bims-biprem Biomed News
on Bioprinting for regenerative medicine
Issue of 2024–04–28
twelve papers selected by
Seerat Maqsood, University of Teramo
  1. A review of biomacromolecule-based 3D bioprinting strategies for structure-function integrated repair of skin tissues.
  2. Three-Dimensional Printing Strategies for Enhanced Hydrogel Applications.
  3. Applications of 3D Bioprinting Technology to Brain Cells and Brain Tumor Models: Special Emphasis to Glioblastoma.
  4. Advancements and Challenges in Hydrogel Engineering for Regenerative Medicine.
  5. 3D printing technology and its combination with nanotechnology in bone tissue engineering.
  6. 3D Printing of Dental Prostheses: Current and Emerging Applications.
  7. Recent Advances in 3D Cultures.
  8. 3D bioprinted aged human post-infarct myocardium tissue model.
  9. Human mesenchymal stromal cells-laden crosslinked hyaluronic acid-alginate bioink for 3D bioprinting applications in tissue engineering.
  10. Coaxial 3D Bioprinting Process Research and Performance Tests on Vascular Scaffolds.
  11. 3D printing of Rg3-loaded hydrogel scaffolds: anti-inflammatory and scar-formation related collagen inhibitory effects for scar-free wound healing.
  12. Paediatric clinical study of 3D printed personalised medicines for rare metabolic disorders.
  1. Int J Biol Macromol. 2024 Apr 18. pii: S0141-8130(24)02428-0. [Epub ahead of print] 131623
    A review of biomacromolecule-based 3D bioprinting strategies for structure-function integrated repair of skin tissues.
    Hao Liu, Fei Xing, Peiyun Yu, Man Zhe, Xin Duan, Ming Liu, Zhou Xiang, Ulrike Ritz.
      When skin is damaged or affected by diseases, it often undergoes irreversible scar formation, leading to aesthetic concerns and psychological distress for patients. In cases of extensive skin defects, the patient's life can be severely compromised. In recent years, 3D printing technology has emerged as a groundbreaking approach to skin tissue engineering, offering promising solutions to various skin-related conditions. 3D bioprinting technology enables the precise fabrication of structures by programming the spatial arrangement of cells within the skin tissue and subsequently printing skin replacements either in a 3D bioprinter or directly at the site of the defect. This study provides a comprehensive overview of various biopolymer-based inks, with a particular emphasis on chitosan (CS), starch, alginate, agarose, cellulose, and fibronectin, all of which are natural polymers belonging to the category of biomacromolecules. Additionally, it summarizes artificially synthesized polymers capable of enhancing the performance of these biomacromolecule-based bioinks, thereby composing hybrid biopolymer inks aimed at better application in skin tissue engineering endeavors. This review paper examines the recent advancements, characteristics, benefits, and limitations of biological 3D bioprinting techniques for skin tissue engineering. By utilizing bioinks containing seed cells, hydrogels with bioactive factors, and biomaterials, complex structures resembling natural skin can be accurately fabricated in a layer-by-layer manner. The importance of biological scaffolds in promoting skin wound healing and the role of 3D bioprinting in skin tissue regeneration processes is discussed. Additionally, this paper addresses the challenges and constraints associated with current 3D bioprinting technologies for skin tissue and presents future perspectives. These include advancements in bioink formulations, full-thickness skin bioprinting, vascularization strategies, and skin appendages bioprinting.
    Keywords:  3D bioprinting; Bioinks; Bioprinting; Skin; Tissue engineering
    DOI:  https://doi.org/10.1016/j.ijbiomac.2024.131623
  2. Gels. 2024 Mar 25. pii: 220. [Epub ahead of print]10(4):
    Three-Dimensional Printing Strategies for Enhanced Hydrogel Applications.
    Hossein Omidian, Kwadwo Mfoafo.
      This study explores the dynamic field of 3D-printed hydrogels, emphasizing advancements and challenges in customization, fabrication, and functionalization for applications in biomedical engineering, soft robotics, and tissue engineering. It delves into the significance of tailored biomedical scaffolds for tissue regeneration, the enhancement in bioinks for realistic tissue replication, and the development of bioinspired actuators. Additionally, this paper addresses fabrication issues in soft robotics, aiming to mimic biological structures through high-resolution, multimaterial printing. In tissue engineering, it highlights efforts to create environments conducive to cell migration and functional tissue development. This research also extends to drug delivery systems, focusing on controlled release and biocompatibility, and examines the integration of hydrogels with electronic components for bioelectronic applications. The interdisciplinary nature of these efforts highlights a commitment to overcoming material limitations and optimizing fabrication techniques to realize the full potential of 3D-printed hydrogels in improving health and well-being.
    Keywords:  3D-printed hydrogels; biofabrication; drug delivery systems; soft robotics; tissue engineering
    DOI:  https://doi.org/10.3390/gels10040220
  3. ACS Biomater Sci Eng. 2024 Apr 25.
    Applications of 3D Bioprinting Technology to Brain Cells and Brain Tumor Models: Special Emphasis to Glioblastoma.
    Ilkay Irem Ozbek, Hale Saybasili, Kutlu O Ulgen.
      Primary brain tumor is one of the most fatal diseases. The most malignant type among them, glioblastoma (GBM), has low survival rates. Standard treatments reduce the life quality of patients due to serious side effects. Tumor aggressiveness and the unique structure of the brain render the removal of tumors and the development of new therapies challenging. To elucidate the characteristics of brain tumors and examine their response to drugs, realistic systems that mimic the tumor environment and cellular crosstalk are desperately needed. In the past decade, 3D GBM models have been presented as excellent platforms as they allowed the investigation of the phenotypes of GBM and testing innovative therapeutic strategies. In that scope, 3D bioprinting technology offers utilities such as fabricating realistic 3D bioprinted structures in a layer-by-layer manner and precisely controlled deposition of materials and cells, and they can be integrated with other technologies like the microfluidics approach. This Review covers studies that investigated 3D bioprinted brain tumor models, especially GBM using 3D bioprinting techniques and essential parameters that affect the result and quality of the study like frequently used cells, the type and physical characteristics of hydrogel, bioprinting conditions, cross-linking methods, and characterization techniques.
    Keywords:  3D in vitro models; bioinks; drug screening; tumor microenvironment
    DOI:  https://doi.org/10.1021/acsbiomaterials.3c01569
  4. Gels. 2024 Mar 30. pii: 238. [Epub ahead of print]10(4):
    Advancements and Challenges in Hydrogel Engineering for Regenerative Medicine.
    Hossein Omidian, Sumana Dey Chowdhury, Renae L Wilson.
      This manuscript covers the latest advancements and persisting challenges in the domain of tissue engineering, with a focus on the development and engineering of hydrogel scaffolds. It highlights the critical role of these scaffolds in emulating the native tissue environment, thereby providing a supportive matrix for cell growth, tissue integration, and reducing adverse reactions. Despite significant progress, this manuscript emphasizes the ongoing struggle to achieve an optimal balance between biocompatibility, biodegradability, and mechanical stability, crucial for clinical success. It also explores the integration of cutting-edge technologies like 3D bioprinting and biofabrication in constructing complex tissue structures, alongside innovative materials and techniques aimed at enhancing tissue growth and functionality. Through a detailed examination of these efforts, the manuscript sheds light on the potential of hydrogels in advancing regenerative medicine and the necessity for multidisciplinary collaboration to navigate the challenges ahead.
    Keywords:  biofabrication; hydrogel technology; regenerative medicine; stem cell differentiation; tissue engineering
    DOI:  https://doi.org/10.3390/gels10040238
  5. Biomed Eng Lett. 2024 May;14(3): 451-464
    3D printing technology and its combination with nanotechnology in bone tissue engineering.
    Yuezhou Wu, Yucheng Ji, Zhuocheng Lyu.
      With the graying of the world's population, the morbidity of age-related chronic degenerative bone diseases, such as osteoporosis and osteoarthritis, is increasing yearly, leading to an increased risk of bone defects, while current treatment methods face many problems, such as shortage of grafts and an incomplete repair. Therefore, bone tissue engineering offers an alternative solution for regenerating and repairing bone tissues by constructing bioactive scaffolds with porous structures that provide mechanical support to damaged bone tissue while promoting angiogenesis and cell adhesion, proliferation, and activity. 3D printing technology has become the primary scaffold manufacturing method due to its ability to precisely control the internal pore structure and complex spatial shape of bone scaffolds. In contrast, the fast development of nanotechnology has provided more possibilities for the internal structure and biological function of scaffolds. This review focuses on the application of 3D printing technology in bone tissue engineering and nanotechnology in the field of bone tissue regeneration and repair, and explores the prospects for the integration of the two technologies.
    Keywords:  3D printing technology; Bioactive scaffold; Bone tissue engineering; Nanotechnology
    DOI:  https://doi.org/10.1007/s13534-024-00350-x
  6. J Compos Sci. 2023 Feb;pii: 80. [Epub ahead of print]7(2):
    3D Printing of Dental Prostheses: Current and Emerging Applications.
    Fereshte Rezaie, Masoud Farshbaf, Mohammad Dahri, Moein Masjedi, Reza Maleki, Fatemeh Amini, Jonathan Wirth, Keyvan Moharamzadeh, Franz E Weber, Lobat Tayebi.
      Revolutionary fabrication technologies such as three-dimensional (3D) printing to develop dental structures are expected to replace traditional methods due to their ability to establish constructs with the required mechanical properties and detailed structures. Three-dimensional printing, as an additive manufacturing approach, has the potential to rapidly fabricate complex dental prostheses by employing a bottom-up strategy in a layer-by-layer fashion. This new technology allows dentists to extend their degree of freedom in selecting, creating, and performing the required treatments. Three-dimensional printing has been narrowly employed in the fabrication of various kinds of prostheses and implants. There is still an on-demand production procedure that offers a reasonable method with superior efficiency to engineer multifaceted dental constructs. This review article aims to cover the most recent applications of 3D printing techniques in the manufacturing of dental prosthetics. More specifically, after describing various 3D printing techniques and their advantages/disadvantages, the applications of 3D printing in dental prostheses are elaborated in various examples in the literature. Different 3D printing techniques have the capability to use different materials, including thermoplastic polymers, ceramics, and metals with distinctive suitability for dental applications, which are discussed in this article. The relevant limitations and challenges that currently limit the efficacy of 3D printing in this field are also reviewed. This review article has employed five major scientific databases, including Google Scholar, PubMed, ScienceDirect, Web of Science, and Scopus, with appropriate keywords to find the most relevant literature in the subject of dental prostheses 3D printing.
    Keywords:  3D printing; dental crown and bridge; dental implants; dental prostheses
    DOI:  https://doi.org/10.3390/jcs7020080
  7. Int J Mol Sci. 2024 Apr 10. pii: 4189. [Epub ahead of print]25(8):
    Recent Advances in 3D Cultures.
    Vittorio Picchio, Roberto Gaetani, Isotta Chimenti.
      Methods and protocols for creating complex 3D cell culture systems have been rapidly advancing in the past decade from the perspective of biomaterials [...].
    DOI:  https://doi.org/10.3390/ijms25084189
  8. Health Sci Rep. 2024 Apr;7(4): e1945
    3D bioprinted aged human post-infarct myocardium tissue model.
    Gozde Basara, Lara Ece Celebi, George Ronan, Victoria Discua Santos, Pinar Zorlutuna.
       Background and Aims: Fibrotic tissue formed after myocardial infarction (MI) can be as detrimental as MI itself. However, current in vitro cardiac fibrosis models fail to recapitulate the complexities of post-MI tissue. Moreover, although MI and subsequent fibrosis is most prominent in the aged population, the field suffers from inadequate aged tissue models. Herein, an aged human post-MI tissue model, representing the native microenvironment weeks after initial infarction, is engineered using three-dimensional bioprinting via creation of individual bioinks to specifically mimic three distinct regions: remote, border, and scar.
    Methods: The aged post-MI tissue model is engineered through combination of gelatin methacryloyl, methacrylated hyaluronic acid, aged type I collagen, and photoinitiator at variable concentrations with different cell types, including aged human induced pluripotent stem cell-derived cardiomyocytes, endothelial cells, cardiac fibroblasts, and cardiac myofibroblasts, by introducing a methodology which utilizes three printheads of the bioprinter to model aged myocardium. Then, using cell-specific proteins, the cell types that comprised each region are confirmed using immunofluorescence. Next, the beating characteristics are analyzed. Finally, the engineered aged post-MI tissue model is used as a benchtop platform to assess the therapeutic effects of stem cell-derived extracellular vesicles on the scar region.
    Results: As a result, high viability (>74%) was observed in each region of the printed model. Constructs demonstrated functional behavior, exhibiting a beating velocity of 6.7 μm/s and a frequency of 0.3 Hz. Finally, the effectiveness of hiPSC-EV and MSC-EV treatment was assessed. While hiPSC-EV treatment showed no significant changes, MSC-EV treatment notably increased cardiomyocyte beating velocity, frequency, and confluency, suggesting a regenerative potential.
    Conclusion: In conclusion, we envision that our approach of modeling post-MI aged myocardium utilizing three printheads of the bioprinter may be utilized for various applications in aged cardiac microenvironment modeling and testing novel therapeutics.
    Keywords:  3D bioprinting; extracellular vesicles; human induced pluripotent stem cell‐derived cardiac fibroblasts; human induced pluripotent stem cell‐derived cardiomyocyte; myocardial infarction; post‐MI models; therapeutics
    DOI:  https://doi.org/10.1002/hsr2.1945
  9. Drug Deliv Transl Res. 2024 Apr 25.
    Human mesenchymal stromal cells-laden crosslinked hyaluronic acid-alginate bioink for 3D bioprinting applications in tissue engineering.
    Cristina Galocha-León, Cristina Antich, Ana Voltes-Martínez, Juan A Marchal, Mireia Mallandrich, Lyda Halbaut, Eliana B Souto, Patricia Gálvez-Martín, Beatriz Clares-Naveros.
      Three-dimensional (3D) bioprinting is considered one of the most advanced tools to build up materials for tissue engineering. The aim of this work was the design, development and characterization of a bioink composed of human mesenchymal stromal cells (hMSC) for extrusion through nozzles to create these 3D structures that might potentially be apply to replace the function of damaged natural tissue. In this study, we focused on the advantages and the wide potential of biocompatible biomaterials, such as hyaluronic acid and alginate for the inclusion of hMSC. The bioink was characterized for its physical (pH, osmolality, degradation, swelling, porosity, surface electrical properties, conductivity, and surface structure), mechanical (rheology and printability) and biological (viability and proliferation) properties. The developed bioink showed high porosity and high swelling capacity, while the degradation rate was dependent on the temperature. The bioink also showed negative electrical surface and appropriate rheological properties required for bioprinting. Moreover, stress-stability studies did not show any sign of physical instability. The developed bioink provided an excellent environment for the promotion of the viability and growth of hMSC cells. Our work reports the first-time study of the effect of storage temperature on the cell viability of bioinks, besides showing that our bioink promoted a high cell viability after being extruded by the bioprinter. These results support the suggestion that the developed hMSC-composed bioink fulfills all the requirements for tissue engineering and can be proposed as a biological tool with potential applications in regenerative medicine and tissue engineering.
    Keywords:  Bioink; Biomaterials; Human mesenchymal stromal cells; Regenerative medicine; Tissue engineering
    DOI:  https://doi.org/10.1007/s13346-024-01596-9
  10. Micromachines (Basel). 2024 Mar 29. pii: 463. [Epub ahead of print]15(4):
    Coaxial 3D Bioprinting Process Research and Performance Tests on Vascular Scaffolds.
    Jiarun Sun, Youping Gong, Manli Xu, Huipeng Chen, Huifeng Shao, Rougang Zhou.
      Three-dimensionally printed vascularized tissue, which is suitable for treating human cardiovascular diseases, should possess excellent biocompatibility, mechanical performance, and the structure of complex vascular networks. In this paper, we propose a method for fabricating vascularized tissue based on coaxial 3D bioprinting technology combined with the mold method. Sodium alginate (SA) solution was chosen as the bioink material, while the cross-linking agent was a calcium chloride (CaCl2) solution. To obtain the optimal parameters for the fabrication of vascular scaffolds, we first formulated theoretical models of a coaxial jet and a vascular network. Subsequently, we conducted a simulation analysis to obtain preliminary process parameters. Based on the aforementioned research, experiments of vascular scaffold fabrication based on the coaxial jet model and experiments of vascular network fabrication were carried out. Finally, we optimized various parameters, such as the flow rate of internal and external solutions, bioink concentration, and cross-linking agent concentration. The performance tests showed that the fabricated vascular scaffolds had levels of satisfactory degradability, water absorption, and mechanical properties that meet the requirements for practical applications. Cellular experiments with stained samples demonstrated satisfactory proliferation of human umbilical vein endothelial cells (HUVECs) within the vascular scaffold over a seven-day period, observed under a fluorescent inverted microscope. The cells showed good biocompatibility with the vascular scaffold. The above results indicate that the fabricated vascular structure initially meet the requirements of vascular scaffolds.
    Keywords:  3D bioprinting; biological scaffold; coaxial jet; finite element analysis; vascular network
    DOI:  https://doi.org/10.3390/mi15040463
  11. J Mater Chem B. 2024 Apr 22.
    3D printing of Rg3-loaded hydrogel scaffolds: anti-inflammatory and scar-formation related collagen inhibitory effects for scar-free wound healing.
    Xusen Wang, Pengyu Wei, Cewen Hu, Huajing Zeng, Zengjie Fan.
      During the process of wound healing, the stimulation of inflammatory factors often leads to abnormal proliferation of blood vessels and collagen, ultimately resulting in scar formation. To address this challenge, we fabricate a novel dermal extracellular matrix (DECM) hydrogel scaffold loaded with ginsenoside Rg3 (Rg3) using 3D printing technology. Mesoporous silica nanoparticles (MSNs) are introduced into the system to encase the Rg3 to control its release rate and enhance its bioavailability. We systematically evaluate the biological, physicochemical, and wound healing properties of this scaffold. In vitro studies demonstrate that the hydrogel exhibits excellent biocompatibility and solid-like rheological properties, ensuring its successful printing. In vivo studies reveal that the composite hydrogel scaffolds effectively accelerate wound healing and achieve scar-free wound healing within three weeks. Histological and immunohistochemical (IHC) analyses show that the composite hydrogel scaffolds reduce the inflammatory response and inhibit excessive collagen accumulation. These combined effects underscore the potential of our approach in effectively inhibiting scar formation.
    DOI:  https://doi.org/10.1039/d3tb02941g
  12. Int J Pharm. 2024 Apr 19. pii: S0378-5173(24)00374-0. [Epub ahead of print]657 124140
    Paediatric clinical study of 3D printed personalised medicines for rare metabolic disorders.
    Lucía Rodríguez-Pombo, María José de Castro-López, Paula Sánchez-Pintos, Jose Maria Giraldez-Montero, Patricija Januskaite, Goretti Duran-Piñeiro, M Dolores Bóveda, Carmen Alvarez-Lorenzo, Abdul W Basit, Alvaro Goyanes, Maria L Couce.
      Rare diseases are infrequent, but together they affect up to 6-10 % of the world's population, mainly children. Patients require precise doses and strict adherence to avoid metabolic or cardiac failure in some cases, which cannot be addressed in a reliable way using pharmaceutical compounding. 3D printing (3DP) is a disruptive technology that allows the real-time personalization of the dose and the modulation of the dosage form to adapt the medicine to the therapeutic needs of each patient. 3D printed chewable medicines containing amino acids (citrulline, isoleucine, valine, and isoleucine and valine combinations) were prepared in a hospital setting, and the efficacy and acceptability were evaluated in comparison to conventional compounded medicines in six children. The inclusion of new flavours (lemon, vanilla and peach) to obtain more information on patient preferences and the implementation of a mobile app to obtain patient feedback in real-time was also used. The 3D printed medicines controlled amino acid levels within target levels as well as the conventional medicines. The deviation of citrulline levels was narrower and closer within the target concentration with the chewable formulations. According to participants' responses, the chewable formulations were well accepted and can improve adherence and quality of life. For the first time, 3DP enabled two actives to be combined in the same formulation, reducing the number of administrations. This study demonstrated the benefits of preparing 3D printed personalized treatments for children diagnosed with rare metabolic disorders using a novel technology in real clinical practice.
    Keywords:  Additive manufacturing of drug products; Direct ink writing; Patient acceptability of formulations; Pediatrics; Polypills; Precision pharmaceuticals and drug delivery systems; Semi-solid extrusion 3D printing
    DOI:  https://doi.org/10.1016/j.ijpharm.2024.124140
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