bims-biprem Biomed News
on Bioprinting for regenerative medicine
Issue of 2024‒04‒14
sixteen papers selected by
Seerat Maqsood, University of Teramo



  1. Curr Med Imaging. 2024 Apr 08.
      BACKGROUND: The recent advancements and detailed studies in the field of 3D bioprinting have made it a promising avenue in the field of organ shortage, where many patients die awaiting transplantation. The main challenges bioprinting faces are precision during printing, vascularization, and cell proliferation. Additionally, overcoming these shortcomings requires experts from engineering, medicine, physics, etc., and if accomplished, it will significantly benefit humankind.OBJECTIVE: This paper covers the general roadmap of the bioprinting process, different kinds of bioinks, and available bioprinters. The paper also includes designing the anatomical structure, which is the first phase of the bioprinting process, and how AI has facilitated this entire process of 3D printing in healthcare and associated applications like medical modelling and disease modelling.
    METHODS: The process of 3D bioprinting involves meticulous structure designing of the anatomical structure under study, which forms the base of the entire bioprinting process. One of the significant applications of 3D printing in healthcare is Medical Modelling and Disease Modelling, which requires the detection of disease in anatomy and its delineation from the rest of anatomy for meticulous creation of ROI using sophisticated segmentation software(s) for the construction of 3D models of diseased anatomy and healthy anatomical surroundings.
    CONCLUSION: The study concluded that bioprinting is the future of the worldwide organ transplantation crisis. Anatomical accuracy is an important aspect that must be considered while producing 3D models. The reproduction of patient-specific 3D models requires human rights and ethics approval under four principles of ethics in healthcare: autonomy, non-maleficence, beneficence, and justice.
    Keywords:  3D printing; Artificial Intelligence; Bioinks; Bioprinters; Healthcare; Segmentation
    DOI:  https://doi.org/10.2174/0115734056259274231019061329
  2. Regen Biomater. 2024 ;11 rbae026
      [This corrects the article DOI: 10.1093/rb/rbad058.].
    DOI:  https://doi.org/10.1093/rb/rbae026
  3. Materials (Basel). 2024 Feb 05. pii: 769. [Epub ahead of print]17(3):
      Precision manufacturing requirements are the key to ensuring the quality and reliability of biomedical implants. The powder bed fusion (PBF) technique offers a promising solution, enabling the creation of complex, patient-specific implants with a high degree of precision. This technology is revolutionizing the biomedical industry, paving the way for a new era of personalized medicine. This review explores and details powder bed fusion 3D printing and its application in the biomedical field. It begins with an introduction to the powder bed fusion 3D-printing technology and its various classifications. Later, it analyzes the numerous fields in which powder bed fusion 3D printing has been successfully deployed where precision components are required, including the fabrication of personalized implants and scaffolds for tissue engineering. This review also discusses the potential advantages and limitations for using the powder bed fusion 3D-printing technology in terms of precision, customization, and cost effectiveness. In addition, it highlights the current challenges and prospects of the powder bed fusion 3D-printing technology. This work offers valuable insights for researchers engaged in the field, aiming to contribute to the advancement of the powder bed fusion 3D-printing technology in the context of precision manufacturing for biomedical applications.
    Keywords:  additive manufacturing; biomedical applications; implants; powder bed fusion; precision manufacturing
    DOI:  https://doi.org/10.3390/ma17030769
  4. HardwareX. 2024 Jun;18 e00527
      The engineering of new 3D bioprinting approaches has shown great promise in the field of tissue engineering and disease modelling. However, the high cost of commercial 3D bioprinters has limited their accessibility, especially to those laboratories in resource-limited settings. Moreover, the need for a 3D bioprinting system capable of dispensing multiple materials is growing apace. Therefore, the development of a Microfluidic-assisted Open Source 3D bioprinting System (MOS3S) for the engineering of hierarchical tissues is needed to progress in fabricating functional tissues, but with a technology accessible to a wider range of researchers. The MOS3S platform is designed to allow the deposition of biomaterial inks using microfluidic printheads or coaxial nozzles for the in-situ crosslinking and scaffolds fabrication. The coupling of 3D printed syringe pumps with the motion control system is used for driving the tunable extrusion of inks for the fabrication of centimeter scale hierarchical lattice constructs for tissue engineering purposes. MOS3S performance have been validated to fabricate high-resolution structures with coaxial microfluidic technology, opening to new frontiers for seminal studies in pre-clinical disease modelling and tissue regeneration.
    Keywords:  3D-bioprinting; Hydrogel; Microfluidic; Open-source; Tissue Engineering
    DOI:  https://doi.org/10.1016/j.ohx.2024.e00527
  5. Wound Repair Regen. 2024 Apr 11.
      Both cutaneous radiation injury and radiation combined injury (RCI) could have serious skin traumas, which are collectively referred to as radiation-associated skin injuries in this paper. These two types of skin injuries require special managements of wounds, and the therapeutic effects still need to be further improved. Cutaneous radiation injuries are common in both radiotherapy patients and victims of radioactive source accidents, which could lead to skin necrosis and ulcers in serious conditions. At present, there are still many challenges in management of cutaneous radiation injuries including early diagnosis, lesion assessment, and treatment prognosis. Radiation combined injuries are special and important issues in severe nuclear accidents, which often accompanied by serious skin traumas. Mass victims of RCI would be the focus of public health concern. Three-dimensional (3D) bioprinting, as a versatile and favourable technique, offers effective approaches to fabricate biomimetic architectures with bioactivity, which provides potentials for resolve the challenges in treating radiation-associated skin injuries. Combining with the cutting-edge advances in 3D skin bioprinting, the authors analyse the damage characteristics of skin wounds in both cutaneous radiation injury and RCI and look forward to the potential value of 3D skin bioprinting for the treatments of radiation-associated skin injuries.
    Keywords:  3D bioprinting; cutaneous radiation injury; ionising radiation; radiation combined injury; skin
    DOI:  https://doi.org/10.1111/wrr.13181
  6. J Pharm Bioallied Sci. 2024 Feb;16(Suppl 1): S8-S10
      The proper treatment of diseases has greatly benefited from dental technological advancements. The dentist may view, precisely measure, and create models of both hard and soft tissue using 3D printing. The most cutting-edge technique in dentistry is 3D printing; but it also lacks the user-training trainee. In this paper, we will demonstrate how it is employed in various dental procedures.
    Keywords:  3D printing; application of 3D printing; dentistry
    DOI:  https://doi.org/10.4103/jpbs.jpbs_457_23
  7. J Pharm Bioallied Sci. 2024 Feb;16(Suppl 1): S423-S426
      Introduction: The rapid advancement of 3D printing technology has opened new avenues for patient-specific prosthodontic rehabilitation. This study aimed to explore the impact of 3D printing technology on prosthodontic outcomes and patient satisfaction through a comparative analysis.Materials and Methods: A total of 100 patients requiring prosthodontic rehabilitation were recruited for this study. The patients were randomly divided into two groups: the experimental group, where 3D printing technology was utilized for the fabrication of patient-specific prostheses, and the control group, where conventional fabrication techniques were employed. Various parameters were assessed, including prosthesis fit, occlusion, esthetics, and patient-reported outcomes such as comfort and satisfaction. Digital measurements and subjective evaluations were conducted to compare the outcomes between the two groups. Statistical analysis was performed using appropriate tests.
    Results: Preliminary findings indicated that the use of 3D printing technology in prosthodontic rehabilitation resulted in superior prosthesis fit, enhanced occlusal stability, and improved esthetics compared to conventional methods. Moreover, patients in the experimental group reported higher levels of comfort and overall satisfaction. The advantages of 3D printing technology were observed across different types of prosthodontic restorations, including crowns, bridges, and dentures. These results highlight the potential of 3D printing technology to revolutionize patient-specific prosthodontic rehabilitation. By facilitating precise fabrication, customization, and improved functional outcomes, 3D printing can enhance the overall quality of prosthodontic care. Further long-term studies are warranted to validate these findings and explore the cost-effectiveness and long-term durability of 3D-printed prostheses.
    Conclusion: In conclusion, this study demonstrates that the integration of 3D printing technology in patient-specific prosthodontic rehabilitation holds great promise for achieving optimal functional and esthetic outcomes. The findings contribute to advancing prosthodontic practices and provide valuable insights for clinicians and researchers seeking to incorporate this innovative technology into their treatment protocols.
    Keywords:  3D printing technology; comparative study; esthetics; occlusion; patient satisfaction; patient-specific prosthodontic rehabilitation; prosthesis fit
    DOI:  https://doi.org/10.4103/jpbs.jpbs_643_23
  8. Biomaterials. 2024 Apr 08. pii: S0142-9612(24)00100-5. [Epub ahead of print]308 122566
      Achieving sufficient bone regeneration in large segmental defects is challenging, with the structure of bone repair scaffolds and their loaded bioactive substances crucial for modulating the local osteogenic microenvironment. This study utilized digital laser processing (DLP)-based 3D printing technology to successfully fabricate high-precision methacryloylated polycaprolactone (PCLMA) bionic bone scaffold structures. Adipose-derived stem cell-engineered nanovesicles (ADSC-ENs) were uniformly and stably modified onto the bionic scaffold surface using a perfusion device, constructing a conducive microenvironment for tissue regeneration and long bone defect repair through the scaffold's structural design and the vesicles' biological functions. Scanning electron microscopy (SEM) examination of the scaffold surface confirmed the efficient loading of ADSC-ENs. The material group loaded with vesicles (PCLMA-BAS-ENs) demonstrated good cell compatibility and osteogenic potential when analyzed for the adhesion and osteogenesis of primary rabbit bone marrow mesenchymal stem cells (BMSCs) on the material surface. Tested in a 15 mm critical rabbit radial defect model, the PCLMA-BAS-ENs scaffold facilitated near-complete bone defect repair after 12 weeks. Immunofluorescence and proteomic results indicated that the PCLMA-BAS-ENs scaffold significantly improved the osteogenic microenvironment at the defect site in vivo, promoted angiogenesis, and enhanced the polarization of macrophages towards M2 phenotype, and facilitated the recruitment of BMSCs. Thus, the PCLMA-BAS-ENs scaffold was proven to significantly promote the repair of large segmental bone defects. Overall, this strategy of combining engineered vesicles with highly biomimetic scaffolds to promote large-segment bone tissue regeneration holds great potential in orthopedic and other regenerative medicine applications.
    Keywords:  Bionic scaffold; DLP 3D printing; Engineered vesicles; Microenvironment modulation
    DOI:  https://doi.org/10.1016/j.biomaterials.2024.122566
  9. ACS Appl Bio Mater. 2024 Apr 08.
      Mycelium is the root-like network of fungi. Mycelium biocomposites prepared by template replication (molding) can function as environmentally friendly alternatives to conventional polystyrene foams, which are energy- and carbon-intensive to manufacture. Recently, several studies have shown that 3D bioprinting technologies can be used to produce high value functional mycelium products with intricate geometries that are otherwise difficult or impossible to achieve via template replication. A diverse range of nutrients, thickeners, and gelling agents can be combined to produce hydrogels suitable for 3D bioprinting. 3D bioprinting with hydrogel formulations infused with living fungi produces engineered living materials that continue to grow after bioprinting is complete. However, a hydrogel formulation optimized for intricate 3D bioprinting of Pleurotus ostreatus mycelium, which is among the strains most commonly used in mycelium biocomposite fabrication, has yet to be described. Here, we design and evaluate a versatile hydrogel formulation consisting of malt extract (nutrient), carboxymethylcellulose and cornstarch (thickeners), and agar (gelling agent), all of which are easily sourced food grade reagents. We also outline a reproducible workflow to infuse this hydrogel with P. ostreatus liquid culture for 3D bioprinting of intricate structures comprised of living P. ostreatus mycelium and characterize the changes in height and mass as well as hardness of the prints during mycelium growth. Finally, we demonstrate that the workflow does not require a sterile bioprinting environment to achieve successful prints and that the same mycelium-infused hydrogel can be supplemented with additives such as sawdust to produce mycelium biocomposite objects. These findings demonstrate that 3D bioprinting using mycelium-based feedstocks could be a promising biofabrication technique to produce engineered living materials for applications such as mushroom cultivation, food preparation, or construction of the built environment.
    Keywords:  additive manufacturing; biocomposites; bioink; engineered living materials; fungi; living hybrid materials
    DOI:  https://doi.org/10.1021/acsabm.4c00048
  10. Curr Probl Cardiol. 2024 Apr 08. pii: S0146-2806(24)00207-X. [Epub ahead of print] 102568
      Cardiovascular disease (CVD), exemplified by coronary artery disease (CAD), is a global health concern, escalating in prevalence and burden. The etiology of CAD is intricate, involving different risk factors. CVD remains a significant cause of mortality, driving the need for innovative interventions like percutaneous coronary intervention and vascular stents. These stents aim to minimize restenosis, thrombosis, and neointimal hyperplasia while providing mechanical support. Notably, the challenges of achieving ideal stent characteristics persist. An emerging avenue to address this involves enhancing the mechanical performance of polymeric bioresorbable stents using additive manufacturing techniques And Three-dimensional (3D) printing, encompassing various manufacturing technologies, has transcended its initial concept to become a tangible reality in the medical field. The technology's evolution presents a significant opportunity for pharmaceutical and medical industries, enabling the creation of targeted drugs and swift production of medical implants. It revolutionizes medical procedures, transforming the strategies of doctors and surgeons. Patient-specific 3D-printed anatomical models are now pivotal in precision medicine and personalized treatment approaches. Despite its ongoing development, additive manufacturing in healthcare is already integrated into various medical applications, offering substantial benefits to a sector under pressure for performance and cost reduction. In this review primarily emphasizes stent technology, different types of stents, highlighting its application with some potential complications. Here we also address their benefits, potential issues, effectiveness, indications, and contraindications. In future it can potentially reduce complications and help in improving patients' outcomes. 3DP technology offers the promise to customize solutions for complex CVD conditions and help or fostering a new era of precision medicine in cardiology.
    Keywords:  3-dimensional printing (3D Printing); Bare Metal Stents (BMS); Drug Eluting Stents (DES). Computed Tomography (CT); Dual antiplatelet treatment (DAPT); Everolimus eluting stents (EES); In-Stent Restenosis (ISR); Magnetic Resonance Imaging (MRI); Myocardial Infarction (MI); Paclitaxel Eluting Stent (PES); Percutaneous Coronary Intervention (PCI); Stent Thrombosis (ST); Zotarolimus-Eluting Stent (ZES); bioresorbable vascular scaffolds (BRS); coronary artery disease (CAD)
    DOI:  https://doi.org/10.1016/j.cpcardiol.2024.102568
  11. Front Bioeng Biotechnol. 2024 ;12 1383010
      Gelatin Methacryloyl (GelMA) is one of the most used biomaterials for a wide range of applications, such as drug delivery, disease modeling and tissue regeneration. GelMA is obtained from gelatin, which can be derived from different sources (e.g., bovine skin, and porcine skin), through substitution of reactive amine and hydroxyl groups with methacrylic anhydride (MAA). The degree of functionalization (DoF) can be tuned by varying the MAA amount used; thus, different protocols, with different reaction efficiency, have been developed, using various alkaline buffers (e.g., phosphate-buffered saline, DPBS, or carbonate-bicarbonate solution). Obviously, DoF modulation has an impact on the final GelMA properties, so a deep investigation on the features of the obtained hydrogel must be carried on. The purpose of this study is to investigate how different gelatin sources and synthesis methods affect GelMA properties, as literature lacks direct and systematic comparisons between these parameters, especially between synthesis methods. The final aim is to facilitate the choice of the source or synthesis method according to the needs of the desired application. Hence, chemical and physical properties of GelMA formulations were assessed, determining the DoFs, mechanical and viscoelastic properties by rheological analysis, water absorption by swelling capacity and enzymatic degradation rates. Biological tests with lung adenocarcinoma cells (A549) were performed. Moreover, since 3D bioprinting is a rapidly evolving technology thanks to the possibility of precise deposition of cell-laden biomaterials (bioinks) to mimic the 3D structures of several tissues, the potential of different GelMA formulations as bioinks have been tested with a multi-material approach, revealing its printability and versatility in various applications.
    Keywords:  GelMA bioink; bioprinting; multimaterial 3D printing; sacrifical polymer; scaffold
    DOI:  https://doi.org/10.3389/fbioe.2024.1383010
  12. Front Bioeng Biotechnol. 2024 ;12 1363380
      Introduction: Autologous platelet concentrate (APC) are pro-angiogenic and can promote wound healing and tissue repair, also in combination with other biomaterials. However, challenging defect situations remain demanding. 3D bioprinting of an APC based bioink encapsulated in a hydrogel could overcome this limitation with enhanced physio-mechanical interface, growth factor retention/secretion and defect-personalized shape to ultimately enhance regeneration.Methods: This study used extrusion-based bioprinting to create a novel bioink of alginate/cellulose hydrogel loaded with thrombocyte concentrate. Chemico-physical testing exhibited an amorphous structure characterized by high shape fidelity. Cytotoxicity assay and incubation of human osteogenic sarcoma cells (SaOs2) exposed excellent biocompatibility. enzyme-linked immunosorbent assay analysis confirmed pro-angiogenic growth factor release of the printed constructs, and co-incubation with HUVECS displayed proper cell viability and proliferation. Chorioallantoic membrane (CAM) assay explored the pro-angiogenic potential of the prints in vivo. Detailed proteome and secretome analysis revealed a substantial amount and homologous presence of pro-angiogenic proteins in the 3D construct.
    Results: This study demonstrated a 3D bioprinting approach to fabricate a novel bioink of alginate/cellulose hydrogel loaded with thrombocyte concentrate with high shape fidelity, biocompatibility, and substantial pro-angiogenic properties.
    Conclusion: This approach may be suitable for challenging physiological and anatomical defect situations when translated into clinical use.
    Keywords:  additive manufacturing; bioprinting; hydrogel; platelet rich fibrin; reconstruction
    DOI:  https://doi.org/10.3389/fbioe.2024.1363380
  13. Front Bioeng Biotechnol. 2024 ;12 1347666
      3D structures are crucial to biological function in the human body, driving interest in their in vitro fabrication. Advances in shape-morphing materials allow the assembly of 3D functional materials with the ability to modulate the architecture, flexibility, functionality, and other properties of the final product that suit the desired application. The principles of these techniques correspond to the principles of origami and kirigami, which enable the transformation of planar materials into 3D structures by folding, cutting, and twisting the 2D structure. In these approaches, materials responding to a certain stimulus will be used to manufacture a preliminary structure. Upon applying the stimuli, the architecture changes, which could be considered the fourth dimension in the manufacturing process. Here, we briefly summarize manufacturing techniques, such as lithography and 3D printing, that can be used in fabricating complex structures based on the aforementioned principles. We then discuss the common architectures that have been developed using these methods, which include but are not limited to gripping, rolling, and folding structures. Then, we describe the biomedical applications of these structures, such as sensors, scaffolds, and minimally invasive medical devices. Finally, we discuss challenges and future directions in using shape-morphing materials to develop biomimetic and bioinspired designs.
    Keywords:  biosensors; kirigami; minimally invasive surgery; origami; shape-morphing materials; smart materials; tissue engineering
    DOI:  https://doi.org/10.3389/fbioe.2024.1347666
  14. Burns Trauma. 2024 ;12 tkae008
      Background: Small-diameter vascular grafts have become the focus of attention in tissue engineering. Thrombosis and aneurysmal dilatation are the two major complications of the loss of vascular access after surgery. Therefore, we focused on fabricating 3D printed electrospun vascular grafts loaded with tetramethylpyrazine (TMP) to overcome these limitations.Methods: Based on electrospinning and 3D printing, 3D-printed electrospun vascular grafts loaded with TMP were fabricated. The inner layer of the graft was composed of electrospun poly(L-lactic-co-caprolactone) (PLCL) nanofibers and the outer layer consisted of 3D printed polycaprolactone (PCL) microfibers. The characterization and mechanical properties were tested. The blood compatibility and in vitro cytocompatibility of the grafts were also evaluated. Additionally, rat abdominal aortas were replaced with these 3D-printed electrospun grafts to evaluate their biosafety.
    Results: Mechanical tests demonstrated that the addition of PCL microfibers could improve the mechanical properties. In vitro experimental data proved that the introduction of TMP effectively inhibited platelet adhesion. Afterwards, rat abdominal aorta was replaced with 3D-printed electrospun grafts. The 3D-printed electrospun graft loaded with TMP showed good biocompatibility and mechanical strength within 6 months and maintained substantial patency without the occurrence of acute thrombosis. Moreover, no obvious aneurysmal dilatation was observed.
    Conclusions: The study demonstrated that 3D-printed electrospun vascular grafts loaded with TMP may have the potential for injured vascular healing.
    Keywords:  3D printing; Aneurysmal dilatation; Electrospinning; Tetramethylpyrazine; Thrombosis; Vascular graft
    DOI:  https://doi.org/10.1093/burnst/tkae008
  15. ACS Appl Bio Mater. 2024 Apr 09.
      Salivary glands (SGs) play a vital role in maintaining oral health through the production and release of saliva. Injury to SGs can lead to gland hypofunction and a decrease in saliva secretion manifesting as xerostomia. While symptomatic treatments for xerostomia exist, effective permanent solutions are still lacking, emphasizing the need for innovative approaches. Significant progress has been made in the field of three-dimensional (3D) SG bioengineering for applications in gland regeneration. This has been achieved through a major focus on cell culture techniques, including soluble cues and biomaterial components of the 3D niche. Cells derived from both adult and embryonic SGs have highlighted key in vitro characteristics of SG 3D models. While still in its first decade of exploration, SG spheroids and organoids have so far served as crucial tools to study SG pathophysiology. This review, based on a literature search over the past decade, covers the importance of SG cell types in the realm of their isolation, sourcing, and culture conditions that modulate the 3D microenvironment. We discuss different biomaterials employed for SG culture and the current advances made in bioengineering SG models using them. The success of these 3D cellular models are further evaluated in the context of their applications in organ transplantation and in vitro disease modeling.
    Keywords:  Bioengineering; Disease modeling; Extra cellular matrix; Organoids; Salivary glands; Spheroids; Three-dimensional culture; Transplantation
    DOI:  https://doi.org/10.1021/acsabm.4c00028
  16. ACS Appl Mater Interfaces. 2024 Apr 08.
      Three-dimensional (3D)-printed biodegradable polymer scaffolds are at the forefront of personalized constructs for bone tissue engineering. However, it remains challenging to create a biological microenvironment for bone growth. Herein, we developed a novel yet feasible approach to facilitate biomimetic mineralization via self-adaptive nanotopography, which overcomes difficulties in the surface biofunctionalization of 3D-printed polycaprolactone (PCL) scaffolds. The building blocks of self-adaptive nanotopography were PCL lamellae that formed on the 3D-printed PCL scaffold via surface-directed epitaxial crystallization and acted as a linker to nucleate and generate hydroxyapatite crystals. Accordingly, a uniform and robust mineralized layer was immobilized throughout the scaffolds, which strongly bound to the strands and had no effect on the mechanical properties of the scaffolds. In vitro cell culture experiments revealed that the resulting scaffold was biocompatible and enhanced the proliferation and osteogenic differentiation of mouse embryolous osteoblast cells. Furthermore, we demonstrated that the resulting scaffold showed a strong capability to accelerate in vivo bone regeneration using a rabbit bone defect model. This study provides valuable opportunities to enhance the application of 3D-printed scaffolds in bone repair, paving the way for translation to other orthopedic implants.
    Keywords:  3D-Printed scaffold; Biomimetic mineralization; Bone repair; Osteogenesis; Self-adaptive nanotopology
    DOI:  https://doi.org/10.1021/acsami.4c02636