bims-biprem Biomed News
on Bioprinting for regenerative medicine
Issue of 2023–12–03
seventeen papers selected by
Seerat Maqsood, University of Teramo



  1. Saudi Dent J. 2023 Nov;35(7): 876-882
      The prime focus of regenerative periodontal therapy is to reconstruct or regenerate the lost periodontium, including both hard and soft tissues. Over the years, periodontics has witnessed different regenerative modalities, such as bone grafts, guided tissue membranes, growth factors, stem cell technology, 3D printing, etc. 3D printing is a newly emerging manufacturing technology that finds applications in diverse fields, including aerospace, defense, art and design, medical and dental field. Originally developed for non-biological applications, 3D printing has undergone modifications to print biocompatible materials and living cells to minimize any potential compromise on cell viability. Thus, the utilisation of 3D printing in the regeneration of lost periodontal tissues represents a novel approach that facilitates optimal cell interactions and promotes the successful regeneration of biological tissues.
    Keywords:  3D Bioprinting; 3D printing; Additive manufacturing; Periodontal regeneration; Stereolithography; Tissue engineering
    DOI:  https://doi.org/10.1016/j.sdentj.2023.07.002
  2. Int J Biol Macromol. 2023 Nov 29. pii: S0141-8130(23)05403-X. [Epub ahead of print] 128504
      The repair and regeneration of the injured tissues or organs is a major challenge for biomedicine, and the emerging 3D bioprinting technology as a class of promising techniques in biomedical research for the development of tissue engineering and regenerative medicine. Chitosan-based bioinks, as the natural biomaterials, are considered as ideal materials for 3D bioprinting to design and fabricate the various scaffold due to their unique dynamic reversibility and fantastic biological properties. Our review aims to provide an overview of chitosan-based bioinks for in vitro tissue repair and regeneration, starting from modification of chitosan that affect these bioprinting processes. In addition, we summarize the advances in chitosan-based bioinks used in the various 3D printing strategies. Moreover, the biomedical applications of chitosan-based bioinks are discussed, primarily centered on regenerative medicine and tissue modeling engineering. Finally, current challenges and future opportunities in this field are discussed. The combination of chitosan-based bioinks and 3D bioprinting will hold promise for developing novel biomedical scaffolds for tissue or organ repair and regeneration.
    Keywords:  3D printing; Bioink; Chitosan; Tissue repair
    DOI:  https://doi.org/10.1016/j.ijbiomac.2023.128504
  3. Indian J Orthop. 2023 Dec;57(12): 1949-1967
       Purpose: 3D bioprinting is capable of rapidly producing small-scale human-based tissue models, or organoids, for pathology modeling, diagnostics, and drug development. With the use of 3D bioprinting technology, 3D functional complex tissue can be created by combining biocompatible materials, cells, and growth factor. In today's world, 3D bioprinting may be the best solution for meeting the demand for organ transplantation. It is essential to examine the existing literature with the objective to identify the future trend in terms of application of 3D bioprinting, different bioprinting techniques, and selected tissues by the researchers, it is very important to examine the existing literature. To find trends in 3D bioprinting research, this work conducted an systematic literature review of 3D bioprinting.
    Methodology: This literature provides a thorough study and analysis of research articles on bioprinting from 2000 to 2022 that were extracted from the Scopus database. The articles selected for analysis were classified according to the year of publication, articles and publishers, nation, authors who are working in bioprinting area, universities, biomaterial used, and targeted applications.
    Findings: The top nations, universities, journals, publishers, and writers in this field were picked out after analyzing research publications on bioprinting. During this study, the research themes and research trends were also identified. Furthermore, it has been observed that there is a need for additional research in this domain for the development of bioink and their properties that can guide practitioners and researchers while selecting appropriate combinations of biomaterials to obtain bioink suitable for mimicking human tissue.
    Significance of the Research: This research includes research findings, recommendations, and observations for bioprinting researchers and practitioners. This article lists significant research gaps, future research directions, and potential application areas for bioprinting.
    Novelty: The review conducted here is mainly focused on the process of collecting, organizing, capturing, evaluating, and analyzing data to give a deeper understanding of bioprinting and to identify potential future research trends.
    Keywords:  3D bioprinting; Bioink; Biomaterials; Meta-analysis; Systematic literature review
    DOI:  https://doi.org/10.1007/s43465-023-01000-7
  4. Curr Pharm Des. 2023 Nov 23.
      A revolutionary shift in healthcare has been sparked by the development of 3D printing, propelling us into an era replete with boundless opportunities for personalized DDS (Drug Delivery Systems). Precise control of the kinetics of drug release can be achieved through 3D printing, improving treatment efficacy and patient compliance. Additionally, 3D printing facilitates the co-administration of multiple drugs, simplifying treatment regimens. The technology offers rapid prototyping and manufacturing capabilities, reducing development timelines and costs. The seamless integration of advanced algorithms and artificial neural networks (ANN) augments the precision and efficacy of 3D printing, propelling us toward the forefront of personalized medicine. This comprehensive review delves into the regulatory frontiers governing 3D printable drug delivery systems, with an emphasis on adhering to rigorous safety protocols to ensure the well-being of patients by leveraging the latest advancements in 3D printing technologies powered by artificial intelligence. The paradigm promises superior therapeutic outcomes and optimized medication experiences and sets the stage for an immersive future within the Metaverse, wherein healthcare seamlessly converges with virtual environments to unlock unparalleled possibilities for personalized treatments.
    Keywords:  3D printing; Metaverse; algorithms; artificial neural networks; drug delivery system; healthcare.; personalized medicine; selective laser sintering
    DOI:  https://doi.org/10.2174/0113816128275872231105183036
  5. Macromol Biosci. 2023 Nov 29. e2300376
      Even with the current advancements in wound management, addressing most skin injuries and wounds continues to pose a significant obstacle for the healthcare industry. As a result, researchers are now focusing on creating innovative materials utilizing cellulose and its derivatives. Cellulose, the most abundant biopolymer in nature, has unique properties that make it a promising material for wound healing, such as biocompatibility, tunable physiochemical characteristics, accessibility, and low cost. 3D bioprinting technology has enabled the production of cellulose-based wound dressings with complex structures that mimic the extracellular matrix. The inclusion of bioactive molecules such as growth factors offers the ability to aid in promoting wound healing, while cellulose creates an ideal environment for controlled release of these biomolecules and moisture retention. The use of 3D bioprinted cellulose-based wound dressings has potential benefits for managing chronic wounds, burns, and painful wounds by promoting wound healing and reducing the risk of infection. This review provides an up-to-date summary of cellulose-based dressings manufactured by 3D bioprinting techniques by looking into wound healing biology, biofabrication methods, cellulose derivatives, and the existing cellulose bioinks targeted towards wound healing. This article is protected by copyright. All rights reserved.
    Keywords:  3D bioprinting; Wound healing; biofabrication; biopolymers; cellulose
    DOI:  https://doi.org/10.1002/mabi.202300376
  6. Small Methods. 2023 Nov 27. e2301121
      3D printing is now recognized as a significant tool for medical research and clinical practice, leading to the emergence of medical 3D printing technology. It is essential to improve the properties of 3D-printed products to meet the demand for medical use. The core of generating qualified 3D printing products is to develop advanced materials and processes. Taking advantage of nanomaterials with tunable and distinct physical, chemical, and biological properties, integrating nanotechnology into 3D printing creates new opportunities for advancing medical 3D printing field. Recently, some attempts are made to improve medical 3D printing through nanotechnology, providing new insights into developing advanced medical 3D printing technology. With high-resolution 3D printing technology, nano-structures can be directly fabricated for medical applications. Incorporating nanomaterials into the 3D printing material system can improve the properties of the 3D-printed medical products. At the same time, nanomaterials can be used to expand novel medical 3D printing technologies. This review introduced the strategies and progresses of improving medical 3D printing through nanotechnology and discussed challenges in clinical translation.
    Keywords:  3D printing; clinical translation; medical 3D printing; medical products; nanomaterials
    DOI:  https://doi.org/10.1002/smtd.202301121
  7. Biomater Biosyst. 2023 Dec;12 100084
      Thanks to its natural complexity and functionality, decellularized extracellular matrix (dECM) serves as an excellent foundation for creating highly cell-compatible bioinks and bioresins. This enables the bioprinted cells to thrive in an environment that closely mimics their native ECM composition and offers customizable biomechanical properties. To formulate dECM bioinks and bioresins, one must first pulverize and/or solubilize the dECM into non-crosslinked fragments, which can then be chemically modified as needed. In bioprinting, the solubilized dECM-derived material is typically deposited and/or crosslinked in a layer-by-layer fashion to build 3D hydrogel structures. Since the introduction of the first liver-derived dECM-based bioinks, a wide variety of decellularized tissue have been employed in bioprinting, including kidney, heart, cartilage, and adipose tissue among others. This review aims to summarize the critical steps involved in tissue-derived dECM bioprinting, starting from the decellularization of the ECM to the standardized formulation of bioinks and bioresins, ultimately leading to the reproducible bioprinting of tissue constructs. Notably, this discussion also covers photocrosslinkable dECM bioresins, which are particularly attractive due to their ability to provide precise spatiotemporal control over the gelation in bioprinting. Both in extrusion printing and vat photopolymerization, there is a need for more standardized protocols to fully harness the unique properties of dECM-derived materials. In addition to mammalian tissues, the most recent bioprinting approaches involve the use of microbial extracellular polymeric substances in bioprinting of bacteria. This presents similar challenges as those encountered in mammalian cell printing and represents a fascinating frontier in bioprinting technology.
    Keywords:  Bioink; Bioresin; Decellularized extracellular matrix; Extracellular polymeric substances; Extrusion bioprinting; Vat photopolymerization
    DOI:  https://doi.org/10.1016/j.bbiosy.2023.100084
  8. Microb Biotechnol. 2023 Dec 02.
      Three dimensional printing has emerged as a widely acceptable strategy for the fabrication of mammalian cell laden constructs with complex microenvironments for tissue engineering and regenerative medicine. More recently 3D printed living materials containing microorganisms have been developed and matured into living biofilms. The potential for engineered 3D biofilms as in vitro models for biomedical applications, such as antimicrobial susceptibility testing, and environmental applications, such as bioleaching, bioremediation, and wastewater purification, is extensive but the need for an in-depth understanding of the structure-function relationship between the complex construct and the microorganism response still exists. This review discusses 3D printing fabrication methods for engineered biofilms with specific structural features. Next, it highlights the importance of bioink compositions and 3D bioarchitecture design. Finally, a brief overview of current and potential applications of 3D printed biofilms in environmental and biomedical fields is discussed.
    DOI:  https://doi.org/10.1111/1751-7915.14360
  9. 3D Print Med. 2023 Nov 27. 9(1): 33
       BACKGROUND: Medical three dimensional (3D) printing is performed for neurosurgical and otolaryngologic conditions, but without evidence-based guidance on clinical appropriateness. A writing group composed of the Radiological Society of North America (RSNA) Special Interest Group on 3D Printing (SIG) provides appropriateness recommendations for neurologic 3D printing conditions.
    METHODS: A structured literature search was conducted to identify all relevant articles using 3D printing technology associated with neurologic and otolaryngologic conditions. Each study was vetted by the authors and strength of evidence was assessed according to published guidelines.
    RESULTS: Evidence-based recommendations for when 3D printing is appropriate are provided for diseases of the calvaria and skull base, brain tumors and cerebrovascular disease. Recommendations are provided in accordance with strength of evidence of publications corresponding to each neurologic condition combined with expert opinion from members of the 3D printing SIG.
    CONCLUSIONS: This consensus guidance document, created by the members of the 3D printing SIG, provides a reference for clinical standards of 3D printing for neurologic conditions.
    Keywords:  3D printing; Additive Manufacturing; Anatomic model; And Neurosurgery; Appropriateness; Guidelines; Neurology; Quality; Radiology
    DOI:  https://doi.org/10.1186/s41205-023-00192-w
  10. 3D Print Med. 2023 Nov 30. 9(1): 34
       BACKGROUND: Medical three-dimensional (3D) printing has demonstrated utility and value in anatomic models for vascular conditions. A writing group composed of the Radiological Society of North America (RSNA) Special Interest Group on 3D Printing (3DPSIG) provides appropriateness recommendations for vascular 3D printing indications.
    METHODS: A structured literature search was conducted to identify all relevant articles using 3D printing technology associated with vascular indications. Each study was vetted by the authors and strength of evidence was assessed according to published appropriateness ratings.
    RESULTS: Evidence-based recommendations for when 3D printing is appropriate are provided for the following areas: aneurysm, dissection, extremity vascular disease, other arterial diseases, acute venous thromboembolic disease, venous disorders, lymphedema, congenital vascular malformations, vascular trauma, vascular tumors, visceral vasculature for surgical planning, dialysis access, vascular research/development and modeling, and other vasculopathy. Recommendations are provided in accordance with strength of evidence of publications corresponding to each vascular condition combined with expert opinion from members of the 3DPSIG.
    CONCLUSION: This consensus appropriateness ratings document, created by the members of the 3DPSIG, provides an updated reference for clinical standards of 3D printing for the care of patients with vascular conditions.
    Keywords:  3D printing; Additive manufacturing; Anatomic model; Appropriateness; Quality; Radiology; Rapid prototyping; Vascular disease; Vascular surgery
    DOI:  https://doi.org/10.1186/s41205-023-00196-6
  11. Plast Reconstr Surg Glob Open. 2023 Nov;11(11): e5433
      We present a technique for treating orbital floor fractures using three-dimensional (3D) printing technology and a preoperative template based on the mirror image of the unaffected orbit. Our patient, a 56-year-old man, experienced persistent diplopia in the upward direction and left enophthalmos after previous open reduction internal fixation surgery. To address these complications, we used a simulation of the ideal orbital floor from computed tomography images and used a 3D printer to create a template. Subsequently, an absorbable plate was molded intraoperatively based on this template. Notably, the plate fit seamlessly into the fracture site without requiring any adjustment, reducing the operation time. Postoperative computed tomography scans confirmed successful reduction, improved visual function, and the absence of complications. Our method offers a precise and efficient approach to reconstructing fractured orbital floors. By leveraging 3D printing technology and preoperative templates, surgeons can enhance postoperative outcomes and minimize patient burden. Further investigations are warranted to assess the long-term effectiveness and cost-effectiveness of this technique. Our findings highlight the potential of this approach to improve treatment strategies for patients with orbital floor fractures.
    DOI:  https://doi.org/10.1097/GOX.0000000000005433
  12. Crit Rev Ther Drug Carrier Syst. 2024 ;41(3): 95-130
      While using three-dimensional printing, materials are deposited layer by layer in accordance with the digital model created by computer-aided design software. Numerous research teams have shown interest in this technology throughout the last few decades to produce various dosage forms in the pharmaceutical industry. The number of publications has increased since the first printed medicine was approved in 2015 by Food and Drug Administration. Considering this, the idea of creating complex, custom-made structures that are loaded with pharmaceuticals for tissue engineering and dose optimization is particularly intriguing. New approaches and techniques for creating unique medication delivery systems are made possible by the development of additive manufacturing keeping in mind the comparative advantages it has over conventional methods of manufacturing medicaments. This review focuses on three-dimensional printed formulations grouped in orally disintegrated tablets, buccal films, implants, suppositories, and microneedles. The various types of techniques that are involved in it are summarized. Additionally, challenges and applications related to three-dimensional printing of pharmaceuticals are also being discussed.
    DOI:  https://doi.org/10.1615/CritRevTherDrugCarrierSyst.2023046832
  13. Cureus. 2023 Oct;15(10): e47979
      Three-dimensional (3D) printing refers to a wide range of additive manufacturing processes that enable the construction of structures and models. It has been rapidly adopted for a variety of surgical applications, including the printing of patient-specific anatomical models, implants and prostheses, external fixators and splints, as well as surgical instrumentation and cutting guides. In comparison to traditional methods, 3D-printed models and surgical guides offer a deeper understanding of intricate maxillofacial structures and spatial relationships. This review article examines the utilization of 3D printing in orthognathic surgery, particularly in the context of treatment planning. It discusses how 3D printing has revolutionized this sector by providing enhanced visualization, precise surgical planning, reduction in operating time, and improved patient communication. Various databases, including PubMed, Google Scholar, ScienceDirect, and Medline, were searched with relevant keywords. A total of 410 articles were retrieved, of which 71 were included in this study. This article concludes that the utilization of 3D printing in the treatment planning of orthognathic surgery offers a wide range of advantages, such as increased patient satisfaction and improved functional and aesthetic outcomes.
    Keywords:  bilateral lefort ii osteotomy; digital dentistry; lefort i osteotomy; oral and maxillofacial surgeon; orthodontic surgery
    DOI:  https://doi.org/10.7759/cureus.47979
  14. Int J Biol Macromol. 2023 Nov 27. pii: S0141-8130(23)05348-5. [Epub ahead of print] 128449
      The present work explores the 3D extrusion printing of ferulic acid (FA)-containing alginate dialdehyde (ADA)-gelatin (GEL) scaffolds with a wide spectrum of biophysical and pharmacological properties. The tailored addition of FA (≤0.2 %) increases the crosslinking between FA and GEL in the presence of calcium chloride (CaCl2) and microbial transglutaminase, as confirmed using trinitrobenzenesulfonic acid (TNBS) assay. In agreement with an increase in crosslinking density, a higher viscosity of ADA-GEL with FA incorporation was achieved, leading to better printability. Importantly, FA release, enzymatic degradation and swelling were progressively reduced with an increase in FA loading to ADA-GEL, over 28 days. Similar positive impact on antibacterial properties with S. epidermidis strains as well as antioxidant properties were recorded. Intriguingly, FA incorporated ADA-GEL supported murine pre-osteoblast proliferation with reduced osteosarcoma cell proliferation over 7 days in culture, implicating potential anticancer property. Most importantly, FA-incorporated and cell-encapsulated ADA-GEL can be extrusion printed to shape fidelity-compliant multilayer scaffolds, which also support pre-osteoblast cells over 7 days in culture. Taken together, the present study unequivocally establishes the significant potential of 3D bioprinting of ADA-GEL-FA ink to obtain structurally stable scaffolds with a broad spectrum of biophysical and therapeutically significant properties, for bone tissue engineering applications.
    Keywords:  3D bioprinting; Alginate; Phytotherapeutic agents
    DOI:  https://doi.org/10.1016/j.ijbiomac.2023.128449
  15. Front Bioeng Biotechnol. 2023 ;11 1305023
      The cell spheroid technology, which greatly enhances cell-cell interactions, has gained significant attention in the development of in vitro liver models. However, existing cell spheroid technologies still have limitations in improving hepatocyte-extracellular matrix (ECM) interaction, which have a significant impact on hepatic function. In this study, we have developed a novel bioprinting technology for decellularized ECM (dECM)-incorporated hepatocyte spheroids that could enhance both cell-cell and -ECM interactions simultaneously. To provide a biomimetic environment, a porcine liver dECM-based cell bio-ink was developed, and a spheroid printing process using this bio-ink was established. As a result, we precisely printed the dECM-incorporated hepatocyte spheroids with a diameter of approximately 160-220 μm using primary mouse hepatocyte (PMHs). The dECM materials were uniformly distributed within the bio-printed spheroids, and even after more than 2 weeks of culture, the spheroids maintained their spherical shape and high viability. The incorporation of dECM also significantly improved the hepatic function of hepatocyte spheroids. Compared to hepatocyte-only spheroids, dECM-incorporated hepatocyte spheroids showed approximately 4.3- and 2.5-fold increased levels of albumin and urea secretion, respectively, and a 2.0-fold increase in CYP enzyme activity. These characteristics were also reflected in the hepatic gene expression levels of ALB, HNF4A, CPS1, and others. Furthermore, the dECM-incorporated hepatocyte spheroids exhibited up to a 1.8-fold enhanced drug responsiveness to representative hepatotoxic drugs such as acetaminophen, celecoxib, and amiodarone. Based on these results, it can be concluded that the dECM-incorporated spheroid printing technology has great potential for the development of highly functional in vitro liver tissue models for drug toxicity assessment.
    Keywords:  3D bioprinting; cell-ECM interaction; dECM-incorporated hepatocyte spheroid; decellularization; liver tissue engineering
    DOI:  https://doi.org/10.3389/fbioe.2023.1305023
  16. Regen Ther. 2023 Dec;24 617-629
       Introduction: Bones are easily damaged. Biomimetic scaffolds are involved in tissue engineering. This study explored polydopamine (PDA)-coated poly lactic-co-glycolic acid (PLGA)-magnesium oxide (MgO) scaffold properties and its effects on bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation.
    Methods: PLGA/MgO scaffolds were prepared by low-temperature 3D printing technology and PDA coatings were prepared by immersion method. Scaffold structure was observed by scanning electron microscopy with an energy dispersive spectrometer (SEM-EDS), fourier transform infrared spectrometer (FTIR). Scaffold hydrophilicity, compressive/elastic modulus, and degradation rates were analyzed by water contact angle measurement, mechanical tests, and simulated-body fluid immersion. Rat BMSCs were cultured in scaffold extract. Cell activity on days 1, 3, and 7 was detected by MTT. Cells were induced by osteogenic differentiation, followed by evaluation of alkaline phosphatase (ALP) activity on days 3, 7, and 14 of induction and Osteocalcin, Osteocalcin, and Collagen I expressions.
    Results: The prepared PLGA/MgO scaffolds had dense microparticles. With the increase of MgO contents, the hydrophilicity was enhanced, scaffold degradation rate was accelerated, magnesium ion release rate and scaffold extract pH value were increased, and cytotoxicity was less when magnesium mass ratio was less than 10%. Compared with other scaffolds, compressive and elastic modulus of PLGA/MgO (10%) scaffolds were increased; BMSCs incubated with PLGA/MgO (10%) scaffold extract had higher ALP activity and Osteocalcin, Osteopontin, and Collagen I expressions. PDA coating was prepared in PLGA/MgO (10%) scaffolds and the mechanical properties were not affected. PLGA/MgO (10%)/PDA scaffolds had better hydrophilicity and biocompatibility and promoted BMSC osteogenic differentiation.
    Conclusion: Low-temperature 3D printing PLGA/MgO (10%)/PDA scaffolds had good hydrophilicity and biocompatibility, and were conducive to BMSC osteogenic differentiation.
    Keywords:  Bone marrow mesenchymal stem cell; Low-temperature three-dimensional printing; Magnesium oxide; Osteogenic differentiation; Physical and chemical properties; Poly lactic-co-glycolic acid; Polydopamine; Scaffold materials
    DOI:  https://doi.org/10.1016/j.reth.2023.09.015