bims-biprem Biomed News
on Bioprinting for regenerative medicine
Issue of 2024–12–29
twelve papers selected by
Seerat Maqsood, University of Teramo



  1. Biomimetics (Basel). 2024 Dec 01. pii: 733. [Epub ahead of print]9(12):
      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.
    Keywords:  3D bioprinting; bioinks; biomimetics; biomimicry; microfluidics; organ-on-a-chip; regenerative medicine; retinal cells; retinal disease models; retinal tissue engineering; tissue scaffolds
    DOI:  https://doi.org/10.3390/biomimetics9120733
  2. J Tissue Eng. 2024 Jan-Dec;15:15 20417314241309183
      Tissue engineering and in vitro modeling of the airways and lungs in the respiratory system are of substantial research and clinical importance. In vitro airway and lung models aim to improve treatment options for airway and lung repair and advance respiratory pathophysiological research. The construction of biomimetic native airways and lungs with tissue-specific biological, mechanical, and configurable features remains challenging. Bioprinting, an emerging 3D printing technology, is promising for the development of airway, lung, and disease models, allowing the incorporation of cells and biologically active molecules into printed constructs in a precise and reproducible manner to recreate the airways, lung architecture, and in vitro microenvironment. Herein, we present a review of airway and lung bioprinting for applications in tissue engineering and in vitro modeling. The key pathophysiological characteristics of the airway, lung interstitium, and alveoli are described. The bioinks recently used in 3D bioprinting of the airways and lungs are summarized. Furthermore, we propose a bioink categorization based on the structural characteristics of the lungs and airways. Finally, the challenges and opportunities in the research on biofabrication of airways and lungs are discussed.
    Keywords:  Bioprinting; bioinks for airways and lungs; lung disease; tissue engineering; trachea
    DOI:  https://doi.org/10.1177/20417314241309183
  3. J Biomater Sci Polym Ed. 2024 Dec 23. 1-21
      Bone tissue engineering is a promising approach to address the increasing need for bone repair. Scaffolds play a crucial role in providing the structural framework for cell growth and differentiation. 3D printing offers precise control over scaffold design and fabrication. Polymers and inorganic compounds such as magnetic nanoparticles (MNPs) are used to create biocompatible and functional scaffolds. MNPs enhance mechanical properties, facilitate drug delivery, and enable the real-time monitoring of bone regeneration. This review highlights the potential of polymer-based 3D-printed magnetic scaffolds in advancing bone regenerative medicine.
    Keywords:  3D-printed scaffold; Magnetic nanoparticles (MNPs); bone tissue engineering; magnetic scaffold
    DOI:  https://doi.org/10.1080/09205063.2024.2444077
  4. J Funct Biomater. 2024 Dec 19. pii: 383. [Epub ahead of print]15(12):
      With the development of 3D bioprinting and the creation of innovative biocompatible materials, several new approaches have brought advantages to patients and surgical teams. Increasingly more bone defects are now treated using 3D-bioprinted prostheses and implementing new solutions relies on the ability of engineers and medical teams to identify methods of anchoring 3D-printed prostheses and to reveal the potential influence of bioactive materials on surrounding tissues. In this paper, we described why limb salvage surgery based on 3D bioprinting is a reliable and effective alternative to amputations, and why this approach is considered the new standard in modern medicine. The preliminary results of 3D bioprinting in one of the most challenging fields in surgery are promising for the future of machine-based medicine, but also for the possibility of replacing various parts from the human body with bioactive-based constructs. In addition, besides the materials and constructs that are already tested and applied in the human body, we also reviewed bioactive materials undergoing in vitro or in vivo testing with great potential for human applications in the near future. Also, we explored the recent advancements in clinically available 3D-bioprinted constructs and their relevance in this field.
    Keywords:  3D bioprinting; biocompatible; electron beam melting; limb salvage surgery; prostheses
    DOI:  https://doi.org/10.3390/jfb15120383
  5. Biomater Sci. 2024 Dec 24.
      In bone tissue engineering, manufacturing bone tissue constructs that closely replicate physiological features for regenerative repair remains a significant challenge. In recent years, the advent of indirect 3D printing technology has overcome the stringent material demands, confined resolution, and structural control challenges inherent to direct 3D printing. By utilizing sacrificial templates, the natural structures and physiological functions of bone tissues can be precisely duplicated. It facilitates the fabrication of vascularized and biomimetic bone constructs that are similar to natural counterparts. Hence, indirect 3D printing technology is increasingly recognized as a promising option for bone regenerative therapies. Based on the aforementioned research hotspots, this review outlines the classification and techniques of indirect 3D printing, along with the associated printing materials and methodologies. More importantly, a detailed summary of the clinical application prospects of indirect 3D printing in the regeneration of bone, cartilage and osteochondral tissues is provided, along with exploring the current challenges and outlook of this technology.
    DOI:  https://doi.org/10.1039/d4bm01374c
  6. J Funct Biomater. 2024 Dec 18. pii: 381. [Epub ahead of print]15(12):
      Surgery is considered the gold standard for treating melanoma, but the high recurrence rate after surgery still remains as a major challenge. Therefore, using doxorubicin (DOX) as a model drug, this study investigated the 3D printing of anticancer drug-loaded hydrogel blend scaffolds for inhibiting post-operation melanoma recurrence and for promoting tissue regeneration. Three-dimensional printing could successfully produce methacrylate-modified chitosan (CSMA) and methylcellulose (MC) hydrogel blend scaffolds. Polymer blend inks exhibited satisfactory printability, and the printed porous scaffolds showed good biocompatibility and mechanical properties. Three-dimensionally printed DOX-loaded hydrogel scaffolds displayed controlled drug release, which may effectively prevent/impede tumor recurrence after surgery. Furthermore, combining 3D printing and bioprinting, DOX-loaded and rat bone marrow mesenchymal stem cell (rBMSC)-laden scaffolds were created for assessing local DOX delivery on healthy tissues. Within the 14-day culture period, rBMSCs encapsulated in multilayered scaffolds that were incorporated with DOX displayed rejuvenated cell viability. The 3D printed and bioprinted dual purpose hydrogel scaffolds have the promise of combating tumor recurrence and providing structural support for tissue regeneration.
    Keywords:  bioprinting; drug delivery; hydrogel blend; scaffold; three-dimensional printing; tissue regeneration
    DOI:  https://doi.org/10.3390/jfb15120381
  7. Adv Sci (Weinh). 2024 Dec 25. e2412554
      Porous thermal insulating ceramics play a pivotal role in both industrial processes and daily life by offering effective insulation solutions that reduce energy consumption, enhance building comfort, and contribute to the sustainability of industrial production. This review offers a comprehensive examination of porous thermal insulating ceramics produced by 3D printing, providing an in-depth analysis of various 3D printing techniques and materials used to produce porous ceramics, detailing the fabrication processes, advantages, and limitations of these methods. Recent advances in 3D printed porous thermal insulating ceramics are thoroughly examined, with a particular focus on pore structure design and optimization strategies for high-performance thermal insulation. This review also addresses the challenges and barriers to widespread adoption while highlighting future research directions and emerging trends poised to drive innovation. By showcasing the transformative potential of 3D printing in revolutionizing traditional porous ceramics manufacturing methods and enhancing thermal insulation performance, this review underscores the critical role of 3D printed porous ceramics in advancing thermal insulation technology.
    Keywords:  3D printing; artificial intelligence; pore structures; porous ceramics; thermal insulation
    DOI:  https://doi.org/10.1002/advs.202412554
  8. Stem Cell Reports. 2024 Dec 10. pii: S2213-6711(24)00323-0. [Epub ahead of print] 102379
      Organoids form through the sel f-organizing capabilities of stem cells to produce a variety of differentiated cell and tissue types. Most organoid models, however, are limited in terms of the structure and function of the tissues that form, in part because it is difficult to regulate the cell type, arrangement, and cell-cell/cell-matrix interactions within these systems. In this article, we will discuss the engineering approaches to generate more complex organoids with improved function and translational relevance, as well as their advantages and disadvantages. Additionally, we will explore how biofabrication strategies can manipulate the cell composition, 3D organization, and scale-up of organoids, thus improving their utility for disease modeling, drug screening, and regenerative medicine applications.
    Keywords:  3D bioprinting; biofabrication; organoids; spheroids; stem cells; vascularization
    DOI:  https://doi.org/10.1016/j.stemcr.2024.11.009
  9. Gels. 2024 Nov 28. pii: 780. [Epub ahead of print]10(12):
      The abundance of hyaluronic acid (HA) in human tissues attracts its thorough research in tissue regenerating scaffolds and 3D bioprintable hydrogel preparation. Though methacrylation of HA can lead to photo-crosslinkable hydrogels, the catalyst has toxicity concerns, and the hydrogel is not suitable for creating stable complex 3D structures using extrusion 3D bioprinting. In this study, a dual crosslinking on methacrylated HA is introduced, using cysteamine-grafted HA and varying concentrations of 2-hydroxy ethyl acrylate. The resultant hydrogel is suitable for extrusion 3D printing (or bioprinting), mechanically robust, self-standing, stable in phosphate-buffered saline at 37 °C for more than 42 days, has high water absorption capacity with a low swelling ratio (1.5), and exhibits self-healing and adhesive properties. Complex 3D structures like ears and pyramid shapes with more than 2 cm of height are 3D printed using the optimized composition. All the synthesized hydrogels have shown nontoxicity and cell-supportiveness. Loading of cells, tetracycline, and bovine serum albumin into the hydrogel led to better bioink properties such as cell attachment, growth, and proliferation for osteoblast cells. The test results suggest that this hydrogel is biocompatible and has potential for 3D bioprinting of self-standing structures in bioink form in tissue engineering and regenerative medicine.
    Keywords:  2-hydroxyethyl acrylate; 3D bioprinting; cysteamine; hyaluronic acid hydrogel; self-healing
    DOI:  https://doi.org/10.3390/gels10120780
  10. Gels. 2024 Dec 14. pii: 829. [Epub ahead of print]10(12):
      This study investigates 3D extrusion bioinks for cartilage tissue engineering by characterizing the physical properties of 3D-printed scaffolds containing varying alginate and polyvinyl alcohol (PVA) concentrations. We systematically investigated the effects of increasing PVA and alginate concentrations on swelling, degradation, and the elastic modulus of printed hydrogels. Swelling decreased significantly with increased PVA concentrations, while degradation rates rose with higher PVA concentrations, underscoring the role of PVA in modulating hydrogel matrix stability. The highest elastic modulus value was achieved with a composite of 5% PVA and 20% alginate, reaching 0.22 MPa, which approaches that of native cartilage. These findings demonstrate that adjusting PVA and alginate concentrations enables the development of bioinks with tailored physical and mechanical properties, supporting their potential use in cartilage tissue engineering and other biomedical applications.
    Keywords:  3D bioprinting; 3D scaffold; PVA; alginate; bioink; cartilage; hydrogel; matrix; polyvinyl alcohol; tissue engineering
    DOI:  https://doi.org/10.3390/gels10120829
  11. PLoS One. 2024 ;19(12): e0316199
      Complex liver cancer is often difficult to expose or dissect, and the surgery is often challenging. 3D-printed models may realistically present 3D anatomical structure, which has certain value in planning and training of liver surgery. However, the existing 3D-printed models are all monolithic models, which are difficult to reuse and limited in clinical application. It is also rare to carry fluorescence to accurately present tumor lesions. Here we report reusable fluorescent assembled 3D-printed models to mimic minimally invasive resection of complex liver cancer. Based on the models, multiple copies of liver lesion structure assembled accessories can be printed for the same patient or different patients, ensuring the quantity and quality of simulated surgical training, and greatly reducing the cost of simulated surgical training. The addition of fluorescence is helpful in accurately presenting tumor lesions. The reusable fluorescent assembled 3D-printed models may mimic minimally invasive resection of complex liver cancer, demonstrating potential value in simulated surgery.
    DOI:  https://doi.org/10.1371/journal.pone.0316199
  12. Gels. 2024 Dec 17. pii: 831. [Epub ahead of print]10(12):
      Three-dimensional (3D) models with improved biomimicry are essential to reduce animal experimentation and drive innovation in tissue engineering. In this study, we investigate the use of alginate-based materials as polymeric inks for 3D bioprinting of osteogenic models using human bone marrow stem/stromal cells (hBMSCs). A composite bioink incorporating alginate, nano-hydroxyapatite (nHA), type I collagen (Col) and hBMSCs was developed and for extrusion-based printing. Rheological tests performed on crosslinked hydrogels confirm the formation of solid-like structures, consistently indicating a superior storage modulus in relation to the loss modulus. The swelling behavior analysis showed that the addition of Col and nHA into an alginate matrix can enhance the swelling rate of the resulting composite hydrogels, which maximizes cell proliferation within the structure. The LIVE/DEAD assay outcomes demonstrate that the inclusion of nHA and Col did not detrimentally affect the viability of hBMSCs over seven days post-printing. PrestoBlueTM revealed a higher hBMSCs viability in the alginate-nHA-Col hydrogel compared to the remaining groups. Gene expression analysis revealed that alginate-nHA-col bioink favored a higher expression of osteogenic markers, including secreted phosphoprotein-1 (SPP1) and collagen type 1 alpha 2 chain (COL1A2) in hBMSCs after 14 days, indicating the pro-osteogenic differentiation potential of the hydrogel. This study demonstrates that the incorporation of nHA and Col into alginate enhances osteogenic potential and therefore provides a bioprinted model to systematically study osteogenesis and the early stages of tissue maturation in vitro.
    Keywords:  alginate; bioink; bioprinting; bone regeneration; collagen; human bone marrow stem/stromal cells; hydroxyapatite
    DOI:  https://doi.org/10.3390/gels10120831