bims-biprem Biomed News
on Bioprinting for regenerative medicine
Issue of 2024–02–25
thirteen papers selected by
Seerat Maqsood, University of Teramo
  1. Calcium Phosphate Biomaterials for 3D Bioprinting in Bone Tissue Engineering.
  2. Preparation of Corneal Tissue Matrix Bioink for 3D Bioprinting.
  3. Additive Manufacturing Applications in Biosensors Technologies.
  4. Applications, advancements, and challenges of 3D bioprinting in organ transplantation.
  5. Three-Dimensional Bioprinting of Strontium-Modified Controlled Assembly of Collagen Polylactic Acid Composite Scaffold for Bone Repair.
  6. The Integration of 3D Virtual Reality and 3D Printing Technology as Innovative Approaches to Preoperative Planning in Neuro-Oncology.
  7. Ultrasound Mediated Polymerization for Cell Delivery, Drug Delivery, and 3D Printing.
  8. Embedded 3D Bioprinting for Engineering Miniaturized In Vitro Tumor Models.
  9. 3D Printing Cervical Implant Scaffolds Incorporated with Drug-Loaded Carboxylated Chitosan Microspheres for Long-Term Anti-HPV Protein Delivery.
  10. An Intelligent and Efficient Workflow for Path-Oriented 3D Bioprinting of Tubular Scaffolds.
  11. Development of 3D Printed pNIPAM-Chitosan Scaffolds for Dentoalveolar Tissue Engineering.
  12. Recent Developments in 3D-(Bio)printed Hydrogels as Wound Dressings.
  13. A 3D Bioprinted Human Neurovascular Unit Model of Glioblastoma Tumor Growth.
  1. Biomimetics (Basel). 2024 Feb 06. pii: 95. [Epub ahead of print]9(2):
    Calcium Phosphate Biomaterials for 3D Bioprinting in Bone Tissue Engineering.
    Nelli Tolmacheva, Amitava Bhattacharyya, Insup Noh.
      Three-dimensional bioprinting is a promising technology for bone tissue engineering. However, most hydrogel bioinks lack the mechanical and post-printing fidelity properties suitable for such hard tissue regeneration. To overcome these weak properties, calcium phosphates can be employed in a bioink to compensate for the lack of certain characteristics. Further, the extracellular matrix of natural bone contains this mineral, resulting in its structural robustness. Thus, calcium phosphates are necessary components of bioink for bone tissue engineering. This review paper examines different recently explored calcium phosphates, as a component of potential bioinks, for the biological, mechanical and structural properties required of 3D bioprinted scaffolds, exploring their distinctive properties that render them favorable biomaterials for bone tissue engineering. The discussion encompasses recent applications and adaptations of 3D-printed scaffolds built with calcium phosphates, delving into the scientific reasons behind the prevalence of certain types of calcium phosphates over others. Additionally, this paper elucidates their interactions with polymer hydrogels for 3D bioprinting applications. Overall, the current status of calcium phosphate/hydrogel bioinks for 3D bioprinting in bone tissue engineering has been investigated.
    Keywords:  3D bioprinting; bone; calcium phosphates; hydroxyapatite; octacalcium phosphate; tissue engineering
    DOI:  https://doi.org/10.3390/biomimetics9020095
  2. Methods Mol Biol. 2024 ;2764 15-20
    Preparation of Corneal Tissue Matrix Bioink for 3D Bioprinting.
    Shibu Chameettachal, Falguni Pati.
      There are many protocols available to decellularize tissues for the preparation of bioink for 3D bioprinting purposes. Almost all the methods comprise multiple chemicals and enzymes in different combinations. Here we describe the usage of sodium chloride that enables the decellularization of corneal tissues from human and animal sources, which is a simple, rapid, and detergent-free method, unlike conventional decellularization protocols. The method described here is for cornea tissue decellularization and its digestion and bioink preparation for 3D bioprinting applications. We demonstrate the efficient decellularization of tissues by retaining the extracellular matrix.
    Keywords:  Bioink; Cornea; Decellularization; Extracellular matrix; Sodium chloride
    DOI:  https://doi.org/10.1007/978-1-0716-3674-9_2
  3. Biosensors (Basel). 2024 Jan 23. pii: 60. [Epub ahead of print]14(2):
    Additive Manufacturing Applications in Biosensors Technologies.
    Abraham Abbey Paul, Adedamola D Aladese, Robert S Marks.
      Three-dimensional (3D) printing technology, also known as additive manufacturing (AM), has emerged as an attractive state-of-the-art tool for precisely fabricating functional materials with complex geometries, championing several advancements in tissue engineering, regenerative medicine, and therapeutics. However, this technology has an untapped potential for biotechnological applications, such as sensor and biosensor development. By exploring these avenues, the scope of 3D printing technology can be expanded and pave the way for groundbreaking innovations in the biotechnology field. Indeed, new printing materials and printers would offer new possibilities for seamlessly incorporating biological functionalities within the growing 3D scaffolds. Herein, we review the additive manufacturing applications in biosensor technologies with a particular emphasis on extrusion-based 3D printing modalities. We highlight the application of natural, synthetic, and composite biomaterials as 3D-printed soft hydrogels. Emphasis is placed on the approach by which the sensing molecules are introduced during the fabrication process. Finally, future perspectives are provided.
    Keywords:  3D (bio)printing; additive manufacturing; bioinks; biosensors; polymers
    DOI:  https://doi.org/10.3390/bios14020060
  4. Biomater Sci. 2024 Feb 20.
    Applications, advancements, and challenges of 3D bioprinting in organ transplantation.
    Guobin Huang, Yuanyuan Zhao, Dong Chen, Lai Wei, Zhiping Hu, Junbo Li, Xi Zhou, Bo Yang, Zhishui Chen.
      To date, organ transplantation remains an effective method for treating end-stage diseases of various organs. In recent years, despite the continuous development of organ transplantation technology, a variety of problems restricting its progress have emerged one after another, and the shortage of donors is at the top of the list. Bioprinting is a very useful tool that has huge application potential in many fields of life science and biotechnology, among which its use in medicine occupies a large area. With the development of bioprinting, advances in medicine have focused on printing cells and tissues for tissue regeneration and reconstruction of viable human organs, such as the heart, kidneys, and bones. In recent years, with the development of organ transplantation, three-dimensional (3D) bioprinting has played an increasingly important role in this field, giving rise to many unsolved problems, including a shortage of organ donors. This review respectively introduces the development of 3D bioprinting as well as its working principles and main applications in the medical field, especially in the applications, and advancements and challenges of 3D bioprinting in organ transplantation. With the continuous update and progress of printing technology and its deeper integration with the medical field, many obstacles will have new solutions, including tissue repair and regeneration, organ reconstruction, etc., especially in the field of organ transplantation. 3D printing technology will provide a better solution to the problem of donor shortage.
    DOI:  https://doi.org/10.1039/d3bm01934a
  5. Polymers (Basel). 2024 Feb 11. pii: 498. [Epub ahead of print]16(4):
    Three-Dimensional Bioprinting of Strontium-Modified Controlled Assembly of Collagen Polylactic Acid Composite Scaffold for Bone Repair.
    Weiwei Sun, Wenyu Xie, Kun Hu, Zongwen Yang, Lu Han, Luhai Li, Yuansheng Qi, Yen Wei.
      In recent years, the incidence of bone defects has been increasing year by year. Bone transplantation has become the most needed surgery after a blood transfusion and shows a rising trend. Three-dimensional-printed implants can be arbitrarily shaped according to the defects of tissues and organs to achieve perfect morphological repair, opening a new way for non-traumatic repair and functional reconstruction. In this paper, strontium-doped mineralized collagen was first prepared by an in vitro biomimetic mineralization method and then polylactic acid was homogeneously blended with the mineralized collagen to produce a comprehensive bone repair scaffold by a gas extrusion 3D printing method. Characterization through scanning electron microscopy, X-ray diffraction, and mechanical testing revealed that the strontium-functionalized composite scaffold exhibits an inorganic composition and nanostructure akin to those of human bone tissue. The scaffold possesses uniformly distributed and interconnected pores, with a compressive strength reaching 21.04 MPa. The strontium doping in the mineralized collagen improved the biocompatibility of the scaffold and inhibited the differentiation of osteoclasts to promote bone regeneration. This innovative composite scaffold holds significant promise in the field of bone tissue engineering, providing a forward-thinking solution for prospective bone injury repair.
    Keywords:  3D bioprinting; PLA; bone tissue engineering; controlled assembly; mineralized collagen
    DOI:  https://doi.org/10.3390/polym16040498
  6. J Pers Med. 2024 Feb 07. pii: 187. [Epub ahead of print]14(2):
    The Integration of 3D Virtual Reality and 3D Printing Technology as Innovative Approaches to Preoperative Planning in Neuro-Oncology.
    Pablo González-López, Artem Kuptsov, Cristina Gómez-Revuelta, Jaime Fernández-Villa, Javier Abarca-Olivas, Roy T Daniel, Torstein R Meling, Juan Nieto-Navarro.
      Our study explores the integration of three-dimensional (3D) virtual reality (VR) and 3D printing in neurosurgical preoperative planning. Traditionally, surgeons relied on two-dimensional (2D) imaging for complex neuroanatomy analyses, requiring significant mental visualization. Fortunately, nowadays advanced technology enables the creation of detailed 3D models from patient scans, utilizing different software. Afterwards, these models can be experienced through VR systems, offering comprehensive preoperative rehearsal opportunities. Additionally, 3D models can be 3D printed for hands-on training, therefore enhancing surgical preparedness. This technological integration transforms the paradigm of neurosurgical planning, ensuring safer procedures.
    Keywords:  3D printing technology; neuroanatomy; surgical planning; surgical simulation; virtual reality
    DOI:  https://doi.org/10.3390/jpm14020187
  7. Small Methods. 2024 Feb 20. e2301197
    Ultrasound Mediated Polymerization for Cell Delivery, Drug Delivery, and 3D Printing.
    Lior Debbi, Majd Machour, Daniel Dahis, Hagit Shoyhet, Margarita Shuhmaher, Ruth Potter, Yael Tabory, Idit Goldfracht, Itiel Dennis, Tom Blechman, Theodor Fuchs, Haim Azhari, Shulamit Levenberg.
      Safe and accurate in situ delivery of biocompatible materials is a fundamental requirement for many biomedical applications. These include sustained and local drug release, implantation of acellular biocompatible scaffolds, and transplantation of cells and engineered tissues for functional restoration of damaged tissues and organs. The common practice today includes highly invasive operations with major risks of surgical complications including adjacent tissue damage, infections, and long healing periods. In this work, a novel non-invasive delivery method is presented for scaffold, cells, and drug delivery deep into the body to target inner tissues. This technology is based on acousto-sensitive materials which are polymerized by ultrasound induction through an external transducer in a rapid and local fashion without additional photoinitiators or precursors. The applicability of this technology is demonstrated for viable and functional cell delivery, for drug delivery with sustained release profiles, and for 3D printing. Moreover, the mechanical properties of the delivered scaffold can be tuned to the desired target tissue as well as controlling the drug release profile. This promising technology may shift the paradigm for local and non-invasive material delivery approach in many clinical applications as well as a new printing method - "acousto-printing" for 3D printing and in situ bioprinting.
    Keywords:  cell delivery; drug delivery; non-invasive bioprinting; ultrasound mediated polymerization
    DOI:  https://doi.org/10.1002/smtd.202301197
  8. Methods Mol Biol. 2024 ;2764 279-288
    Embedded 3D Bioprinting for Engineering Miniaturized In Vitro Tumor Models.
    Maria V Monteiro, Marta Rocha, Vítor M Gaspar, João F Mano.
      Embedded extrusion 3D bioprinting is a rapidly emerging additive manufacturing methodology that provides a precise spatial deposition of synthetic or natural-origin low-viscosity bioinks during the extrusion printing process. Such a strategy has to date unlocked the freeform extrusion biofabrication of complex micro-to-macro-scale living architectures for numerous applications, including tissue engineering and in vitro disease modeling. In this chapter, we describe a suspension bioprinting methodology leveraging a continuous viscoelastic biopolymer supporting bath functionalized with divalent calcium cations to enable a rapid processing of user-defined bioinks toward architecturally complex 3D in vitro tumor models. This highly simple and cost-effective viscoelastic supporting bath enables a full freeform biofabrication of cell-laden 3D tumor-mimetic architectures that exhibit structural stability in culture post-printing. The cytocompatibility of the supporting bath, its ease of removal from biofabricated living constructs, and its adaptability for processing different ECM-mimetic bioinks open avenues for multi-scale fabrication of numerous types of physiomimetic 3D tumor models for preclinical screening of candidate therapeutics.
    Keywords:  Biofabrication; Embedded extrusion bioprinting; In vitro tumor models; Preclinical therapies screening; Supporting bath
    DOI:  https://doi.org/10.1007/978-1-0716-3674-9_18
  9. ACS Biomater Sci Eng. 2024 Feb 18.
    3D Printing Cervical Implant Scaffolds Incorporated with Drug-Loaded Carboxylated Chitosan Microspheres for Long-Term Anti-HPV Protein Delivery.
    Jingyuan Ji, Chenjia Zhao, Chen Hua, Lu Lu, Yuan Pang, Wei Sun.
      As attempting personalized medicine, 3D-printed tissue engineering scaffolds are employed to combine with therapeutic proteins/peptides especially in the clinical treatment of infectious diseases, genetic diseases, and cancers. However, current drug-loading methods, such as immersion and encapsulation, usually lead to the burst release of the drugs. To address these issues, we proposed an integrated strategy toward the long-term controlled release of protein. In this study, patient-customized 3D scaffolds incorporated with drug-loaded microspheres were printed to realize the effective delivery of the anti-human papillomavirus (anti-HPV) protein after cervical conization in the treatment of cervical cancer. The 3D-printed scaffold could provide mechanical support to the defect site and ensure local release of the drug to avoid systemic administration. Meanwhile, microspheres serve as functional components to prevent the inactivation of proteins, as well as regulate their release period to meet the time requirement of different treatment courses. The research also utilized bovine serum albumin as a model protein to validate the feasibility of these scaffolds as a generic technology platform. The bioactivity of the released anti-HPV protein was validated using a pseudovirus model, which demonstrated that the microsphere encapsulation would not cause protein denaturation during the scaffold fabrication process. Besides, 3D-printed scaffolds incorporated with carboxylated chitosan microspheres were biocompatible and beneficial for cell attachment, which have been demonstrated by favorable cell viability and better coverage results for HeLa and HFF-1. This study highlights the great potential of scaffolds incorporated with microspheres to serve as tissue engineering candidate products with the function of effective protein delivery in a long-term controlled manner and personalized shapes for clinical trials.
    Keywords:  3D printing; 3D scaffold; anti-HPV protein; drug delivery; microsphere
    DOI:  https://doi.org/10.1021/acsbiomaterials.3c01594
  10. 3D Print Addit Manuf. 2024 Feb 01. 11(1): 323-332
    An Intelligent and Efficient Workflow for Path-Oriented 3D Bioprinting of Tubular Scaffolds.
    Timo Baroth, Sebastian Loewner, Henrik Heymann, Fabian Cholewa, Holger Blume, Cornelia Blume.
      Modern 3D printing is a valuable tool for tissue engineering (TE), and the fabrication of complex geometries such as tubular scaffolds with adaptable structure, for example, as replacements for intestines, bronchi, esophagus, or vessels, could contribute to standardized procedures in the future of regenerative medicine. However, high-precision bioprinting of scaffolds for tubular TE applications remain a major challenge and is an arduous endeavor with currently available three-axis bioprinters, which are limited to planar, layer-by-layer printing processes. In this work, a novel, straightforward workflow for creating toolpaths and command sets for tubular scaffolds is presented. By combining a custom software application with commercial 3D design software, a comparatively large degree of design freedom was achieved while ensuring ease of use and extensibility for future research needs. As a hardware platform, two commercial 3D bioprinters were retrofitted with a rotary axis to accommodate cylindrical mandrels as print beds, overcoming the limitations of planar print beds. The printing process using the new method was evaluated in terms of the mechanical, actuation, and synchronization characteristics of the linear and rotating axes, as well as the stability of the printing process. In this context, it became clear that extrusion-based printing processes are very sensitive to positioning errors when used with small nozzles. Despite these technical difficulties, the new process can produce single-layer, multilayer, and multimaterial structures with a wide range of pore geometries. In addition, extrusion-based printing processes can be combined with melt electrowriting to produce durable scaffolds with features in the micrometer to millimeter range. Overall, the suitability of this setup for a wide range of TE applications has thus been demonstrated.
    Keywords:  4-axis printing; mandrel; nonplanar; tubular scaffold; vascular graft
    DOI:  https://doi.org/10.1089/3dp.2022.0201
  11. Gels. 2024 Feb 12. pii: 140. [Epub ahead of print]10(2):
    Development of 3D Printed pNIPAM-Chitosan Scaffolds for Dentoalveolar Tissue Engineering.
    Mehdi Salar Amoli, Resmi Anand, Mostafa EzEldeen, Liesbet Geris, Reinhilde Jacobs, Veerle Bloemen.
      While available treatments have addressed a variety of complications in the dentoalveolar region, associated challenges have resulted in exploration of tissue engineering techniques. Often, scaffold biomaterials with specific properties are required for such strategies to be successful, development of which is an active area of research. This study focuses on the development of a copolymer of poly (N-isopropylacrylamide) (pNIPAM) and chitosan, used for 3D printing of scaffolds for dentoalveolar regeneration. The synthesized material was characterized by Fourier transform infrared spectroscopy, and the possibility of printing was evaluated through various printability tests. The rate of degradation and swelling was analyzed through gravimetry, and surface morphology was characterized by scanning electron microscopy. Viability of dental pulp stem cells seeded on the scaffolds was evaluated by live/dead analysis and DNA quantification. The results demonstrated successful copolymerization, and three formulations among various synthesized formulations were successfully 3D printed. Up to 35% degradability was confirmed within 7 days, and a maximum swelling of approximately 1200% was achieved. Furthermore, initial assessment of cell viability demonstrated biocompatibility of the developed scaffolds. While further studies are required to achieve the tissue engineering goals, the present results tend to indicate that the proposed hydrogel might be a valid candidate for scaffold fabrication serving dentoalveolar tissue engineering through 3D printing.
    Keywords:  3D printing; chitosan; degradability; dental pulp stem cells; pNIPAM
    DOI:  https://doi.org/10.3390/gels10020140
  12. Gels. 2024 Feb 14. pii: 147. [Epub ahead of print]10(2):
    Recent Developments in 3D-(Bio)printed Hydrogels as Wound Dressings.
    Olga Kammona, Evgenia Tsanaktsidou, Costas Kiparissides.
      Wound healing is a physiological process occurring after the onset of a skin lesion aiming to reconstruct the dermal barrier between the external environment and the body. Depending on the nature and duration of the healing process, wounds are classified as acute (e.g., trauma, surgical wounds) and chronic (e.g., diabetic ulcers) wounds. The latter take several months to heal or do not heal (non-healing chronic wounds), are usually prone to microbial infection and represent an important source of morbidity since they affect millions of people worldwide. Typical wound treatments comprise surgical (e.g., debridement, skin grafts/flaps) and non-surgical (e.g., topical formulations, wound dressings) methods. Modern experimental approaches include among others three dimensional (3D)-(bio)printed wound dressings. The present paper reviews recently developed 3D (bio)printed hydrogels for wound healing applications, especially focusing on the results of their in vitro and in vivo assessment. The advanced hydrogel constructs were printed using different types of bioinks (e.g., natural and/or synthetic polymers and their mixtures with biological materials) and printing methods (e.g., extrusion, digital light processing, coaxial microfluidic bioprinting, etc.) and incorporated various bioactive agents (e.g., growth factors, antibiotics, antibacterial agents, nanoparticles, etc.) and/or cells (e.g., dermal fibroblasts, keratinocytes, mesenchymal stem cells, endothelial cells, etc.).
    Keywords:  3D bioprinting; hydrogels; polymers; wound dressings; wound healing
    DOI:  https://doi.org/10.3390/gels10020147
  13. Adv Healthc Mater. 2024 Feb 23. e2302831
    A 3D Bioprinted Human Neurovascular Unit Model of Glioblastoma Tumor Growth.
    Yen-Ting Tung, Yu-Chi Chen, Kristy Derr, Kelli Wilson, Min Jae Song, Marc Ferrer.
      A 3D bioprinted neurovascular unit (NVU) model was developed to study glioblastoma (GBM) tumor growth in a brain-like microenvironment. The NVU model included human primary astrocytes, pericytes and brain microvascular endothelial cells, and patient-derived glioblastoma cells (JHH-520) were used for this study. We used fluorescence reporters with confocal high content imaging to quantitate real-time microvascular network formation and tumor growth. Extensive validation of the NVU-GBM model included immunostaining for brain relevant cellular markers and extracellular matrix components; single cell RNA sequencing to establish physiologically relevant transcriptomics changes; and secretion of NVU and GBM-relevant cytokines. The scRNAseq revealed changes in gene expression and cytokines secretion associated with wound healing/angiogenesis, including the appearance of an endothelial mesenchymal transition (EndMT) cell population. The NVU-GBM model was used to test 18 chemotherapeutics and anti-cancer drugs to assess the pharmacological relevance of the model and robustness for high throughput screening. This article is protected by copyright. All rights reserved.
    Keywords:  3D Bioprinting; High-Throughput Screening; Neurovascular unit; Transcriptomics; glioblastoma
    DOI:  https://doi.org/10.1002/adhm.202302831
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