bims-biprem Biomed News
on Bioprinting for regenerative medicine
Issue of 2024‒08‒04
ten papers selected by
Seerat Maqsood, University of Teramo



  1. Biofabrication. 2024 Jul 30.
      Three-dimensional bioprinting has revolutionized tissue engineering by enabling the fabrication of complex and functional human tissues and organs. An essential component of successful 3D bioprinting is the selection of an appropriate bioink capable of supporting cell proliferation and viability. Plant-derived biomaterials, because of their abundance, biocompatibility, and tunable properties, hold promise as bioink sources, thus offering advantages over animal-derived biomaterials, which carry immunogenic concerns. This comprehensive review explores and analyzes the potential of plant-derived biomaterials as bioinks for 3D bioprinting of human tissues. Modification and optimization of these materials to enhance printability and biological functionality are discussed. Furthermore, cancer research and drug testing applications of the use of plant-based biomaterials in bioprinting various human tissues such as bone, cartilage, skin, and vascular tissues are described. Challenges and limitations, including mechanical integrity, cell viability, resolution, and regulatory concerns, along with potential strategies to overcome them, are discussed. Additionally, this review provides insights into the potential use of plant-based dECM as bioinks, future prospects, and emerging trends in the use of plant-derived biomaterials for 3D bioprinting applications. The potential of plant-derived biomaterials as bioinks for 3D bioprinting of human tissues is highlighted herein. However, further research is necessary to optimize their processing, standardize their properties, and evaluate their long-term in vivo performance. Continued advancements in plant-derived biomaterials have the potential to revolutionize tissue engineering and facilitate the development of functional and regenerative therapies for diverse clinical applications.
    Keywords:  3D bioprinting; Bioink; Biomaterials; Cross Kingdom; Tissue Engineering
    DOI:  https://doi.org/10.1088/1758-5090/ad6932
  2. J Tissue Eng. 2024 Jan-Dec;15:15 20417314241263689
      Bone defect disease seriously endangers human health and affects beauty and function. In the past five years, the three dimension (3D) printed radially graded triply periodic minimal surface (TPMS) porous scaffold has become a new solution for repairing bone defects. This review discusses 3D printing technologies and applications for TPMS scaffolds. To this end, the microstructural effects of 3D printed TPMS scaffolds on bone regeneration were reviewed and the structural characteristics of TPMS, which can promote bone regeneration, were introduced. Finally, the challenges and prospects of using TPMS scaffolds to treat bone defects were presented. This review is expected to stimulate the interest of bone tissue engineers in radially graded TPMS scaffolds and provide a reliable solution for the clinical treatment of personalised bone defects.
    Keywords:  3D printing; TPMS; bone regeneration; microstructure; radial classification
    DOI:  https://doi.org/10.1177/20417314241263689
  3. Biofabrication. 2024 Jul 31.
      Three-dimensional (3D) tissue models have gained recognition for their improved ability to mimic the native cell microenvironment compared to traditional two-dimensional (2D) models. This progress has been driven by advances in tissue-engineering technologies such as 3D bioprinting, a promising method for fabricating biomimetic living tissues. While bioprinting has succeeded in generating various tissues to date, creating neural tissue models remains challenging. In this context, we present an accelerated approach to fabricate 3D sensory neuron (SN) structures using a transgenic human pluripotent stem cell (hPSC)-line that contains an inducible neurogenin-2 (NGN2) expression cassette. The NGN2 hPSC line was first differentiated to neural crest cell (NCC) progenitors, then incorporated into a cytocompatible GelMA-based bioink for 3D bioprinting. Upregulated NGN2 expression in the bioprinted NCCs resulted in induced SN (iSN) populations that exhibited specific cell markers, with 3D analysis revealing widespread neurite outgrowth through the scaffold volume. Calcium imaging demonstrated functional activity of iSNs, including membrane excitability properties and voltage-gated sodium channel (NaV) activity. This efficient approach to generate 3D bioprinted iSN structures streamlines the development of neural tissue models, useful for the study of neurodevelopment and disease states and offering translational potential.
    Keywords:  3D bioprinting; gelatin methacryloyl; human pluripotent stem cells; neural crest; sensory neurons
    DOI:  https://doi.org/10.1088/1758-5090/ad69c4
  4. Med J Armed Forces India. 2024 Jul-Aug;80(4):80(4): 392-398
      The capacity of additive manufacturing and three-dimensional (3D) printing to quickly construct intricate structures and accurate geometries sets them apart from traditional production techniques. The fourth industrial revolution and the digitalization of production were fueled by the emergence of 3D printing, which was made possible by the increasing demand for goods with various designs, functions, and materials. The global influence of 3D printing on healthcare has resulted in the replacement of generic implanted medical devices with patient-customized implants. In the field of oral and maxillofacial surgery, where surgeons use precision medicine daily, this revolution has had a huge influence. Treatments enhanced by 3D technology include orthognathic surgery, complete joint replacement therapy, and trauma. Surgical teams now engage in the 3D design and production of devices at point-of-care treatment facilities with internal infrastructure thanks to the growing and broad adoption of 3D technology in clinical settings. The way doctors approach treatment planning and clinical results are affected greatly by 3D technology. While outlining significant clinical applications, the article presents our viewpoint on the use of 3D-based technology in the field of oral and maxillofacial surgery and the road ahead with the advent of Four-dimensional (4D) printing.
    Keywords:  Future perspective; Stereolithography; Three dimensional planning; Virtual surgery
    DOI:  https://doi.org/10.1016/j.mjafi.2024.05.008
  5. Int J Biol Macromol. 2024 Jul 31. pii: S0141-8130(24)05207-3. [Epub ahead of print] 134402
      3D printed scaffolds have revolutionized the field of regenerative medicine by overcoming the lacunas such as precision, customization, and reproducibility observed through traditional methods of scaffold preparation such as freeze-drying, electrospinning, etc. Combining the advantages of 3D printed scaffolds along with bioactive cues such as signaling molecules can be an effective treatment approach. In the present study, cellulose nanocrystals (CNCs) along with gelatin, in different ratios, were used for scaffold preparation through the direct ink writing technique and thoroughly characterized. The scaffolds showed porous microstructure, high swelling ratio (~390 to 590), degradability and porosity (~65 %). In vitro biocompatibility assays showed high biocompatibility and no toxicity through live-dead, proliferation and hemolysis assay. Further, the optimum formulation was functionalized with nitric oxide (NO)-releasing modified gelatin to enhance the scaffold's biomedical applicability. Functionality assays with this formulation, scratch, and neurite outgrowth showed positive effects of NO on cell migration and neurite length. The study presents the fabrication, modification, and biomedical applicability of the aforementioned inks, which paves new pathways in the field of 3D printing of scaffolds with significant potential for biomedical applications, soft tissue engineering, and wound dressing, for example.
    Keywords:  3D printing; Cellulose nanocrystals; Gelatin; Nitric oxide; Tissue engineering
    DOI:  https://doi.org/10.1016/j.ijbiomac.2024.134402
  6. Front Oncol. 2024 ;14 1384499
      The oncolytic virus represents a promising therapeutic strategy involving the targeted replication of viruses to eliminate cancer cells, while preserving healthy ones. Despite ongoing clinical trials, this approach encounters significant challenges. This study delves into the interaction between an oncolytic virus and extracellular matrix mimics (ECM mimics). A three-dimensional colorectal cancer model, enriched with ECM mimics through bioprinting, was subjected to infection by an oncolytic virus derived from the vaccinia virus (oVV). The investigation revealed prolonged expression and sustained oVV production. However, the absence of a significant antitumor effect suggested that the virus's progression toward non-infected tumoral clusters was hindered by the ECM mimics. Effective elimination of tumoral cells was achieved by introducing an oVV expressing FCU1 (an enzyme converting the prodrug 5-FC into the chemotherapeutic compound 5-FU) alongside 5-FC. Notably, this efficacy was absent when using a non-replicative vaccinia virus expressing FCU1. Our findings underscore then the crucial role of oVV proliferation in a complex ECM mimics. Its proliferation facilitates payload expression and generates a bystander effect to eradicate tumors. Additionally, this study emphasizes the utility of 3D bioprinting for assessing ECM mimics impact on oVV and demonstrates how enhancing oVV capabilities allows overcoming these barriers. This showcases the potential of 3D bioprinting technology in designing purpose-fit models for such investigations.
    Keywords:  bioprinting; colorectal (colon) cancer; hydrogel; oncovirus; tumor
    DOI:  https://doi.org/10.3389/fonc.2024.1384499
  7. Int J Pharm. 2024 Jul 31. pii: S0378-5173(24)00777-4. [Epub ahead of print] 124543
      Gastrointestinal (GI) environment is influenced by several factors (gender, genetics, sex, disease state, food) leading to oral drug absorption variability or to low bioavailability. In this scenario, gastroretentive drug delivery systems (GRDDS) have been developed in order to solve absorption problems, to lead to a more effective local therapy or to allow sustained drug release during a longer time period than the typical oral sustained release dosage forms. Among all GRDDS, floating systems seem to provide a promising and practical approach for achieving a long intra-gastric residence time and sustained release profile. In the last years, a novel technique is being used to manufacture this kind of systems: three-dimensional (3D) printing technology. This technique provides a versatile and easy process to manufacture personalized drug delivery systems. This work presents a systematic review of the main 3D printing based designs proposed up to date to manufacture floating systems. We have also summarized the most important parameters involved in buoyancy and sustained release of the systems, in order to facilitate the scale up of this technology to industrial level. Finally, a section discussing about the influence of materials in drug release, their biocompatibility and safety considerations have been included.
    Keywords:  3D printing; Drug delivery system; Gastroretentive floating system; Personalized medicine
    DOI:  https://doi.org/10.1016/j.ijpharm.2024.124543
  8. Arch Bone Jt Surg. 2024 ;12(7): 441-456
      Objectives: 3D-printing is a rapidly developing technology with applications in orthopaedics including pre-operative planning, intraoperative guides, design of patient specific instruments and prosthetics, and education. Existing literature demonstrates that in the surgical treatment of a wide range of orthopaedic pathology, using 3D printing shows favourable outcomes. Despite this evidence 3D printing is not routinely used in orthopaedic practice. We aim to evaluate the advantages of 3D printing in orthopaedic surgery to demonstrate its widespread applications throughout the field.Methods: We performed a comprehensive systematic review and meta-analysis. AMED, EMBASE, EMCARE, HMIC, PsycINFO, PubMed, BNI, CINAHL and Medline databases were searched using Healthcare Databases Advanced Search (HDAS) platform. The search was conducted to include papers published before 8th November 2020. Clinical trials, journal articles, Randomised Control Trials and Case Series were included across any area of orthopaedic surgery. The primary outcomes measured were operation time, blood loss, fluoroscopy time, bone fusion time and length of hospital stay.
    Results: A total of 65 studies met the inclusion criteria and were reviewed, and 15 were suitable for the meta-analysis, producing a data set of 609 patients. The use of 3D printing in any of its recognised applications across orthopaedic surgery showed an overall reduction in operative time (SMD = -1.30; 95%CI: -1.73, -0.87), reduction in intraoperative blood loss (SMD = -1.58; 95%CI: -2.16, -1.00) and reduction in intraoperative fluoroscopy time (SMD = -1.86; 95%CI: -2.60, -1.12). There was no significant difference in length of hospital stay or in bone fusion time post-operatively.
    Conclusion: The use of 3D printing in orthopaedics leads to an improvement in primary outcome measures showing reduced operative time, intraoperative blood loss and number of times fluoroscopy is used. With its wide-reaching applications and as the technology improves, 3D printing could become a valuable addition to an orthopaedic surgeon's toolbox.
    Keywords:  Orthopedic; Printing; Review; Systematic; Three dimensional
    DOI:  https://doi.org/10.22038/ABJS.2024.74117.3465
  9. Biomacromolecules. 2024 Jul 31.
      In vitro tumor models were successfully constructed by 3D bioprinting; however, bioinks with proper viscosity, good biocompatibility, and tunable biophysical and biochemical properties are highly desirable for tumor models that closely recapitulated the main features of native tumors. Here, we developed a nanocomposite hydrogel bioink that was used to construct ovarian and colon cancer models by 3D bioprinting. The nanocomposite bioink was composed of aldehyde-modified cellulose nanocrystals (aCNCs), aldehyde-modified hyaluronic acid (aHA), and gelatin. The hydrogels possessed tunable gelation time, mechanical properties, and printability by controlling the ratio between aCNCs and gelatin. In addition, ovarian and colorectal cancer cells embedded in hydrogels showed high survival rates and rapid growth. By the combination of 3D bioprinting, ovarian and colorectal tumor models were constructed in vitro and used for drug screening. The results showed that gemcitabine had therapeutic effects on ovarian tumor cells. However, the ovarian tumor model showed drug resistance for oxaliplatin treatment.
    DOI:  https://doi.org/10.1021/acs.biomac.4c00671
  10. 3D Print Med. 2024 Jul 27. 10(1): 25
      BACKGROUND: 3D printing holds great potential of improving examination, diagnosis and treatment planning as well as interprofessional communication in the field of gynecological oncology. In the current manuscript we evaluated five individualized, patient-specific models of cervical cancer FIGO Stage I-III, created with 3D printing, concerning their value for translational oncology.METHODS: Magnetic resonance imaging (MRI) of the pelvis was performed on a 3.0 Tesla MRI, including a T2-weighted isotropic 3D sequence. The MRI images were segmented and transferred to virtual 3D models via a custom-built 3D-model generation pipeline and printed by material extrusion. The 3D models were evaluated by all medical specialties involved in patient care of cervical cancer, namely surgeons, radiologists, pathologists and radiation oncologists. Information was obtained from evaluated profession-specific questionnaires which were filled out after inspecting all five models. The questionnaires included multiple-select questions, questions based on Likert scales (1 = "strongly disagree " or "not at all useful " up to 5 = "strongly agree " or "extremely useful ") and dichotomous questions ("Yes" or "No").
    RESULTS: Surgeons rated the models as useful during surgery (4.0 out of 5) and for patient communication (4.7 out of 5). Furthermore, they believed that the models had the potential to revise the patients' treatment plan (3.7 out of 5). Pathologists evaluated with mean ratings of 3.0 out of 5 for the usefulness of the models in diagnostic reporting and macroscopic evaluation. Radiologist acknowledged the possibility of providing additional information compared to imaging alone (3.7 out of 5). Radiation oncologists strongly supported the concept by rating the models highly for understanding patient-specific pathological characteristics (4.3 out of 5), assisting interprofessional communication (mean 4.3 out of 5) and communication with patients (4.7 out of 5). They also found the models useful for improving radiotherapy treatment planning (4.3 out of 5).
    CONCLUSION: The study revealed that the 3D printed models were generally well-received by all medical disciplines, with radiation oncologists showing particularly strong support. Addressing the concerns and tailoring the use of 3D models to the specific needs of each medical speciality will be essential for realizing their full potential in clinical practice.
    Keywords:  3D printing; Cervical cancer; Interprofessional communication; MRI; Staging; Translational oncology; Treatment planning; Visualization
    DOI:  https://doi.org/10.1186/s41205-024-00229-8