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1
Willson, Kelsey, Anthony Atala, and James J. Yoo. "Bioprinting Au Natural: The Biologics of Bioinks." Biomolecules 11, no. 11 (October 28, 2021): 1593. http://dx.doi.org/10.3390/biom11111593.
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The development of appropriate bioinks is a complex task, dependent on the mechanical and biochemical requirements of the final construct and the type of printer used for fabrication. The two most common tissue printers are micro-extrusion and digital light projection printers. Here we briefly discuss the required characteristics of a bioink for each of these printing processes. However, physical printing is only a short window in the lifespan of a printed construct—the system must support and facilitate cellular development after it is printed. To that end, we provide a broad overview of some of the biological molecules currently used as bioinks. Each molecule has advantages for specific tissues/cells, and potential disadvantages are discussed, along with examples of their current use in the field. Notably, it is stressed that active researchers are trending towards the use of composite bioinks. Utilizing the strengths from multiple materials is highlighted as a key component of bioink development.
2
Zhe, Man, Xinyu Wu, Peiyun Yu, Jiawei Xu, Ming Liu, Guang Yang, Zhou Xiang, Fei Xing, and Ulrike Ritz. "Recent Advances in Decellularized Extracellular Matrix-Based Bioinks for 3D Bioprinting in Tissue Engineering." Materials 16, no. 8 (April 18, 2023): 3197. http://dx.doi.org/10.3390/ma16083197.
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In recent years, three-dimensional (3D) bioprinting has been widely utilized as a novel manufacturing technique by more and more researchers to construct various tissue substitutes with complex architectures and geometries. Different biomaterials, including natural and synthetic materials, have been manufactured into bioinks for tissue regeneration using 3D bioprinting. Among the natural biomaterials derived from various natural tissues or organs, the decellularized extracellular matrix (dECM) has a complex internal structure and a variety of bioactive factors that provide mechanistic, biophysical, and biochemical signals for tissue regeneration and remodeling. In recent years, more and more researchers have been developing the dECM as a novel bioink for the construction of tissue substitutes. Compared with other bioinks, the various ECM components in dECM-based bioink can regulate cellular functions, modulate the tissue regeneration process, and adjust tissue remodeling. Therefore, we conducted this review to discuss the current status of and perspectives on dECM-based bioinks for bioprinting in tissue engineering. In addition, the various bioprinting techniques and decellularization methods were also discussed in this study.
3
Goklany, Sheba. "Conductive Nanomaterials used in Bioinks for 3D Bioprinting." Nano LIFE 11, no. 02 (June 2021): 2130005. http://dx.doi.org/10.1142/s1793984421300053.
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Biofabrication for tissue engineering and regenerative medicine is a rapidly evolving field that incorporates bioprinting or bioassembly for the development of biologically functional products with structural organization using cells, bioactive molecules, and biomaterials. Bioprinting is a biofabrication technology that utilizes biomaterials, living cells, and supporting materials, called bioink, to generate three-dimensional tissue constructs. Bioprinting offers several advantages over traditional scaffolding and microengineering methods such as precise architecture control, high reproducibility, and versatility. The ideal bioink should possess appropriate structural, mechanical, gelation, rheological, chemical, biological, degradation, and biomimetic properties for the desired application of the final product. Several natural and synthetic bioinks have been developed and this review has focused on conductive nanomaterials that have been used in combination with hydrogel materials for bioink synthesis.
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Delkash, Yasaman, Maxence Gouin, Tanguy Rimbeault, Fatemeh Mohabatpour, Petros Papagerakis, Sean Maw, and Xiongbiao Chen. "Bioprinting and In Vitro Characterization of an Eggwhite-Based Cell-Laden Patch for Endothelialized Tissue Engineering Applications." Journal of Functional Biomaterials 12, no. 3 (August 11, 2021): 45. http://dx.doi.org/10.3390/jfb12030045.
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Three-dimensional (3D) bioprinting is an emerging fabrication technique to create 3D constructs with living cells. Notably, bioprinting bioinks are limited due to the mechanical weakness of natural biomaterials and the low bioactivity of synthetic peers. This paper presents the development of a natural bioink from chicken eggwhite and sodium alginate for bioprinting cell-laden patches to be used in endothelialized tissue engineering applications. Eggwhite was utilized for enhanced biological properties, while sodium alginate was used to improve bioink printability. The rheological properties of bioinks with varying amounts of sodium alginate were examined with the results illustrating that 2.0–3.0% (w/v) sodium alginate was suitable for printing patch constructs. The printed patches were then characterized mechanically and biologically, and the results showed that the printed patches exhibited elastic moduli close to that of natural heart tissue (20–27 kPa) and more than 94% of the vascular endothelial cells survived in the examination period of one week post 3D bioprinting. Our research also illustrated the printed patches appropriate water uptake ability (>1800%).
5
Zhang, Chun-Yang, Chao-Ping Fu, Xiong-Ya Li, Xiao-Chang Lu, Long-Ge Hu, Ranjith Kumar Kankala, Shi-Bin Wang, and Ai-Zheng Chen. "Three-Dimensional Bioprinting of Decellularized Extracellular Matrix-Based Bioinks for Tissue Engineering." Molecules 27, no. 11 (May 26, 2022): 3442. http://dx.doi.org/10.3390/molecules27113442.
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Three-dimensional (3D) bioprinting is one of the most promising additive manufacturing technologies for fabricating various biomimetic architectures of tissues and organs. In this context, the bioink, a critical element for biofabrication, is a mixture of biomaterials and living cells used in 3D printing to create cell-laden structures. Recently, decellularized extracellular matrix (dECM)-based bioinks derived from natural tissues have garnered enormous attention from researchers due to their unique and complex biochemical properties. This review initially presents the details of the natural ECM and its role in cell growth and metabolism. Further, we briefly emphasize the commonly used decellularization treatment procedures and subsequent evaluations for the quality control of the dECM. In addition, we summarize some of the common bioink preparation strategies, the 3D bioprinting approaches, and the applicability of 3D-printed dECM bioinks to tissue engineering. Finally, we present some of the challenges in this field and the prospects for future development.
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Chen, Yan, Yingge Zhou, and Chi Wang. "Investigation of Collagen-Incorporated Sodium Alginate Bioprinting Hydrogel for Tissue Engineering." Journal of Composites Science 6, no. 8 (August 4, 2022): 227. http://dx.doi.org/10.3390/jcs6080227.
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Tissue engineering is a promising area that is aimed at tissue regeneration and wound repair. Sodium alginate (SA) has been widely used as one of the most biocompatible materials for tissue engineering. The cost-efficiency and rapid gel ability made SA attractive in would healing and regeneration area. To improve printability and elasticity, many hydrogel-based bioinks were developed by mixing SA with other natural or synthetic polymers. In this paper, composite SA/COL bioink was used for the bioprinting of artificial cartilage tissue mimicries. The results showed that the concentration of both SA and COL has significant effects on filament diameter and merging. A higher concentration of the bioink solution led to better printing fidelity and less deformation. Overall, a higher SA concentration and a lower COL concentration contributed to a lower shrinkage ratio after crosslinking. In summary, the SA/COL composite bioink has favorable rheological properties and this study provided material composition optimization for future bioprinting of engineered tissues.
7
Tolmacheva, Nelli, Amitava Bhattacharyya, and Insup Noh. "Calcium Phosphate Biomaterials for 3D Bioprinting in Bone Tissue Engineering." Biomimetics 9, no. 2 (February 6, 2024): 95. http://dx.doi.org/10.3390/biomimetics9020095.
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Three-dimensional bioprinting is a promising technology for bone tissue engineering. However, most hydrogel bioinks lack the mechanical and post-printing fidelity properties suitable for such hard tissue regeneration. To overcome these weak properties, calcium phosphates can be employed in a bioink to compensate for the lack of certain characteristics. Further, the extracellular matrix of natural bone contains this mineral, resulting in its structural robustness. Thus, calcium phosphates are necessary components of bioink for bone tissue engineering. This review paper examines different recently explored calcium phosphates, as a component of potential bioinks, for the biological, mechanical and structural properties required of 3D bioprinted scaffolds, exploring their distinctive properties that render them favorable biomaterials for bone tissue engineering. The discussion encompasses recent applications and adaptations of 3D-printed scaffolds built with calcium phosphates, delving into the scientific reasons behind the prevalence of certain types of calcium phosphates over others. Additionally, this paper elucidates their interactions with polymer hydrogels for 3D bioprinting applications. Overall, the current status of calcium phosphate/hydrogel bioinks for 3D bioprinting in bone tissue engineering has been investigated.
8
Sanz-Fraile, Héctor, Carolina Herranz-Diez, Anna Ulldemolins, Bryan Falcones, Isaac Almendros, Núria Gavara, Raimon Sunyer, Ramon Farré, and Jorge Otero. "Characterization of Bioinks Prepared via Gelifying Extracellular Matrix from Decellularized Porcine Myocardia." Gels 9, no. 9 (September 13, 2023): 745. http://dx.doi.org/10.3390/gels9090745.
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Since the emergence of 3D bioprinting technology, both synthetic and natural materials have been used to develop bioinks for producing cell-laden cardiac grafts. To this end, extracellular-matrix (ECM)-derived hydrogels can be used to develop scaffolds that closely mimic the complex 3D environments for cell culture. This study presents a novel cardiac bioink based on hydrogels exclusively derived from decellularized porcine myocardium loaded with human-bone-marrow-derived mesenchymal stromal cells. Hence, the hydrogel can be used to develop cell-laden cardiac patches without the need to add other biomaterials or use additional crosslinkers. The scaffold ultrastructure and mechanical properties of the bioink were characterized to optimize its production, specifically focusing on the matrix enzymatic digestion time. The cells were cultured in 3D within the developed hydrogels to assess their response. The results indicate that the hydrogels fostered inter-cell and cell-matrix crosstalk after 1 week of culture. In conclusion, the bioink developed and presented in this study holds great potential for developing cell-laden customized patches for cardiac repair.
9
Lee, Juo, Sungmin Lee, Jae Woon Lim, Iksong Byun, Kyoung-Je Jang, Jin-Woo Kim, Jong Hoon Chung, Jungsil Kim, and Hoon Seonwoo. "Development of Plum Seed-Derived Carboxymethylcellulose Bioink for 3D Bioprinting." Polymers 15, no. 23 (November 21, 2023): 4473. http://dx.doi.org/10.3390/polym15234473.
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Three-dimensional bioprinting represents an innovative platform for fabricating intricate, three-dimensional (3D) tissue structures that closely resemble natural tissues. The development of hybrid bioinks is an actionable strategy for integrating desirable characteristics of components. In this study, cellulose recovered from plum seed was processed to synthesize carboxymethyl cellulose (CMC) for 3D bioprinting. The plum seeds were initially subjected to α-cellulose recovery, followed by the synthesis and characterization of plum seed-derived carboxymethyl cellulose (PCMC). Then, hybrid bioinks composed of PCMC and sodium alginate were fabricated, and their suitability for extrusion-based bioprinting was explored. The PCMC bioinks exhibit a remarkable shear-thinning property, enabling effortless extrusion through the nozzle and maintaining excellent initial shape fidelity. This bioink was then used to print muscle-mimetic 3D structures containing C2C12 cells. Subsequently, the cytotoxicity of PCMC was evaluated at different concentrations to determine the maximum acceptable concentration. As a result, cytotoxicity was not observed in hydrogels containing a suitable concentration of PCMC. Cell viability was also evaluated after printing PCMC-containing bioinks, and it was observed that the bioprinting process caused minimal damage to the cells. This suggests that PCMC/alginate hybrid bioink can be used as a very attractive material for bioprinting applications.
10
Gao, Qiqi, Byoung-Soo Kim, and Ge Gao. "Advanced Strategies for 3D Bioprinting of Tissue and Organ Analogs Using Alginate Hydrogel Bioinks." Marine Drugs 19, no. 12 (December 15, 2021): 708. http://dx.doi.org/10.3390/md19120708.
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Alginate is a natural polysaccharide that typically originates from various species of algae. Due to its low cost, good biocompatibility, and rapid ionic gelation, the alginate hydrogel has become a good option of bioink source for 3D bioprinting. However, the lack of cell adhesive moieties, erratic biodegradability, and poor printability are the critical limitations of alginate hydrogel bioink. This review discusses the pivotal properties of alginate hydrogel as a bioink for 3D bioprinting technologies. Afterward, a variety of advanced material formulations and biofabrication strategies that have recently been developed to overcome the drawbacks of alginate hydrogel bioink will be focused on. In addition, the applications of these advanced solutions for 3D bioprinting of tissue/organ mimicries such as regenerative implants and in vitro tissue models using alginate-based bioink will be systematically summarized.
11
Tuan Mohd Marzuki, Tuan Mohamad Farhan, Mohd Syahir Anwar Hamzah, and Nadirul Hasraf Mat Nayan. "A Review of Bioink Development for 3D Bioprinting: Application in Corneal Tissue Regeneration." Journal of Medical Device Technology 3, no. 2 (December 30, 2024): 113–19. https://doi.org/10.11113/jmeditec.v3.58.
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This review was to describe the state and progress regarding methods for 3D bioprinting applicable for corneal regeneration; these are identified with developments related to bioink and related bioprinting technologies. This review article has pointed out in detail the mechanism of the 3D printing process; it maintains that bioink ideally consists of biomaterial components deriving both from natural and synthetic ones, cells, and biochemical factors, in such ways which could imitate the properties of a native cornea in several respects, in its mechanic, structural, and ultrastructural features. Biocompatibility, transparency, strength for tension, and corresponding rheology were emphasized as relevant. This review discusses recent modalities of bioprinting, including inkjet, extrusion-based, laser-assisted bioprinting, and stereolithography, for their adequacy in corneal tissue engineering. The integrated use of advanced bioprinting techniques combined with optimized bioinks is a highly promising approach in the fabrication of functional corneal tissues for restored vision and the treatment of ocular disorders.
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Ghosh, Prasanta Kumar. "Polymeric hydrogel nanoparticles in drug delivery and bioprinting technologies: a review." MGM Journal of Medical Sciences 11, no. 4 (October 2024): 755–62. https://doi.org/10.4103/mgmj.mgmj_340_24.
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Abstract Multiple kinds of hydrogel polymers, natural and synthetic, are known. Self-assembly and aggregation are their inherent properties. The diverse applications of hydrogel polymers, encompassing natural and synthetic varieties known for their water-swelling capabilities and biocompatibility, have been explored and summarized. Hydrogels are pivotal in medicine, particularly in drug delivery systems, and emerging three-dimensional (3D) bioprinting technologies. Integrating nanoparticles into hydrogels enhances their functionality for targeted drug release and as components of bioinks used in bioprinting aimed at priming and replicating tissue and organ structures. Natural hydrogel polymers are favored for their biocompatibility characteristics in bioinks, while synthetic polymers and nanoparticles contribute to stronger mechanical properties and increased versatility. This study highlights the importance of the nanoparticle-based hydrogel polymer-entrapped drug substances for efficient use in tissue-specific delivery systems. It emphasizes the critical role of bioink development in advancing synthetic organ fabrication via the 3D bioprinting technology.
13
Datta, Sudipto. "Advantage of Alginate Bioinks in Biofabrication for Various Tissue Engineering Applications." International Journal of Polymer Science 2023 (June 7, 2023): 1–20. http://dx.doi.org/10.1155/2023/6661452.
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Bioprinting is fast emerging as a viable technique for organ fabrication. Though various types of bioprinting methods have been developed, the most commonly used bioprinting is extrusion-based bioprinting (EBB). Bioinks are extruded layer-by-layer forming a 3D multicellular construct and scaled up to dimensions depending upon the specific tissue to be regenerated. Among various bioinks, alginate, a natural polysaccharide, has been extensively used because of its good printability in physiologically amenable conditions. Though alginate possesses good printability properties, it promotes little cell–material interaction resulting in limited biofunctionality. Therefore, it becomes necessary to blend/modify alginate to improve the biological properties of bioink without compromising printability. This paper presents a review of the various approaches used to optimize bioprinting with alginate bioinks and their limitations.
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He, Yunfan, Soroosh Derakhshanfar, Wen Zhong, Bingyun Li, Feng Lu, Malcolm Xing, and Xiaojian Li. "Characterization and Application of Carboxymethyl Chitosan-Based Bioink in Cartilage Tissue Engineering." Journal of Nanomaterials 2020 (March 12, 2020): 1–11. http://dx.doi.org/10.1155/2020/2057097.
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Chitosan is a promising natural biomaterial for biological application; however, the weak mechanical performance of pristine chitosan limits its further utilization in hard tissue (such as cartilage) engineering. In this study, a chitosan-based 3D printing bioink with suitable mechanical properties was developed as 3D bioprinting ink for chondrocyte support. Chitosan was first modified by ethylenediaminetetraacetic acid (EDTA) to provide more carboxyl groups followed by physical crosslinking with calcium to increase the hydrogel strength. Dynamic mechanical analysis was carried out to evaluate viscoelastic properties with the addition of modified chitosan. A bioink with a combination of modified and pristine chitosan was formulated for scaffold fabrication via 3D bioprinting technique. Furthermore, cell viability, cell proliferation, and expression of chondrogenic markers were evaluated in vitro in chondrocytes loaded on the bioink. The novel bioink exhibited a favorable mechanical property and promoted cell attachment and chondrogenic gene expression in chondrocytes. Based on these results, we can conclude that the presented bioink could qualify for use in 3D bioprinting in cartilage tissue engineering.
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Stepanovska, Jana, Monika Supova, Karel Hanzalek, Antonin Broz, and Roman Matejka. "Collagen Bioinks for Bioprinting: A Systematic Review of Hydrogel Properties, Bioprinting Parameters, Protocols, and Bioprinted Structure Characteristics." Biomedicines 9, no. 9 (September 1, 2021): 1137. http://dx.doi.org/10.3390/biomedicines9091137.
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Bioprinting is a modern tool suitable for creating cell scaffolds and tissue or organ carriers from polymers that mimic tissue properties and create a natural environment for cell development. A wide range of polymers, both natural and synthetic, are used, including extracellular matrix and collagen-based polymers. Bioprinting technologies, based on syringe deposition or laser technologies, are optimal tools for creating precise constructs precisely from the combination of collagen hydrogel and cells. This review describes the different stages of bioprinting, from the extraction of collagen hydrogels and bioink preparation, over the parameters of the printing itself, to the final testing of the constructs. This study mainly focuses on the use of physically crosslinked high-concentrated collagen hydrogels, which represents the optimal way to create a biocompatible 3D construct with sufficient stiffness. The cell viability in these gels is mainly influenced by the composition of the bioink and the parameters of the bioprinting process itself (temperature, pressure, cell density, etc.). In addition, a detailed table is included that lists the bioprinting parameters and composition of custom bioinks from current studies focusing on printing collagen gels without the addition of other polymers. Last but not least, our work also tries to refute the often-mentioned fact that highly concentrated collagen hydrogel is not suitable for 3D bioprinting and cell growth and development.
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Lee, Juo, Sangbae Park, Sungmin Lee, Hae Yong Kweon, You-Young Jo, Jungsil Kim, Jong Hoon Chung, and Hoon Seonwoo. "Development of Silk Fibroin-Based Non-Crosslinking Thermosensitive Bioinks for 3D Bioprinting." Polymers 15, no. 17 (August 28, 2023): 3567. http://dx.doi.org/10.3390/polym15173567.
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Three-dimensional (3D) bioprinting holds great promise for tissue engineering, allowing cells to thrive in a 3D environment. However, the applicability of natural polymers such as silk fibroin (SF) in 3D bioprinting faces hurdles due to limited mechanical strength and printability. SF, derived from the silkworm Bombyx mori, is emerging as a potential bioink due to its inherent physical gelling properties. However, research on inducing thermosensitive behavior in SF-based bioinks and tailoring their mechanical properties to specific tissue requirements is notably lacking. This study addresses these gaps through the development of silk fibroin-based thermosensitive bioinks (SF-TPBs). Precise modulation of gelation time and mechanical robustness is achieved by manipulating glycerol content without recourse to cross-linkers. Chemical analysis confirms β-sheet conformation in SF-TPBs independent of glycerol concentration. Increased glycerol content improves gelation kinetics and results in rheological properties suitable for 3D printing. Overall, SF-TPBs offer promising prospects for realizing the potential of 3D bioprinting using natural polymers.
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Douglas, Alisa, Yufei Chen, Margarita Elloso, Adam Levschuk, and Marc G. Jeschke. "Bioprinting-By-Design of Hydrogel-Based Biomaterials for In Situ Skin Tissue Engineering." Gels 11, no. 2 (February 3, 2025): 110. https://doi.org/10.3390/gels11020110.
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Burns are one of the most common trauma injuries worldwide and have detrimental effects on the entire body. However, the current standard of care is autologous split thickness skin grafts (STSGs), which induces additional injuries to the patient. Therefore, the development of alternative treatments to replace traditional STSGs is critical, and bioprinting could be the future of burn care. Specifically, in situ bioprinting offers several advantages in clinical applications compared to conventional in vitro bioprinting, primarily due to its ability to deposit bioink directly onto the wound. This review provides an in-depth discussion of the aspects involved in in situ bioprinting for skin regeneration, including crosslinking mechanisms, properties of natural and synthetic hydrogel-based bioinks, various in situ bioprinting methods, and the clinical translation of in situ bioprinting. The current limitations of in situ bioprinting is the ideal combination of bioink and printing mechanism to allow multi-material dispensing or to produce well-orchestrated constructs in a timely manner in clinical settings. However, extensive ongoing research is focused on addressing these challenges, and they do not diminish the significant potential of in situ bioprinting for skin regeneration.
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Xu, Jie, Shuangshuang Zheng, Xueyan Hu, Liying Li, Wenfang Li, Roxanne Parungao, Yiwei Wang, Yi Nie, Tianqing Liu, and Kedong Song. "Advances in the Research of Bioinks Based on Natural Collagen, Polysaccharide and Their Derivatives for Skin 3D Bioprinting." Polymers 12, no. 6 (May 29, 2020): 1237. http://dx.doi.org/10.3390/polym12061237.
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The skin plays an important role in protecting the human body, and wound healing must be set in motion immediately following injury or trauma to restore the normal structure and function of skin. The extracellular matrix component of the skin mainly consists of collagen, glycosaminoglycan (GAG), elastin and hyaluronic acid (HA). Recently, natural collagen, polysaccharide and their derivatives such as collagen, gelatin, alginate, chitosan and pectin have been selected as the matrix materials of bioink to construct a functional artificial skin due to their biocompatible and biodegradable properties by 3D bioprinting, which is a revolutionary technology with the potential to transform both research and medical therapeutics. In this review, we outline the current skin bioprinting technologies and the bioink components for skin bioprinting. We also summarize the bioink products practiced in research recently and current challenges to guide future research to develop in a promising direction. While there are challenges regarding currently available skin bioprinting, addressing these issues will facilitate the rapid advancement of 3D skin bioprinting and its ability to mimic the native anatomy and physiology of skin and surrounding tissues in the future.
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Patrocinio, David, Victor Galván-Chacón, J. Carlos Gómez-Blanco, Sonia P. Miguel, Jorge Loureiro, Maximiano P. Ribeiro, Paula Coutinho, J. Blas Pagador, and Francisco M. Sanchez-Margallo. "Biopolymers for Tissue Engineering: Crosslinking, Printing Techniques, and Applications." Gels 9, no. 11 (November 10, 2023): 890. http://dx.doi.org/10.3390/gels9110890.
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Currently, tissue engineering has been dedicated to the development of 3D structures through bioprinting techniques that aim to obtain personalized, dynamic, and complex hydrogel 3D structures. Among the different materials used for the fabrication of such structures, proteins and polysaccharides are the main biological compounds (biopolymers) selected for the bioink formulation. These biomaterials obtained from natural sources are commonly compatible with tissues and cells (biocompatibility), friendly with biological digestion processes (biodegradability), and provide specific macromolecular structural and mechanical properties (biomimicry). However, the rheological behaviors of these natural-based bioinks constitute the main challenge of the cell-laden printing process (bioprinting). For this reason, bioprinting usually requires chemical modifications and/or inter-macromolecular crosslinking. In this sense, a comprehensive analysis describing these biopolymers (natural proteins and polysaccharides)-based bioinks, their modifications, and their stimuli-responsive nature is performed. This manuscript is organized into three sections: (1) tissue engineering application, (2) crosslinking, and (3) bioprinting techniques, analyzing the current challenges and strengths of biopolymers in bioprinting. In conclusion, all hydrogels try to resemble extracellular matrix properties for bioprinted structures while maintaining good printability and stability during the printing process.
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Abuhamad, Asmaa Y., Syafira Masri, Nur Izzah Md Fadilah, Mohammed Numan Alamassi, Manira Maarof, and Mh Busra Fauzi. "Application of 3D-Printed Bioinks in Chronic Wound Healing: A Scoping Review." Polymers 16, no. 17 (August 29, 2024): 2456. http://dx.doi.org/10.3390/polym16172456.
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Chronic wounds, such as diabetic foot ulcers, pressure ulcers, and venous ulcers, pose significant clinical challenges and burden healthcare systems worldwide. The advent of 3D bioprinting technologies offers innovative solutions for enhancing chronic wound care. This scoping review evaluates the applications, methodologies, and effectiveness of 3D-printed bioinks in chronic wound healing, focusing on bioinks incorporating living cells to facilitate wound closure and tissue regeneration. Relevant studies were identified through comprehensive searches in databases, including PubMed, Scopus, and Web of Science databases, following strict inclusion criteria. These studies employ various 3D bioprinting techniques, predominantly extrusion-based, to create bioinks from natural or synthetic polymers. These bioinks are designed to support cell viability, promote angiogenesis, and provide structural integrity to the wound site. Despite these promising results, further research is necessary to optimize bioink formulations and printing parameters for clinical application. Overall, 3D-printed bioinks offer a transformative approach to chronic wound care, providing tailored and efficient solutions. Continued development and refinement of these technologies hold significant promise for improving chronic wound management and patient outcomes.
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Aghajani, Mohammad, Hamid Reza Garshasbi, Seyed Morteza Naghib, and M. R. Mozafari. "3D Printing of Hydrogel Polysaccharides for Biomedical Applications: A Review." Biomedicines 13, no. 3 (March 17, 2025): 731. https://doi.org/10.3390/biomedicines13030731.
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Additive manufacturing, also known as 3D printing, is becoming more and more popular because of its wide range of materials and flexibility in design. Layer by layer, 3D complex structures can be generated by the revolutionary computer-aided process known as 3D bioprinting. It is particularly crucial for youngsters and elderly patients and is a useful tool for tailored pharmaceutical therapy. A lot of research has been carried out recently on the use of polysaccharides as matrices for tissue engineering and medication delivery. Still, there is a great need to create affordable, sustainable bioink materials with high-quality mechanical, viscoelastic, and thermal properties as well as biocompatibility and biodegradability. The primary biological substances (biopolymers) chosen for the bioink formulation are proteins and polysaccharides, among the several resources utilized for the creation of such structures. These naturally occurring biomaterials give macromolecular structure and mechanical qualities (biomimicry), are generally compatible with tissues and cells (biocompatibility), and are harmonious with biological digesting processes (biodegradability). However, the primary difficulty with the cell-laden printing technique (bioprinting) is the rheological characteristics of these natural-based bioinks. Polysaccharides are widely used because they are abundant and reasonably priced natural polymers. Additionally, they serve as excipients in formulations for pharmaceuticals, nutraceuticals, and cosmetics. The remarkable benefits of biological polysaccharides—biocompatibility, biodegradability, safety, non-immunogenicity, and absence of secondary pollution—make them ideal 3D printing substrates. The purpose of this publication is to examine recent developments and challenges related to the 3D printing of stimuli-responsive polysaccharides for site-specific medication administration and tissue engineering.
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Gill, Amoljit Singh, Parneet Kaur Deol, and Indu Pal Kaur. "An Update on the Use of Alginate in Additive Biofabrication Techniques." Current Pharmaceutical Design 25, no. 11 (August 6, 2019): 1249–64. http://dx.doi.org/10.2174/1381612825666190423155835.
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Background: Solid free forming (SFF) technique also called additive manufacturing process is immensely popular for biofabrication owing to its high accuracy, precision and reproducibility. Method: SFF techniques like stereolithography, selective laser sintering, fused deposition modeling, extrusion printing, and inkjet printing create three dimension (3D) structures by layer by layer processing of the material. To achieve desirable results, selection of the appropriate technique is an important aspect and it is based on the nature of biomaterial or bioink to be processed. Result & Conclusion: Alginate is a commonly employed bioink in biofabrication process, attributable to its nontoxic, biodegradable and biocompatible nature; low cost; and tendency to form hydrogel under mild conditions. Furthermore, control on its rheological properties like viscosity and shear thinning, makes this natural anionic polymer an appropriate candidate for many of the SFF techniques. It is endeavoured in the present review to highlight the status of alginate as bioink in various SFF techniques.
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Nashchekina, Yuliya, Anastasia Militsina, Vladimir Elokhovskiy, Elena Ivan’kova, Alexey Nashchekin, Almaz Kamalov, and Vladimir Yudin. "Precisely Printable Silk Fibroin/Carboxymethyl Cellulose/Alginate Bioink for 3D Printing." Polymers 16, no. 8 (April 9, 2024): 1027. http://dx.doi.org/10.3390/polym16081027.
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Three-dimensional (3D) bioprinting opens up many possibilities for tissue engineering, thanks to its ability to create a three-dimensional environment for cells like an extracellular matrix. However, the use of natural polymers such as silk fibroin in 3D bioprinting faces obstacles such as having a limited printability due to the low viscosity of such solutions. This study addresses these gaps by developing highly viscous, stable, and biocompatible silk fibroin-based inks. The addition of 2% carboxymethyl cellulose sodium and 1% sodium alginate to an aqueous solution containing 2.5 to 5% silk fibroin significantly improves the printability, stability, and mechanical properties of the printed scaffolds. It has been demonstrated that the more silk fibroin there is in bioinks, the higher their printability. To stabilize silk fibroin scaffolds in an aqueous environment, the printed structures must be treated with methanol or ethanol, ensuring the transition from the silk fibroin’s amorphous phase to beta sheets. The developed bioinks that are based on silk fibroin, alginate, and carboxymethyl cellulose demonstrate an ease of printing and a high printing quality, and have a sufficiently good biocompatibility with respect to mesenchymal stromal cells. The printed scaffolds have satisfactory mechanical characteristics. The resulting 3D-printing bioink composition can be used to create tissue-like structures.
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Kostenko, Anastassia, Che J. Connon, and Stephen Swioklo. "Storable Cell-Laden Alginate Based Bioinks for 3D Biofabrication." Bioengineering 10, no. 1 (December 23, 2022): 23. http://dx.doi.org/10.3390/bioengineering10010023.
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Over the last decade, progress in three dimensional (3D) bioprinting has advanced considerably. The ability to fabricate complex 3D structures containing live cells for drug discovery and tissue engineering has huge potential. To realise successful clinical translation, biologistics need to be considered. Refinements in the storage and transportation process from sites of manufacture to the clinic will enhance the success of future clinical translation. One of the most important components for successful 3D printing is the ‘bioink’, the cell-laden biomaterial used to create the printed structure. Hydrogels are favoured bioinks used in extrusion-based bioprinting. Alginate, a natural biopolymer, has been widely used due to its biocompatibility, tunable properties, rapid gelation, low cost, and easy modification to direct cell behaviour. Alginate has previously demonstrated the ability to preserve cell viability and function during controlled room temperature (CRT) storage and shipment. The novelty of this research lies in the development of a simple and cost-effective hermetic system whereby alginate-encapsulated cells can be stored at CRT before being reformulated into an extrudable bioink for on-demand 3D bioprinting of cell-laden constructs. To our knowledge the use of the same biomaterial (alginate) for storage and on-demand 3D bio-printing of cells has not been previously investigated. A straightforward four-step process was used where crosslinked alginate containing human adipose-derived stem cells was stored at CRT before degelation and subsequent mixing with a second alginate. The printability of the resulting bioink, using an extrusion-based bioprinter, was found to be dependent upon the concentration of the second alginate, with 4 and 5% (w/v) being optimal. Following storage at 15 °C for one week, alginate-encapsulated human adipose-derived stem cells exhibited a high viable cell recovery of 88 ± 18%. Stored cells subsequently printed within 3D lattice constructs, exhibited excellent post-print viability and even distribution. This represents a simple, adaptable method by which room temperature storage and biofabrication can be integrated for on-demand bioprinting.
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Kreimendahl, Franziska, Caroline Kniebs, Ana Margarida Tavares Sobreiro, Thomas Schmitz-Rode, Stefan Jockenhoevel, and Anja Lena Thiebes. "FRESH bioprinting technology for tissue engineering – the influence of printing process and bioink composition on cell behavior and vascularization." Journal of Applied Biomaterials & Functional Materials 19 (January 2021): 228080002110288. http://dx.doi.org/10.1177/22808000211028808.
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The rapid and tailored biofabrication of natural materials is of high interest for the field of tissue engineering and regenerative medicine. Scaffolds require both high biocompatibility and tissue-dependent mechanical strength to function as basis for tissue-engineered implants. Thus, natural hydrogels such as fibrin are promising but their rapid biofabrication remains challenging. Printing of low viscosity and slow polymerizing solutions with good spatial resolution can be achieved by freeform reversible embedding of suspended hydrogels (FRESH) bioprinting of cell-laden natural hydrogels. In this study, fibrin and hyaluronic acid were used as single components as well as blended ink mixtures for the FRESH bioprinting. Rheometry revealed that single materials were less viscous than the blended bioink showing higher values for viscosity over a shear rate of 10–1000 s−1. While fibrin showed viscosities between 0.1624 and 0.0017 Pa·s, the blended ink containing fibrin and hyaluronic acid were found to be in a range of 0.1–1 Pa·s. In 3D vascularization assays, formation of vascular structures within the printed constructs was investigated indicating that the printing process did not harm cells and allowed formation of vasculature comparable to moulded control samples. Best values for vascularization were achieved in bioinks consisting of 1.0% fibrin-0.5% hyaluronic acid. The vascular structure area and length were three times higher compared to other tested bioinks, and structure volume as well as number of branches revealed almost four times higher values. In this study, we combined the benefits of the FRESH printing technique with in vitro vascularization, showing that it is possible to achieve a mechanically stable small-scale hydrogel construct incorporating vascular network formation.
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Teixeira, Maria C., Nicole S. Lameirinhas, João P. F. Carvalho, Armando J. D. Silvestre, Carla Vilela, and Carmen S. R. Freire. "A Guide to Polysaccharide-Based Hydrogel Bioinks for 3D Bioprinting Applications." International Journal of Molecular Sciences 23, no. 12 (June 12, 2022): 6564. http://dx.doi.org/10.3390/ijms23126564.
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Three-dimensional (3D) bioprinting is an innovative technology in the biomedical field, allowing the fabrication of living constructs through an approach of layer-by-layer deposition of cell-laden inks, the so-called bioinks. An ideal bioink should possess proper mechanical, rheological, chemical, and biological characteristics to ensure high cell viability and the production of tissue constructs with dimensional stability and shape fidelity. Among the several types of bioinks, hydrogels are extremely appealing as they have many similarities with the extracellular matrix, providing a highly hydrated environment for cell proliferation and tunability in terms of mechanical and rheological properties. Hydrogels derived from natural polymers, and polysaccharides, in particular, are an excellent platform to mimic the extracellular matrix, given their low cytotoxicity, high hydrophilicity, and diversity of structures. In fact, polysaccharide-based hydrogels are trendy materials for 3D bioprinting since they are abundant and combine adequate physicochemical and biomimetic features for the development of novel bioinks. Thus, this review portrays the most relevant advances in polysaccharide-based hydrogel bioinks for 3D bioprinting, focusing on the last five years, with emphasis on their properties, advantages, and limitations, considering polysaccharide families classified according to their source, namely from seaweed, higher plants, microbial, and animal (particularly crustaceans) origin.
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Madhusudhan, Alle, Tejaskumar A. Suhagia, Chhavi Sharma, Saravana Kumar Jaganathan, and Shiv Dutt Purohit. "Carbon Based Polymeric Nanocomposite Hydrogel Bioink: A Review." Polymers 16, no. 23 (November 27, 2024): 3318. http://dx.doi.org/10.3390/polym16233318.
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Carbon-based polymeric nanocomposite hydrogels (NCHs) represent a groundbreaking advancement in biomedical materials by integrating nanoparticles such as graphene, carbon nanotubes (CNTs), carbon dots (CDs), and activated charcoal (AC) into polymeric matrices. These nanocomposites significantly enhance the mechanical strength, electrical conductivity, and bioactivity of hydrogels, making them highly effective for drug delivery, tissue engineering (TE), bioinks for 3D Bioprinting, and wound healing applications. Graphene improves the mechanical and electrical properties of hydrogels, facilitating advanced tissue scaffolding and drug delivery systems. CNTs, with their exceptional mechanical strength and conductivity, enhance rheological properties, facilitating their use as bioinks in supporting complex 3D bioprinting tasks for neural, bone, and cardiac tissues by mimicking the natural structure of tissues. CDs offer fluorescence capabilities for theranostic applications, integrating imaging and therapeutic functions. AC enhances mechanical strength, biocompatibility, and antibacterial effectiveness, making it suitable for wound healing and electroactive scaffolds. Despite these promising features, challenges remain, such as optimizing nanoparticle concentrations, ensuring biocompatibility, achieving uniform dispersion, scaling up production, and integrating multiple functionalities. Addressing these challenges through continued research and development is crucial for advancing the clinical and industrial applications of these innovative hydrogels.
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Pisani, Silvia, Rossella Dorati, Franca Scocozza, Camilla Mariotti, Enrica Chiesa, Giovanna Bruni, Ida Genta, Ferdinando Auricchio, Michele Conti, and Bice Conti. "Preliminary investigation on a new natural based poly(gamma‐glutamic acid)/Chitosan bioink." Journal of Biomedical Materials Research Part B: Applied Biomaterials 108, no. 7 (March 11, 2020): 2718–32. http://dx.doi.org/10.1002/jbm.b.34602.
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Cohen, Roni, Ester-Sapir Baruch, Itai Cabilly, Assaf Shapira, and Tal Dvir. "Modified ECM-Based Bioink for 3D Printing of Multi-Scale Vascular Networks." Gels 9, no. 10 (October 1, 2023): 792. http://dx.doi.org/10.3390/gels9100792.
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The survival and function of tissues depend on appropriate vascularization. Blood vessels of the tissues supply oxygen, and nutrients and remove waste and byproducts. Incorporating blood vessels into engineered tissues is essential for overcoming diffusion limitations, improving tissue function, and thus facilitating the fabrication of thick tissues. Here, we present a modified ECM bioink, with enhanced mechanical properties and endothelial cell-specific adhesion motifs, to serve as a building material for 3D printing of a multiscale blood vessel network. The bioink is composed of natural ECM and alginate conjugated with a laminin adhesion molecule motif (YIGSR). The hybrid hydrogel was characterized for its mechanical properties, biochemical content, and ability to interact with endothelial cells. The pristine and modified hydrogels were mixed with induced pluripotent stem cells derived endothelial cells (iPSCs-ECs) and used to print large blood vessels with capillary beds in between.
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Jung, Chi Sung, Byeong Kook Kim, Junhee Lee, Byoung-Hyun Min, and Sang-Hyug Park. "Development of Printable Natural Cartilage Matrix Bioink for 3D Printing of Irregular Tissue Shape." Tissue Engineering and Regenerative Medicine 15, no. 2 (December 28, 2017): 155–62. http://dx.doi.org/10.1007/s13770-017-0104-8.
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Filippova, Svetlana Yu, Oleg I. Kit, Anastasia O. Sitkovskaya, Irina V. Mezhevova, Nadezhda V. Gnennaya, Tatiana V. Shamova, Sofia V. Timofeeva, et al. "Photo-curing of GelMA A bioink is more preferable than chemical curing for creating 3D models of breast cancer tumor growth." Journal of Clinical Oncology 40, no. 16_suppl (June 1, 2022): e15067-e15067. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.e15067.
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e15067 Background: Biogels based on natural components of the extracellular matrix are traditionally used to obtain 3D models of breast cancer (BC) tumor growth. However, such biogels are difficult to use in 3D bioprinting due to their poor shape retention and suboptimal curing conditions. Artificial biogels based on gelatin methacrylate and/or alginate have a good printability and can include natural components of the extracellular matrix to improve interaction with breast cancer cells. Nevertheless, for successful reconstruction of the tumor microenvironment, not only the composition but also the microstructure of the resulting models is important. The aim of the study was to investigate the effect of gelatin methacrylate and alginate composed bioink curing method on the microstructure of the resulting 3D construct and the morphology of breast cancer cells enclosed in it. Methods: BT20 breast cancer cells were mixed with GelMA A bioink (Cellink, USA) at a concentration of 106 cells/ml. The construct was printed on a BIO X bioprinter (Cellink, USA) at an ink temperature of 26°C, a printing table temperature of 10°C, a pressure of 8 kPa, a print speed of 10 mm/s, and a needle diameter of 22G. Next, the printed constructs were cured chemically by immersion in a 100 mM CaCl2 solution for 1 min or photo-cured by irradiating with light at a wavelength of 405 nm for 20 seconds from a distance of 5 cm. After washing, the constructs with encapsulated cells were incubated in DMEM medium (Gibco, USA) supplemented with 10% FBS (HyClone, USA) for two weeks, after which they were fixed in 10% formalin and embedded in paraffin blocks. The sections were H&E stained and photographed at a magnification of 400X, then the area and roundness of the pores were determined using the ImageJ software. Results: During photo-curing of the printed construct, the pore area on the section averaged 1.5±1.07 µm2 (M±SD, n = 500), which is significantly less than with chemical curing (4.5±0.9 µm2, n = 500) (α = 0.05, df = 998). At the same time, the pores had an irregular shape (roundness 2.5±0.6, n = 500), which indicates their communication, in contrast to the chemically cured construct, the pores of which were almost perfectly round (roundness 1.2±0.2 M±SD, n = 500). BT20 culture cells encapsulated in bioink had an elongated process shape, as if squeezing through the fine-mesh structure of the light-cured construct, while in the chemically cured construct they had a rounded shape, not going beyond the boundaries of the pores. Conclusions: When creating 3D tumor growth models of breast cancer using bioinks based on gelatin methacrylate and alginate, photocuring is preferable, as it allows creating a spongy microstructure of communicating pores. Such a structure supports cell migration and helps maintain cell morphology close to that observed in vivo.
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Wu, Kevin Y., Rahma Osman, Natalie Kearn, and Ananda Kalevar. "Three-Dimensional Bioprinting for Retinal Tissue Engineering." Biomimetics 9, no. 12 (December 1, 2024): 733. https://doi.org/10.3390/biomimetics9120733.
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Three-dimensional bioprinting (3DP) is transforming the field of regenerative medicine by enabling the precise fabrication of complex tissues, including the retina, a highly specialized and anatomically complex tissue. This review provides an overview of 3DP’s principles, its multi-step process, and various bioprinting techniques, such as extrusion-, droplet-, and laser-based methods. Within the scope of biomimicry and biomimetics, emphasis is placed on how 3DP potentially enables the recreation of the retina’s natural cellular environment, structural complexity, and biomechanical properties. Focusing on retinal tissue engineering, we discuss the unique challenges posed by the retina’s layered structure, vascularization needs, and the complex interplay between its numerous cell types. Emphasis is placed on recent advancements in bioink formulations, designed to emulate retinal characteristics and improve cell viability, printability, and mechanical stability. In-depth analyses of bioinks, scaffold materials, and emerging technologies, such as microfluidics and organ-on-a-chip, highlight the potential of bioprinted models to replicate retinal disease states, facilitating drug development and testing. While challenges remain in achieving clinical translation—particularly in immune compatibility and long-term integration—continued innovations in bioinks and scaffolding are paving the way toward functional retinal constructs. We conclude with insights into future research directions, aiming to refine 3DP for personalized therapies and transformative applications in vision restoration.
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Castro Thomazi, Vinicius, Natasha Maurmann, and Patricia Pranke. "Bioprinting for Skin: Current Approaches, Technological Advancements and the Role of Artificial Intelligence." International Journal of Advances in Medical Biotechnology - IJAMB 6, no. 2 (December 1, 2024): 114–30. https://doi.org/10.52466/ijamb.v6i2.135.
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Bioprinting is a technique adapted from 3D printing to create biological constructs, including high-quality skin substitutes. It matches or exceeds the quality of traditional fabrication methods, offering precision, consistency and speed, critical attributes for large-scale production. A variety of materials are used, most of them natural, such as alginate, chitosan and gelatin, with cells incorporated into the bioink. These cells may belong to the replicated tissue or include stem cells that can differentiate into the desired cell types. Bioprinting enables precise placement of the skin’s layers: hypodermis, dermis and epidermis, allowing for replication of the skin’s complex architecture. Notably, bioprinted skin constructs can closely resemble native tissue, even forming structures like hair follicles and glands as the incorporated cells grow, migrate and differentiate. Artificial intelligence (AI) and machine learning (ML) have recently been applied to enhance efficiency, precision and success. AI tools reduce trial and error by optimizing parameters, bioink composition and quality control. This review explores bioprinting methods, materials and advancements, including in situ bioprinting, the use of robotic devices and the emerging role of artificial intelligence.
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Vieira de Souza, Thaís, Sonia Maria Malmonge, and Arnaldo R. Santos. "Development of a chitosan and hyaluronic acid hydrogel with potential for bioprinting utilization: A preliminary study." Journal of Biomaterials Applications 36, no. 2 (June 9, 2021): 358–71. http://dx.doi.org/10.1177/08853282211024164.
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Bioprinting is a technique that has been applied in the areas of tissue engineering and regenerative medicine (TERM). Natural polymer-based hydrogels are known for their favorable biocompatible properties, as well as attractive biomaterials for cell encapsulation. These hydrogels provide an aqueous three-dimensional environment with biologically relevant chemical and physical signals, mimicking the natural environment of the extracellular matrix (ECM). Chitosan (CHI) and hyaluronic acid (HA) have been widely researched for biomedical applications. Bioinks are “ink” formulations, usually hydrogels, that allow the printing of living cells. This work proposes the development of a low cost and simple chitosan CHI-AH hydrogel with potential to become a bioink. At physiological temperature, the biomaterials form a hydrogel. The material developed was characterized by the analysis of morphology, cytotoxicity, and cell viability. FTIR showed the characteristic vibrational bands of chitosan and HA. No difference in swelling was observed between the different formulations studied, although SEM showed architectural differences between the hydrogels obtained. Extract cytotoxicity testing showed that the hydrogel is not cytotoxic. The direct toxicity test also revealed the absence of toxicity, but the cells had difficulty migrating into the gel, probably because of its density. These data were confirmed by SEM. Further testing are ongoing to better understand the gel’s characteristics to improve the limitations found so far.
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Mohd, Nurulhuda, Masfueh Razali, Mariyam Jameelah Ghazali, and Noor Hayaty Abu Kasim. "Current Advances of Three-Dimensional Bioprinting Application in Dentistry: A Scoping Review." Materials 15, no. 18 (September 15, 2022): 6398. http://dx.doi.org/10.3390/ma15186398.
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Three-dimensional (3D) bioprinting technology has emerged as an ideal approach to address the challenges in regenerative dentistry by fabricating 3D tissue constructs with customized complex architecture. The dilemma with current dental treatments has led to the exploration of this technology in restoring and maintaining the function of teeth. This scoping review aims to explore 3D bioprinting technology together with the type of biomaterials and cells used for dental applications. Based on PRISMA-ScR guidelines, this systematic search was conducted by using the following databases: Ovid, PubMed, EBSCOhost and Web of Science. The inclusion criteria were (i) cell-laden 3D-bioprinted construct; (ii) intervention to regenerate dental tissue using bioink, which incorporates living cells or in combination with biomaterial; and (iii) 3D bioprinting for dental applications. A total of 31 studies were included in this review. The main 3D bioprinting technique was extrusion-based approach. Novel bioinks in use consist of different types of natural and synthetic polymers, decellularized extracellular matrix and spheroids with encapsulated mesenchymal stem cells, and have shown promising results for periodontal ligament, dentin, dental pulp and bone regeneration application. However, 3D bioprinting in dental applications, regrettably, is not yet close to being a clinical reality. Therefore, further research in fabricating ideal bioinks with implantation into larger animal models in the oral environment is very much needed for clinical translation.
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Khalida Fakhruddin, Belal Yahya Hussein Al-Tam, Abdallah Nasser Sayed, Zarin Mesbah, Angelique Maryann Pereira Anthony Jerald Pereira, Al Ameerah Elza Toto Syaputri, and Mohamad Ikhwan Jamaludin. "3D Bioprinting: Introduction and Recent Advancement." Journal of Medical Device Technology 1, no. 1 (October 8, 2022): 25–29. http://dx.doi.org/10.11113/jmeditec.v1n1.13.
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In the additive manufacturing method known as 3D bioprinting, living cells and nutrients are joined with organic and biological components to produce synthetic structures that resemble natural human tissues. To put it another way, bioprinting is a type of 3D printing that can create anything from bone tissue and blood vessels to living tissues for a range of medical purposes, including tissue engineering and drug testing and discovery. During the bioprinting process, a solution of a biomaterial or a mixture of several biomaterials in the hydrogel form, usually encapsulating the desired cell types, which are termed as bioink, is used for creating tissue constructs. This bioink can be cross-linked or stabilised during or immediately after bioprinting to generate the designed construct's final shape, structure, and architecture. This report thus offers a comprehensive review of the 3D bioprinting technology along with associated 3D bioprinting methods including ink-jet printing, extrusion printing, stereolithography, laser-assisted bioprinting and microfluidic techniques. We also focus on the types of materials, cell source, maturing, the implant of various representative tissue and organs, including blood vessels, bone and cartilage as well as recent advancements related to 3D bioprinting technology.
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Pahlevanzadeh, Farnoosh, Hamidreza Mokhtari, Hamid Reza Bakhsheshi-Rad, Rahmatollah Emadi, Mahshid Kharaziha, Ali Valiani, S. Ali Poursamar, Ahmad Fauzi Ismail, Seeram RamaKrishna, and Filippo Berto. "Recent Trends in Three-Dimensional Bioinks Based on Alginate for Biomedical Applications." Materials 13, no. 18 (September 8, 2020): 3980. http://dx.doi.org/10.3390/ma13183980.
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Three-dimensional (3D) bioprinting is an appealing and revolutionary manufacturing approach for the accurate placement of biologics, such as living cells and extracellular matrix (ECM) components, in the form of a 3D hierarchical structure to fabricate synthetic multicellular tissues. Many synthetic and natural polymers are applied as cell printing bioinks. One of them, alginate (Alg), is an inexpensive biomaterial that is among the most examined hydrogel materials intended for vascular, cartilage, and bone tissue printing. It has also been studied pertaining to the liver, kidney, and skin, due to its excellent cell response and flexible gelation preparation through divalent ions including calcium. Nevertheless, Alg hydrogels possess certain negative aspects, including weak mechanical characteristics, poor printability, poor structural stability, and poor cell attachment, which may restrict its usage along with the 3D printing approach to prepare artificial tissue. In this review paper, we prepare the accessible materials to be able to encourage and boost new Alg-based bioink formulations with superior characteristics for upcoming purposes in drug delivery systems. Moreover, the major outcomes are discussed, and the outstanding concerns regarding this area and the scope for upcoming examination are outlined.
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Szychlinska, Marta Anna, Fabio Bucchieri, Alberto Fucarino, Alfredo Ronca, and Ugo D’Amora. "Three-Dimensional Bioprinting for Cartilage Tissue Engineering: Insights into Naturally-Derived Bioinks from Land and Marine Sources." Journal of Functional Biomaterials 13, no. 3 (August 12, 2022): 118. http://dx.doi.org/10.3390/jfb13030118.
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In regenerative medicine and tissue engineering, the possibility to: (I) customize the shape and size of scaffolds, (II) develop highly mimicked tissues with a precise digital control, (III) manufacture complex structures and (IV) reduce the wastes related to the production process, are the main advantages of additive manufacturing technologies such as three-dimensional (3D) bioprinting. Specifically, this technique, which uses suitable hydrogel-based bioinks, enriched with cells and/or growth factors, has received significant consideration, especially in cartilage tissue engineering (CTE). In this field of interest, it may allow mimicking the complex native zonal hyaline cartilage organization by further enhancing its biological cues. However, there are still some limitations that need to be overcome before 3D bioprinting may be globally used for scaffolds’ development and their clinical translation. One of them is represented by the poor availability of appropriate, biocompatible and eco-friendly biomaterials, which should present a series of specific requirements to be used and transformed into a proper bioink for CTE. In this scenario, considering that, nowadays, the environmental decline is of the highest concerns worldwide, exploring naturally-derived hydrogels has attracted outstanding attention throughout the scientific community. For this reason, a comprehensive review of the naturally-derived hydrogels, commonly employed as bioinks in CTE, was carried out. In particular, the current state of art regarding eco-friendly and natural bioinks’ development for CTE was explored. Overall, this paper gives an overview of 3D bioprinting for CTE to guide future research towards the development of more reliable, customized, eco-friendly and innovative strategies for CTE.
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Tuladhar, Slesha, Scott Clark, and Ahasan Habib. "Tuning Shear Thinning Factors of 3D Bio-Printable Hydrogels Using Short Fiber." Materials 16, no. 2 (January 6, 2023): 572. http://dx.doi.org/10.3390/ma16020572.
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Among various available 3D bioprinting techniques, extrusion-based three-dimensional (3D) bioprinting allows the deposition of cell-laden bioink, ensuring predefined scaffold architecture that may offer living tissue regeneration. With a combination of unique characteristics such as biocompatibility, less cell toxicity, and high water content, natural hydrogels are a great candidate for bioink formulation for the extrusion-based 3D bioprinting process. However, due to its low mechanical integrity, hydrogel faces a common challenge in maintaining structural integrity. To tackle this challenge, the rheological properties, specifically the shear thinning behavior (reduction of viscosity with increasing the applied load/shear rate on hydrogels) of a set of hybrid hydrogels composed of cellulose-derived nanofiber (TEMPO-mediated nano-fibrillated cellulose, TO-NFC), carboxymethyl cellulose (CMC), and commonly used alginate, were explored. A total of 46 compositions were prepared using higher (0.5% and 1.0%) and lower percentages (0.005% and 0.01%) of TO-NFC, 1–4% of CMC, and 1–4% of alginate to analyze the shear thinning factors such as the values of n and K, which were determined for each composition from the flow diagram and co-related with the 3D printability. The ability to tune shear thinning factors with various ratios of a nanofiber can help achieve a 3D bio-printed scaffold with defined scaffold architecture.
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Kanokova, Denisa, Roman Matejka, Margit Zaloudkova, Jan Zigmond, Monika Supova, and Jana Matejkova. "Active Media Perfusion in Bioprinted Highly Concentrated Collagen Bioink Enhances the Viability of Cell Culture and Substrate Remodeling." Gels 10, no. 5 (May 5, 2024): 316. http://dx.doi.org/10.3390/gels10050316.
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The bioprinting of high-concentrated collagen bioinks is a promising technology for tissue engineering and regenerative medicine. Collagen is a widely used biomaterial for bioprinting because of its natural abundance in the extracellular matrix of many tissues and its biocompatibility. High-concentrated collagen hydrogels have shown great potential in tissue engineering due to their favorable mechanical and structural properties. However, achieving high cell proliferation rates within these hydrogels remains a challenge. In static cultivation, the volume of the culture medium is changed once every few days. Thus, perfect perfusion is not achieved due to the relative increase in metabolic concentration and no medium flow. Therefore, in our work, we developed a culture system in which printed collagen bioinks (collagen concentration in hydrogels of 20 and 30 mg/mL with a final concentration of 10 and 15 mg/mL in bioink) where samples flow freely in the culture medium, thus enhancing the elimination of nutrients and metabolites of cells. Cell viability, morphology, and metabolic activity (MTT tests) were analyzed on collagen hydrogels with a collagen concentration of 20 and 30 mg/mL in static culture groups without medium exchange and with active medium perfusion; the influence of pure growth culture medium and smooth muscle cells differentiation medium was next investigated. Collagen isolated from porcine skins was used; every batch was titrated to optimize the pH of the resulting collagen to minimize the difference in production batches and, therefore, the results. Active medium perfusion significantly improved cell viability and activity in the high-concentrated gel, which, to date, is the most limiting factor for using these hydrogels. In addition, based on SEM images and geometry analysis, the cells remodel collagen material to their extracellular matrix.
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Ibrahim, Eman Assem, Moamen Mohsen Sarhan, Salah Ezzelarab, and Mona K. Marei. "A scoping review on the potential of three-dimensional bioprinting in auricular cartilage regeneration." SRM Journal of Research in Dental Sciences 15, no. 3 (July 2024): 111–20. http://dx.doi.org/10.4103/srmjrds.srmjrds_43_24.
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ABSTRACT Background: The human ear significantly influences facial appearance. Auricular abnormalities can arise from many causes, and the cartilage cannot self-regenerate. Three-dimensional (3D) printing and computer-aided design/computer-aided manufacturing technology are used to create auricular prostheses through various methods to mirror the healthy ear. Despite advancements, challenges such as natural skin tones and growth accommodation persist. Bioprinting, using “Bioink” for precise cell placement, offers promising improvements for cartilage replacement and personalized auricular tissue regeneration. Aim: This review discussed recent and groundbreaking research in regenerative medicine for the auricular cartilage. The clinical studies of 3D bioprinting are the main topic of this review. This review aimed to clarify the transition from 3D printing of auricular prostheses to 3D bioprinting of patient-specific auricular tissues. Methods: The literature underwent a scoping review, making use of the keywords “Bioink, maxillofacial prosthetics, patient need, maxillofacial, additive manufacturing, auricular prosthesis, 3D bioprinting AND auricle, 3D bioprinting, auricle, cartilage, and Clinical applications of 3D bioprinting of auricle in children’s patients. Researchers searched the Cochrane, Google Scholar, ScienceDirect, and PubMed databases. Studies using cell-laden, 3D bioprinted constructs, Bioink containing living cells, or interventions to regenerate cartilage or auricle tissue, as well as the use of tissue-engineered 3D bioprinting in the maxillofacial regions, primarily in children, were included. Full texts, abstracts, and titles were all previewed. Significant groundbreaking studies were included after reference searching. The search timeline was between 2018 and 2022. Results: A total of 242 papers were assessed for title and abstract, with 13 judged appropriate for inclusion. Ninety-nine articles were removed, primarily because they were off-topic (unrelated) or not in English. A total of 13 publications were considered for study. Conclusions: Recent research has shown the potential of 3D bioprinting for tissue regeneration in both in vitro and in animal models. Human studies that have implanted 3D bioprinted auricles are still in their initial stages; however, the results are promising.
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Naranda, Jakob, Matej Bračič, Matjaž Vogrin, and Uroš Maver. "Recent Advancements in 3D Printing of Polysaccharide Hydrogels in Cartilage Tissue Engineering." Materials 14, no. 14 (July 16, 2021): 3977. http://dx.doi.org/10.3390/ma14143977.
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The application of hydrogels coupled with 3-dimensional (3D) printing technologies represents a modern concept in scaffold development in cartilage tissue engineering (CTE). Hydrogels based on natural biomaterials are extensively used for this purpose. This is mainly due to their excellent biocompatibility, inherent bioactivity, and special microstructure that supports tissue regeneration. The use of natural biomaterials, especially polysaccharides and proteins, represents an attractive strategy towards scaffold formation as they mimic the structure of extracellular matrix (ECM) and guide cell growth, proliferation, and phenotype preservation. Polysaccharide-based hydrogels, such as alginate, agarose, chitosan, cellulose, hyaluronan, and dextran, are distinctive scaffold materials with advantageous properties, low cytotoxicity, and tunable functionality. These superior properties can be further complemented with various proteins (e.g., collagen, gelatin, fibroin), forming novel base formulations termed “proteo-saccharides” to improve the scaffold’s physiological signaling and mechanical strength. This review highlights the significance of 3D bioprinted scaffolds of natural-based hydrogels used in CTE. Further, the printability and bioink formation of the proteo-saccharides-based hydrogels have also been discussed, including the possible clinical translation of such materials.
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Doyle, S., D. Winrow, T. Aregbesola, J. Martin, E. Pernevik, V. Kuzmenko, L. Howard, K. Thompson, M. Johnson, and C. Coleman. "FABRICATION OF A HIGH-THROUGHPUT 3D-PRINTED OSTEOGENIC CORAL-CONTAINING SCAFFOLD." Orthopaedic Proceedings 106-B, SUPP_1 (January 2, 2024): 129. http://dx.doi.org/10.1302/1358-992x.2024.1.129.
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In 2021 the bone grafting market was worth €2.72 billion globally. As allograft bone has a limited supply and risk of disease transmission, the demand for synthetic grafting substitutes (BGS) continues to grow while allograft bone grafts steadily decrease. Synthetic BGS are low in mechanical strength and bioactivity, inspiring the development of novel grafting materials, a traditionally laborious and expensive process. Here a novel BGS derived from sustainably grown coral was evaluated. Coral-derived scaffolds are a natural calcium carbonate bio-ceramic, which induces osteogenesis in bone marrow mesenchymal stem cells (MSCs), the cells responsible for maintaining bone homeostasis and orchestrating fracture repair. By 3D printing MSCs in coral-laden bioinks we utilise high throughput (HT) fabrication and evaluation of osteogenesis, overcoming the limitations of traditional screening methods.MSC and coral-laden GelXA (CELLINK) bioinks were 3D printed in square bottom 96 well plates using a CELLINK BIO X printer with pneumatic adapter Samples were non-destructively monitored during the culture period, evaluating both the sample and the culture media for metabolism (PrestoBlue), cytotoxicity (lactose dehydrogenase (LDH)) and osteogenic differentiation (alkaline phosphatase (ALP)). Endpoint, destructive assays used included qRT-PCR and SEM imaging.The inclusion of coral in the printed bioink was biocompatable with the MSCs, as reflected by maintained metabolism and low LDH release. The inclusion of coral induced osteogenic differentiation in the MSCs as seen by ALP secretion and increased RUNX2, collagen I and osteocalcin transcription.Sustainably grown coral was successfully incorporated into bioinks, reproducibly 3D printed, non-destructively monitored throughout culture and induced osteogenic differentiation in MSCs. This HT fabrication and monitoring workflow offers a faster, less labour-intensive system for the translation of bone substitute materials to clinic.Acknowledgements: This work was co-funded by Enterprise Ireland and Zoan Biomed through Innovation Partnership IP20221024.
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Majhi, P. S., and K. Pramanik. "Development of three‐dimensional printed microfibrous structures using sodium alginate/silk fibroin bioink for tissue engineering application." Materialwissenschaft und Werkstofftechnik 54, no. 12 (December 2023): 1542–53. http://dx.doi.org/10.1002/mawe.202200215.
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AbstractTissue engineering is a method that involves incorporating cells using scaffold elements and growth factors to support the development or replacement of worn tissue and organs. Scaffolds, with proper form and dimension, along with natural physical and chemical features, are continually in need of improving performance and repairing damaged tissue. In this work, microfibrous three‐dimensional scaffolds composed of sodium alginate and silk fibroin natural polymers are reported. Sodium alginate/silk fibroin scaffolds were fabricated by three‐dimensional printing technique using aqueous sodium alginate/silk fibroin blends with weight ratios of 60/40, 70/30, 80/20, and 90/10. Sodium alginate/silk fibroin: (70/30) exhibited regulated swelling and degradation, responses with a tensile strength of 0.75±0.013 MPa. All the scaffolds had shown protein adsorption over 350 μg exhibiting their suitability as substrates for cell adhesion. The fabricated sodium alginate/silk fibroin scaffolds are hydrophilic and biocompatible as apparent from the contact angle, protein adsorption, 3‐[4, 5‐dimethylthiazole‐2‐yl]‐2, 5‐diphenyltetrazolium bromide (MTT) assay, and cell attachment studies. In vitro‐biomineralization study showed higher apatite layer deposition ability of the sodium alginate/silk fibroin: 70/30 scaffold. The result suggests that sodium alginate/silk fibroin: 70/30 scaffold might be used as a potential platform for tissue engineering application.
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Matejkova, Jana, Denisa Kanokova, Monika Supova, and Roman Matejka. "A New Method for the Production of High-Concentration Collagen Bioinks with Semiautonomic Preparation." Gels 10, no. 1 (January 15, 2024): 66. http://dx.doi.org/10.3390/gels10010066.
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It is believed that 3D bioprinting will greatly help the field of tissue engineering and regenerative medicine, as live patient cells are incorporated into the material, which directly creates a 3D structure. Thus, this method has potential in many types of human body tissues. Collagen provides an advantage, as it is the most common extracellular matrix present in all kinds of tissues and is, therefore, very natural for cells and the organism. Hydrogels with highly concentrated collagen make it possible to create 3D structures without additional additives to crosslink the polymer, which could negatively affect cell proliferation and viability. This study established a new method for preparing highly concentrated collagen bioinks, which does not negatively affect cell proliferation and viability. The method is based on two successive neutralizations of the prepared hydrogel using the bicarbonate buffering mechanisms of the 2× enhanced culture medium and pH adjustment by adding NaOH. Collagen hydrogel was used in concentrations of 20 and 30 mg/mL dissolved in acetic acid with a concentration of 0.05 and 0.1 wt.%. The bioink preparation process is automated, including colorimetric pH detection and adjustment. The new method was validated using bioprinting and subsequent cultivation of collagen hydrogels with incorporated stromal cells. After 96 h of cultivation, cell proliferation and viability were not statistically significantly reduced.
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Galocha-León, Cristina, Cristina Antich, Beatriz Clares-Naveros, Ana Voltes-Martínez, Juan Antonio Marchal, and Patricia Gálvez-Martín. "Design and Characterization of Biomimetic Hybrid Construct Based on Hyaluronic Acid and Alginate Bioink for Regeneration of Articular Cartilage." Pharmaceutics 16, no. 11 (November 7, 2024): 1422. http://dx.doi.org/10.3390/pharmaceutics16111422.
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Background/Objectives: Three-dimensional bioprinting technology has enabled great advances in the treatment of articular cartilage (AC) defects by the biofabrication of biomimetic constructs that restore and/or regenerate damaged tissue. In this sense, the selection of suitable cells and biomaterials to bioprint constructs that mimic the architecture, composition, and functionality of the natural extracellular matrix (ECM) of the native tissue is crucial. In the present study, a novel cartilage-like biomimetic hybrid construct (CBC) was developed by 3D bioprinting to facilitate and promote AC regeneration. Methods: The CBC was biofabricated by the co-bioprinting of a bioink based on hyaluronic acid (HA) and alginate (AL) loaded with human mesenchymal stromal cells (hMSCs), with polylactic acid supporting the biomaterial, in order to mimic the microenvironment and structural properties of native AC, respectively. The CBC was biologically in vitro characterized. In addition, its physiochemical characteristics were evaluated in order to determine if the presence of hMSCs modified its properties. Results: Results from biological analysis demonstrated that CBC supported the high viability and proliferation of hMSCs, facilitating chondrogenesis after 5 weeks in vitro. The evaluation of physicochemical properties in the CBCs confirmed that the CBC developed could be suitable for use in cartilage tissue engineering. Conclusions: The results demonstrated that the use of bioprinted CBCs based on hMSC-AL/HA-bioink for AC repair could enhance the regeneration and/or formation of hyaline cartilaginous tissue.
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Nguyen, Thai Phuong Thao, Phuong Hien Le, and Thi-Hiep Nguyen. "A review on injectable hydrogels from xanthan gum for biomedical applications." Ministry of Science and Technology, Vietnam 64, no. 1 (March 15, 2022): 53–62. http://dx.doi.org/10.31276/vjste.64(1).53-62.
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Xanthan gum (XG) is recognised as one of the most popular natural polymers extensively used today due to its biode-gradable and biocompatible properties, and, therefore, XG can be used to produce hydrogels with other polymers to expand its uses. However, at present, there has not been much research on preparing injectable hydrogels from XG. Moreover, up to now, there are only a limited number of review articles related to this topic. This review will provide a well-organised and somewhat extensive presentation of previous studies that have been executed on injectable hydrogels from XG. Also, applications have been using XG to fabricate injectable hydrogels such as cartilage tissue engineering, bone tissue engineering, delivery system, and bioink will be reviewed.
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Zhang, Yi, Dezhi Zhou, Jianwei Chen, Xiuxiu Zhang, Xinda Li, Wenxiang Zhao, and Tao Xu. "Biomaterials Based on Marine Resources for 3D Bioprinting Applications." Marine Drugs 17, no. 10 (September 28, 2019): 555. http://dx.doi.org/10.3390/md17100555.
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Three-dimensional (3D) bioprinting has become a flexible tool in regenerative medicine with potential for various applications. Further development of the new 3D bioprinting field lies in suitable bioink materials with satisfied printability, mechanical integrity, and biocompatibility. Natural polymers from marine resources have been attracting increasing attention in recent years, as they are biologically active and abundant when comparing to polymers from other resources. This review focuses on research and applications of marine biomaterials for 3D bioprinting. Special attention is paid to the mechanisms, material requirements, and applications of commonly used 3D bioprinting technologies based on marine-derived resources. Commonly used marine materials for 3D bioprinting including alginate, carrageenan, chitosan, hyaluronic acid, collagen, and gelatin are also discussed, especially in regards to their advantages and applications.
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Loureiro, Jorge, Sónia P. Miguel, Victor Galván-Chacón, David Patrocinio, José Blas Pagador, Francisco M. Sánchez-Margallo, Maximiano P. Ribeiro, and Paula Coutinho. "Three-Dimensionally Printed Hydrogel Cardiac Patch for Infarct Regeneration Based on Natural Polysaccharides." Polymers 15, no. 13 (June 26, 2023): 2824. http://dx.doi.org/10.3390/polym15132824.
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Myocardial infarction is one of the more common cardiovascular diseases, and remains the leading cause of death, globally. Hydrogels (namely, those using natural polymers) provide a reliable tool for regenerative medicine and have become a promising option for cardiac tissue regeneration due to their hydrophilic character and their structural similarity to the extracellular matrix. Herein, a functional ink based on the natural polysaccharides Gellan gum and Konjac glucomannan has, for the first time, been applied in the production of a 3D printed hydrogel with therapeutic potential, with the goal of being locally implanted in the infarcted area of the heart. Overall, results revealed the excellent printability of the bioink for the development of a stable, porous, biocompatible, and bioactive 3D hydrogel, combining the specific advantages of Gellan gum and Konjac glucomannan with proper mechanical properties, which supports the simplification of the implantation process. In addition, the structure have positive effects on endothelial cells’ proliferation and migration that can promote the repair of injured cardiac tissue. The results presented will pave the way for simple, low-cost, and efficient cardiac tissue regeneration using a 3D printed hydrogel cardiac patch with potential for clinical application for myocardial infarction treatment in the near future.
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Masri, Syafira, Mazlan Zawani, Izzat Zulkiflee, Atiqah Salleh, Nur Izzah Md Fadilah, Manira Maarof, Adzim Poh Yuen Wen, et al. "Cellular Interaction of Human Skin Cells towards Natural Bioink via 3D-Bioprinting Technologies for Chronic Wound: A Comprehensive Review." International Journal of Molecular Sciences 23, no. 1 (January 1, 2022): 476. http://dx.doi.org/10.3390/ijms23010476.
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Skin substitutes can provide a temporary or permanent treatment option for chronic wounds. The selection of skin substitutes depends on several factors, including the type of wound and its severity. Full-thickness skin grafts (SGs) require a well-vascularised bed and sometimes will lead to contraction and scarring formation. Besides, donor sites for full-thickness skin grafts are very limited if the wound area is big, and it has been proven to have the lowest survival rate compared to thick- and thin-split thickness. Tissue engineering technology has introduced new advanced strategies since the last decades to fabricate the composite scaffold via the 3D-bioprinting approach as a tissue replacement strategy. Considering the current global donor shortage for autologous split-thickness skin graft (ASSG), skin 3D-bioprinting has emerged as a potential alternative to replace the ASSG treatment. The three-dimensional (3D)-bioprinting technique yields scaffold fabrication with the combination of biomaterials and cells to form bioinks. Thus, the essential key factor for success in 3D-bioprinting is selecting and developing suitable bioinks to maintain the mechanisms of cellular activity. This crucial stage is vital to mimic the native extracellular matrix (ECM) for the sustainability of cell viability before tissue regeneration. This comprehensive review outlined the application of the 3D-bioprinting technique to develop skin tissue regeneration. The cell viability of human skin cells, dermal fibroblasts (DFs), and keratinocytes (KCs) during in vitro testing has been further discussed prior to in vivo application. It is essential to ensure the printed tissue/organ constantly allows cellular activities, including cell proliferation rate and migration capacity. Therefore, 3D-bioprinting plays a vital role in developing a complex skin tissue structure for tissue replacement approach in future precision medicine.