bims-biprem Biomed News
on Bioprinting for regenerative medicine
Issue of 2024–02–11
eleven papers selected by
Seerat Maqsood, University of Teramo



  1. Eur Urol Focus. 2024 Feb 06. pii: S2405-4569(24)00009-9. [Epub ahead of print]
      Three-dimensional (3D) bioprinting technology has emerged as a cutting-edge tool for the development of precise and reproducible patient-specific, personalized urological tissue constructs. This capability effectively addresses the existing translational limitations of biomanufacturing and offers extensive potential for urological applications. The revolutionary impact of this technology is poised to transform the treatment landscape for various urological conditions. To fully harness the potential of bioprinted tissue constructs in urological tissue engineering applications, it is essential to prioritize thorough investigations, proactively address potential challenges, and establish robust protocols. By addressing these issues, we can instill confidence in the viability and numerous benefits of bioprinting for urology and ultimately pave the way for better patient outcomes and personalized treatments. PATIENT SUMMARY: Three-dimensional (3D) printing using biological materials (bioprinting) is a revolutionary technology for tissue engineering therapies. This review highlights the latest advances in bioprinting of urological tissue constructs and their potential for application in patient-specific treatments.
    Keywords:  Bioinks; Bioprinting; Reconstruction; Tissue engineering
    DOI:  https://doi.org/10.1016/j.euf.2024.01.006
  2. bioRxiv. 2024 Jan 23. pii: 2024.01.18.576289. [Epub ahead of print]
      Probing how the human neural networks operate is hindered by the lack of reliable human neural tissues amenable for dynamic functional assessment of neural circuits. We developed a 3D bioprinting platform to assemble tissues with defined human neural cell types in a desired dimension using a commercial bioprinter. The printed neuronal progenitors differentiate to neurons and form functional neural circuits in and between tissue layers with specificity within weeks, evidenced by the cortical-to-striatal projection, spontaneous synaptic currents and synaptic response to neuronal excitation. Printed astrocyte progenitors develop into mature astrocytes with elaborated processes and form functional neuron-astrocyte networks, indicated by calcium flux and glutamate uptake in response to neuronal excitation under physiological and pathological conditions. These designed human neural tissues will likely be useful for understanding the wiring of human neural networks, modeling pathological processes, and serving as platforms for drug testing.
    DOI:  https://doi.org/10.1101/2024.01.18.576289
  3. Heliyon. 2024 Feb 15. 10(3): e24593
      3D bioprinting has unlocked new possibilities for generating complex and functional tissues and organs. However, one of the greatest challenges lies in selecting the appropriate seed cells for constructing fully functional 3D artificial organs. Currently, there are no cell sources available that can fulfill all requirements of 3D bioprinting technologies, and each cell source possesses unique characteristics suitable for specific applications. In this review, we explore the impact of different 3D bioprinting technologies and bioink materials on seed cells, providing a comprehensive overview of the current landscape of cell sources that have been used or hold potential in 3D bioprinting. We also summarized key points to guide the selection of seed cells for 3D bioprinting. Moreover, we offer insights into the prospects of seed cell sources in 3D bioprinted organs, highlighting their potential to revolutionize the fields of tissue engineering and regenerative medicine.
    Keywords:  3D bioprinting; Bioink materials; Cell lines; Primary cells; Seed cells; Stem cells
    DOI:  https://doi.org/10.1016/j.heliyon.2024.e24593
  4. Hepatobiliary Surg Nutr. 2024 Feb 01. 13(1): 180-183
      
    Keywords:  3D bioprinting; Colorectal cancer (CRC); chemotherapy; preclinical model; predict
    DOI:  https://doi.org/10.21037/hbsn-24-13
  5. Int J Pharm. 2024 Feb 03. pii: S0378-5173(24)00101-7. [Epub ahead of print]653 123867
      In recent years, the rapid advancement of three-dimensional (3D) printing technology has yielded distinct benefits across various sectors, including pharmaceuticals. The pharmaceutical industry has particularly experienced advantages from the utilization of 3D-printed medications, which have invigorated the development of tailored drug formulations. The approval of 3D-printed drugs by the U.S. Food and Drug Administration (FDA) has significantly propelled personalized drug delivery. Additionally, 3D printing technology can accommodate the precise requirements of pediatric drug dosages and the complexities of multiple drug combinations. This review specifically concentrates on the application of 3D printing technology in pediatric preparations, encompassing a broad spectrum of uses and refined pediatric formulations. It compiles and evaluates the fundamental principles associated with the application of 3D printing technology in pediatric preparations, including its merits and demerits, and anticipates its future progression. The objective is to furnish theoretical underpinning for 3D printing technology to facilitate personalized drug delivery in pediatrics and to advocate for its implementation in clinical settings.
    Keywords:  3D printing; Clinical application; Pediatrics; Personalized medicines; Technology
    DOI:  https://doi.org/10.1016/j.ijpharm.2024.123867
  6. Front Bioeng Biotechnol. 2023 ;11 1252636
      There has been increasing attention to produce porous scaffolds that mimic human bone properties for enhancement of tissue ingrowth, regeneration, and integration. Additive manufacturing (AM) technologies, i.e., three dimensional (3D) printing, have played a substantial role in engineering porous scaffolds for clinical applications owing to their high level of design and fabrication flexibility. To this end, this review article attempts to provide a detailed overview on the main design considerations of porous scaffolds such as permeability, adhesion, vascularisation, and interfacial features and their interplay to affect bone regeneration and osseointegration. Physiology of bone regeneration was initially explained that was followed by analysing the impacts of porosity, pore size, permeability and surface chemistry of porous scaffolds on bone regeneration in defects. Importantly, major 3D printing methods employed for fabrication of porous bone substitutes were also discussed. Advancements of MA technologies have allowed for the production of bone scaffolds with complex geometries in polymers, composites and metals with well-tailored architectural, mechanical, and mass transport features. In this way, a particular attention was devoted to reviewing 3D printed scaffolds with triply periodic minimal surface (TPMS) geometries that mimic the hierarchical structure of human bones. In overall, this review enlighten a design pathway to produce patient-specific 3D-printed bone substitutions with high regeneration and osseointegration capacity for repairing large bone defects.
    Keywords:  3D printing; additive manufacturing; bone defect; regeneration; scaffold; triply periodic minimal surface
    DOI:  https://doi.org/10.3389/fbioe.2023.1252636
  7. Biomater Biosyst. 2024 Mar;13 100087
      Biomaterials that can improve the healing of articular cartilage lesions are needed. To address this unmet need, we developed novel 3D printed silica/poly(tetrahydrofuran)/poly(ε-caprolactone) (SiO2/PTHF/PCL-diCOOH) hybrid scaffolds. Our aim was to carry out essential studies to advance this medical device towards functional validation in pre-clinical trials. First, we show that the chemical composition, microarchitecture and mechanical properties of these scaffolds were not affected by sterilisation with gamma irradiation. To evaluate the systemic and local immunogenic reactivity of the sterilised 3D printed hybrid scaffolds, they were implanted subcutaneously into Balb/c mice. The scaffolds did not trigger a systemic inflammatory response over one week of implantation. The interaction between the host immune system and the implanted scaffold elicited a local physiological reaction with infiltration of mononuclear cells without any signs of a chronic inflammatory response. Then, we investigated how these 3D printed hybrid scaffolds direct chondrogenesis in vitro. Human bone marrow-derived mesenchymal stem/stromal cells (hBM-MSCs) seeded within the 3D printed hybrid scaffolds were cultured under normoxic or hypoxic conditions, with or without chondrogenic supplements. Chondrogenic differentiation assessed by both gene expression and protein production analyses showed that 3D printed hybrid scaffolds support hBM-MSC chondrogenesis. Articular cartilage-specific extracellular matrix deposition within these scaffolds was enhanced under hypoxic conditions (1.7 or 3.7 fold increase in the median of aggrecan production in basal or chondrogenic differentiation media). Our findings show that 3D printed SiO2/PTHF/PCL-diCOOH hybrid scaffolds have the potential to support the regeneration of cartilage tissue.
    Keywords:  3D printed hybrid scaffolds; Chondrogenesis; Mesenchymal stem/stromal cells; Sterilisation; Subcutaneous implantation
    DOI:  https://doi.org/10.1016/j.bbiosy.2024.100087
  8. Stem Cell Rev Rep. 2024 Feb 06.
      Inherited and non-inherited retinopathies can affect distinct cell types, leading to progressive cell death and visual loss. In the last years, new approaches have indicated exciting opportunities to treat retinopathies. Cell therapy in retinitis pigmentosa, age-related macular disease, and glaucoma have yielded encouraging results in rodents and humans. The first two diseases mainly impact the photoreceptors and the retinal pigmented epithelium, while glaucoma primarily affects the ganglion cell layer. Induced pluripotent stem cells and multipotent stem cells can be differentiated in vitro to obtain specific cell types for use in transplant as well as to assess the impact of candidate molecules aimed at treating retinal degeneration. Moreover, stem cell therapy is presented in combination with newly developed methods, such as gene editing, Müller cells dedifferentiation, sheet & drug delivery, virus-like particles, optogenetics, and 3D bioprinting. This review describes the recent advances in this field, by presenting an updated panel based on cell transplants and related therapies to treat retinopathies.
    Keywords:  3D bioprinting; Cell therapy; Gene editing; Induced pluripotent stem cell; Optogenetics; Retina
    DOI:  https://doi.org/10.1007/s12015-024-10689-4
  9. J Mater Chem B. 2024 Feb 05.
      Three-dimensional (3D) printing of bone scaffolds using digital light processing (DLP) bioprinting technology empowers the treatment of patients suffering from bone disorders and defects through the fabrication of cell-laden patient-specific scaffolds. Here, we demonstrate the visible-light-induced photo-crosslinking of methacrylate-κ-carrageenan (MA-κ-CA) mixed with bioactive silica nanoparticles (BSNPs) to fabricate 3D composite hydrogels using digital light processing (DLP) printing. The 3D printing of complex bone structures, such as the gyroid, was demonstrated with high precision and resolution. DLP-printed 3D composite hydrogels of MA-κ-CA-BSNP were prepared and systematically assessed for their macroporous structure, swelling, and degradation characteristics. The viscosity, rheological, and mechanical properties were also investigated for the influence of nanoparticle incorporation in the MA-κ-CA hydrogels. The in vitro study performed with MC3T3-E1 pre-osteoblast-laden scaffolds of MA-κ-CA-BSNP revealed high cell viability, no cytotoxicity, and proliferation over 21 days with markedly enhanced osteogenic differentiation compared to neat polymeric scaffolds. Furthermore, no inflammation was observed in the 21-day study involving the in vivo examination of DLP-printed 3D composite scaffolds in a Wistar rat model. Overall, the observed results for the DLP-printed 3D composite scaffolds of MA-κ-CA and BSNP demonstrate their biocompatibility and suitability for bone tissue engineering.
    DOI:  https://doi.org/10.1039/d3tb02179c
  10. Biomed Pharmacother. 2024 Feb 05. pii: S0753-3322(24)00109-4. [Epub ahead of print]172 116228
       BACKGROUND: Linezolid has been reported to protect against chronic bone and joint infection. In this study, linezolid was loaded into the 3D printed poly (lactic-co-glycolic acid) (PLGA) scaffold with nano-hydroxyapatite (HA) to explore the effect of this composite scaffold on infected bone defect (IBD).
    METHODS: PLGA scaffolds were produced using the 3D printing method. Drug release of linezolid was analyzed by elution and high-performance liquid chromatography assay. PLGA, PLGA-HA, and linezolid-loaded PLGA-HA scaffolds, were implanted into the defect site of a rabbit radius defect model. Micro-CT, H&E, and Masson staining, and immunohistochemistry were performed to analyze bone infection and bone healing. Evaluation of viable bacteria was performed. The cytocompatibility of 3D-printed composite scaffolds in vitro was detected using human bone marrow mesenchymal stem cells (BMSCs). Long-term safety of the scaffolds in rabbits was evaluated.
    RESULTS: The linezolid-loaded PLGA-HA scaffolds exhibited a sustained release of linezolid and showed significant antibacterial effects. In the IBD rabbit models implanted with the scaffolds, the linezolid-loaded PLGA-HA scaffolds promoted bone healing and attenuated bone infection. The PLGA-HA scaffolds carrying linezolid upregulated the expression of osteogenic genes including collagen I, runt-related transcription factor 2, and osteocalcin. The linezolid-loaded PLGA-HA scaffolds promoted the proliferation and osteogenesis of BMSCs in vitro via the PI3K/AKT pathway. Moreover, the rabbits implanted with the linezolid-loaded scaffolds showed normal biochemical profiles and normal histology, which suggested the safety of the linezolid-loaded scaffolds.
    CONCLUSION: Overall, the linezolid-loaded PLGA-HA scaffolds fabricated by 3D printing exerts significant bone repair and anti-infection effects.
    Keywords:  Bone defects; Bone regeneration; Infection; Linezolid; PLGA-HA; Scaffolds
    DOI:  https://doi.org/10.1016/j.biopha.2024.116228
  11. Beijing Da Xue Xue Bao Yi Xue Ban. 2024 Feb 18. 56(1): 161-166
       OBJECTIVE: To explore the short-term outcomes of 3D-printing stand-alone artificial vertebral body (AVB) in the surgical procedure of anterior cervical corpectomy and fusion (ACCF).
    METHODS: Following the proposal of IDEAL (idea, development, exploration, assessment, and long-term follow-up) framework, we designed and conducted this single-armed, retrospective cohort study. The patients with cervical spondylotic myelopathy were recruited, and these patients exclusively received the surgical procedure of single-level ACCF in our single center. After the process of corpectomy, the size was tailored using different trials and the most suitable stand-alone AVB was then implanted. This AVB was manufactured by the fashion of 3D-printing. Two pairs of screws were inserted in an inclined way into the adjacent vertebral bodies, to stabilize the AVB. The participants were regularly followed-up after the operation. Their clinical data were thoroughly reviewed. We assessed the neurological status according to Japanese Orthopedic Association (JOA) scale. We determined the fusion based on imaging examination six months after the operation. The recorded clinical data were analyzed using specific software and they presented in suitable styles. Paired t test was employed in comparison analysis.
    RESULTS: In total, there were eleven patients being recruited eventually. The patients were all followed up over six months after the operation. The mean age of the cohort was (57.2±10.2) years. The mean operation time was (76.1±23.1) min and the median bleeding volume was 150 (100, 200) mL. The postoperative course was uneventful for all the cases. Dysphagia, emergent hematoma, and deterioration of neurological function did not occur. Mean JOA scores were 13.2±2.2 before the operation and 16.3±0.8 at the final follow-up, which were significantly different (P < 0.001). The mean recovery rate of neurological function was 85.9%. By comparing the imaging examinations postoperatively and six months after the operation, we found that the average subsidence length was (1.2±1.1) mm, and that there was only one cases (9.1%) of the severe subsidence (>3 mm). We observed significant improvement of cervical lordosis after the operation (P=0.013). All the cases obtained solid fusion.
    CONCLUSION: 3D-printing stand-alone AVB presented favorable short-term outcome in one-level ACCF in this study. The fusion rate of this zero-profile prosthesis was satisfactory and the complication rate was relatively low.
    Keywords:  3D-printing; Artificial vertebral body; Cervical spondylotic myelopathy; Stand-alone; Zero-profile