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PRISMA flow diagram depicting literature search, exclusion process, eligibility criteria, and final included papers. One hundred and eighteen papers were included without publication date restriction (search performed on April 15th, 2019).
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Nowadays, bioprinting is rapidly evolving and hydrogels are a key component for its success. In this sense, synthesis of hydrogels, as well as bioprinting process, and cross-linking of bioinks represent different challenges for the scientific community. A set of unified criteria and a common framework are missing, so multidisciplinary research team...
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The regeneration of cardiac tissue is a multidisciplinary research field aiming to improve the health condition of the post-heart attack patient. Indeed, myocardial tissue has a poor ability to self-regenerate after severe damage. The scientific efforts focused on the research of a biomaterial able to adapt to heart tissue, thus guaranteeing the in...
Citations
... Gelatin is usually mixed with other materials, such as alginate or collagen, and is used in DIW, inkjet, and LAB printing techniques. 59,60 (iii) GelMA: GelMa is a modified gelatin engineered with methacrylamide and methacrylate groups. In contrast to gelatin, GelMa is irreversibly photocrosslinkable by adding photo-initiator groups, thus preventing gel dissolution at body temperature. ...
The shortages in human tissue and organ donors have made clinical therapy relatively challenging. Therefore, research has been initiated over the last decades to develop artificial tissues and organs, particularly from cell and tissue cultures. Three-dimensional (3D) bioprinting is a recent technology capable of building structures for implantation, and these constructs closely resemble native tissues, such as skin, liver, connective tissues, and supportive tissues (bone and cartilage). In this review, we briefly introduce the structure, function, and development of bone tissues, followed by a detailed discussion on 3D bioprinting techniques, materials, and their recent advancements for clinical applications.
... All these properties mimic the structure of the natural ECM [23]. AL is able to form reticular structures by Ca 2+ ions facilitating its use in bioprinting [24]. CaCl 2 has been used in previous studies as part of an AL solution for the generation of hydrogels [25], and it has been also used as a base component in the manufacture of polymers by electrospinning [26,27] with limited cytotoxic rises. ...
Three-dimensional (3D) bioprinting is considered one of the most advanced tools to build up materials for tissue engineering. The aim of this work was the design, development and characterization of a bioink composed of human mesenchymal stromal cells (hMSC) for extrusion through nozzles to create these 3D structures that might potentially be apply to replace the function of damaged natural tissue. In this study, we focused on the advantages and the wide potential of biocompatible biomaterials, such as hyaluronic acid and alginate for the inclusion of hMSC. The bioink was characterized for its physical (pH, osmolality, degradation, swelling, porosity, surface electrical properties, conductivity, and surface structure), mechanical (rheology and printability) and biological (viability and proliferation) properties. The developed bioink showed high porosity and high swelling capacity, while the degradation rate was dependent on the temperature. The bioink also showed negative electrical surface and appropriate rheological properties required for bioprinting. Moreover, stress-stability studies did not show any sign of physical instability. The developed bioink provided an excellent environment for the promotion of the viability and growth of hMSC cells. Our work reports the first-time study of the effect of storage temperature on the cell viability of bioinks, besides showing that our bioink promoted a high cell viability after being extruded by the bioprinter. These results support the suggestion that the developed hMSC-composed bioink fulfills all the requirements for tissue engineering and can be proposed as a biological tool with potential applications in regenerative medicine and tissue engineering.
Graphical abstract
... water) are extensively considered as a source of biomaterial inks. Extensive surveys [17,18] report that the most used are alginate (33.3%), gelatin (16%), gelatin methacryloyl (GelMa, 13.2%), hyaluronic acid (HA, 9%), cellulose (9%), followed by collagen, polyethylene glycol (PEG), agar/agarose, chitosan, and polycaprolactone (PCL). Based on our bibliographic investigations, which include studies by Gungor-Ozkerim et al. [19] and Fu et al. [20], Table 2 outlines the rheological properties of the primary biomaterials used for printing inks. ...
... Through heuristic exploration, we identified the most feasible candidate mixtures. Note that collagen, gelatin, HA, chitosan, cellulose, SA, and GelMA are widely used for 3D bioprinting studies [17,19], and organic food wastes were considered to investigate their industrial recyclability. Cellulose, charcoal, HA, collagen, and glycerin were purchased from Korea Similac inc., and kaolin clay from WASP, Italy. ...
Persistent architectural interest in material recycling and biodegradability is driving the utilization of living materials in construction. In this study, the authors explored the use of natural powder mixed bioprintable hydrogels for cold-processing, robot-assisted extrusion additive manufacturing (EAM). We sought to develop a building-scale bio-composite ink capable of rapid gelation, vertical stacking, and minimal dry shrinkage for large 3D printing. Assorted combinations of natural polymeric and organic powders were empirically compounded to evaluate their extrudabil-ity and shape durability. The research revealed that a hydrogel construct consisting of xanthan gum, chlorella, cellulose, eggshell, and charcoal exhibited optimal performance, attributed to the composition's ability to enhance flowability while maintaining structural strength. Utilizing this ink, architectural designs were prototyped to showcase real-scale feasibility. Mechanical testing demonstrated that the architectural form of the bio-sourced mixture performed comparably to traditional materials, indicating its viability for future 3D printing in building construction.
... 3 By employing hydrogels as the primary bioink material, extrusion-based 3D bioprinting, the most commonly used type of 3D printing in tissue engineering applications, enables the placement of biological materials typically within a supportive matrix, mimicking the environment of native tissues for a variety of applications. 1,[4][5][6] Hydrogels are hydrophilic polymer materials with several advantages for 3D bioprinting, including biocompatibility, tunable extrudability and printability, biodegradability, and the ability to encapsulate and deliver bioactive molecules and living cells. These features make hydrogels ideal for creating functional biomimetic constructs that promote cellular response, tissue regeneration, and specific functions aligned with the intended objectives. ...
... 6 Researchers are actively addressing these challenges through various strategies, including modifying hydrogel composition with reinforcing agents, optimizing crosslinking methods, and applying post-printing treatments. 5,[21][22][23][24][25][26][27][28] Gelatin is a heterogeneous mixture of polypeptides obtained by controlled hydrolysis of collagen with celladhesive ligands such as the tripeptide Arg-Gly-Asp (RGD) sequence. Gelatin is a low-cost biodegradable protein with molecular weight ranging from 15 to 400 kDa. ...
Hydrogels are a key component in bioinks and biomaterial inks for bioprinting due to their biocompatibility and printability at room temperature. The research described in the present paper contributes to the advancement of bioprinting by studying the effect of bioactive borate glass (BBG) incorporated into hydrogels on printability and physical properties. In this study, we fabricated 3D-printed hydrogel scaffolds using gelatin and alginate hydrogel mixture incorporated with various amounts of BBG, a bioceramic rich in therapeutic ions including boron, calcium, copper, and zinc. We investigated the effect of incorporating BBG on the density, viscosity, physical interactions, chemical structure, and shear thinning behavior of gelatin-alginate hydrogel biomaterial ink at different temperatures. After 3D printing and crosslinking of scaffolds, we measured mechanical properties and printing outcomes. The near-optimal extrusion temperature and pressure for uniform extrusion of hydrogel filaments at various BBG contents were determined. We compared the printing outcomes by quantifying the uniformity of printed filaments and shape fidelity of printed scaffolds. The rheological analysis showed that the addition of BBG increased the viscosity of the biomaterial inks and Young's modulus of the 3D-printed scaffolds. Biomaterial inks with a dynamic viscosity within the range of 4.5-6.5 Pa·s showed the best printability across all samples. In conclusion, the inclusion of BBG contributes to a substantial improvement in the physical properties and printability of 3D-printed gelatin-alginate hydrogels.
... The incorporation of gelatin provides control over the rheological properties, thereby enhancing printability, all while preserving the durability characteristics during culture. Additionally, this bioink allows for cardiomyocyte contractility and the formation of endothelial cell networks (Mancha Sánchez et al., 2020). ...
Myocardial infarction is one of the major causes of mortality as well as morbidity around the world. Currently available treatment options face a number of drawbacks, hence cardiac tissue engineering, which aims to bioengineer functional cardiac tissue, for application in tissue repair, patient specific drug screening and disease modeling, is being explored as a viable alternative. To achieve this, an appropriate combination of cells, biomimetic scaffolds mimicking the structure and function of the native tissue, and signals, is necessary. Among scaffold fabrication techniques, three-dimensional printing, which is an additive manufacturing technique that enables to translate computer-aided designs into 3D objects, has emerged as a promising technique to develop cardiac patches with a highly defined architecture. As a further step toward the replication of complex tissues, such as cardiac tissue, more recently 3D bioprinting has emerged as a cutting-edge technology to print not only biomaterials, but also multiple cell types simultaneously. In terms of bioinks, biomaterials isolated from natural sources are advantageous, as they can provide exceptional biocompatibility and bioactivity, thus promoting desired cell responses. An ideal biomimetic cardiac patch should incorporate additional functional properties, which can be achieved by means of appropriate functionalization strategies. These are essential to replicate the native tissue, such as the release of biochemical signals, immunomodulatory properties, conductivity, enhanced vascularization and shape memory effects. The aim of the review is to present an overview of the current state of the art regarding the development of biomimetic 3D printed natural biomaterial-based cardiac patches, describing the 3D printing fabrication methods, the natural-biomaterial based bioinks, the functionalization strategies, as well as the in vitro and in vivo applications.
... The compromise between printability and biological functionality remains one of the key challenges in the formulation of extrusion biomaterial inks and (cell-containing) bioinks. 1 This balance limits the choice of materials that can be printed and used routinely in extrusion bioprinting, despite the large variety of biomaterials available. 8,9 Several approaches have been developed to print materials that lack ideal rheological properties. For example, assisted bioprinting strategies take advantage of an additional material, like gelatin, that can be used either as a sacrificial support matrix or as a sacrificial ink. ...
Extrusion three-dimensional (3D) bioprinting is a
promising technology with many applications in the biomedical
and tissue engineering fields. One of the key limitations for the
widespread use of this technology is the narrow window of
printability that results from the need to have bioinks with
rheological properties that allow the extrusion of continuous
filaments while maintaining high cell viability within the materials
during and after printing. In this work, we use Carbopol (CBP) as
rheology modifier for extrusion printing of biomaterials that are
typically nonextrudable or present low printability. We show that
low concentrations of CBP can introduce the desired rheological
properties for a wide range of formulations, allowing the use of
polymers with different cross-linking mechanisms and the
introduction of additives and cells. To explore the opportunities and limitations of CBP as a rheology modifier, we used ink
formulations based on poly(ethylene glycol)diacrylate with extrusion 3D printing to produce soft, yet stable, hydrogels with tunable mechanical properties. Cell-laden constructs made with such inks presented high viability for cells seeded on top of cross-linked materials and cells incorporated within the bioink during printing, showing that the materials are noncytotoxic and the printed structures do not degrade for up to 14 days. To our knowledge, this is the first report of the use of CBP-containing bioinks to 3Dprint complex cell-laden structures that are stable for days and present high cell viability. The use of CBP to obtain highly printable inks can accelerate the evolution of extrusion 3D bioprinting by guaranteeing the required rheological properties and expanding the number of materials that can be successfully printed. This will allow researchers to develop and optimize new bioinks focusing on the biochemical, cellular, and mechanical requirements of the targeted applications rather than the rheology needed to achieve good printability.
... Besides mechanical strength, biocompatibility is a crucial requirement for the application of a biomaterial in a medical environment (Mancha Sánchez et al., 2020). ...
Critical-sized bone defects resulting from trauma, inflammation, and tumor resections are individual in their size and shape. Implants for the treatment of such defects have to consider biomechanical and biomedical factors, as well as the individual conditions within the implantation site. In this context, 3D printing technologies offer new possibilities to design and produce patient-specific implants reflecting the outer shape and internal structure of the replaced bone tissue. The selection or modification of materials used in 3D printing enables the adaption of the implant, by enhancing the osteoinductive or biomechanical properties. In this study, scaffolds with bone spongiosa-inspired structure for extrusion-based 3D printing were generated. The computer aided design process resulted in an up scaled and simplified version of the bone spongiosa. To enhance the osteoinductive properties of the 3D printed construct, polycaprolactone (PCL) was combined with 20% (wt) calcium phosphate nano powder (CaP). The implants were designed in form of a ring structure and revealed an irregular and interconnected porous structure with a calculated porosity of 35.2% and a compression strength within the range of the natural cancellous bone. The implants were assessed in terms of biocompatibility and osteoinductivity using the osteosarcoma cell line MG63 and patient-derived mesenchymal stem cells in selected experiments. Cell growth and differentiation over 14 days were monitored using confocal laser scanning microscopy, scanning electron microscopy, deoxyribonucleic acid (DNA) quantification, gene expression analysis, and quantitative assessment of calcification. MG63 cells and human mesenchymal stem cells (hMSC) adhered to the printed implants and revealed a typical elongated morphology as indicated by microscopy. Using DNA quantification, no differences for PCL or PCL-CaP in the initial adhesion of MG63 cells were observed, while the PCL-based scaffolds favored cell proliferation in the early phases of culture up to 7 days. In contrast, on PCL-CaP, cell proliferation for MG63 cells was not evident, while data from PCR and the levels of calcification, or alkaline phosphatase activity, indicated osteogenic differentiation within the PCL-CaP constructs over time. For hMSC, the highest levels in the total calcium content were observed for the PCL-CaP constructs, thus underlining the osteoinductive properties.
... Naturally derived biomaterials are often used because they share more similarities with the extracellular matrix (ECM) of human tissue. 58 This also applies for cornea bioprinting. Common natural biomaterials include collagen, gelatin, methacrylated gelatin (GelMA), alginate, chitosan, hyaluronic acid, agarose, and cellulose. ...
... 81 Furthermore, it is inexpensive, making it one of the most widely used biomaterials for bioprinting. 58 Divalent cations are needed for the gelation process, with Ca² + being the most commonly used, although it has a higher affinity for Sr² + and Ba² + . 82 To increase the long-term stability of alginate hydrogels, Ba 2+ ions have been utilized. ...
... 90 It is also one of the most commonly used biomaterials in bioprinting. 58 However, under normal conditions, HA is not found in corneas. 91 Furthermore, HA is limited in corneal tissue engineering (including bioprinting) due to its association with lymphangiogenesis in the limbus; however, this requires further investigation. ...
The cornea is the outermost layer of the eye and serves to protect the eye and enable vision by refracting light. The need for cornea organ donors remains high, and the demand for an artificial alternative continues to grow. 3D bioprinting is a promising new method to create artificial organs and tissues. 3D bioprinting offers the precise spatial arrangement of biomaterials and cells to create 3D constructs. As the cornea is an avascular tissue which makes it more attractive for 3D bioprinting, it could be one of the first tissues to be made fully functional via 3D bioprinting. This review discusses the most common 3D bioprinting technologies and biomaterials used for 3D bioprinting corneal models. Additionally, the current state of 3D bioprinted corneal models, especially specific characteristics such as light transmission, biomechanics, and marker expression, and in vivo studies are discussed. Finally, the current challenges and future prospects are presented.
... The materials of 3D-bioprinted hydrogel dressings are effective and smart biomaterials that can be made from natural (such as collagen, ALG, and gelatin) or synthetic (like synthetic fibers, peptides, and elastomers) materials. Although hydrogels of natural origin offer advantages such as easy recognition of cellular growth factors and biomolecules, as well as their natural degradation by the body, synthetic hydrogels are more popularly used in 3D bioprinting due to their improved mechanical properties, biocompatibility, and having less batch-to-batch variation [280]. ...
The vulnerability of skin wounds has made efficient wound dressing a challenging issue for decades, seeking to mimic the natural microenvironment of cells to facilitate cell binding, augmen- tation, and metamorphosis. Many three-dimensional (3D) bioprinted hydrogel-based configurations have been developed using high-tech devices to overcome the limitations of traditional dressing ma- terials. Based on a material perspective, this review examines current state-of-the-art 3D bioprinting for hydrogel-based dressings, including both their advantages and limitations. Accordingly, their po- tential applications in terms of their performance in vitro and in vivo, as well as their adaptability to clinical settings, were investigated. Moreover, different configurations of 3D bioprinters are discussed. Finally, a roadmap for advancing wound dressings fabricated with 3D bioprinting is presented.
... The implementation of EBB relies on various operational parameters; (a) Extrusion pressure or velocity; (b) Nozzle geometry (i.e., cylindrical, or conical, convergence angle of conical geometry [66]) and nozzle diameter; (c) Cartridge temperature and platform temperature; (d) Axial velocity of the printhead in the x-and y-direction; pre-flow and post-flow time; (e) Path-height and path-space [47,[67][68][69][70][71]. These parameters directly impact bioprint resolution (the precision of the bioink filament) [47], consequently its shape fidelity, as well as cell viability through changes in bioink shear stress. ...
... Having highlighted the temperature dependence and thixotropy of bioink, it should be stated that enhanced molecular interactions inside the bioink could influence the temperature dependence and thixotropy behaviour of bioink [101,114]. Different molecular interactions, resulting in cross-linked matrix (thus the gelation of bioink) are usually necessary for the maintenance of bioprint shape fidelity and cell viability [69,119,120]. This enhanced molecular interaction is termed cross-linkingit is the formation of bonds between polymeric chains in the bioink. ...
... On the other hand, chemically cross-linked hydrogels are formed by covalent bonds, thus providing irreversible and strong interaction with the polymeric matrix. A covalently cross-linked network can be initiated by: chemical reagents, which may be cytotoxic; enzymatic reactions; ultraviolet photopolymerisation etc. [7,43,69,132]. A comprehensive review of cross-linking has been reported in literature [7,132,133]. ...
