Abstract

     Magnetic nanoparticles (MNPs) represent an advanced tool in the medical field because they can be modified according to biomedical approaches and guided by an external magnetic field in the human body. The first objective of this review is to exemplify some promising applications in the medical field, including smart drug-delivery systems, therapies against cancer cells, radiotherapy, improvements in diagnostics using magnetic resonance imaging (MRI), and tissue engineering. Complementarily, the second objective is to illustrate the mechanisms of action and theoretical foundations related to magnetoresponsive materials.

Introduction

     Magnetic nanoparticles (MNPs) are nanoscale particles (1–100 nm) that can be guided through an external magnetic field due to their superparamagnetic, ferrimagnetic, and ferromagnetic properties, which may provide features for biomedical applications. MNPs with superparamagnetic properties are of special interest because they exhibit strong magnetic interactions under an external magnetic field, which disappear once the external magnetic field is removed. This property allows for the design of ferrofluids, since MNPs can be stabilized in solutions because they do not present magnetic interactions when the external magnetic field is switched off; and allows for in vivo performance, as in (i) cell marking [1], (ii) drug systems guided by a magnetic field [2], (iii) image contrast agents [3], and (iv) as heat generators in hyperthermia treatments [4].

     MNPs generally contains two main parts: the core and the coating. The core presents a predominant quantum effect, which commonly incorporates magnetic elements such as Fe, Ni, or Co as well as their corresponding oxides, while the coating is responsible for stabilizing and protecting the core from the chemical effects of the medium [5]. The coating also plays an essential role since it provides specific properties and functions to the nucleus; for example, biocompatible natural polymers, such as chitosan or cellulose, work as cargo vectors of therapeutic agents to release in a controlled manner (Figure 1). Due to these characteristics, biomedical device synthesis has shown great interest in low toxic superparamagnetic MNPs, to avoid embolization or other secondary effects for the patient at the molecular or cellular level [6].

Conclusions

     MNPs, in combination with superconducting magnets, have begun to play an essential role in advances in areas such as MDDS, MRI, and hyperthermia, among other fields. Therefore, it is crucial to continue the synthesis of MNPs and de

Abstract

Keywords

1. Introduction

2. MFNPs-based magnetoresponsive effects for biomedical applications

3. Conclusion and perspectives

Declaration of competing interest

Acknowledgments

References

Abstract

One of the most attractive features of magnetic ferrite nanoparticles (MFNPs) in biomedical application is that they can mediate external magnetic field to produce local magnetic field, magnetic thermal and magnetic force effects. These generated effects can later be utilized in the diagnosis and treatment of various diseases. The application performance is mainly determined by the nano-magnetism of MFNPs. Therefore, by modulating the magnetic properties, the improved magnetic resonance (MR) signals, magnetothermal, and magnetomechanical effects of the MFNPs can be achieved. In this review, we summarize the strategies used in the engineering of MFNPs to enhance MR imaging sensitivity and magnetic thermal conversion efficiencies. We will also discuss the detailed magnetoresponsive mechanism arising from the critical magnetic properties of MFNPs. Furthermore, we will highlight the recent progresses of the engineered MFNPs in biomedical applications, with emphasis in MR signal amplification, magnetothermal, and magnetomechanical response in biomedical applications.

1. Introduction

Since ancient Greek time, lodestone, i.e., bulk magnetite (Fe3O4), has been used in the treatment of common ailments. With the advancement in nano-biotechnology, the applications of such magnetic ferrite nanoparticles (MFNPs) have evolved, which extends to the modern biomedicine and clinical study [[1], [2], [3], [4], [5], [6], [7]]. As biological tissues are transparent to magnetic fields, the most attractive advantage of MFNPs in biomedical applications is that they can complete various functions triggered by invisible, tissue-penetrating magnetic field [8,9]. For instance, natural magnetotactic bacteria build iron oxide nanoparticles (IONPs) in a chain configuration to generate a permanent dipole in their cells so as to navigate toward their favorable habitats by sensing the Earth’s magnetic field [10]. These MFNPs possess good biocompatibility, which have already been used as imaging and therapeutic agents in preclinical and clinical settings [2,3,11]. As a result of the excellent magnetoresponsive properties of MFNPs, numerous exciting in vivo biomedical applications are created. These include imaging for non-invasive diagnosis of diseases [12], treatment of diseases with hyperthermia [13], magnetically driven nanorobots [14], magnetic activation of ion channel for cell signaling [15], manipulation of cell’s function and fate [16,17], and so on. Despite the good establishment of these concepts, there is a significant challenge in obtaining effective MFNPs that can achieve full functionality via the efficient conversion of the external energy of magnetic field. As such, due to their poor conversion ability, this greatly hinders their transition from bench to bed.

2-1- Introduction

2-2- 3D printing techniques for metallic biomaterials

2-3- 3D printed metallic biomaterials

2-4- Challenges, potential and current active research in 3D printing of metallic biomaterials

2-5- Conclusion References

2-1- Introduction

Among the three-dimensional (3D) printing, or officially known as additive manufacturing (AM), techniques, the powder bed fusion (PBF) and directed energy deposition (DED) are most commonly used to process metals directly as they have the capability to produce high-quality parts that are fully dense. According to ISO/ ASTM 52900:2017, PBF is a group of AM processes in which thermal energy selectively fuses regions of a powder bed, while DED is another group of AM processes in which focused thermal energy is used to fuse materials by melting as they are being deposited. In the academia, there has been extensive studies applying 3D printing in tissue engineering (Sudarmadji et al., 2011; Yeong et al., 2009; Wiria et al., 2007; Yang et al., 2002). For example, tissue scaffolds for cardiac and bone have been fabricated successfully (Chua and Yeong, 2014; Yeong et al., 2004). These applications have mainly focused on using polymers; however, in recent years, there has been growing interest in using metallic biomaterials to create implants. This is made possible with the advancement in 3D printing and accelerated development of printable materials. In this chapter the application of these two groups of AM technologies in fabrication of metallic biomaterials is described, with specific focus on metals that are biocompatible and commonly used such as 316L stainless steel, titanium-6aluminum-4vanadium (Ti6Al4V), and cobalt-chromium-molybdenum (CoCrMo).

1- Introduction

2- Deposition techniques for 3D printing of biomaterials

3- Materials for 3D printing of biomaterials

4- Applications of 3D printed biomaterials

5- 4D printing and its applications for biomaterials

6- Conclusions and future perspectives

References

Introduction

Three-dimensional printing (3D printing) or additive manufacturing (AM) promises to produce complex devices formulated from biomaterials and bioinspired materials from designs that are patient-specific. Since its advent as presurgical visualization technique and fabrication of tooling molds, 3D printing has evolved to yield bespoke devices, implants, scaffolds, diagnostic devices, and drug-delivery systems. As a result of recent public interest and affordable printing platforms, there is the desire to utilize this exciting technology for personalized health care. However, before AM can become a ubiquitous tool for the regeneration of complex tissues, such as bone, cartilage, muscles, vessels, nerves, and complex organs with multifaceted three-dimensional microarchitecture (e.g., kidneys, lymphoid organs), a number of technological limitations must be overcome. The development of advanced bioinks for 3D and 4D printing through the rational design of novel materials and their implementation as functional biomaterials through ever-expanding deposition techniques has improved the diversity and functionality of printed constructs outside of the traditional biofabrication window [1]. While there is the necessity for a compromise between suitability for purpose and biocompatibility, recent developments in materials science and bioink formulations have resulted in an improved range of solutions for biofabrication platforms. New biologically relevant printing formulations with highly consistent and accurate deposition parameters, attractive mechanical properties, high cytocompatibility, and the ability to modulate cellular functions are now being developed and offer prospects as biomaterials for use in a multitude of different applications; however, further work is needed before these novel materials become common place. In this chapter, we explore some of the approaches being pursued to achieve these targets in common 3D and 4D printing techniques, including an overview of the state-of-the-art technologies and formulations used in novel materials and bioinks, which are currently being developed, the techniques which are being utilized to produce 3D and 4D constructs, and the applications for which these new materials may be employed in. Key examples are highlighted to demonstrate the progress of this emerging technology and limitations to its development identified.

The area of biomaterials is a continuous research area. Among others, stainless steels are also used in medical applications such as fracture plates, wires, sutures and implants etc. Surgical grade 316 L stainless steel is specifically used for medical application. It primarily contains nickel, chromium and molybdenum wherein the purpose of nickel is to retain the FCC structure of stainless steel almost at any temperature unlike conventional steel which has ferrite (BCC structure) in ambient temperature. Also, nickel imparts a polished and glossy finish to surgical grade stainless steel which is an important factor to keep it hygienic. But, the harmful effect of nickel on human body has been investigated and reported for quite some time now. The adverse effect of nickel (Ni) ions that release from stainless steel upon crevice and pitting corrosion has led to the evolution of Ni-free stainless steel with high nitrogen content. This paper briefly reviews the effect of nickel release in human body and let go the presence of nickel in stainless steel by uplifting nitrogen content in it. Furthermore, the groundbreaking findings on Nifree stainless steel in last 10 years are presented and the possibilities of further developments have been hypothesized.

Introduction

Metals are predominantly used as implants in biomedical industries. The foremost criterion for choosing any implant material is its biocompatibility. The reason for choosing metallic implant is its superior mechanical strength and corrosion resistance. The most commonly used biomedical alloys are grade 5 Ti6Al4V, CoCrMo and stainless steel (AISI 316L) [1,2]. The fabrication of stainless steel is comparatively easier than Ti-alloys and CoCr alloys. Although stainless steel is used as implants at places but its application is confined to bone healing, screws and fixations. Stainless steel is present in three microstructures which are austenite, martensite and ferrite. There is one other kind which is the duplex stainless steel; it basically contains both austenite and ferrite structure [3]. These structures are attributed to proper adjustments in its chemistry which later reflects in its properties. For instance, austenitic steel doesn’t possess ferromagnetism properties like its counterpart martensitic and ferrite steel. One of the preferential attribute of implants is the non-existence of ferromagnetic property which is why austenitic stainless steels are preferred over martensitic and ferrite steels for implant material. The other advantages of austenitic steels are their FCC structure, low yield strength to tensile strength ratio, better formability and corrosion resistance among others. 316 L Stainless steel is basically Fe-based alloys containing carbon (C of maximum 0.03%), chromium (Cr of atleast 16%) and nickel (Ni of atleast 10%). Homogenous corrosion resistance is the most important characteristics of stainless steel. Corrosion resistance is not an intrinsic property but the behavior of material surface in interaction with environment.

1- Introduction

2- Materials and methods

3- Results

4- Discussion

References

Abstract

Objective. The aim of this study is to investigate bone healing ability of niobium-containing bioactive glasses in rat femur model with quantitative and qualitative measurements through x-ray computed microtomography.
Methods. Niobium-containing bioactive powders and scaffolds were produced by sol–gel route (BAGNb). Glasses without niobium addition were produced as well (BAG). Five groups were used: BAGNb powders, BAG powders, BAGNb scaffolds, BAG scaffolds and, as a control group, autogenous bone was used. Materials were implanted in the femur of male rats (Wistar Lineage n= 10) and the healing was observed after 15, 30 and 60 days. After the post-operative times, samples were scanned by X-ray microcomputed tomography where morphometric measurements and the mineral density were assessed in image software.
Results. No postoperative complications were observed after surgery. BAGNb glasses presented higher mineral deposition, which was observed in the relative volume of bone and the mineral density when compared BAG groups. In these parameters, no statistical difference was found between BAGNb and autogenous bone. The BAGNb powders presented a higher amount of mineralized tissue when compared to BAGNb scaffolds. The analysis oftrabecular structure showed lower trabecular formation in synthetic materials when compared to autogenous bone.
Significance. Niobium-containing bioactive glasses promoted bone formation comparable to that of the autogenous bone without compromising the quality of the formed bone.

Introduction

Bioactive glasses are a class of synthetic materials that may be used in bone regeneration applications in dentistry [1,2]. The osteoinductive and osteoconductive abilities [3] of these glasses are related to their ion release that promotes bone formation by way of two mechanisms, specifically 1) the formation of a carbonated hydroxyapatite layer in the surfaces of the particles [4] and 2) the upregulation of cell activity to stimulate the deposition of bone tissue [5]. Improvements in glass composition and structure may contribute to an improved release of bioactive ions and increased bone formation. The enhancement of bioactive glass composition and production may improve bone regeneration capacity. Niobium has been investigated as biomaterial to be used [6–9] due to its ability to promote mineral deposition [6,7,10,11]. The development of sol–gel-derived, niobium-containing bioactive glasses powders and scaffolds was previously shown [7] and increased mineralization ability was observed for niobium-containing grafts in vitro. Several approaches are used to promote the reestablishment of bone tissue for prosthetic rehabilitation, while autogenous bone remains the gold standard graft for maxillae and mandible reconstructions [12–15]. Synthetic bone substitutes have been used as alternatives that have ensured reduced patient morbidity [13] and comparable bone formation [14]. The placement of dental implants in edentulous patients is additionally related to improved health parameters and an increased quality of life, but may be limited in terms of efficacy by the absence of adequate quality and quantity of bone [15]. The aim of this study was to investigate the bone healing ability of niobium-containing bioactive glasses in a rat femur model according to quantitative and qualitative measurements obtained through X-ray computed microtomography. The working hypothesis is thatthe addition of niobium increased the bone regeneration ability promoted by sol-gel derived bioactive glasses.

1- Introduction

2- Materials

3- Method

4- Results and discussion

5- Conclusions

References

Abstract

In this research, a novel hybrid material bone implant manufacturing through the integration of two materials using additive manufacturing (AM) technology is proposed. Biomimetic application can manufacture high strength biomechanical implants with optimised geometry and mass. The combination of polymers allows a significant leap in the development and production of a great diversity of components and applications of biomaterials. A novel hybrid scaffold with a poly lactic acid (PLA) matrix reinforced with carbohydrate particles (cHA) is analysed using digital surface software in the mass proportions of 100/0, 95/5, 90/10 and 80/20 for application in tissue and regenerative engineering, seeking a higher proposition strength of PLA. Filaments are used to fabricate scaffolds by 3D printing, using the fused deposition method. The frameworks are submitted to bioactivity tests, surface roughness evaluation, apparent porosity and mechanical analysis. Analysis of the microstructure of the composite particle evaluates the 3D surface luminance structure and the profile structure. Cross-sectional views of the specimens are extracted and analysed, and the surface roughness, waviness profile, and Gaussian filter of the structures are observed. In summary the structures are checked and analysed by SEM and EDS where possible, to observe the bioactive behaviour of the materials. The relationship between cHA content and roughness is shown to be proportional. The mechanical properties are shown to be affected by the reduced interaction between the PLA matrix and the cHA particles.

1- Introduction

Findings from population statistical research institutes point to a rising life expectancy in the world population. As humans age, the risk of compromising organs, tissues and the body as a whole increases. Tissue engineering seeks to use biomaterials to replace conventional transplants. A biomaterial is defined as any substance or combination of materials, other than drugs or synthetic natural materials, which can be used, for any period, to partially substitute for any tissue, organ or function of the body for the purpose of maintaining or improving the lifespan of an individual [1]. A fundamental requirement of a biomaterial used in clinical medicine is that it is biocompatible, that is, it can coexist with human tissue without causing any undesirable or inappropriate effects [2, 3]. Biomaterials can be classified into three main categories: bioinert, intolerant materials that are not capable of inducing any biological interfacial bond between the implant and the host tissue [4, 5]; bioactive, capable of interacting with body tissues, forming chemical or biological bonds and favouring the development of processes such as implant fixation, colonisation and tissue regeneration; and bioreabsorbable, materials that are gradually reabsorbed until they disappear entirely and are wholly replaced by new tissue in vivo. In general, biomaterials can be classified into: natural, from plants and animals; and synthetic, which can be sub-categorised into metals, synthetic polymers, ceramics and composites [6, 7].

The success of reconstructive orbital surgery depends on diverse aspects related to the preoperative evaluation of the trawnatic deformity, the design and manufacturing of the implant, and the surgical protocol. Patients who suffered disruption of the eyeball following direct or indirect ocular trauma often present an untreated fracture of one or more orbital walls. Usually the fracture involves the floor and/or the medial wall of the orbit, with consequent vertical dystopia and asymmetry of the ocular prosthesis compared to the controlateral side. Ocular and orbital volwne are critical in these cases. The primary goal for orbital reconstruction is repairing the fractured wall by restoring the skeletal cavity and the orbital volume [1, 2]. In this regard, image-guidance technology is useful for the design of anatomic orbital implants, particularly for two-walled defects involving the floor and medial wall [3]. Custom implants can also be utilized for DOl: 10.2316IP.20J7.852-045 260 reconstruction of irregular defects or when there is a significant bone loss [4, 5]. The problems connected with the previous cited approach are related to the high cost of the surgical procedure due both to the planning phase and, particularly, to the manufacturing of a preformed titanium orbital implant. The present paper reports on a case of secondary reconstruction of the orbital cavity due to a 35- year-old displaced fracture of the orbital floor. The paper consists of a computer-assisted approach, based on anatomical modelling and custom-made mould fabrication via selective laser sintering, for manufacturing a preformed orbital implant. Such in-office procedure offers precise and predictable results of orbital reconstruction. Moreover, it reduces at the same time the surgical time, morbidity, and it is a low-cost surgical procedure. Such an approach is suggested for achieving accurate results both in secondary and primary reconstruction of the orbital wall. To date, surgeons have three main choices for the reconstruction of orbital walls: (1) to shape the implant directly on the patient orbital wall during the surgery, (2) to implant a preformed titanium plate or a 3D printed, custom-made titanium mesh, and (3) to model the implant on the 3D printed mould of the pathological orbital wall (with the fracture virtually closed). The three diverse procedures show some disadvantages. In the first case, the repetitive trial fitting of the implant can be traumatic to the periorbital tissues and the geometry and placement of the implant could be not accurate. In the second case, the main problem is related to the costs connected with the manufacturing of the implant. In fact, to date 3D printed titanium orbital implants, manufactured via electron beam melting (EBM) 0 direct metal sintering (DMS), have costs between 3000€ and 5000€. The costs of prefabricated titanium orbital plates or meshes range between 250€ (KLS Martin) and 600€ to 800€ (Synthes, West Chester, PA) [5]. In the last case, the main issue is the time required to the surgeon to manually model the implant on the mould and then re-adjust the shape of the plate on the patient. An example of this methodology is reported in [5], where Vehmeijer et al.