bims-biprem Biomed News
on Bioprinting for regenerative medicine
Issue of 2024‒06‒30
fourteen papers selected by
Seerat Maqsood, University of Teramo



  1. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2024 Jun 15. 38(6): 763-768
      Objective: To review the research progress on the application of three-dimensional (3D) bioprinting technology in auricle repair and reconstruction.Methods: The recent domestic and international research literature on 3D printing and auricle repair and reconstruction was extensively reviewed, and the concept of 3D bioprinting technology and research progress in auricle repair and reconstruction were summarized.
    Results: The auricle possesses intricate anatomical structure and functionality, necessitating precise tissue reconstruction and morphological replication. Hence, 3D printing technology holds immense potential in auricle reconstruction. In contrast to conventional 3D printing technology, 3D bioprinting technology not only enables the simulation of auricular outer shape but also facilitates the precise distribution of cells within the scaffold during fabrication by incorporating cells into bioink. This approach mimics the composition and structure of natural tissues, thereby favoring the construction of biologically active auricular tissues and enhancing tissue repair outcomes.
    Conclusion: 3D bioprinting technology enables the reconstruction of auricular tissues, avoiding potential complications associated with traditional autologous cartilage grafting. The primary challenge in current research lies in identifying bioinks that meet both the mechanical requirements of complex tissues and biological criteria.
    Keywords:  Three-dimensional bioprinting technology; auricle repair and reconstruction; bioink; tissue engineered scaffold
    DOI:  https://doi.org/10.7507/1002-1892.202403001
  2. Biofabrication. 2024 Jun 28.
      Traditional three-dimensional (3D) bioprinting has always been associated with the challenge of print fidelity of complex geometries due to the gel-like nature of the bioinks. Embedded 3D bioprinting has emerged as a potential solution to print complex geometries using proteins and polysaccharides-based bioinks. This study demonstrated the Freeform Reversible Embedding of Suspended Hydrogels (FRESH) 3D bioprinting method of chitosan bioink to 3D bioprint complex geometries. 4.5% chitosan was dissolved in an alkali solvent to prepare the bioink. Rheological evaluation of the bioink described its shear-thinning nature. The power law equation was fitted to the shear rate-viscosity plot. The flow index value was less than 1, categorizing the material as pseudo-plastic. The chitosan bioink was extruded into another medium, a thermo-responsive 4.5% gelatin hydrogel. This hydrogel provides support to the growing print structures while printing. After this, the 3D bioprinted structure was crosslinked with 60° C water to stabilize the structure. Using this method, we have 3D bioprinted complex biological structures like the human tri-leaflet heart valve, a section of a human right coronary arterial tree, a scale-down outer structure of the human kidney, and a human ear. Additionally, we have shown the mechanical tunability and suturability of the 3D bioprinted structures. This demonstrates the capability of the chitosan bioink and FRESH method for 3D bioprinting of biological models for surgical training and planning.
    Keywords:  3D bioprinting; Chitosan bioink; FRESH; Hydrogel; organ model
    DOI:  https://doi.org/10.1088/1758-5090/ad5d18
  3. Micromachines (Basel). 2024 Jun 15. pii: 791. [Epub ahead of print]15(6):
      3D printing represents an emerging technology in several fields, including engineering, medicine, and chemistry [...].
    DOI:  https://doi.org/10.3390/mi15060791
  4. Gels. 2024 Jun 05. pii: 387. [Epub ahead of print]10(6):
      Bacterial cellulose is a biocompatible biomaterial with a unique macromolecular structure. Unlike plant-derived cellulose, bacterial cellulose is produced by certain bacteria, resulting in a sustainable material consisting of self-assembled nanostructured fibers with high crystallinity. Due to its purity, bacterial cellulose is appealing for biomedical applications and has raised increasing interest, particularly in the context of 3D printing for tissue engineering and regenerative medicine applications. Bacterial cellulose can serve as an excellent bioink in 3D printing, due to its biocompatibility, biodegradability, and ability to mimic the collagen fibrils from the extracellular matrix (ECM) of connective tissues. Its nanofibrillar structure provides a suitable scaffold for cell attachment, proliferation, and differentiation, crucial for tissue regeneration. Moreover, its mechanical strength and flexibility allow for the precise printing of complex tissue structures. Bacterial cellulose itself has no antimicrobial activity, but due to its ideal structure, it serves as matrix for other bioactive molecules, resulting in a hybrid product with antimicrobial properties, particularly advantageous in the management of chronic wounds healing process. Overall, this unique combination of properties makes bacterial cellulose a promising material for manufacturing hydrogels and 3D-printed scaffolds, advancing the field of tissue engineering and regenerative medicine.
    Keywords:  3D printing; bacterial cellulose; hydrogel; ink; tissue engineering; wound healing
    DOI:  https://doi.org/10.3390/gels10060387
  5. Health Sci Rep. 2024 Jun;7(6): e2205
      Background and Aims: The advent of 3D printing has revolutionized plastic surgery and prosthetic devices, providing personalized solutions for patients with traumatic injuries, deformities, and appearance-related conditions. This review offers a comprehensive overview of 3D printing's applications, advantages, limitations, and future prospects in these fields.Methods: A literature search was conducted in PubMed, Google Scholar, and Scopus for studies on 3D printing in plastic surgery.
    Results: 3D printing has significantly contributed to personalized medical interventions, with benefits like enhanced design flexibility, reduced production time, and improved patient outcomes. Using computer-aided design (CAD) software, precise models tailored to a patient's anatomy can be created, ensuring better fit, functionality, and comfort. 3D printing allows for intricate geometries, leading to improved aesthetic outcomes and patient-specific prosthetic limbs and orthoses. The historical development of 3D printing, key milestones, and breakthroughs are highlighted. Recent progress in bioprinting and tissue engineering shows promising applications in regenerative medicine and transplantation. The integration of AI and automation with 3D printing enhances surgical planning and outcomes. Emerging trends in patient-specific treatment planning and precision medicine are potential game-changers. However, challenges like technical considerations, economic implications, and ethical issues exist. Addressing these challenges and advancing research in materials, design processes, and long-term outcomes are crucial for widespread adoption.
    Conclusion: The review underscores the increasing adoption of 3D printing in healthcare and its impact on plastic surgery and prosthetic devices. It emphasizes the importance of evaluating the current state and addressing knowledge gaps through future research to foster further advancements.
    Keywords:  3D printing; customization; plastic surgery; prosthetic devices
    DOI:  https://doi.org/10.1002/hsr2.2205
  6. Adv Healthc Mater. 2024 Jun 25. e2400957
      Cell spheroids (esp. organoids) as three-dimensional (3D) culture platforms are popular models for representing cell-cell and cell-extracellular matrix (ECM) interactions, bridging the gap between 2D cell cultures and natural tissues. 3D cell models with spatially organized multiple cell types are preferred for gaining comprehensive insights into tissue pathophysiology and constructing in vitro tissues and disease models because of the complexities of natural tissues. In recent years, an assembly strategy using cell spheroids (or organoids) as living building blocks has been developed to construct complex 3D tissue models with spatial organization. Here, we provide a comprehensive overview of recent advances in multi-spheroid assembly studies. The different mechanisms of the multi-spheroid assembly techniques, i.e., automated directed assembly, noncontact remote assembly, and programmed self-assembly, are introduced. The processing steps, advantages, and technical limitations of the existing methodologies are summarized. Applications of the multi-spheroid assembly strategies in disease modeling, drug screening, tissue engineering and organogenesis are reviewed. Finally, this review concludes by emphasizing persistent issues and our perspectives, encouraging researchers to adopt multi-spheroid assembly techniques for generating advanced 3D cell models that better resemble real tissues. This article is protected by copyright. All rights reserved.
    Keywords:  assembly strategies; cancer research; cell spheroids; complex 3D models; tissue regeneration
    DOI:  https://doi.org/10.1002/adhm.202400957
  7. Pharmaceuticals (Basel). 2024 Jun 17. pii: 797. [Epub ahead of print]17(6):
      To create a review of the published scientific literature on the benefits and potential perspectives of the use of 3D bio-nitrification in the field of pharmaceutics. This work was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for reporting meta-analyses and systematic reviews. The scientific databases PubMed, Scopus, Google Scholar, and ScienceDirect were used to search and extract data using the following keywords: 3D bioprinting, drug research and development, personalized medicine, pharmaceutical companies, clinical trials, drug testing. The data points to several aspects of the application of bioprinting in pharmaceutics were reviewed. The main applications of bioprinting are in the development of new drug molecules as well as in the preparation of personalized drugs, but the greatest benefits are in terms of drug screening and testing. Growth in the field of 3D printing has facilitated pharmaceutical applications, enabling the development of personalized drug screening and drug delivery systems for individual patients. Bioprinting presents the opportunity to print drugs on demand according to the individual needs of the patient, making the shape, structure, and dosage suitable for each of the patient's physical conditions, i.e., print specific drugs for controlled release rates; print porous tablets to reduce swallowing difficulties; make transdermal microneedle patches to reduce patient pain; and so on. On the other hand, bioprinting can precisely control the distribution of cells and biomaterials to build organoids, or an Organ-on-a-Chip, for the testing of drugs on printed organs mimicking specified disease characteristics instead of animal testing and clinical trials. The development of bioprinting has the potential to offer customized drug screening platforms and drug delivery systems meeting a range of individualized needs, as well as prospects at different stages of drug development and patient therapy. The role of bioprinting in preclinical and clinical testing of drugs is also of significant importance in terms of shortening the time to launch a medicinal product on the market.
    Keywords:  3D bioprinting; clinical trials; drug research and development; drug testing; personalized medicine; pharmaceutical company
    DOI:  https://doi.org/10.3390/ph17060797
  8. Mol Biol Rep. 2024 Jun 24. 51(1): 781
      Mesenchymal Stem Cells, mesodermal origin and multipotent stem cells, have ability to differentiate into vascular endothelial cells. The cells are squamous in morphology, inlining, and protecting blood vessel tissue, as well as maintaining homeostatic conditions. ECs are essential in vascularization and blood vessels formation. The differentiation process, generally carried out in 2D culture systems, were relied on growth factors induction. Therefore, an artificial extracellular matrix with relevant mechanical properties is essential to build 3D culture models. Various 3D fabrication techniques, such as hydrogel-based and fibrous scaffolds, scaffold-free, and co-culture to endothelial cells were reviewed and summarized to gain insights. The obtained MSCs-derived ECs are shown by the expression of endothelial gene markers and tubule-like structure. In order to mimicking relevant vascular tissue, 3D-bioprinting facilitates to form more complex microstructures. In addition, a microfluidic chip with adequate flow rate allows medium perfusion, providing mechanical cues like shear stress to the artificial vascular vessels.
    Keywords:  3D culture systems; Chemical inductions; Endothelial cells; Mesenchymal stem cells; Shear stress
    DOI:  https://doi.org/10.1007/s11033-024-09743-8
  9. Biosensors (Basel). 2024 Jun 08. pii: 301. [Epub ahead of print]14(6):
      Three-dimensional (3D) printing presents a compelling alternative for fabricating microfluidic devices, circumventing certain limitations associated with traditional soft lithography methods. Microfluidics play a crucial role in the biomedical sciences, particularly in the creation of tissue spheroids and pharmaceutical research. Among the various 3D printing techniques, light-driven methods such as stereolithography (SLA), digital light processing (DLP), and photopolymer inkjet printing have gained prominence in microfluidics due to their rapid prototyping capabilities, high-resolution printing, and low processing temperatures. This review offers a comprehensive overview of light-driven 3D printing techniques used in the fabrication of advanced microfluidic devices. It explores biomedical applications for 3D-printed microfluidics and provides insights into their potential impact and functionality within the biomedical field. We further summarize three light-driven 3D printing strategies for producing biomedical microfluidic systems: direct construction of microfluidic devices for cell culture, PDMS-based microfluidic devices for tissue engineering, and a modular SLA-printed microfluidic chip to co-culture and monitor cells.
    Keywords:  3D printing; microfluidics; tissue culture
    DOI:  https://doi.org/10.3390/bios14060301
  10. Cells. 2024 Jun 19. pii: 1065. [Epub ahead of print]13(12):
      Bone tissue injuries within oral and dental contexts often present considerable challenges because traditional treatments may not be able to fully restore lost or damaged bone tissue. Novel approaches involving stem cells and targeted 3D scaffolds have been investigated in the search for workable solutions. The use of scaffolds in stem cell-assisted bone regeneration is a crucial component of tissue engineering techniques designed to overcome the drawbacks of traditional bone grafts. This study provides a detailed review of scaffold applications for bone regeneration with stem cells in dentistry. This review focuses on scaffolds and stem cells while covering a broad range of studies explaining bone regeneration in dentistry through the presentation of studies conducted in this field. The role of different stem cells in regenerative medicine is covered in great detail in the reviewed literature. These studies have addressed a wide range of subjects, including the effects of platelet concentrates during dental surgery or specific combinations, such as human dental pulp stem cells with scaffolds for animal model bone regeneration, to promote bone regeneration in animal models. Noting developments, research works consider methods to improve vascularization and explore the use of 3D-printed scaffolds, secretome applications, mesenchymal stem cells, and biomaterials for oral bone tissue regeneration. This thorough assessment outlines possible developments within these crucial regenerative dentistry cycles and provides insights and suggestions for additional study. Furthermore, alternative creative methods for regenerating bone tissue include biophysical stimuli, mechanical stimulation, magnetic field therapy, laser therapy, nutritional supplements and diet, gene therapy, and biomimetic materials. These innovative approaches offer promising avenues for future research and development in the field of bone tissue regeneration in dentistry.
    Keywords:  bone regeneration; dental applications; scaffold; stem cells; tissue engineering
    DOI:  https://doi.org/10.3390/cells13121065
  11. Mater Today Bio. 2024 Jun;26 101111
      Human induced pluripotent stem cell (hiPSC)-derived mesenchymal stem cells (iMSCs) are ideal candidates for the production of standardised and scalable bioengineered bone grafts. However, stable induction and osteogenic differentiation of iMSCs pose challenges in the industry. We developed a precise differentiation method to produce homogeneous and fully differentiated iMSCs. In this study, we established a standardised system to prepare iMSCs with increased osteogenic potential and improved bioactivity by introducing a CHIR99021 (C91)-treated osteogenic microenvironment (COOME). COOME enhances the osteogenic differentiation and mineralisation of iMSCs via canonical Wnt signalling. Global transcriptome analysis and co-culturing experiments indicated that COOME increased the pro-angiogenesis/neurogenesis activity of iMSCs. The superior osteogenic differentiation and mineralisation abilities of COOME-treated iMSCs were also confirmed in a Bio3D module generated using a polycaprolactone (PCL) and cell-integrated 3D printing (PCI3D) system, which is the closest model to in vivo research. This COOME-treated iMSCs differentiation system offers a new perspective for generating highly osteogenic, bioactive, and anatomically matched grafts for clinical applications.Statement of significance: Although human induced pluripotent stem cell-derived MSCs (iMSCs) are ideal seed cells for synthetic bone implants, the challenges of stable induction and osteogenic differentiation hinder their clinical application. This study established a standardised system for the scalable preparation of iMSCs with improved osteogenic potential by combining our precise iMSC differentiation method with the CHIR99021 (C91)-treated osteocyte osteogenic microenvironment (COOME) through the activation of canonical Wnt signalling. Moreover, COOME upregulated the pro-angiogenic and pro-neurogenic capacities of iMSCs, which are crucial for the integration of implanted bone grafts. The superior osteogenic ability of COOME-treated iMSCs was confirmed in Bio3D modules generated using PCL and cell-integrated 3D printing systems, highlighting their functional potential in vivo. This study contributes to tissue engineering by providing insights into the functional differentiation of iMSCs for bone regeneration.
    Keywords:  3D bioprinting; Human induced pluripotent stem cell; Mesenchymal stem cell; Osteogenic microenvironment; Wnt signalling
    DOI:  https://doi.org/10.1016/j.mtbio.2024.101111
  12. ACS Nano. 2024 Jun 28.
      Three-dimensional (3D) bioprinting has advantages for constructing artificial skin tissues in replicating the structures and functions of native skin. Although many studies have presented improved effect of printing skin substitutes in wound healing, using hydrogel inks to fabricate 3D bioprinting architectures with complicated structures, mimicking mechanical properties, and appropriate cellular environments is still challenging. Inspired by collagen nanofibers withstanding stress and regulating cell behavior, a patterned nanofibrous film was introduced to the printed hydrogel scaffold to fabricate a composite artificial skin substitute (CASS). The artificial dermis was printed using gelatin-hyaluronan hybrid hydrogels containing human dermal fibroblasts with gradient porosity and integrated with patterned nanofibrous films simultaneously, while the artificial epidermis was formed by seeding human keratinocytes upon the dermis. The collagen-mimicking nanofibrous film effectively improved the tensile strength and fracture resistance of the CASS, making it sewable for firm implantation into skin defects. Meanwhile, the patterned nanofibrous film also provided the biological cues to guide cell behavior. Consequently, CASS could effectively accelerate the regeneration of large-area skin defects in mouse and pig models by promoting re-epithelialization and collagen deposition. This research developed an effective strategy to prepare composite bioprinting architectures for enhancing mechanical property and regulating cell behavior, and CASS could be a promising skin substitute for treating large-area skin defects.
    Keywords:  3D bioprinting; artificial skin substitute; improving mechanical property; patterned nanofibrous film; regulating cell behavior
    DOI:  https://doi.org/10.1021/acsnano.4c04088
  13. Cytotechnology. 2024 Aug;76(4): 363-401
      In the fields of tissue engineering and regenerative medicine, extracellular vesicles (EVs) have become viable therapeutic tools. EVs produced from stem cells promote tissue healing by regulating the immune system, enhancing cell proliferation and aiding remodeling processes. Recently, EV has gained significant attention from researchers due to its ability to treat various diseases. Unlike stem cells, stem cell-derived EVs show lower immunogenicity, are less able to overcome biological barriers, and have a higher safety profile. This makes the use of EVs derived from cell-free stem cells a promising alternative to whole-cell therapy. This review focuses on the biogenesis, isolation, and characterization of EVs and highlights their therapeutic potential for bone fracture healing, wound healing, and neuronal tissue repair and treatment of kidney and intestinal diseases. Additionally, this review discusses the potential of EVs for the treatment of cancer, COVID-19, and HIV. In summary, the use of EVs derived from stem cells offers a new horizon for applications in tissue engineering and regenerative medicine.
    Keywords:  Cell free therapy; Disease management; Exosomes; Extracellular vesicles; Stem cells; Tissue engineering
    DOI:  https://doi.org/10.1007/s10616-024-00631-4
  14. Pharmaceutics. 2024 Jun 11. pii: 790. [Epub ahead of print]16(6):
      Gastroretentive drug delivery systems (GRDDSs) have gained substantial attention in the last 20 years due to their ability to retain the drug in the stomach for an extended time, thus promoting an extended release and high bioavailability for a broad range of active pharmaceutical ingredients (APIs) that are pH-sensitive and/or have a narrow absorption window. The currently existing GRDDSs include floating, expanding, mucoadhesive, magnetic, raft-forming, ion-exchanging, and high-density systems. Although there are seven types of systems, the main focus is on floating, expanding, and mucoadhesive systems produced by various techniques, 3D printing being one of the most revolutionary and currently studied ones. This review assesses the newest production technologies and briefly describes the in vitro and in vivo evaluation methods, with the aim of providing a better overall understanding of GRDDSs as a novel emerging strategy for targeted drug delivery.
    Keywords:  3D printing; bioadhesive systems; drug delivery systems; floating systems; gastroretentive; swelling systems
    DOI:  https://doi.org/10.3390/pharmaceutics16060790