bims-biprem Biomed News
on Bioprinting for regenerative medicine
Issue of 2024‒03‒10
ten papers selected by
Seerat Maqsood, University of Teramo



  1. J Mater Chem B. 2024 Mar 04.
      While three-dimensional (3D) printing excels at fabricating static constructs, it fails to emulate the dynamic behavior of native tissues or the temporal programmability desired for medical devices. Four-dimensional (4D) printing is an advanced additive manufacturing technology capable of fabricating constructs that can undergo pre-programmed changes in shape, property, or functionality when exposed to specific stimuli. In this Perspective, we summarize the advances in materials chemistry, 3D printing strategies, and post-printing methodologies that collectively facilitate the realization of temporal dynamics within 4D-printed soft materials (hydrogels, shape-memory polymers, liquid crystalline elastomers), ceramics, and metals. We also discuss and present insights about the diverse biomedical applications of 4D printing, including tissue engineering and regenerative medicine, drug delivery, in vitro models, and medical devices. Finally, we discuss the current challenges and emphasize the importance of an application-driven design approach to enable the clinical translation and widespread adoption of 4D printing.
    DOI:  https://doi.org/10.1039/d4tb00006d
  2. Adv Drug Deliv Rev. 2024 Mar 04. pii: S0169-409X(24)00059-0. [Epub ahead of print] 115237
      Organoid cultures offer a valuable platform for studying organ-level biology, allowing for a closer mimicry of human physiology compared to traditional two-dimensional cell culture systems or non-primate animal models. While many organoid cultures use cell aggregates or decellularized extracellular matrices as scaffolds, they often lack precise biochemical and biophysical microenvironments. In contrast, three-dimensional (3D) bioprinting allows precise placement of organoids or spheroids, providing enhanced spatial control and facilitating the direct fusion for the formation of large-scale functional tissues in vitro. In addition, 3D bioprinting enables fine tuning of biochemical and biophysical cues to support organoid development and maturation. With advances in the organoid technology and its potential applications across diverse research fields such as cell biology, developmental biology, disease pathology, precision medicine, drug toxicology, and tissue engineering, organoid imaging has become a crucial aspect of physiological and pathological studies. This review highlights the recent advancements in imaging technologies that have significantly contributed to organoid research. Additionally, we discuss various bioprinting techniques, emphasizing their applications in organoid bioprinting. Integrating 3D imaging tools into a bioprinting platform allows real-time visualization while facilitating quality control, optimization, and comprehensive bioprinting assessment. Similarly, combining imaging technologies with organoid bioprinting can provide valuable insights into tissue formation, maturation, functions, and therapeutic responses. This approach not only improves the reproducibility of physiologically relevant tissues but also enhances understanding of complex biological processes. Thus, careful selection of bioprinting modalities, coupled with appropriate imaging techniques, holds the potential to create a versatile platform capable of addressing existing challenges and harnessing opportunities in these rapidly evolving fields.
    Keywords:  3D bioprinting; Biofabrication; Biomedicine; Imaging; Organoids
    DOI:  https://doi.org/10.1016/j.addr.2024.115237
  3. Adv Sci (Weinh). 2024 Mar 06. e2308381
      3D bioprinting techniques have enabled the fabrication of irregular large-sized tissue engineering scaffolds. However, complicated customized designs increase the medical burden. Meanwhile, the integrated printing process hinders the cellular uniform distribution and local angiogenesis. A novel approach is introduced to the construction of sizable tissue engineering grafts by employing hydrogel 3D printing for modular bioadhesion assembly, and a poly (ethylene glycol) diacrylate (PEGDA)-gelatin-dopamine (PGD) hydrogel, photosensitive and adhesive, enabling fine microcage module fabrication via DLP 3D printing is developed. The PGD hydrogel printed micocages are flexible, allowing various shapes and cell/tissue fillings for repairing diverse irregular tissue defects. In vivo experiments demonstrate robust vascularization and superior graft survival in nude mice. This assembly strategy based on scalable 3D printed hydrogel microcage module could simplify the construction of tissue with large volume and complex components, offering promise for diverse large tissue defect repairs.
    Keywords:  3D bioprinting; 3D printing; assembly; bioadhesion; hydrogel; tissue engineering
    DOI:  https://doi.org/10.1002/advs.202308381
  4. Int J Biol Macromol. 2024 Mar 05. pii: S0141-8130(24)01407-7. [Epub ahead of print]264(Pt 1): 130604
      Skin, the largest organ in the body, blocks the entry of environmental pollutants into the system. Any injury to this organ allows infections and other harmful substances into the body. 3D bioprinting, a state-of-the-art technique, is suitable for fabricating cell culture scaffolds to heal chronic wounds rapidly. This study uses starch extracted from Maranta arundinacea (Arrowroot plant) (AS) and gellan gum (GG) to develop a bioink for 3D printing a scaffold capable of hosting animal cells. Field emission scanning electron microscopy (FE-SEM) and X-ray diffraction analysis (XRD) prove that the isolated AS is analogous to commercial starch. The cell culture scaffolds developed are superior to the existing monolayer culture. Infrared microscopy shows the AS-GG interaction and elucidates the mechanism of hydrogel formation. The physicochemical properties of the 3D-printed scaffold are analyzed to check the cell adhesion and growth; SEM images have confirmed that the AS-GG printed scaffold can support cell growth and proliferation, and the MTT assay shows good cell viability. Cell behavioral and migration studies reveal that cells are healthy. Since the scaffold is biocompatible, it can be 3D printed to any shape and structure and will biodegrade in the requisite time.
    Keywords:  3D printing; Bioink; Hydrogel
    DOI:  https://doi.org/10.1016/j.ijbiomac.2024.130604
  5. Acta Biomater. 2024 Mar 06. pii: S1742-7061(24)00117-X. [Epub ahead of print]
      Bone metastasis primarily occurs when breast, prostate, or lung cancers disseminate tumoral cells into bone tissue, leading to a range of complications in skeletal tissues and, in severe cases, paralysis resulting from spinal cord compression. Unfortunately, our understanding of pathophysiological mechanisms is incomplete and the translation of bone metastasis research into the clinic has been slow, mainly due to the lack of credible ex vivo and in vivo models to study the disease progression. Development of reliable and rational models to study how tumor cells become circulating cells and then invade and sequentially colonize the bone are in great need. Advances in tissue engineering technologies offers reliable 3D tissue alternatives which answer relevant research questions towards the understanding of cancer evolution and key functional properties of metastasis progression as well as prognosis of therapeutic approach. Here we performed an overview of cellular mechanisms involved in bone metastasis including a short summary of normal bone physiology and metastasis initiation and progression. Also, we comprehensively summarized current advances and methodologies in fabrication of reliable bone tumor models based on state-of-the-art printing technologies which recapitulate structural and biological features of native tissue. STATEMENT OF SIGNIFICANCE: This review provides a comprehensive summary of the collective findings in relation to various printed bone metastasis models utilized for investigating specific bone metastasis diseases, related characteristic functions and chemotherapeutic drug screening. These tumoral models are comprehensively evaluated and compared, in terms of their ability to recapitulate physiological metastasis microenvironment. Various biomaterials (natural and synthetic polymers and ceramic based substrates) and printing strategies and design architecture of models used for printing of 3D bone metastasis models are discussed here. This review clearly out-lines current challenges and prospects for 3D printing technologies in bone metastasis research by focusing on the required perspective models for clinical application of these technologies in chemotherapeutic drug screening.
    Keywords:  3D biomimetic tumoral models; Biomaterials; Bone metastasis; Printing/bioprinting technologies
    DOI:  https://doi.org/10.1016/j.actbio.2024.02.046
  6. Small. 2024 Mar 03. e2307750
      As an innovative technology, four-dimentional (4D) printing is built upon the principles of three-dimentional (3D) printing with an additional dimension: time. While traditional 3D printing creates static objects, 4D printing generates "responsive 3D printed structures", enabling them to transform or self-assemble in response to external stimuli. Due to the dynamic nature, 4D printing has demonstrated tremendous potential in a range of industries, encompassing aerospace, healthcare, and intelligent devices. Nanotechnology has gained considerable attention owing to the exceptional properties and functions of nanomaterials. Incorporating nanomaterials into an intelligent matrix enhances the physiochemical properties of 4D printed constructs, introducing novel functions. This review provides a comprehensive overview of current applications of nanomaterials in 4D printing, exploring their synergistic potential to create dynamic and responsive structures. Nanomaterials play diverse roles as rheology modifiers, mechanical enhancers, function introducers, and more. The overarching goal of this review is to inspire researchers to delve into the vast potential of nanomaterial-enabled 4D printing, propelling advancements in this rapidly evolving field.
    Keywords:  4D Printing; nanocomposites; nanomaterials; shape memory materials
    DOI:  https://doi.org/10.1002/smll.202307750
  7. Biomater Adv. 2024 Feb 28. pii: S2772-9508(24)00059-1. [Epub ahead of print]159 213816
      Tissue engineering (TE) has sparked interest in creating scaffolds with customizable properties and functional bioactive sites. However, due to limitations in medical practices and manufacturing technologies, it is challenging to replicate complex porous frameworks with appropriate architectures and bioactivity in vitro. To address these challenges, herein, we present a green approach that involves the amino acid (l-lysine) initiated polymerization of ɛ-caprolactone (CL) to produce modified polycaprolactone (PCL) with favorable active sites for TE applications. Further, to better understand the effect of morphology and porosity on cell attachment and proliferation, scaffolds of different geometries with uniform and interconnected pores are designed and fabricated, and their properties are evaluated in comparison with commercial PCL. The scaffold morphology and complex internal micro-architecture are imaged by micro-computed tomography (micro-CT), revealing pore size in the range of ~300-900 μm and porosity ranging from 30 to 70 %, while based on the geometry of scaffolds the compressive strength varied from 143 ± 19 to 214 ± 10 MPa. Additionally, the degradation profiles of fabricated scaffolds are found to be influenced by both the chemical nature and product design, where Lys-PCL-based scaffolds with better porosity and lower crystallinity degraded faster than commercial PCL scaffolds. According to in vitro studies, Lys-PCL scaffolds have produced an environment that is better for cell adhesion and proliferation. Moreover, the scaffold design affects the way cells interact; Lys-PCL with zigzag geometry has demonstrated superior in vitro vitality (>90 %) and proliferation in comparison to other designs. This study emphasizes the importance of enhancing bioactivity while meeting morphology and porosity requirements in the design of scaffolds for tissue engineering applications.
    Keywords:  Additive manufacturing; Amino acid; Micro-computed tomography; Polycaprolactone
    DOI:  https://doi.org/10.1016/j.bioadv.2024.213816
  8. Adv Mater. 2024 Mar 04. e2312263
      Four-dimensional (4D) printing has attracted tremendous worldwide attention during the past decade. This technology enables the shape, property, or functionality of printed structures to change with time in response to diverse external stimuli, making the original static structures alive. The revolutionary 4D-printing technology offers remarkable benefits in controlling the geometric and functional reconfiguration, thereby showcasing immense potential across diverse fields, including biomedical engineering, electronics, robotics, and photonics. Here, a comprehensive review of the latest achievements on 4D printing using various types of materials and different additive manufacturing techniques is presented. The state-of-the-art strategies implemented in harnessing various 4D-printed structures are highlighted, which involve materials design, stimuli, functionalities, and applications. The machine learning approach explored for 4D printing is also discussed. Finally, the perspectives on the current challenges and future trends toward further development in 4D printing are summarized. This article is protected by copyright. All rights reserved.
    Keywords:  4D printing; functionality; multi-materiall; stimuli-responsive materials
    DOI:  https://doi.org/10.1002/adma.202312263
  9. Clin Case Rep. 2024 Mar;12(3): e8630
      This research investigates the trueness and precision of 3D printing technology in dental applications, specifically focusing on dimensional variations observed in models printed at different angles. The methodology involved importing a dental model into slicing software, adjusting its orientation, and implementing support structures for stability. Subsequently, the model underwent 3D printing five times for each orientation using appropriate equipment and underwent post-processing steps, including cleaning, washing, and UV-light post-curing. The printed models were then scanned using a specialized desktop scanner for further analysis. Accuracy assessment was carried out using dedicated software, employing an algorithm for precise alignment by comparing the scanned files. Color deviation maps were utilized to visually represent variations, aiming to evaluate how positioning during printing influences the trueness and precision of 3D-printed dental models. Trueness and precision analyses involved the Shapiro-Wilk test for normality and a one-way ANOVA to compare means of three independent groups, with statistical analyses conducted using IBM SPSS Statistics software. The color maps derived from 3D comparisons revealed positive and negative deviations, represented by distinct colors. Comparative results indicated that models positioned at 0° exhibited the least dimensional deviation, whereas those at 90° showed the highest. Regarding precision, models printed at 0° demonstrated the highest reproducibility, while those at 15° exhibited the lowest. Based on the desired level of precision, it is recommended that printed models be produced at an inclination angle of 0°.
    Keywords:  3D print; accuracy; dental model; resin; software; trueness
    DOI:  https://doi.org/10.1002/ccr3.8630
  10. Int J Biol Macromol. 2024 Mar 06. pii: S0141-8130(24)01499-5. [Epub ahead of print] 130696
      There has been significant progress in the field of three-dimensional (3D) bioprinting technology, leading to active research on creating bioinks capable of producing structurally and functionally tissue-mimetic constructs. Ti3C2Tx MXene nanoparticles (NPs), promising two-dimensional nanomaterials, are being investigated for their potential in muscle regeneration due to their unique physicochemical properties. In this study, we integrated MXene NPs into composite hydrogels made of gelatin methacryloyl (GelMA) and hyaluronic acid methacryloyl (HAMA) to develop bioinks (namely, GHM bioink) that promote myogenesis. The prepared GHM bioinks were found to offer excellent printability with structural integrity, cytocompatibility, and microporosity. Additionally, MXene NPs within the 3D bioprinted constructs encouraged the differentiation of C2C12 cells into skeletal muscle cells without additional support of myogenic agents. Genetic analysis indicated that representative myogenic markers both for early and late myogenesis were significantly up-regulated. Moreover, animal studies demonstrated that GHM bioinks contributed to enhanced regeneration of skeletal muscle while reducing immune responses in mice models with volumetric muscle loss (VML). Our results suggest that the GHM hydrogel can be exploited to craft a range of strategies for the development of a novel bioink to facilitate skeletal muscle regeneration because these MXene-incorporated composite materials have the potential to promote myogenesis.
    Keywords:  3D bioprinting; Hydrogel; MXene nanoparticles; Myogenesis; Skeletal muscle regeneration; Volumetric muscle loss
    DOI:  https://doi.org/10.1016/j.ijbiomac.2024.130696