical time, incomplete healing of the donor site and others. Three-dimensional (3D) printing technology is an innovative technique that allows the fabrication of personalized implants and scaffolds that fit the precise anatomy of an individual’s defect and, therefore, has attracted significant attention during the last few decades, especially among head and neck surgeons. Here we discuss the most relevant applications of the 3D printing technology in the oral and maxillofacial surgery field. We further show different clinical examples of patients who were treated at our institute using the 3D technology and discuss the indications, different technologies, complications, and their clinical outcomes. We demonstrate that 3D technology may provide a powerful tool used for reconstruction of various OMF defects, enabling optimal clinical results in the suitable cases. Full article

(This article belongs to the Special Issue 3D Printing and Nanotechnology in Biology and Medical Applications)

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17 pages, 4309 KiB

Open AccessArticle

PLGA Membranes Functionalized with Gelatin through Biomimetic Mussel-Inspired Strategy

by Irene Carmagnola, Valeria Chiono, Gerardina Ruocco, Annachiara Scalzone, Piergiorgio Gentile, Paola Taddei and Gianluca Ciardelli

Nanomaterials 2020, 10(11), 2184; https://0-doi-org.brum.beds.ac.uk/10.3390/nano10112184 - 02 Nov 2020

Cited by 12 | Viewed by 3314

Abstract

Electrospun membranes have been widely used as scaffolds for soft tissue engineering due to their extracellular matrix-like structure. A mussel-inspired coating approach based on 3,4-dihydroxy-DL-phenylalanine (DOPA) polymerization was proposed to graft gelatin (G) onto poly(lactic-co-glycolic) acid (PLGA) electrospun membranes. PolyDOPA coating allowed grafting of gelatin to PLGA fibers without affecting their bulk characteristics, such as molecular weight and thermal properties. PLGA electrospun membranes were dipped in a DOPA solution (2 mg/mL, Tris/HCl 10 mM, pH 8.5) for 7 h and then incubated in G solution (2 mg/mL, Tris/HCl 10 mM, pH 8.5) for 16 h. PLGA fibers had an average diameter of 1.37 ± 0.23 µm. Quartz crystal microbalance with dissipation technique (QCM-D) analysis was performed to monitor DOPA polymerization over time: after 7 h the amount of deposited polyDOPA was 71 ng/cm². After polyDOPA surface functionalization, which was, also revealed by Raman spectroscopy, PLGA membranes maintained their fibrous morphology, however the fiber size and junction number increased. Successful functionalization with G was demonstrated by FTIR-ATR spectra, which showed the presence of G adsorption bands at 1653 cm⁻¹ (Amide I) and 1544 cm⁻¹ (Amide II) after G grafting, and by the Kaiser Test, which revealed a higher amount of amino groups for G functionalized membranes. Finally, the biocompatibility of the developed substrates and their ability to induce cell growth was assessed using Neonatal Normal Human Dermal Fibroblasts. Full article

(This article belongs to the Special Issue 3D Printing and Nanotechnology in Biology and Medical Applications)

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13 pages, 3488 KiB

Open AccessArticle

Inkjet Printing of Synthesized Melanin Nanoparticles as a Biocompatible Matrix for Pharmacologic Agents

by Matthew Ballard, Ashkan Shafiee, Elinor Grage, Max DeMarco, Anthony Atala and Elham Ghadiri

Nanomaterials 2020, 10(9), 1840; https://0-doi-org.brum.beds.ac.uk/10.3390/nano10091840 - 15 Sep 2020

Cited by 5 | Viewed by 3551

Abstract

Melanin is a natural biopigment that is produced by melanocytes and can be found in most living organisms. The unique physical and chemical properties of melanin render it potentially useful for numerous applications, particularly those in which a biocompatible functional material is required. Herein, we introduce one important technology in which melanin can be utilized: a drug delivery system in terms of a biocompatible matrix. However, extracting melanin from different biological sources is costly and time-consuming and introduces variabilities in terms of chemical structure, properties, and functions. Hence, a functionally reproducible system is hard to achieve using biologically extracted melanin. Here we report the synthesis of melanin nanoparticles of controlled uniform sizes and chemical characteristics. The optical, chemical, and structural characteristics of synthesized nanoparticles were characterized by optical confocal photoluminescence (PL) imaging, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and Zeta potentiometry. The melanin nanoparticles have 100 nm size and a narrow size distribution. The advantage of a nanoparticle structure is its enhanced surface-to-volume ratio compared to bulk pigments, which is important for applications in which controlling the microscopic surface area is essential. Using the inkjet printing technique, we developed melanin thin films with minimum ink waste and loaded them with methylene blue (our representative drug) to test the drug-loading ability of the melanin nanoparticles. Inkjet printing allowed us to create smooth uniform films with precise deposition and minimum ink-waste. The spectroscopic analysis confirmed the attachment of the “drug” onto the melanin nanoparticles as a matrix. Hence, our data identify melanin as a material system to integrate into drug release applications. Full article

(This article belongs to the Special Issue 3D Printing and Nanotechnology in Biology and Medical Applications)

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13 pages, 4241 KiB

Open AccessArticle

Materials Testing for the Development of Biocompatible Devices through Vat-Polymerization 3D Printing

by Gustavo González, Désirée Baruffaldi, Cinzia Martinengo, Angelo Angelini, Annalisa Chiappone, Ignazio Roppolo, Candido Fabrizio Pirri and Francesca Frascella

Nanomaterials 2020, 10(9), 1788; https://0-doi-org.brum.beds.ac.uk/10.3390/nano10091788 - 09 Sep 2020

Cited by 39 | Viewed by 4443

Abstract

Light-based 3D printing techniques could be a valuable instrument in the development of customized and affordable biomedical devices, basically for high precision and high flexibility in terms of materials of these technologies. However, more studies related to the biocompatibility of the printed objects are required to expand the use of these techniques in the health sector. In this work, 3D printed polymeric parts are produced in lab conditions using a commercial Digital Light Processing (DLP) 3D printer and then successfully tested to fabricate components suitable for biological studies. For this purpose, different 3D printable formulations based on commercially available resins are compared. The biocompatibility of the 3D printed objects toward A549 cell line is investigated by adjusting the composition of the resins and optimizing post-printing protocols; those include washing in common solvents and UV post-curing treatments for removing unreacted and cytotoxic products. It is noteworthy that not only the selection of suitable materials but also the development of an adequate post-printing protocol is necessary for the development of biocompatible devices. Full article

(This article belongs to the Special Issue 3D Printing and Nanotechnology in Biology and Medical Applications)

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23 pages, 4978 KiB

Open AccessArticle

Collagen Hybrid Formulations for the 3D Printing of Nanostructured Bone Scaffolds: An Optimized Genipin-Crosslinking Strategy

by Giorgia Montalbano, Giorgia Borciani, Giorgia Cerqueni, Caterina Licini, Federica Banche-Niclot, Davide Janner, Stefania Sola, Sonia Fiorilli, Monica Mattioli-Belmonte, Gabriela Ciapetti and Chiara Vitale-Brovarone

Nanomaterials 2020, 10(9), 1681; https://0-doi-org.brum.beds.ac.uk/10.3390/nano10091681 - 27 Aug 2020

Cited by 38 | Viewed by 5336

Abstract

Bone-tissue regeneration induced by biomimetic bioactive materials is the most promising approach alternative to the clinical ones used to treat bone loss caused by trauma or diseases such as osteoporosis. The goal is to design nanostructured bioactive constructs able to reproduce the physiological environment: By mimicking the natural features of bone tissue, the cell behavior during the regeneration process may be addressed. At present, 3D-printing technologies are the only techniques able to design complex structures avoiding constraints of final shape and porosity. However, this type of biofabrication requires complex optimization of biomaterial formulations in terms of specific rheological and mechanical properties while preserving high biocompatibility. In this work, we combined nano-sized mesoporous bioactive glasses enriched with strontium ions with type I collagen, to formulate a bioactive ink for 3D-printing technologies. Moreover, to avoid the premature release of strontium ions within the crosslinking medium and to significantly increase the material mechanical and thermal stability, we applied an optimized chemical treatment using ethanol-dissolved genipin solutions. The high biocompatibility of the hybrid system was confirmed by using MG-63 and Saos-2 osteoblast-like cell lines, further highlighting the great potential of the innovative nanocomposite for the design of bone-like scaffolds. Full article

(This article belongs to the Special Issue 3D Printing and Nanotechnology in Biology and Medical Applications)

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10 pages, 2115 KiB

Open AccessArticle

Decellularized Skin Extracellular Matrix (dsECM) Improves the Physical and Biological Properties of Fibrinogen Hydrogel for Skin Bioprinting Applications

by Adam M Jorgensen, Zishuai Chou, Gregory Gillispie, Sang Jin Lee, James J Yoo, Shay Soker and Anthony Atala

Nanomaterials 2020, 10(8), 1484; https://0-doi-org.brum.beds.ac.uk/10.3390/nano10081484 - 29 Jul 2020

Cited by 41 | Viewed by 5346

Abstract

Full-thickness skin wounds are a significant clinical burden in the United States. Skin bioprinting is a relatively new technology that is under investigation as a new treatment for full-thickness injuries, and development of hydrogels with strong physical and biological characteristics are required to improve both structural integrity of the printed constructs while allowing for a more normal extracellular matrix milieu. This project aims to evaluate the physical and biological characteristics of fibrinogen hydrogel supplemented with decellularized human skin-derived extracellular matrix (dsECM). The hybrid hydrogel improves the cell viability and structural strength of bioprinted skin constructs. Scanning electron microscopy demonstrates that the hybrid hydrogel is composed of both swelling bundles interlocked in a fibrin network, similar to healthy human skin. This hybrid hydrogel has improved rheological properties and shear thinning properties. Extrusion-based printing of the fibrinogen hydrogel + dsECM demonstrates significant improvement in crosshatch pore size. These findings suggest that incorporating the properties of dsECM and fibrinogen hydrogels will improve in vivo integration of the bioprinted skin constructs and support of healthy skin wound regeneration. Full article

(This article belongs to the Special Issue 3D Printing and Nanotechnology in Biology and Medical Applications)

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15 pages, 2556 KiB

Open AccessArticle

Application of a Micro Free-Flow Electrophoresis 3D Printed Lab-on-a-Chip for Micro-Nanoparticles Analysis

by Federica Barbaresco, Matteo Cocuzza, Candido Fabrizio Pirri and Simone Luigi Marasso

Nanomaterials 2020, 10(7), 1277; https://0-doi-org.brum.beds.ac.uk/10.3390/nano10071277 - 30 Jun 2020

Cited by 18 | Viewed by 3745

Abstract

The present work describes a novel microfluidic free-flow electrophoresis device developed by applying three-dimensional (3D) printing technology to rapid prototype a low-cost chip for micro- and nanoparticle collection and analysis. Accurate reproducibility of the device design and the integration of the inlet and outlet ports with the proper tube interconnection was achieved by the additive manufacturing process. Test prints were performed to compare the glossy and the matte type of surface finish. Analyzing the surface topography of the 3D printed device, we demonstrated how the best reproducibility was obtained with the glossy device showing a 5% accuracy. The performance of the device was demonstrated by a free-flow zone electrophoresis application on micro- and nanoparticles with different dimensions, charge surfaces and fluorescent dyes by applying different separation voltages up to 55 V. Dynamic light scattering (DLS) measurements and ultraviolet−visible spectroscopy (UV−Vis) analysis were performed on particles collected at the outlets. The percentage of particles observed at each outlet was determined in order to demonstrate the capability of the micro free-flow electrophoresis (µFFE) device to work properly in dependence of the applied electric field. In conclusion, we rapid prototyped a microfluidic device by 3D printing, which ensured micro- and nanoparticle deviation and concentration in a reduced operation volume and hence suitable for biomedical as well as pharmaceutical applications. Full article

(This article belongs to the Special Issue 3D Printing and Nanotechnology in Biology and Medical Applications)

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14 pages, 5963 KiB

Open AccessArticle

Fabrication of 3D-Printed Biodegradable Porous Scaffolds Combining Multi-Material Fused Deposition Modeling and Supercritical CO₂ Techniques

by Raúl Sanz-Horta, Carlos Elvira, Alberto Gallardo, Helmut Reinecke and Juan Rodríguez-Hernández

Nanomaterials 2020, 10(6), 1080; https://0-doi-org.brum.beds.ac.uk/10.3390/nano10061080 - 31 May 2020

Cited by 22 | Viewed by 4684

Abstract

The fabrication of porous materials for tissue engineering applications in a straightforward manner is still a current challenge. Herein, by combining the advantages of two conventional methodologies with additive manufacturing, well-defined objects with internal and external porosity were produced. First of all, multi-material fused deposition modeling (FDM) allowed us to prepare structures combining poly (ε-caprolactone) (PCL) and poly (lactic acid) (PLA), thus enabling to finely tune the final mechanical properties of the printed part with modulus and strain at break varying from values observed for pure PCL (modulus 200 MPa, strain at break 1700%) and PLA (modulus 1.2 GPa and strain at break 5–7%). More interestingly, supercritical CO₂ (SCCO₂) as well as the breath figures mechanism (BFs) were additionally employed to produce internal (pore diameters 80–300 µm) and external pores (with sizes ranging between 2 and 12 μm) exclusively in those areas where PCL is present. This strategy will offer unique possibilities to fabricate intricate structures combining the advantages of additive manufacturing (AM) in terms of flexibility and versatility and those provided by the SCCO₂ and BFs to finely tune the formation of porous structures. Full article

(This article belongs to the Special Issue 3D Printing and Nanotechnology in Biology and Medical Applications)

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14 pages, 2357 KiB

Open AccessArticle

3D-Printed Concentration-Controlled Microfluidic Chip with Diffusion Mixing Pattern for the Synthesis of Alginate Drug Delivery Microgels

by Shixuan Cai, Hongyan Shi, Guoqian Li, Qilu Xue, Lei Zhao, Fu Wang and Bo Hu

Nanomaterials 2019, 9(10), 1451; https://0-doi-org.brum.beds.ac.uk/10.3390/nano9101451 - 12 Oct 2019

Cited by 16 | Viewed by 3574

Abstract

Alginate as a good drug delivery vehicle has excellent biocompatibility and biodegradability. In the ionic gelation process between alginate and Ca²⁺, the violent reaction is the absence of a well-controlled strategy in the synthesizing calcium alginate (CaA) microgels. In this study, a concentration-controlled microfluidic chip with central buffer flow was designed and 3D-printed to well-control the synthesis process of CaA microgels by the diffusion mixing pattern. The diffusion mixing pattern in the microfluidic chip can slow down the ionic gelation process in the central stream. The particle size can be influenced by channel length and flow rate ratio, which can be regulated to 448 nm in length and 235 nm in diameter. The delivery ratio of Doxorubicin (Dox) in CaA microgels are up to 90% based on the central stream strategy. CaA@Dox microgels with pH-dependent release property significantly enhances the cell killing rate against human breast cancer cells (MCF-7). The diffusion mixing pattern gives rise to well-controlled synthesis of CaA microgels, serving as a continuous and controllable production process for advanced drug delivery systems. Full article

(This article belongs to the Special Issue 3D Printing and Nanotechnology in Biology and Medical Applications)

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