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Recent Trends on Additive Manufacturing Biomaterial Composites in Tissue Regeneration Future Perspectives, Challenges, and Road Maps to Clinics for Biomedical Applications—A Review
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The ability of alginates to form hydrogel solutions makes them a promising biomaterial for three-dimensional (3D) printing. Researchers are investigating several techniques to improve the alginate hydrogels’ quality, such as using alginate-based nanocomposites as materials for 3D printing. This review examines the material of alginate-based composites, the printing technique, and the applications of 3D printing alginate-based composites. Material composites for 3D printing include alginate with clay, a combination of alginate with polymers or biopolymers, and a mixture of alginate with metal oxide and carbon. The 3D printing material from alginate combined with polymers is usually used in the medical and green packaging industries, whereas a mixture of alginate with clay, metal oxide, and carbon 3D printing material is utilized in the environmental field. When considering printing procedures, extrusion techniques are the most affordable. Furthermore, the purpose of alginate composite characterization is to determine the impact generated by the material combinations. This characterization is carried out based on the intended application. However, it is common to employ mechanical, thermal, rheological, scanning electron, XRD, and FTIR analysis to identify the fundamental characteristics of the alginate composite according to research.
Improvements in Tissue Engineering and Regenerative Medicine (TERM)-type technologies have allowed the development of specific materials that, together with a better understanding of bone tissue structure, have provided new pathways to obtain biomaterials for bone tissue regeneration. In this manuscript, bioabsorbable materials are presented as emerging materials in tissue engineering therapies related to bone lesions because of their ability to degrade in physiological environments while the regeneration process is completed. This comprehensive review aims to explore the studies, published since its inception (2010s) to the present, on bioabsorbable composite materials based on PLA and PCL polymeric matrix reinforced with Mg, which is also bioabsorbable and has recognized osteoinductive capacity. The research collected in the literature reveals studies based on different manufacturing and dispersion processes of the reinforcement as well as the physicochemical analysis and corresponding biological evaluation to know the osteoinductive capacity of the proposed PLA/Mg and PCL/Mg composites. In short, this review shows the potential of these composite materials and serves as a guide for those interested in bioabsorbable materials applied in bone tissue engineering.
3D Printing (3DP) technology has revolutionized the field of the use of bioceramics for maxillofacial and periodontal applications, offering unprecedented control over the shape, size, and structure of bioceramic implants. In addition, bioceramics have become attractive materials for these applications due to their biocompatibility, biostability, and favorable mechanical properties. However, despite their advantages, bioceramic implants are still associated with inferior biological performance issues after implantation, such as slow osseointegration, inadequate tissue response, and increased risk of implant failure. To address these challenges, researchers have been developing strategies to improve the biological performance of 3D printed bioceramic implants. The purpose of this review is to provide an overview of 3DP techniques and strategies for bioceramic materials designed for bone regeneration. The review also addresses the use and incorporation of active biomolecules in 3D printed bioceramic constructs to stimulate bone regeneration. By controlling the surface roughness, and chemical composition of the implant, the construct can be tailored to promote osseointegration and reduce the risk of adverse tissue reactions. Additionally, growth factors, such as bone morphogenic proteins (rhBMP-2) and pharmacologic agent (dipyridamole), can be incorporated to promote the growth of new bone tissue. Incorporating porosity into bioceramic constructs can improve bone tissue formation and the overall biological response of the implant. As such, by employing surface modification, combining with other materials, and incorporation of 3DP workflow can lead to better patient healing outcomes.
3D printing technology is an emerging method that gained extensive attention from researchers worldwide, especially in the health and medical fields. Biopolymers are an emerging class of materials offering excellent properties and flexibility for additive manufacturing. Biopolymers are widely used in biomedical applications in biosensing, immunotherapy, drug delivery, tissue engineering and regeneration, implants, and medical devices. Various biodegradable and non-biodegradable polymeric materials are considered as bio-ink for 3d printing. Here, we offer an extensive literature review on the current applications of synthetic biopolymers in the field of 3D printing. A trend in the publication of biopolymers in the last 10 years are focused on the review by analyzing more than 100 publications. Their application and classification based on biodegradability are discussed. The various studies, along with their practical applications, are elaborated in the subsequent sections for polyethylene, polypropylene, polycaprolactone, polylactide, etc. for biomedical applications. The disadvantages of various biopolymers are discussed, and future perspectives like combating biocompatibility problems using 3D printed biomaterials to build compatible prosthetics are also discussed and the potential application of using resin with the combination of biopolymers to build customized implants, personalized drug delivery systems and organ on a chip technologies are expected to open a new set of chances for the development of healthcare and regenerative medicine in the future.
Graphical Abstract
Three–dimensional bioprinting is an advanced tissue fabrication technique that allows printing complex structures with precise positioning of multiple cell types layer–by–layer. Compared to other bioprinting methods, extrusion bioprinting has several advantages to print large–sized tissue constructs and complex organ models due to large build volume. Extrusion bioprinting using sacrificial, support and embedded strategies have been successfully employed to facilitate printing of complex and hollow structures. Embedded bioprinting is a gel–in–gel approach developed to overcome the gravitational and overhanging limits of bioprinting to print large–sized constructs with a micron–scale resolution. In embedded bioprinting, deposition of bioinks into the microgel or granular support bath will be facilitated by the sol–gel transition of the support bath through needle movement inside the granular medium. This review outlines various embedded bioprinting strategies and the polymers used in the embedded systems with advantages, limitations, and efficacy in the fabrication of complex vascularized tissues or organ models with micron–scale resolution. Further, the essential requirements of support bath systems like viscoelasticity, stability, transparency and easy extraction to print human scale organs are discussed. Additionally, the organs or complex geometries like vascular constructs, heart, bone, octopus and jellyfish models printed using support bath assisted printing methods with their anatomical features are elaborated. Finally, the challenges in clinical translation and the future scope of these embedded bioprinting models to replace the native organs are envisaged.
Three-dimensional printing technology has fundamentally revolutionized the product development processes in several industries. Three-dimensional printing enables the creation of tailored prostheses and other medical equipment, anatomical models for surgical planning and training, and even innovative means of directly giving drugs to patients. Polymers and their composites have found broad usage in the healthcare business due to their many beneficial properties. As a result, the application of 3D printing technology in the medical area has transformed the design and manufacturing of medical devices and prosthetics. Polymers and their composites have become attractive materials in this industry because of their unique mechanical, thermal, electrical, and optical qualities. This review article presents a comprehensive analysis of the current state-of-the-art applications of polymer and its composites in the medical field using 3D printing technology. It covers the latest research developments in the design and manufacturing of patient-specific medical devices, prostheses, and anatomical models for surgical planning and training. The article also discusses the use of 3D printing technology for drug delivery systems (DDS) and tissue engineering. Various 3D printing techniques, such as stereolithography, fused deposition modeling (FDM), and selective laser sintering (SLS), are reviewed, along with their benefits and drawbacks. Legal and regulatory issues related to the use of 3D printing technology in the medical field are also addressed. The article concludes with an outlook on the future potential of polymer and its composites in 3D printing technology for the medical field. The research findings indicate that 3D printing technology has enormous potential to revolutionize the development and manufacture of medical devices, leading to improved patient outcomes and better healthcare services.
Achieving lightweight, high-strength, and biocompatible composites is a crucial objective in the field of tissue engineering. Intricate porous metallic structures, such as lattices, scaffolds, or triply periodic minimal surfaces (TPMSs), created via the selective laser melting (SLM) technique, are utilized as load-bearing matrices for filled ceramics. The primary metal alloys in this category are titanium-based Ti6Al4V and iron-based 316L, which can have either a uniform cell or a gradient structure. Well-known ceramics used in biomaterial applications include titanium dioxide (TiO2), zirconium dioxide (ZrO2), aluminum oxide (Al2O3), hydroxyapatite (HA), wollastonite (W), and tricalcium phosphate (TCP). To fill the structures fabricated by SLM, an appropriate ceramic is employed through the spark plasma sintering (SPS) method, making them suitable for in vitro or in vivo applications following minor post-processing. The combined SLM-SPS approach offers advantages , such as rapid design and prototyping, as well as assured densification and consolidation, although challenges persist in terms of large-scale structure and molding design. The individual or combined application of SLM and SPS processes can be implemented based on the specific requirements for fabricated sample size, shape complexity, densification, and mass productivity. This flexibility is a notable advantage offered by the combined processes of SLM and SPS. The present article provides an overview of metal-ceramic composites produced through SLM-SPS techniques. Mg-W-HA demonstrates promise for load-bearing biomedical applications, while Cu-TiO2-Ag exhibits potential for virucidal activities. Moreover, a functionally graded lattice (FGL) structure, either in radial or longitudinal directions, offers enhanced advantages by allowing adjustability and control over porosity, roughness, strength, and material proportions within the composite.
Additive manufacturing (AM) has emerged as a transformative technology capable of fabricating complex geometries and multi-material structures across various industries. Despite its potential, challenges persist in terms of limited material selection, anisotropic properties, and achieving functional microstructures in polymer and metal composites. Field-assisted additive manufacturing (FAAM) employs external fields like acoustic, magnetic, and electric fields. It has shown promise in addressing these limitations by controlling filler orientation and concentration in polymeric composites and improving surface finish and microstructure in metals. This review paper provides a comprehensive analysis of the state-of-the-art FAAM processes for polymer and metal composites, focusing on material compatibility, the mechanics of each field, and their integration with AM technologies as well as current applications, limitations, and potential future directions in the development of FAAM processes. Enhancing FAAM process understanding can create tailored anisotropic composites, enabling innovative applications in aerospace, automotive, biomedical fields, and beyond.
The use of additive manufacturing, or 3D printing, has progressed beyond prototyping to produce intricate and valuable finished goods. The potential of additive manufacturing has increased across numerous industries due to the expansion of materials, such as high-performance metals and polymers, and advancements in machine capabilities , such as multi-material printing. By enabling complex designs, reduced waste, and quick production, it has the potential to revolutionize the consumer goods, healthcare, automotive manufacturing, and aerospace industries. The development of specialized scaffolds has been made possible by the precise control that additive manufacturing provides over the internal structure of porous materials. This technology has revolutionized tissue engineering and regenerative medicine. Furthermore, it has made it possible to create individualized implants and prosthetics that improve patient comfort and outcomes in orthopedic and dental applications. Also, it provides flexibility in design and customization for individualized implants and prosthetics in orthopedic and dental applications. Design flexibility, waste reduction, improved biocompatibility, quick prototyping, and cost-effectiveness are benefits of additive manufacturing for implants. For personalized healthcare, regenerative medicine, and better patient outcomes, additive manufacturing holds promise as the technology develops with further advancements in printing speed, resolution, and scalability.
Three-dimensional (3-D) printing is elevating various growth in production viewpoint both at nanoscale and macro-scales. 3-D printing is being scouted for numerous bio-pharmaceutical administration and creation of nano-medicines employing supplementary production methods and shows assurance in capability in satisfying the demands for a patient-based customized approach. The previous outcome features the accessibility of novel natural bio-materials and finely designed polymeric substances, which can be created as unique 3-D printed nano-materials for numerous bio-pharmaceutical administrations as nano-medicines. Nano-medicine is described as the utilization of nanoscience in fabricating nano-materials for various pharmaceutical utilization, comprising identification, cure, scan, stopping, and management of diseases. Nano-medicine has also displayed a huge effect in the creation and evolve an accurate drug. In contrary the "one-size-fits-all" benchmark for the traditional drug is a personalized, structured, or accurate drug considering the variation in numerous characteristics, comprising genetics and pharmacokinetics of various victims, which have exhibited better outcomes over traditional cures. This article highlights the approaches advancements in the design and development of customized-made nano-medicine employing 3-D printing science.
Tissue-mimicking materials (TMMs) typically used for ultrasound phantoms include gelatin, agarose and polyvinyl alcohol (PVA). These materials have shown sufficient similarity in ultrasound parameters compared to human tissue. Despite their extensive use for years to generate ultrasound phantoms, no simple and easily reproducible way to generate complex, wall-less ultrasound flow phantoms has been introduced. Commercially available ultrasound flow phantoms are limited to simple flow geometries that do not reflect the complex blood flow in humans. Flow phantoms with complex geometries presented in scientific publications either have walls between TMMs and the flow channel, are limited to one material, or are complicated to produce. In this contribution, we present a method using 3D printing and soluble filament that allows for the reliable and consistent production of complex flow geometries with the typical materials used for ultrasound phantoms and without any walls.
The escalating demands for smart biomedical systems ignite a significantly growing influence of three‐dimensional (3D) printing technology. Recognized as a revolutionary and potent fabrication tool, 3D printing possesses unparalleled capabilities for generating customized functional devices boasting intricate and meticulously controlled architectures while enabling the integration of multiple functional materials. These distinctive advantages arouse a growing inclination toward customization and miniaturization, thereby facilitating the development of cutting‐edge biomedical systems. In this comprehensive review, the prevalent 3D printing technologies employed in biomedical applications are presented. Moreover, focused attention is paid to the latest advancements in harnessing 3D printing to fabricate smart biomedical systems, with specific emphasis on exemplary ongoing research encompassing biomedical examination systems, biomedical treatment systems, as well as veterinary medicine. In addition to illuminating the promising potential inherent in 3D printing for this rapidly evolving field, the prevailing challenges impeding its further progression are also discussed. By shedding light on recent achievements and persisting obstacles, this review aims to inspire future breakthroughs in the realm of smart biomedical systems.
Additive Manufacturing (AM) demonstrates significant potential with rapid growth and widespread industrial adoption. To support the integration and innovation of AM technologies, the development of guidance tools and support methods are crucial, and a technological roadmap can assist in this effort. Despite its widespread use in production processes, the need for further research on the potential impact of AM remains significant. The full impact of AM is still uncertain and lacks consensus, highlighting the need for increased knowledge and investment from the scientific community and organizations. While the benefits of AM are recognized, the challenges of its adoption are not entirely known. AM will bring changes in the way organizations create, distribute, and derive value. Thus, in this article, a roadmap for AM is proposed and presented as a tool to map technological knowledge on the implementation and evolution of AM and serve as a strategic guide for organizations. The methodology for its elaboration involves three phases: planning and preparation, roadmap development, and review and update. Through a literature review, database and project consultation, and questionnaires to Portuguese companies that use AM in their production process it was possible to characterize the AM technology and through the visual format, based on a time horizon, summarize in a common framework all the information about the current and future state of AM in Portugal. The results of this study show that research and development initiatives are essential to promote the evolution of knowledge of the AM technology. Throughout this study and with the development of the roadmap it is anticipated that in the near future the AM will be widely used for prototyping and manufacturing of components and may be used for direct production in the short to medium term. It was also found that the main obstacles to the implementation of AM are the economic/productivity factors and the shortage of professionals with knowledge and skills in the area.
Cardiovascular disease is the world’s leading cause of death, and there is a substantial clinical need for transplantable blood vessels. Through tissue vascular engineering technology, large blood vessel grafts with significant clinical effects have been synthesized. However, synthesizing vascular valves, small vessels up to 6 mm in diameter, and capillary networks up to 500 μm in diameter remains challenging due to the lack of precise manufacturing techniques. In particular, constructing a microvascular network in thick tissue is the technical bottleneck of organ transplantation. Three-dimensional (3D) bioprinting is a computer-assisted layer-by-layer deposition method that can deposit cells and biomaterials at a predetermined location, according to an accurate digital 3D model, to build a delicate and complex bionic structure. This review discusses the progress and limitations of 3D bioprinting in preparing large vessels and valves, small-diameter vessels, and microvascular networks. This paper focuses on improved printing technology and innovative bio-ink materials. The future application of 3D bioprinting is prospected in generating artificial blood vessel grafts and vascularized organs with full biological function.
Porous structures with sizes between the submicrometer and nanometer scales can be produced using efficient and adaptable electrospinning technology. However, to approximate desirable structures, the construction lacks mechanical sophistication and conformance and requires three-dimensional solitary or multifunctional structures. The diversity of high-performance polymers and blends has enabled the creation of several porous structural conformations for applications in advanced materials science, particularly in biomedicine. Two promising technologies can be combined, such as electrospinning with 3D printing or additive manufacturing, thereby providing a straightforward yet flexible technique for digitally controlled shape-morphing fabrication. The hierarchical integration of configurations is used to imprint complex shapes and patterns onto mesostructured, stimulus-responsive electrospun fabrics. This technique controls the internal stresses caused by the swelling/contraction mismatch in the in-plane and interlayer regions, which, in turn, controls the morphological characteristics of the electrospun membranes. Major innovations in 3D printing, along with additive manufacturing, have led to the production of materials and scaffold systems for tactile and wearable sensors, filtration structures, sensors for structural health monitoring, tissue engineering, biomedical scaffolds, and optical patterning. This review discusses the synergy between 3D printing and electrospinning as a constituent of specific microfabrication methods for quick structural prototypes that are expected to advance into next-generation constructs. Furthermore, individual techniques, their process parameters, and how the fabricated novel structures are applied holistically in the biomedical field have never been discussed in the literature. In summary, this review offers novel insights into the use of electrospinning and 3D printing as well as their integration for cutting-edge applications in the biomedical field.
Direct Ink Writing (DIW), which is widely used for developing functional 3D scaffolds that have robust structural integrity for the growth of target tissues/cells, has emerged as an appealing method for biomedical applications. The production of 3D structures involves three separate but interconnected stages (material development, printing process, and post-printing treatment), whose effectiveness is influenced by several factors that therefore make it challenging to optimize the entire procedure. By studying the material processability and leveling the printing settings, this study proposes a three-step method to enhance the ink property design and the printer’s performance. The recommended approach is focused on the thorough study of alginate–gelatin hydrogel properties, which is a commonly used ink in biomedical applications, due to its natural origin through marine flora, as well as the development process parameters and their intercorrelations. Principal Component Analysis in comparison with K-means clustering was applied to reveal material properties that are highly correlated with additive manufacturing (AM) processability, and Taguchi’s Design of Experiments (DOE) determined the printing settings (primary and secondary) for achieving optimum printing accuracy. PCA results were affirmed by K-means clustering and showed that viscosity, m, G′ and G″ govern blends’ printing behavior while application of DOE led to 85% pore area printability.
ZrO2 nanoparticles have received substantially increased attention in every field of life owing to their wide range of applications. Zirconium oxide is a commercially economical, non-hazardous, and sustainable metal oxide having diversified potential applications. ZrO2 NPs play a vast role in the domain of medicine and pharmacy such as anticancer, antibacterial, and antioxidant agents and tissue engineering owing to their reliable curative biomedical applications. In this review article, we address all of the medical and biomedical applications of ZrO2 NPs prepared through various approaches in a critical way. ZrO2 is a bio-ceramic substance that has received increased attention in biomimetic scaffolds owing to its high mechanical strength, excellent biocompatibility, and high chemical stability. ZrO2 NPs have demonstrated potential anticancer activity against various cancer cells. ZrO2-based nanomaterials have exhibited potential antibacterial activity against various bacterial strains and have also demonstrated excellent antioxidant activity. The ZrO2 nanocomposite also exhibits highly sensitive biosensing activity toward the sensing of glucose and other biological species.
4D printing has emerged as a transformative technology in the field of biomedical engineering, offering the potential for dynamic, stimuli-responsive structures with applications in tissue engineering, drug delivery, medical devices, and diagnostics. This review paper provides a comprehensive analysis of the advancements, challenges, and future directions of 4D printing in biomedical engineering. We discuss the development of smart materials, including stimuli-responsive polymers, shape-memory materials, and bio-inks, as well as the various fabrication techniques employed, such as direct-write assembly, stereolithography, and multi-material jetting. Despite the promising advances, several challenges persist, including material limitations related to biocompatibility, mechanical properties, and degradation rates; fabrication complexities arising from the integration of multiple materials, resolution and accuracy, and scalability; and regulatory and ethical considerations surrounding safety and efficacy. As we explore the future directions for 4D printing, we emphasise the need for material innovations, fabrication advancements, and emerging applications such as personalised medicine, nanomedicine, and bioelectronic devices. Interdisciplinary research and collaboration between material science, biology, engineering, regulatory agencies, and industry are essential for overcoming challenges and realising the full potential of 4D printing in the biomedical engineering landscape.
The skin is the body's first line of defence, and its physiology is complex. When injury occurs, the skin goes through a complex recovery process, and there is the risk of developing a chronic wound. Therefore, proper wound care is critical during the healing process. In response to clinical needs, wound dressings have been developed. There are several types of wound dressings available for wound healing, but there are still many issues to overcome. With its high controllability and resolution, 3D printing technology is widely regarded as the technology of the next global industrial and manufacturing revolution, and it is a key driving force in the development of wound dressings. Here, we briefly introduce the wound healing mechanism, organize the history and the main technologies of 3D bioprinting, and discuss the application as well as the future direction of development of 3D bioprinting technology in the field of wound dressings.
With the advancement of additive manufacturing (AM), customized vascular stents can now be fabricated to fit the curvatures and sizes of a narrowed or blocked blood vessel, thereby reducing the possibility of thrombosis and restenosis. More importantly, AM enables the design and fabrication of complex and functional stent unit cells that would otherwise be impossible to realize with conventional manufacturing techniques. Additionally, AM makes fast design iterations possible while also shortening the development time of vascular stents. This has led to the emergence of a new treatment paradigm in which custom and on-demand-fabricated stents will be used for just-in-time treatments. This review is focused on the recent advances in AM vascular stents aimed at meeting the mechanical and biological requirements. First, the biomaterials suitable for AM vascular stents are listed and briefly described. Second, we review the AM technologies that have been so far used to fabricate vascular stents as well as the performances they have achieved. Subsequently, the design criteria for the clinical application of AM vascular stents are discussed considering the currently encountered limitations in materials and AM techniques. Finally, the remaining challenges are highlighted and some future research directions are proposed to realize clinically-viable AM vascular stents. STATEMENT OF SIGNIFICANCE: Vascular stents have been widely used for the treatment of vascular disease. The recent progress in additive manufacturing (AM) has provided unprecedented opportunities for revolutionizing traditional vascular stents. In this manuscript, we review the applications of AM to the design and fabrication of vascular stents. This is an interdisciplinary subject area that has not been previously covered in the published review articles. Our objective is to not only present the state-of-the-art of AM biomaterials and technologies but to also critically assess the limitations and challenges that need to be overcome to speed up the clinical adoption of AM vascular stents with both anatomical superiority and mechanical and biological functionalities that exceed those of the currently available mass-produced devices.
As a new generation of materials/structures, heterostructure is characterized by heterogeneous zones with dramatically different mechanical, physical or chemical properties. This endows heterostructure with unique interfaces, robust architectures, and synergistic effects, making it a promising option as advanced biomaterials for the highly variable anatomy and complex functionalities of individual patients. However, the main challenges of developing heterostructure lie in the control of crystal/phase evolution and the distribution/fraction of components and structures. In recent years, additive manufacturing techniques have attracted increasing attention in developing heterostructure due to the unique flexibility in tailored structures and synthetic multimaterials. This review focuses on the additive manufacturing of heterostructure for biomedical applications. The structural features and functional mechanisms of heterostructure are summarized. The typical material systems of heterostructure, mainly including metals, polymers, ceramics, and their composites, are presented. And the resulting synergistic effects on multiple properties are also systematically discussed in terms of mechanical, biocompatible, biodegradable, antibacterial, biosensitive and magnetostrictive properties. Next, this work outlines the research progress of additive manufacturing employed in developing heterostructure from the aspects of advantages, processes, properties, and applications. This review also highlights the prospective utilization of heterostructure in biomedical fields, with particular attention to bioscaffolds, vasculatures, biosensors and biodetections. Finally, future research directions and breakthroughs of heterostructure are prospected with focus on their more prospective applications in infection prevention and drug delivery.
Biopolymers are promising environmentally benign materials applicable in multifarious applications. They are especially favorable in implantable biomedical devices thanks to their excellent unique properties, including bioactivity, renewability, bioresorbability, biocompatibility, biodegradability, and hydrophilicity. Additive manufacturing (AM) is a flexible and intricate manufacturing technology, which is widely used to fabricate biopolymer-based customized products and structures for advanced healthcare systems. Three-dimensional (3D) printing of these sustainable materials is applied in functional clinical settings including wound dressing, drug delivery systems, medical implants, and tissue engineering. The present review highlights recent advancements in different types of biopolymers, such as proteins and polysaccharides, which are employed to develop different biomedical products by using extrusion, vat polymerization, laser, and inkjet 3D printing techniques in addition to normal bioprinting and four-dimensional (4D) bioprinting techniques. This review also incorporates the influence of nanoparticles on the biological and mechanical performances of 3D-printed tissue scaffolds. This work also addresses current challenges as well as future developments of environmentally friendly polymeric materials manufactured through the AM techniques. Ideally, there is a need for more focused research on the adequate blending of these biodegradable biopolymers for achieving useful results in targeted biomedical areas. We envision that biopolymer-based 3D-printed composites have the potential to revolutionize the biomedical sector in the near future.
Additive manufacturing or 3D printing technologies might advance the fabrication sector of personalised biomaterials with high-tech precision. The selection of optimal precursor materials is considered the first key-step for the development of new printable filaments destined for the fabrication of products with diverse orthopaedic/dental applications. The selection route of precursor materials proposed in this study targeted two categories of materials: prime materials, for the polymeric matrix (acrylonitrile butadiene styrene (ABS), polylactic acid (PLA)); and reinforcement materials (natural hydroxyapatite (HA) and graphene nanoplatelets (GNP) of different dimensions). HA was isolated from bovine bones (HA particles size < 40 μm, <100 μm, and >125 μm) through a reproducible synthesis technology. The structural (FTIR-ATR, Raman spectroscopy), morphological (SEM), and, most importantly, in vitro (indirect and direct contact studies) features of all precursor materials were comparatively evaluated. The polymeric materials were also prepared in the form of thin plates, for an advanced cell viability assessment (direct contact studies). The overall results confirmed once again the reproducibility of the HA synthesis method. Moreover, the biological cytotoxicity assays established the safe selection of PLA as a future polymeric matrix, with GNP of grade M as a reinforcement and HA as a bioceramic. Therefore, the obtained results pinpointed these materials as optimal for future composite filament synthesis and the 3D printing of implantable structures.
Three dimensional (3D) bioprinting is a rapidly developing and emerging field in medicine and engineering. It allows for the production of three-dimensional structures that mimic body tissue function, which can be used in drug delivery and medical research such as cancer studies. In addition, bioprinting can provide patients with specific, controlled microstructures that mimic their natural geometries, increasing the rate of take-up with tissue implants and ongoing success. Towards that, a comprehensive review on the development of biomaterials, osseous tissues, bone and the vascular tissue bioprinting was conducted. These provide an insight into the latest research trends, difficulties, and understanding of the technologies used. Before implementation to replicate a human organ, there are variety of limitations to overcome together with the questions of ethics. Though bioprinting is still in its infancy period, it can play a vital role in tissue engineering in near future.
Magnesium (Mg) and its alloys, with their mechanical behavior, biodegradable material with unique antibacterial features, and nontoxicity, find potential application in the field of Biomedical nevertheless, its high level of reactivity limits its usage. One promising way to enhance mechanical behavior is to fabricate Mg-based alloy using the powder metallurgy (PM) technique. The corrosion resistance of these alloys is influenced owing to the introduced plastic deformation. In this work, three pure Mg samples (Mg-Al-Zr-Mn, Mg-Nd-Zr, Mg-Nd-Zn-Zr) were fabricated using the PM technique applying a pressure of 2 MPa for compacting. All the fabricated samples were tested for their density, and it was noted that Mg-Al-Zr-Mn and Mg-Nd-Zr possess the lowest density. XRD analysis was conducted on all PM samples to determine the intermediate phases present in the fabricated samples. Furthermore, the compacted samples were subjected to a Vickers microhardness, corrosion test, and in vitro cytotoxicity. The Mg-Nd-Zn-Zr alloy showed 20.77% more microhardness than the Mg-Al-Zr-Mn alloy. The electrochemical corrosion characteristic of the fabricated PM samples was analyzed using the electrochemical impedance spectroscopy carried out in Ringer's solution and was linked with the microstructural analysis of the corrosion process. The samples' corrosion potential, current, and rate were determined from this test, and it was observed that the Mg-Nd-Zr-Zn showed a minimum corrosion rate. Upon studying the cytotoxicity test, it was evaluated that the Mg-Nd-Zn-Zr alloy exhibited cytotoxicity of 0% and cell viability more significant than 99%. Among the researched PM samples, Mg-Nd-Zn-Zr showed better properties and hence can be recommended for the manufacturing of implants for biomedical applications.
A growing interest in creating advanced biomaterials with specific physical and chemical properties is currently being observed. These high-standard materials must be capable to integrate into biological environments such as the oral cavity or other anatomical regions in the human body. Given these requirements, ceramic biomaterials offer a feasible solution in terms of mechanical strength, biological functionality, and biocompatibility. In this review, the fundamental physical, chemical, and mechanical properties of the main ceramic biomaterials and ceramic nanocomposites are drawn, along with some primary related applications in biomedical fields, such as orthopedics, dentistry, and regenerative medicine. Furthermore, an in-depth focus on bone-tissue engineering and biomimetic ceramic scaffold design and fabrication is presented.
Sustainability has been a global awareness due to the serious reduction of synthetic materials, especially petroleum. Many
sectors and researchers have shifted toward lignocellulosic fibers from biomass wastes to replace synthetic fibers and reinforced
bio-based polymer composites. The shift in composite landscape toward green composites is due to their availability,
low carbon emission, and biodegradability. Generally, green composites can be hybridized with various lignocellulosic fibers
and they have high potential in the civil and automotive fields due to their mechanical performance. Nevertheless, research
has found that they have inappropriate matches for the unique material attributes of green composites even though many
studies have covered this topic. Studies on the mechanical performance of hybrid natural fibers green composites are still
very limited. Overall, there are various mechanical properties of hybrid lignocellulosic fibers depending on their physical
properties, orientation and sequence, treatments, polymers, and fabrication methods. From these considerations, a series of
matching application properties are explained: these include structural applications for many industries. Thus, this review
article establishes critical discussions on the mechanical properties of hybrid natural fibers reinforced biopolymer green
composites. Some studies have identified the research gaps and deduced that the potential applications of hybrid green
composites have not been explored.
Zinc (Zn)-based biodegradable metals (BMs) fabricated through conventional manufacturing methods exhibit adequate mechanical strength, moderate degradation behavior, acceptable biocompatibility, and bioactive functions. Consequently, they are recognized as a new generation of bioactive metals and show promise in several applications. However, conventional manufacturing processes face formidable limitations for the fabrication of customized implants, such as porous scaffolds for tissue engineering, which are future direction towards precise medicine. As a metal additive manufacturing technology, laser powder bed fusion (L-PBF) has the advantages of design freedom and formation precision by using fine powder particles to reliably fabricate metallic implants with customized structures according to patient-specific needs. The combination of Zn-based BMs and L-PBF has become a prominent research focus in the fields of biomaterials as well as biofabrication. Substantial progresses have been made in this interdisciplinary field recently. This work reviewed the current research status of Zn-based BMs manufactured by L-PBF, covering critical issues including powder particles, structure design, processing optimization, chemical compositions, surface modification, microstructure, mechanical properties, degradation behaviors, biocompatibility, and bioactive functions, and meanwhile clarified the influence mechanism of powder particle composition, structure design, and surface modification on the biodegradable performance of L-PBF Zn-based BM implants. Eventually, it was closed with the future perspectives of L-PBF of Zn-based BMs, putting forward based on state-of-the-art development and practical clinical needs.
Alginate–gelatin coacervation has been studied by considering different experimental parameters, such as gelatin preheating, pH, alginate–gelatin ratio and their respective concentrations, and salt effect. Results were assessed in terms of size and polydispersion via dynamic light scattering, electrostatic charge in the surface by zeta potential measurements, electrostatic interaction forces by static light scattering, stability by turbidimetry and viscoelastic and pseudoplastic behavior by rheology (oscillatory and statistical analysis). According to the results, gelatin structure has to be previously modified to induce the proper interactions with a subsequent pH reduction. Specifically, stable coacervates (according to turbidimetry and dynamic light scattering) with a size of 300–600 nm and a polydispersion lower than 0.25 were obtained after preheating the gelatin at 37°C and with a subsequent pH reduction until 4–5 for an alginate–gelatin ratio between 1:4 and 1:6. However, different experimental conditions promote an unsuccessful coacervation, obtaining always precipitates and/or coacervates with a wider particle size distribution. Furthermore, in order to study the effect of the temperature on the coacervates, different cooling–heating cycles were applied on them over a week, showing the stability of the thermo‐reversible coacervates for almost 5 days. Also, the interactions were characterized via static light scattering, analyzing the second virial coefficient. Moreover, rheological oscillatory results can be used to identify a proper coacervation due to the increase of the storage modulus. However, no significant changes were observed with statistical analysis due to the highly diluted character of the precursor solutions. These results highlighted how a proper combination of different experimental conditions, mainly temperature to promote a partial gelatin unraveling as well as pH reduction, is required to successfully produce coacervates. Finally, salt effect was proven to induce precipitation when NaCl was increasingly added to solutions of stable coacervates.
This chapter delves into the promising future prospects of 3D printing for pharmaceutical and biomedical applications, with a specific focus on novel polymeric excipients. As 3D printing continues to revolutionize drug and medical device manufacturing, the integration of innovative polymeric materials holds immense potential for creating customized dosage forms, implants, and tissue scaffolds. This overview highlights the evolving landscape of 3D printing technology, emphasizing the crucial role of cutting-edge polymeric excipients in enhancing drug delivery precision, therapeutic efficacy, and patient outcomes, thereby shaping the future of pharmaceutical and biomedical advancements.
This chapter deals with the main biomedical applications of the fused filament fabrication (FFF) 3D printing technology. It begins with an overview of the main groups of 3D printing technologies. After, a detailed explanation of the FFF technique is presented, focusing on the main process parameters, the characteristics of the 3D printers, and the different materials that can be used, both polymeric materials and composite materials. Then, the biomedical applications of the FFF technology are addressed, which include 3D scaffolds for cell culture, surgical models, and prostheses. Fabrication of complex porous structures of the extracellular matrix, surgical guides used to help surgeons during medical intervention, and prostheses mimicking bone mechanical properties are discussed. The chapter closes with future perspectives of FFF in medicine, paying particular attention to the development of new materials, and the main conclusions that can be extracted from the use of FFF in biomedical applications.
In the present study, corrosion properties and biocompatibility of as-built and as-polished Ti-6Al-4V samples fabricated by Electron Beam Melting (EBM) and Selective Laser Melting (SLM) were investigated and compared with a conventional sample as a reference. Optical microscope, Scanning Electron Microscope equipped with Energy Dispersive Spectroscopy, and X-ray diffraction analysis were employed for studying the microstructure and composition of the samples. Polarization, electrochemical impedance, and immersion tests were carried out to investigate the corrosion behavior and bioactivity of the samples in the Simulated Body Fluid solution. The results revealed that the EBM samples exhibited a superior corrosion resistance compared to the SLM one, thanks to the absence of low corrosion resistant α′ martensitic phases and a higher fraction of β phase in the EBM samples. It was also observed that while the wrought Ti-6Al-4V samples had a higher corrosion current density than the additively manufactured ones, both EBM and SLM processes had a lower corrosion resistance in the as-built state than in the as-polished. The immersion tests in the SBF solution revealed a more significant bioactivity for the EBM samples than the SLM samples. Higher levels of the β phase in the EBM microstructure stimulated the nucleation and growth of the apatite on the sample surface. Also, higher surface roughness in the as-built samples improved the bioactivity by increasing the metal/electrolyte interface and thus forming more OH − groups on the Ti alloy surface.
This research investigates the impact of heat treatment on the microstructure, hardness, and corrosion resistance of 17-4 PH SS (stainless steel) processed by Selective Laser Manufacturing (SLM) in Phosphate Buffer Solution (PBS) and compared to its commercial wrought counterparts. The SLM process produced a segregated microstructure with significant variations in composition and phases. Post-process heat treatment resulted in a uniform and reproducible microstructure in the SLM samples with a significant improvement in corrosion resistance in the solubilised samples and a remarkable hardening in the solubilised and aged samples. Additionally, heat-treated SLM samples showed no relevant release of metallic elements to PBS electrolyte after 75 days of immersion, indicating its potential use as a biomaterial. The study concludes that the manufacturing process used to produce SS have a significant impact on its properties, moreover, post-build treatment improve microstructure providing uniformity which positively impact in the corrosion resistance. The electrochemical results also suggest that, after homogenization, the additively produced 17-4 PH SS shows a better behaviour in biological environment than the wrought 17-4 PH SS.
In recent years, hydrogels have been widely used in the biomedical field as materials with excellent bionic structures and biological properties. Among them, the excellent comprehensive properties of natural polymer hydrogels represented by sodium alginate have attracted the great attention of researchers. At the same time, by physically blending sodium alginate with other materials, the problems of poor cell adhesion and mechanical properties of sodium alginate hydrogels were directly improved without chemical modification of sodium alginate. The composite blending of multiple materials can also improve the functionality of sodium alginate hydrogels, and the prepared composite hydrogel also has a larger application field. In addition, based on the adjustable viscosity of sodium alginate-based hydrogels, sodium alginate-based hydrogels can be loaded with cells to prepare biological ink, and the scaffold can be printed out by 3D printing technology for the repair of bone defects. This paper first summarizes the improvement of the properties of sodium alginate and other materials after physical blending. Then, it summarizes the application progress of sodium alginate-based hydrogel scaffolds for bone tissue repair based on 3D printing technology in recent years. Moreover, we provide relevant opinions and comments to provide a theoretical basis for follow-up research.
Significant attention has been drawn in recent years to develop porous scaffolds for tissue engineering. In general, porous scaffolds are used for non-load bearing applications. However, various metallic scaffolds have been investigated extensively for hard tissue repair due to their favorable mechanical and biological properties. Stainless steel (316L) and titanium (Ti) alloys are the most commonly used material for metallic scaffolds. Although stainless steel and Ti alloys are employed as scaffold materials, it might result in complications such as stress shielding, local irritation, interference with radiography, etc. related to the permanent implants. To address the above-mentioned complications, degradable metallic scaffolds have emerged as a next generation material. Among the all metallic degradable scaffold materials, magnesium (Mg) based material has gained significant attention owing to its advantageous mechanical properties and excellent biocompatibility in a physiological environment. Therefore, Mg based materials can be projected as load bearing degradable scaffolds, which can provide structural support toward the defected hard tissue during the healing period. Moreover, advanced manufacturing techniques such as solvent cast 3D printing, negative salt pattern molding, laser perforation, and surface modifications can make Mg based scaffolds promising for hard tissue repair. In this article, we focus on the advanced fabrication techniques which can tune the porosity of the degradable Mg based scaffold favorably and improve its biocompatibility.
Hybrid additive manufacturing is a promising method of producing metal biomedical implants in which benefits associated with subtractive and additive manufacturing are combined. Poor surface quality is the prime drawback associate with additively manufactured implant components. Detailed analysis on the different metal-based additive manufacturing processes such as laser engineering net shaping, selective laser melting, wire arc additive manufacturing, and electron beam melting is elaborated in the paper, along with their limitations. However, to improve the surface roughness of the implants, tool paths are generated through a geometric modeling software for multi-axis CNC to perform the surface finishing operation. Various possibilities and challenges of hybrid additive manufacturing for biomedical implants are also discussed.KeywordsHybrid additive manufacturingCAD modelingTool path generationCNC machiningKnee joint implant
Advanced regenerative therapy aims to repair pathologically damaged tissue by cell transplantation in conjunction with supporting scaffolds. Gelatin-based scaffolds have attracted much attention in recent years due to their great bio-affinity that encourages the regeneration of tissues. Nowadays, by strengthening gelatin-based systems, cutting-edge methods like 3D bioprinting, freeze-drying, microfluidics and gelatin functionalization have shown excellent mimicry of natural tissue. The fabrication of porous gelatin-based scaffolds for wider tissue engineering applications including skin, cartilage, bone, liver, and cardiovascular is reviewed in this work. Additionally, the crosslinking procedures and the physicochemical characteristics of the gelatin-based scaffolds are also studied. Now, gelatin is considered one of the highest potential biomaterials for impending trends in which the gelatin-based scaffolds are used as a support structure for regenerative therapy.