Bioink Research Articles

Low-Concentration Gelatin Methacryloyl Hydrogel with Tunable 3D Extrusion Printability and Cytocompatibility: Exploring Quantitative Process Science and Biophysical Properties.

Three-dimensional (3D) bioprinting of hydrogels with a wide spectrum of compositions has been widely investigated. Despite such efforts, a comprehensive understanding of the correlation among the process science, buildability, and biophysical properties of the hydrogels for a targeted clinical application has not been developed in the scientific community. In particular, the quantitative analysis across the entire developmental path for 3D extrusion bioprinting of such scaffolds is not widely reported. In the present work, we addressed this gap by using widely investigated biomaterials, such as gelatin methacryloyl (GelMA), as a model system. Using extensive experiments and quantitative analysis, we analyzed how the individual components of methacrylated carboxymethyl cellulose (mCMC), needle-shaped nanohydroxyapatite (nHAp), and poly(ethylene glycol)diacrylate (PEGDA) with GelMA as baseline matrix of the multifunctional bioink can influence the biophysical properties, printability, and cellular functionality. The complex interplay among the biomaterial ink formulations, viscoelastic properties, and printability toward the large structure buildability (structurally stable cube scaffolds with 15 mm edge) has been explored. Intriguingly, the incorporation of PEGDA into the GelMA/mCMC matrix offered improved compressive modulus (∼40-fold), reduced swelling ratio (∼2-fold), and degradation rates (∼30-fold) compared to pristine GelMA. The correlation among microstructural pore architecture, biophysical properties, and cytocompatibility is also established for the biomaterial inks. These photopolymerizable bio(material)inks served as the platform for the growth and development of bone and cartilage matrix when human mesenchymal stem cells (hMSCs) are either seeded on two-dimensional (2D) substrates or encapsulated on 3D scaffolds. Taken together, this present study unequivocally establishes a significant step forward in the development of a broad spectrum of shape-fidelity compliant bioink for the 3D bioprinting of multifunctional scaffolds and emphasizes the need for invoking more quantitative analysis in establishing process-microstructure-property correlation.

Recent advances in the design and development of bioink formulations for various biomedical applications

Creating functioning tissue constructions via bioprinting holds great promise for replacing diseased or damaged tissues, which employs precise control over the geometry and composition of the build. This is an emerging technique that offers highly reproducible and accurate computerized oversight over the constructed structures, potentially opening the door to high-throughput production. Tissue constructions are made by the bioprinting method using a solution of a biomaterial or a combination of multiple biomaterials in the hydrogel form, known as the bioink, which often encapsulates the appropriate cell types. Hydrogels' aqueous and three-dimensional networked environment has made them an attractive contender for the bio-ink formulation of 3D printing in recent times. Bio ink-based composites have however made significant progress in treating wounds, repairing muscles, bone, and tissue, and delivering drugs. The current review offers a cutting-edge update on the creation of various bio ink formulations and their uses in the biomedical industry. The various methods of fabrication—laser-based, extrusion-based, and inkjet-based bioprinting—are explained, illustrated, and contrasted. Benefits and drawbacks of every method are discussed along with the bioprinting approach's difficulties, restrictions, and potential future directions. Natural, synthetic, and hybrid materials utilized as bioinks are also examined.

Gelatin Methacryloyl (GelMA)-Based Biomaterial Inks: Process Science for 3D/4D Printing and Current Status.

Tissue engineering for injured tissue replacement and regeneration has been a subject of investigation over the last 30 years, and there has been considerable interest in using additive manufacturing to achieve these goals. Despite such efforts, many key questions remain unanswered, particularly in the area of biomaterial selection for these applications as well as quantitative understanding of the process science. The strategic utilization of biological macromolecules provides a versatile approach to meet diverse requirements in 3D printing, such as printability, buildability, and biocompatibility. These molecules play a pivotal role in both physical and chemical cross-linking processes throughout the biofabrication, contributing significantly to the overall success of the 3D printing process. Among the several bioprintable materials, gelatin methacryloyl (GelMA) has been widely utilized for diverse tissue engineering applications, with some degree of success. In this context, this review will discuss the key bioengineering approaches to identify the gelation and cross-linking strategies that are appropriate to control the rheology, printability, and buildability of biomaterial inks. This review will focus on the GelMA as the structural (scaffold) biomaterial for different tissues and as a potential carrier vehicle for the transport of living cells as well as their maintenance and viability in the physiological system. Recognizing the importance of printability toward shape fidelity and biophysical properties, a major focus in this review has been to discuss the qualitative and quantitative impact of the key factors, including microrheological, viscoelastic, gelation, shear thinning properties of biomaterial inks, and printing parameters, in particular, reference to 3D extrusion printing of GelMA-based biomaterial inks. Specifically, we emphasize the different possibilities to regulate mechanical, swelling, biodegradation, and cellular functionalities of GelMA-based bio(material) inks, by hybridization techniques, including different synthetic and natural biopolymers, inorganic nanofillers, and microcarriers. At the close, the potential possibility of the integration of experimental data sets and artificial intelligence/machine learning approaches is emphasized to predict the printability, shape fidelity, or biophysical properties of GelMA bio(material) inks for clinically relevant tissues.

Role Of 3-D Bioprinting In Forensics- A Review

3D bio-printing involves directly depositing a mixture of high-density living cells and a bio-ink is printed out in an overlapping process by the 3D bio-printer, which is under the design and control of computer. The term bioprinting describes the simultaneous positioning of biomaterials and living cells in a prescribed layer by layer stacking organization to create engineered tissue and organs. The process of Freeform Reversible Embedding of Suspended Hydrogels (FRESH) is a printing method that extrudes bio inks into a yield-stress support bath that holds the bio inks in place until they cure. In-situ 3D bioprinting is a kind of bio-printing which is directly printed onto or into the damaged tissue or organ. This review specifically focuses the current development of FRESH bioprinting and in situ bioprinting and the various challenges and legal considerations in this field.

A new shear-thinning nanocomposite hydrogel from GelMA-GO for soft tissue engineering

The use of bio ink materials for fabricating scaffolds is the best option to replace aggressive surgery. This study aims to formulate an injectable hydrogel with suitable structural, mechanical, and rheological properties for tissue engineering applications. In this respect, gelatin methacrylate (GelMA) nanocomposites with different amounts of the modified graphene oxide nanoplates (0.25, 0.5, 0.75, and 1 wt%) were fabricated. The effect of the nanoplates on the structural, degradability, mechanical, rheological, and biological properties of the nanocomposites were evaluated. The results revealed that the functionalization of graphene oxide with dopamine (GOPD) resulted in the formation of a layer of polydopamine on the surface of the nanoplates, which developed the interaction of graphene oxide with GelMA chains. Adding GOPD to GelMA from 0 to 1 wt% decreased the water absorption (0.3 times) and its weight loss percentage (0.2 times). The addition of 0.5 wt% of GOPD to GelMA improved the compressive strength (7.5 times) and compressive modulus (7 times) compared to the GelMA hydrogel. Also, a similar amount of GOPD developed the thin shear properties of GelMA by three logarithmic units. Besides, the addition of the modified graphene oxide nanoplates to GelMA enhanced cell viability (93.26%) after 72 h of cell seeding. The proper behavior of the GelMA hydrogel with 0.5% GOPD, and its stability during the 3D printing process was confirmed. Accordingly, the injectable GelMA hydrogel containing dopamine-modified graphene oxide could be a proper candidate for tissue engineering expenditures.

PH Measuring Pad for Underpad

Measuring the pH is very important to reveal the possible health problem risks of pets with early diagnosis, to enhance their quality of life and prevent negative effects on their health. However, measuring the pH level of cats and dogs urine’s is very painful and stressful process,especially during their birth duration. Accordingly, to support parents and veterinarians in this urine collection process, ‘pH Measuring pad for underpad’ project is studied. Using this ped will be quick, painless and guiding method.
 In addtion to these, environmental pollution which is known by all over the world is increasing. In order to prevent this pollution, several projects has been studied in this issue and also, all raw materials have been selected as be bio-based. In this newly studies under pad project, when animal health is considered, raw materials selection is made on the basis of protecting the nature. The product which contains special indicator emphasizes the innovative aspect of the project by perforemin health checks for pets. The raw materials which use in this project is selected from having higher mechanical properties ones and also, their processability is evaluated. Formulation is obtained by mixing suitable raw materials in certain proportions. 
 First of all, there is a print on top of this pad. This print is made with a bio ink which includes pH indicator. By means of this ink, after the pets leave their urine on the pad, observing of color change can be possible according to the urine’s pH level. Ideally, urine’s pH value should be aroud 6.5 for cats and dogs as be considere a healthy level. IF the pH is acisic (below 5.5/6) or alkaline (above 7/7.5), there may be bacteria, crystals, an imbalnce in blood values or a sign of illness, which can have a nagative impact on pet’s health. In addtion to this, the carrier breathable film which is used in the desing of the ‘pH measuring pad for underpad’ is produced with using low density polyethylene (LDPE) obtained from renewable resoruces (green). The non-woven fabric is produced from soybean protein fibers. While, These fibers are biodegradable, soybean protein fiber or SPF, is the only renewable botanical protein fiber that can be touch today. SPF is a unique active fiber. Also it contains 16 amino acids that are healty and nourishing for the skin.
 Keyword: indicator, bio, pad Giriş

Tailoring of mesoporous bioactive glass composite scaffold via thermal extrusion based 3D bioprinting and scrutiny on bone tissue engineering characteristics

In the recent years, mesoporous bioactive glass (MBG) based 3D printed scaffolds have been envisaged widely for bone tissue engineering potential. The earlier reports on 3D printed MBG based scaffolds for bone tissue engineering application are dedicated to pneumatic extrusion, which involves utilization of solvent and tedious process steps for preparation of bio ink. In order to overcome these limitations, the current work aims to develop 3D printed MBG based biomimetic composite scaffold via thermal extrusion process, which is devoid from solvent. It is well known that it is highly challenging to process pure MBG based inorganic/ceramic materials into 3D printed constructs due to lack of flexibility. Therefore, poly(caprolactone) (PCL) which exhibits bio inert nature towards formation of hydroxyapatite is used as the binder in order to impart flexibility during thermal extrusion process. The novelty of the current work lies in optimization of 3D printing parameters in order to fabricate MBG/PCL based composite construct, which mimics the natural bone composition with inorganic to organic ratio of 70:30 with hierarchical pore architecture and evaluation of its bone tissue engineering characteristics, which has not been documented earlier in the best of our knowledge. Through SBF studies, it is revealed that the 3D printed PCL/MBG composite scaffold helps in the formation of hydroxyapatite biomineral, which is lacking in the case of PCL scaffold. The presence of MBG in the PCL matrix is also found to support cellular proliferation and osteogenic differentiation, which is also reflected in terms of calcium mineralization and up regulation of osteogenic genes. This indicates that the 3D printed PCL/MBG composite scaffold mimicking the natural bone composition seems to hold promising potential for bone tissue engineering.

The Use of Bio-Inks and the Era of Bioengineering and Tooth Regeneration

Objective: To review existing literature and provide an update on the current use of Bio-Inks and potential future use. Material and Methods: A MeSH keyword search was conducted to find out relevant articles for this short review. Results: Bio inks used in 3D printing grafting require various properties essential for the selection. Combining multiple methods and improved properties is essential for developing successful bio-inks for 3D grafting of functional tissues and tooth pulp regeneration from stem cells. To date, researchers have made many efforts to grow teeth based on stem cells and inculcate regeneration of teeth along with surrounding tissues like alveolar bones and periodontal ligaments. Conclusion: 3D printing with Bio-Inks requires strict adherence to safety protocols for successful outcomes, making it difficult to employ this routinely.

Materials for creating tissue-engineered constructs using 3D bioprinting: cartilaginous and soft tissue restoration

3D Bioprinting is a dynamically developing technology for tissue engineering and regenerative medicine. The main advantage of this technique is its ability to reproduce a given scaffold geometry and structure both in terms of the shape of the tissue-engineered construct and the distribution of its components. The key factor in bioprinting is bio ink, a cell-laden biocompatible material that mimics extracellular matrix. To meet all the requirements, the bio ink must include not only the main material, but also other components ensuring cell proliferation, differentiation and scaffold performance as a whole. The purpose of this review is to describe the most common materials applicable in bioprinting, consider their properties, prospects and limitations in cartilage restoration.

3D bioprinting–a step towards heart tissue regeneration

Heart disease and cardiovascular disease is a very serious and growing public health issue. Tissue-engineering has great potential and great strength for regeneration, remolding, and growth. In the case of heart failure, Allografting has been used. 3D bioprinting has a great impact in the field of cardiovascular tissue engineering. It has been observed that 3D Bioprinting is used to construct an artificial heart for transplantation and used to create myocardial cells in case of injury. Recent studies showed that biomaterial used in the treatment of myocardial dysfunction is decellularized cardiac extracellular matrix hydrogel in adults. Collagen, Alginate gelatin, hyaluronic acid, and deECM scaffolds were used as biomaterials in 3D bioprinting. It has been shown that scaffold used with ECM was used to support there generation process A new 3D bioprinting technology was developed in which cells were collected into spheroids and printed on a needle array according to desirable characteristics. Different bio inks such as laser, extrusion, droplet, and stereolithography are used here. Electric stimulation is key to the contractility of cardiomyocytes. A physical cardiac replica was created by image processing software that creates 3D structures. In holographic display 3D, full hearts of patients were printed in flexible material. A process is demonstrated to fabricate robust valves of the heart using the3D bioprinting technique. MRI or CT scans were used to obtained 3D images of the aorta.3D bioprinting plays a huge role in knowing the aortic anatomy involves the aortic valve area and morphology of the root. Recent advances demonstrated that 3D bioprinting can assist in ventricular device placement and perform a specific function in a complex with (CHD) Congenital heart defects. 3D bioprinting holds great prom

Tissue Engineering – The Current Scenario & Innovations

Tissue engineering is an emerging field in medical arena which combines the knowledge of science and engineering to accomplish the increasing demands to aid the damaged tissues or even a whole organ. With time various methods of tissue engineering such as traditional scaffold method ,advanced 3D bioprinting technology and the use of bio ink (the extracellular matrix materials) have become popular at various medical levels. Scaffold is a 3D structure which results in tissue formation by providing space for cells to attach, to proliferate in various directions & by secreting extracellular matrix. Also, the recent development is the use of decellularised extracellular material i.e. dECM as bio-ink to generate vascular organs like Kidney & Heart. Textiles have been playing an indispensable role in tissue engineering as it provide superior methods over other ways to fabricate scaffold. The use of smart biomaterial based scaffolds costs less and is more effective which gives advantage to tailor the tissues according to individual's tissue structure . This paper reviews the application of textiles technology in tissue engineering, various approaches of tissue engineering from traditional to the currently used approach , recent advances and its indications.

Prediction of Bio-Polymer Characteristics by Applying Rentato Panelli Mathematical Model

Recently, the intense interest for bio-polymer for biomedical applications has gone up. This interest was due to patients researchers, and the medical world seeking for effective solutions to their serious challenges, such as the need to repair or, replace, substitute organs or tissues. In current article, Rentato Panelli mathematical equation utilize to understand and track parameters refer to a physical significant, deformation nature and shape memory degree and of two types of bio-polymer derivative mixtures, Avicel 102 and Sodium Starch Glycolate (SSG). Panelli constants were stated by using combination of two, known, bio polymer in term of deformation and shape memory specifications to validate of the equation parameters to predict this characteristics for unknown materials which may be part of human body or cardiovascular artificial parts. Constants and coefficients for equation measured by applying low pressure ranging from 15 to 75 Mpa. The issues emerging from the findings relate specifically to depth in-die analysis. The most interesting findings was the Panelli equation parameters are perfectly valid in representing bio-polymer characteristics under stress. These parameters and characteristics are able to assess the features of the bio-polymer which sometimes become beyond the scope unless defined by using specific instrumentation. In addition, these parameters can decide the applied pressure that achieve particular density in the manufacturing conditions. These parameters determine process conditions that produce desired biomedical engineering application as bio ink for 3D printing, artificial organs, and drug delivery system which is difficult or rather impossible without use classical methods.

Key technology of 3D bio-printing and its application in orthopedics

Bone defect repairing and reconstruction has been a hot research topic in orthopedics for a long time. Tissue engineering and stem cell technology have made a series of important achievements in promoting bone regeneration to treat bone defect. In recent years, 3D bio-printing, which combining with 3D printing, tissue engineering and stem cell technology, has significant advantages in optimizing the geometry, mechanical properties and biological functions of repairing tissue for bone defect by accurately controlling the shape and internal structure of scaffolds, and printing biomaterials, stem cells and (or) cells into three-dimensional biological functional structures. A series of important progress has been achieved. The common printing methods for bio-printing related to orthopedic include: Inkjet 3D bioprinting; microextrusion 3D bioprinting; laser-assisted 3D bioprinting; stereolithography; microvalve based 3D bioprinting. Various printing methods and principles are not the same, and each has advantages and disadvantages, and the applicable bio ink is also different. The key technologies of orthopedic bio-3D printing include: the methods of image data acquisition and 3D structure design; development and application of composite bio-scaffold materials suitable for 3D printing, tissue engineering and bone-enhancing effect; stem cell selection for ensuring graft biological performance and induced pluripotent stem cell technology; in vitro bioreactor technology for improving the maturity and biocharacterization of bioprinted tissues. The literature published in the field of biological 3D printing research has continued to grow at a high rate since 2008. Using the bibliometric analysis software VOSviewer to create a co-word matrix for high-frequency keywords and to draw a keyword co-occurrence network map analysis, biological 3D printing research hotspots are the use of tissue engineering methods to 3D printed tissue scaffolds, while studying cell survival and drug effects. The instruments and methods of bio-3D printing are also one of the research hotspots.

Synthesis, Characterization, and 3D Printing of an Isosorbide-Based, Light-Curable, Degradable Polymer for Potential Application in Maxillofacial Reconstruction.

Although emergence of bone tissue engineering techniques has revolutionized the field of maxillofacial reconstruction, the successful translation of such products, especially concerning larger sized defects, still remains a significant challenge. Light-curable methacrylate-based polymers have ideal properties for bone repair. These materials are also suitable for 3D printing which can be applicable for restoration of both function and aesthetics. The main objective of this research was to synthesize a mechanically stable and biologically functional polymer for reconstruction of complex craniofacial defects. The experimental work initially involved synthesis of (((3R,3aR,6S,6aR)-hexahydrofuro[3,2-b]furan-3,6-diyl)bis(oxy))bis(ethane-2,1-diyl)bis((4-methyl-3-oxopent-4-en-1-yl)carbamate), CSMA-1, and ((((((((((((3R,3aR,6S,6aR)-hexahydrofuro[3,2-b]furan-3,6-diyl)bis(oxy))bis(ethane-2,1 diyl))bis(oxy))bis(carbonyl))bis(azanediyl))bis(methylene))bis(3,3,5-trimethylcyclohexane-5,1-diyl))bis(azanediyl))bis(carbonyl))bis(oxy))bis(ethane-2,1-diyl)bis(2-methylacrylate), CSMA-2; nuclear magnetic resonance analysis confirmed formation of the monomers, and composite samples were fabricated respectively by exposing 11 mm diameter discs to blue light. Modulus of elasticity was determined using a biaxial flexural test and the values were found to be between 1 and 3 GPa in CSMA-1, CSMA-2, and their composites. In vitro cell culture, using human bone marrow-derived mesenchymal stem cells, confirmed nontoxicity of the samples and finally 3D printing allowed direct photo-polymerization and setting of the bio ink into a 3D construct.

Micro powder poly lactic acid/carbon black composite as a bio printing ink

Bio toners represent a novel class of electrostatic imaging powders which provide sustainability, compostability and bio-degradability. Due to the advantages of bio toners, this paper focused on the preparation of a bio-based micro powdered composite derived from poly lactic acid and carbon black to apply it as an electrophotographic printing bio ink. The bio toner was characterized by particle size analyzer, differential scanning calorimetry, scanning electron microscopy, Fourier-transform infrared spectroscopy and thermogravimetric analysis. The viscoelastic properties were calculated with rheometrics mechanical spectrometer. These properties were then used to estimate the strain deformation of the toner as it passes through the nip with arbitrary residence time and nip pressure as a function of gel content. The outcomes of this study proved that the poly lactic acid is an appropriate polymer for the production of toners in terms of processing, printing efficiency. The bio toners' results demonstrated the promising and worthy outcomes in comparison to commercially available petroleum-based toners.

Advancement of Bio inks in three Dimensional Bioprinting

Advancement of Bio inks in three Dimensional Bioprinting

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