bims-biprem Biomed News
on Bioprinting for regenerative medicine
Issue of 2023–11–05
thirteen papers selected by
Seerat Maqsood, University of Teramo
  1. Embedded 3D bioprinting - An emerging strategy to fabricate biomimetic & large vascularized tissue constructs.
  2. Applications of Scaffolds in Tissue Engineering: Current Utilization and Future Prospective.
  3. Intelligent Vascularized 3D/4D/5D/6D-Printed Tissue Scaffolds.
  4. Decellularized tracheal scaffold as a promising 3D scaffold for tissue engineering applications.
  5. Enhancing Craniofacial Bone Reconstruction with Clinically Applicable 3D Bioprinted Constructs.
  6. Three-Dimensional Printing of Polycaprolactone/Nano-Hydroxyapatite Composite Scaffolds with a Pore Size of 300/500 µm is Histocompatible and Promotes Osteogenesis Using Rabbit Cortical Bone Marrow Stem Cells.
  7. Application of 3D printing technology in tumor diagnosis and treatment.
  8. A novel perfusion bioreactor promotes the expansion of pluripotent stem cells in a 3D-bioprinted tissue chamber.
  9. 3D-Printed Flat-Bone-Mimetic Bioceramic Scaffolds for Cranial Restoration.
  10. 3D-printed PCL scaffolds with anatomy-inspired bionic stratified structures for the treatment of growth plate injuries.
  11. A 3d In Vitro Cortical Tissue Model Based on Dense Collagen to Study The Effects of Gamma Radiation on Neuronal Function.
  12. Three-Dimensional Acoustic Assembly Device for Mass Manufacturing of Cell Spheroids.
  13. 3D printing technology to produce intraoral stents for head and neck radiotherapy: A scoping review.
  1. Bioact Mater. 2024 Feb;32 356-384
    Embedded 3D bioprinting - An emerging strategy to fabricate biomimetic & large vascularized tissue constructs.
    Harshavardhan Budharaju, Dhakshinamoorthy Sundaramurthi, Swaminathan Sethuraman.
      Three-dimensional bioprinting is an advanced tissue fabrication technique that allows printing complex structures with precise positioning of multiple cell types layer-by-layer. Compared to other bioprinting methods, extrusion bioprinting has several advantages to print large-sized tissue constructs and complex organ models due to large build volume. Extrusion bioprinting using sacrificial, support and embedded strategies have been successfully employed to facilitate printing of complex and hollow structures. Embedded bioprinting is a gel-in-gel approach developed to overcome the gravitational and overhanging limits of bioprinting to print large-sized constructs with a micron-scale resolution. In embedded bioprinting, deposition of bioinks into the microgel or granular support bath will be facilitated by the sol-gel transition of the support bath through needle movement inside the granular medium. This review outlines various embedded bioprinting strategies and the polymers used in the embedded systems with advantages, limitations, and efficacy in the fabrication of complex vascularized tissues or organ models with micron-scale resolution. Further, the essential requirements of support bath systems like viscoelasticity, stability, transparency and easy extraction to print human scale organs are discussed. Additionally, the organs or complex geometries like vascular constructs, heart, bone, octopus and jellyfish models printed using support bath assisted printing methods with their anatomical features are elaborated. Finally, the challenges in clinical translation and the future scope of these embedded bioprinting models to replace the native organs are envisaged.
    Keywords:  Bioinks; Bioprinting; Complex bioprinting; Embedded bioprinting; Organ models bioprinting; Supportive bioprinting
    DOI:  https://doi.org/10.1016/j.bioactmat.2023.10.012
  2. Curr Gene Ther. 2023 Oct 26.
    Applications of Scaffolds in Tissue Engineering: Current Utilization and Future Prospective.
    Shikha Yadav, Javed Khan, Agrima Yadav.
      Current regenerative medicine tactics focus on regenerating tissue structures pathologically modified by cell transplantation in combination with supporting scaffolds and biomolecules. Natural and synthetic polymers, bioresorbable inorganic and hybrid materials, and tissue decellularized were deemed biomaterials scaffolding because of their improved structural, mechanical, and biological abilities.Various biomaterials, existing treatment methodologies and emerging technologies in the field of Three-dimensional (3D) and hydrogel processing, and the unique fabric concerns for tissue engineering. A scaffold that acts as a transient matrix for cell proliferation and extracellular matrix deposition, with subsequent expansion, is needed to restore or regenerate the tissue. Diverse technologies are combined to produce porous tissue regenerative and tailored release of bioactive substances in applications of tissue engineering. Tissue engineering scaffolds are crucial ingredients. This paper discusses an overview of the various scaffold kinds and their material features and applications. Tabulation of the manufacturing technologies for fabric engineering and equipment, encompassing the latest fundamental and standard procedures.
    Keywords:  Biomaterials; Hydrogels; Polymers; Scaffolds; Tissue engineering
    DOI:  https://doi.org/10.2174/0115665232262167231012102837
  3. Nanomicro Lett. 2023 Oct 31. 15(1): 239
    Intelligent Vascularized 3D/4D/5D/6D-Printed Tissue Scaffolds.
    Xiaoyu Han, Qimanguli Saiding, Xiaolu Cai, Yi Xiao, Peng Wang, Zhengwei Cai, Xuan Gong, Weiming Gong, Xingcai Zhang, Wenguo Cui.
      Blood vessels are essential for nutrient and oxygen delivery and waste removal. Scaffold-repairing materials with functional vascular networks are widely used in bone tissue engineering. Additive manufacturing is a manufacturing technology that creates three-dimensional solids by stacking substances layer by layer, mainly including but not limited to 3D printing, but also 4D printing, 5D printing and 6D printing. It can be effectively combined with vascularization to meet the needs of vascularized tissue scaffolds by precisely tuning the mechanical structure and biological properties of smart vascular scaffolds. Herein, the development of neovascularization to vascularization to bone tissue engineering is systematically discussed in terms of the importance of vascularization to the tissue. Additionally, the research progress and future prospects of vascularized 3D printed scaffold materials are highlighted and presented in four categories: functional vascularized 3D printed scaffolds, cell-based vascularized 3D printed scaffolds, vascularized 3D printed scaffolds loaded with specific carriers and bionic vascularized 3D printed scaffolds. Finally, a brief review of vascularized additive manufacturing-tissue scaffolds in related tissues such as the vascular tissue engineering, cardiovascular system, skeletal muscle, soft tissue and a discussion of the challenges and development efforts leading to significant advances in intelligent vascularized tissue regeneration is presented.
    Keywords:  Additive manufacturing; Intelligent; Osteogenesis; Tissue engineering; Vascularization
    DOI:  https://doi.org/10.1007/s40820-023-01187-2
  4. Tissue Cell. 2023 Oct 25. pii: S0040-8166(23)00246-X. [Epub ahead of print]85 102258
    Decellularized tracheal scaffold as a promising 3D scaffold for tissue engineering applications.
    Aida Nahumi, Maryam Peymani, Asadollah Asadi, Arash Abdolmaleki, Yassin Panahi.
      Tissue engineering is a science that uses the combination of scaffolds, cells, and active biomolecules to make tissue in order to restore or maintain its function and improve the damaged tissue or even an organ in the laboratory. The purpose of this research was to study the characteristics and biocompatibility of decellularized sheep tracheal scaffolds and also to investigate the differentiation of Adipose-derived stem cells (AD-MSCs) into tracheal cells. After the decellularization of sheep tracheas through the detergent-enzyme method, histological evaluations, measurement of biochemical factors, measurement of DNA amount, and photographing the ultrastructure of the samples by scanning electron microscopy (SEM), they were also evaluated mechanically. Further, In order to check the viability and adhesion of stem cells to the decellularized scaffolds, adipose mesenchymal stem cells were cultured on the scaffolds, and the 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT) assay was performed. The expression analysis of the intended genes for the differentiation of mesenchymal stem cells into tracheal cells was evaluated by the real-time PCR method. These results show that the prepared scaffolds are an ideal model for engineering applications, have high biocompatibility, and that the tracheal scaffold provides a suitable environment for the differentiation of ADMSCs. This review provides a basis for future research on tracheal decellularization scaffolds, serves as a suitable model for organ regeneration, and paves the way for their use in clinical medicine.
    Keywords:  Adipose-derived stem cells; Extracellular matrix (ECM); Scaffold; Tissue engineering; Trachea
    DOI:  https://doi.org/10.1016/j.tice.2023.102258
  5. Adv Healthc Mater. 2023 Oct 31. e2302508
    Enhancing Craniofacial Bone Reconstruction with Clinically Applicable 3D Bioprinted Constructs.
    Hyeongjin Lee, Carlos Kengla, Han Su Kim, Ickhee Kim, Jae-Gu Cho, Eric Renteria, Kyungsup Shin, Anthony Atala, James J Yoo, Sang Jin Lee.
      Medical imaging and 3D bioprinting can be used to create patient-specific bone scaffolds with complex shapes and controlled inner architectures. This study investigated the effectiveness of a biomimetic approach to scaffold design by employing geometric control. The biomimetic scaffold with a dense external layer showed improved bone regeneration compared to the control scaffold. New bone filled the defected region in the biomimetic scaffolds, while the control scaffolds only presented new bone at the boundary. Histological examination also showed effective bone regeneration in the biomimetic scaffolds, while fibrotic tissue ingrowth was observed in the control scaffolds. These findings suggest that the biomimetic bone scaffold, designed to minimize competition for fibrotic tissue formation in the bony defect, can enhance bone regeneration. This study underscores the notion that patient-specific anatomy can be accurately translated into a 3D bioprinting strategy through medical imaging, leading to the fabrication of constructs with significant clinical relevance. This article is protected by copyright. All rights reserved.
    Keywords:  bioprinting; bone, osteoconductivity; regeneration; scaffold; tissue engineering
    DOI:  https://doi.org/10.1002/adhm.202302508
  6. Ann Transplant. 2023 Oct 31. 28 e940365
    Three-Dimensional Printing of Polycaprolactone/Nano-Hydroxyapatite Composite Scaffolds with a Pore Size of 300/500 µm is Histocompatible and Promotes Osteogenesis Using Rabbit Cortical Bone Marrow Stem Cells.
    Yang Yang, Bing Qiu, Zhuxing Zhou, Chaoran Hu, Jia Li, Cheng Zhou.
      BACKGROUND Many patients have bone defects that exceed the healing size. This study aimed to construct polycaprolactone/nano-hydroxyapatite (PCL/nHA) composite scaffolds with different pore sizes and investigate the osteogenesis and histocompatibility of cortical bone mesenchymal stem cells (BMSCs-C) seeded on it after inoculation. MATERIAL AND METHODS After mixing PCL and nHA proportionally, three-dimensional (3D) printing was used to print scaffolds. Porosity, compressive strength, and elastic modulus of PCL/nHA scaffolds were tested. The proliferation of BMSCs-C cells was examined and osteogenesis, chondrogenesis, and adipogenesis were evaluated. BMSCs-C cells were inoculated into 3D printing scaffolds, and histocompatibility between BMSCs-C cells and scaffolds was observed by the cell count kit (CCK-8) assay and LIVE/DEAD staining. After inoculating BMSCs-C cells into scaffolds, alkaline phosphatase (ALP) activity and calcium content were measured. RESULTS There was no obvious difference in characteristics between the 3 PCL/nHA composite scaffolds. The porosity, compressive strength, and elastic modulus of the 300/500-μm scaffold were between those of the 300-μm and 500-μm scaffolds. With increasing pore size, the mechanical properties of the scaffold decrease. BMSCs-C cells demonstrated faster growth and better osteogenic, adipogenic, and chondrogenic differentiation; therefore, BMSCs-C cells were selected as seed cells. PCL/nHA composite scaffolds with different pore sizes had no obvious toxicity and demonstrated good biocompatibility. All scaffolds showed higher ALP activity and calcium content. CONCLUSIONS The 300/500 μm mixed pore size scaffold took into account the mechanical properties of the 300 μm scaffold and the cell culture area of the 500 μm scaffold, therefore, 300/500 μm scaffold is a better model for the construction of tissue engineering scaffolds.
    DOI:  https://doi.org/10.12659/AOT.940365
  7. Biomed Mater. 2023 Nov 02.
    Application of 3D printing technology in tumor diagnosis and treatment.
    Jinmei Wu, Bing Liang, Shuoqiao Lu, Jinlan Xie, Yan Song, Lude Wang, Lingfeng Gao, Zaiyin Huang.
      3D printing technology is an increasing approach consisting of material manufacturing through the selective incremental delamination of materials to form a 3D structure to produce products. This technology has different advantages, including low cost, short time, diversification, and high precision. Widely adopted additive manufacturing technologies enable the creation of diagnostic tools and expand treatment options. Coupled with its rapid deployment, 3D printing is endowed with high customizability that enables users to build prototypes in shorts amounts of time which translates into faster adoption in the medical field. This review mainly summarizes the application of 3D printing technology in the diagnosis and treatment of cancer, including the challenges and the prospects combined with other technologies applied to the medical field.
    Keywords:  3D printing technology; Cancer; Diagnosis; Sensor; Treatment
    DOI:  https://doi.org/10.1088/1748-605X/ad08e1
  8. Biofabrication. 2023 Oct 31.
    A novel perfusion bioreactor promotes the expansion of pluripotent stem cells in a 3D-bioprinted tissue chamber.
    Elizabeth R Komosa, Wei-Han Lin, Bhushan Mahadik, Marisa Bazzi, DeWayne Townsend, John P Fisher, Brenda M Ogle.
      While the field of tissue engineering has progressed rapidly with the advent of 3D bioprinting and human induced pluripotent stem cells (hiPSCs), impact is limited by a lack of functional, thick tissues. One way around this limitation is to 3D bioprint tissues laden with hiPSCs. In this way, the iPSCs can proliferate to populate the thick tissue mass prior to parenchymal cell specification. Here we design a perfusion bioreactor for an hiPSC-laden, 3D-bioprinted chamber with the goal of proliferating the hiPSCs throughout the structure prior to differentiation to generate a thick tissue model. The bioreactor, fabricated with digital light projection, was optimized to perfuse the interior of the hydrogel chamber without leaks and to provide fluid flow around the exterior as well, maximizing nutrient delivery throughout the chamber wall. After 7 days of culture, we found that intermittent perfusion (15 seconds every 15 minutes) at 3mL/min provides a 1.9-fold increase in the density of stem cell colonies in the engineered tissue relative to analogous chambers cultured under static conditions. We also observed a more uniform distribution of colonies within the tissue wall of perfused structures relative to static controls, reflecting a homogeneous distribution of nutrients from the culture media. hiPSCs remained pluripotent and proliferative with application of fluid flow, which generated wall shear stresses averaging ~1.0 dyn/cm2. Overall, these promising outcomes following perfusion of a stem cell-laden hydrogel support the production of multiple tissue types with improved thickness, and therefore increased function and utility.&#xD.
    Keywords:  3D Bioprinting; Bioreactor; Extracellular Matrix; Proliferation; Stem Cells
    DOI:  https://doi.org/10.1088/1758-5090/ad084a
  9. Research (Wash D C). 2023 ;6 0255
    3D-Printed Flat-Bone-Mimetic Bioceramic Scaffolds for Cranial Restoration.
    Yihang Zhang, Fupo He, Qiang Zhang, Haotian Lu, Shengtao Yan, Xuetao Shi.
      The limitations of autologous bone grafts necessitate the development of advanced biomimetic biomaterials for efficient cranial defect restoration. The cranial bones are typical flat bones with sandwich structures, consisting of a diploe in the middle region and 2 outer compact tables. In this study, we originally developed 2 types of flat-bone-mimetic β-tricalcium phosphate bioceramic scaffolds (Gyr-Comp and Gyr-Tub) by high-precision vat-photopolymerization-based 3-dimensional printing. Both scaffolds had 2 outer layers and an inner layer with gyroid pores mimicking the diploe structure. The outer layers of Gyr-Comp scaffolds simulated the low porosity of outer tables, while those of Gyr-Tub scaffolds mimicked the tubular pore structure in the tables of flat bones. The Gyr-Comp and Gyr-Tub scaffolds possessed higher compressive strength and noticeably promoted in vitro cell proliferation, osteogenic differentiation, and angiogenic activities compared with conventional scaffolds with cross-hatch structures. After implantation into rabbit cranial defects for 12 weeks, Gyr-Tub achieved the best repairing effects by accelerating the generation of bone tissues and blood vessels. This work provides an advanced strategy to prepare biomimetic biomaterials that fit the structural and functional needs of efficacious bone regeneration.
    DOI:  https://doi.org/10.34133/research.0255
  10. Mater Today Bio. 2023 Dec;23 100833
    3D-printed PCL scaffolds with anatomy-inspired bionic stratified structures for the treatment of growth plate injuries.
    Xianggang Wang, Zuhao Li, Jiaqi Liu, Chenyu Wang, Haotian Bai, Xiujie Zhu, Hui Wang, Zhonghan Wang, He Liu, Jincheng Wang.
      The growth plate is a cartilaginous tissue with three distinct zones. Resident chondrocytes are highly organized in a columnar structure, which is critical for the longitudinal growth of immature long bones. Once injured, the growth plate may potentially be replaced by bony bar formation and, consequently, cause limb abnormalities in children. It is well-known that the essential step in growth plate repair is the remolding of the organized structure of chondrocytes. To achieve this, we prepared an anatomy-inspired bionic Poly(ε-caprolactone) (PCL) scaffold with a stratified structure using three-dimensional (3D) printing technology. The bionic scaffold is engineered by surface modification of NaOH and collagen Ⅰ (COL Ⅰ) to promote cell adhesion. Moreover, chondrocytes and bone marrow mesenchymal stem cells (BMSCs) are loaded in the most suitable ratio of 1:3 for growth plate reconstruction. Based on the anatomical structure of the growth plate, the bionic scaffold is designed to have three regions, which are the small-, medium-, and large-pore-size regions. These pore sizes are used to induce BMSCs to differentiate into similar structures such as the growth plate. Remarkably, the X-ray and histological results also demonstrate that the cell-loaded stratified scaffold can successfully rebuild the structure of the growth plate and reduce limb abnormalities, including limb length discrepancies and angular deformities in vivo. This study provides a potential method of preparing a bioinspired stratified scaffold for the treatment of growth plate injuries.
    Keywords:  3D printing; Bionic stratified scaffold; Cartilage tissue engineering; Chondrogenesis; Growth plate injury
    DOI:  https://doi.org/10.1016/j.mtbio.2023.100833
  11. Adv Healthc Mater. 2023 Nov 03. e2301123
    A 3d In Vitro Cortical Tissue Model Based on Dense Collagen to Study The Effects of Gamma Radiation on Neuronal Function.
    Neal M Lojek, Victoria A Williams, Andrew M Rogers, Erno Sajo, Bryan J Black, Chiara E Ghezzi.
      Studies on gamma radiation-induced injury have long been focused on hematopoietic, gastrointestinal, and cardiovascular systems, yet little is known about the effects of gamma radiation on the function of human cortical tissue. The challenge in studying radiation-induced cortical injury is, in part, due to a lack of human tissue models and physiologically relevant readouts. Here, we have developed a physiologically relevant 3D collagen-based cortical tissue model (CTM) for studying the functional response of human iPSC-derived neurons and astrocytes to a sub-lethal radiation exposure (5 Gy). We quantified cytotoxicity, DNA damage, morphology, and extracellular electrophysiology. We reported that 5 Gy exposure significantly increased cytotoxicity, DNA damage, and astrocyte reactivity while significantly decreased neurite length and neuronal network activity. Additionally, we found that clinically deployed radioprotectant amifostine ameliorated the DNA damage, cytotoxicity, and astrocyte reactivity. The CTM provides a critical experimental platform to understand cell-level mechanisms by which GR affects human cortical tissue and to screen prospective radioprotectant compounds. This article is protected by copyright. All rights reserved.
    Keywords:  cortical tissue model; gamma ray; hiPSC; ionizing radiation; natural polymers
    DOI:  https://doi.org/10.1002/adhm.202301123
  12. J Vis Exp. 2023 10 13.
    Three-Dimensional Acoustic Assembly Device for Mass Manufacturing of Cell Spheroids.
    Yuecheng Qian, Xiaoyun Wei, Keke Chen, Mingen Xu.
      Cell spheroids are promising three-dimensional (3D) models that have gained wide applications in many biological fields. This protocol presents a method for manufacturing high-quality and high-throughput cell spheroids using a 3D acoustic assembly device through maneuverable procedures. The acoustic assembly device consists of three lead zirconate titanate (PZT) transducers, each arranged in the X/Y/Z plane of a square polymethyl methacrylate (PMMA) chamber. This configuration enables the generation of a 3D dot-array pattern of levitated acoustic nodes (LANs) when three signals are applied. As a result, cells in the gelatin methacryloyl (GelMA) solution can be driven to the LANs, forming uniform cell aggregates in three dimensions. The GelMA solution is then UV-photocured and crosslinked to serve as a scaffold that supports the growth of cell aggregates. Finally, masses of matured spheroids are obtained and retrieved by subsequently dissolving the GelMA scaffolds under mild conditions. The proposed new 3D acoustic cell assembly device will enable the scale-up fabrication of cell spheroids, and even organoids, offering great potential technology in the biological field.
    DOI:  https://doi.org/10.3791/66078
  13. Spec Care Dentist. 2023 Nov 01.
    3D printing technology to produce intraoral stents for head and neck radiotherapy: A scoping review.
    Maria Emília Mota, Gabriella Torres Schroter, Maria Stella Moreira, Fábio Abreu Alves, Graziella Chagas Jaguar, Rodrigo Nascimento Lopes.
       INTRODUCTION: Radiotherapy remains one of the main treatments for head and neck cancer; however, it is accompanied by acute and chronic adverse effects. Use of three-dimensional (3D) oral stents to modulate radiation intensity to specific target areas have been developed to minimize these adverse effects. This study aimed to present a scoping review of studies published on 3D printing of oral stents and their clinical applicability.
    METHODS: MEDLINE/Pubmed, Scopus, Web of Science and CENTRAL Cochrane data bases were searched, studies selected, and data collected by three independent reviewers up to December 2022. The review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis-Extension for Scoping Reviews (PRISMA-ScR).
    RESULTS: The search resulted in 404 studies and 5 articles fulfilled the eligibility criteria and were considered for this review. Three-dimensional printed intraoral stents were produced for 56 patients with indication for radiotherapy. 3D-printed stents were well-tolerated by all tested patients and demonstrated great reproducibility of maxillomandibular relation, required less time for production and lower cost to manufacture. Two studies showed great protection of healthy tissues with 3D-printed stents during radiotherapy.
    CONCLUSIONS: Three-dimensional printing is promising for production of intraoral stents, however, more studies are needed to improve the technique and further investigate the safety and prevention of oral toxicities from radiotherapy.
    Keywords:  3D printing; head and neck cancer; oral stent; radiotherapy
    DOI:  https://doi.org/10.1111/scd.12936
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