bims-biprem Biomed News
on Bioprinting for regenerative medicine
Issue of 2023–07–02
sixteen papers selected by
Seerat Maqsood, University of Teramo
  1. 3D Bioprinting of Hyaline Articular Cartilage: Biopolymers, Hydrogels, and Bioinks.
  2. Three-Dimensional Bioprinting of Naturally Derived Hydrogels for the Production of Biomimetic Living Tissues: Benefits and Challenges.
  3. Bioinks of Natural Biomaterials for Printing Tissues.
  4. Tissue Engineering Strategies Applied in Bone Regeneration and Bone Repair.
  5. Review on Additives in Hydrogels for 3D Bioprinting of Regenerative Medicine: From Mechanism to Methodology.
  6. Photocrosslinked methacrylated natural macromolecular hydrogels for tissue engineering: A review.
  7. 3D bioprinting of complex tissue scaffolds with in situ homogeneously mixed alginate-chitosan-kaolin bioink using advanced portable biopen.
  8. Science and Technology of Additive Manufacturing Progress: Processes, Materials, and Applications.
  9. Long-Term Follow-Up of a Novel Surgical Option Combining Fibula Free Flap and 3D-Bioprinted, Patient-Specific Polycaprolactone (PCL) Implant for Mandible Reconstruction.
  10. Three-dimensional Functional Neuronal Networks in Free-Standing Bioprinted Hydrogel Constructs.
  11. The Role of Extracellular Matrix (ECM) Adhesion Motifs in Functionalised Hydrogels.
  12. Thoroughly Hydrophilized Electrospun Poly(L-Lactide)/ Poly(ε-Caprolactone) Sponges for Tissue Engineering Application.
  13. Design and evaluation of a 3D-printed, lab-scale perfusion bioreactor for novel biotechnological applications.
  14. Advanced Biomaterials Research in China.
  15. Resorbable Biomaterials Used for 3D Scaffolds in Tissue Engineering: A Review.
  16. Silica Aerogel-Polycaprolactone Scaffolds for Bone Tissue Engineering.
  1. Polymers (Basel). 2023 Jun 15. pii: 2695. [Epub ahead of print]15(12):
    3D Bioprinting of Hyaline Articular Cartilage: Biopolymers, Hydrogels, and Bioinks.
    Larisa T Volova, Gennadiy P Kotelnikov, Igor Shishkovsky, Dmitriy B Volov, Natalya Ossina, Nikolay A Ryabov, Aleksey V Komyagin, Yeon Ho Kim, Denis G Alekseev.
      The musculoskeletal system, consisting of bones and cartilage of various types, muscles, ligaments, and tendons, is the basis of the human body. However, many pathological conditions caused by aging, lifestyle, disease, or trauma can damage its elements and lead to severe disfunction and significant worsening in the quality of life. Due to its structure and function, articular (hyaline) cartilage is the most susceptible to damage. Articular cartilage is a non-vascular tissue with constrained self-regeneration capabilities. Additionally, treatment methods, which have proven efficacy in stopping its degradation and promoting regeneration, still do not exist. Conservative treatment and physical therapy only relieve the symptoms associated with cartilage destruction, and traditional surgical interventions to repair defects or endoprosthetics are not without serious drawbacks. Thus, articular cartilage damage remains an urgent and actual problem requiring the development of new treatment approaches. The emergence of biofabrication technologies, including three-dimensional (3D) bioprinting, at the end of the 20th century, allowed reconstructive interventions to get a second wind. Three-dimensional bioprinting creates volume constraints that mimic the structure and function of natural tissue due to the combinations of biomaterials, living cells, and signal molecules to create. In our case-hyaline cartilage. Several approaches to articular cartilage biofabrication have been developed to date, including the promising technology of 3D bioprinting. This review represents the main achievements of such research direction and describes the technological processes and the necessary biomaterials, cell cultures, and signal molecules. Special attention is given to the basic materials for 3D bioprinting-hydrogels and bioinks, as well as the biopolymers underlying the indicated products.
    Keywords:  biofabrication; bioinks; biopolymers; bioprinters; cells; hyaline articular cartilage; hydrogels; regenerative medicine; scaffolds; signal molecules; three-dimensional bioprinting; tissue engineering; traumatology and orthopaedics
    DOI:  https://doi.org/10.3390/polym15122695
  2. Biomedicines. 2023 Jun 17. pii: 1742. [Epub ahead of print]11(6):
    Three-Dimensional Bioprinting of Naturally Derived Hydrogels for the Production of Biomimetic Living Tissues: Benefits and Challenges.
    Elena Merotto, Piero G Pavan, Martina Piccoli.
      Three-dimensional bioprinting is the process of manipulating cell-laden bioinks to fabricate living structures. Three-dimensional bioprinting techniques have brought considerable innovation in biomedicine, especially in the field of tissue engineering, allowing the production of 3D organ and tissue models for in vivo transplantation purposes or for in-depth and precise in vitro analyses. Naturally derived hydrogels, especially those obtained from the decellularization of biological tissues, are promising bioinks for 3D printing purposes, as they present the best biocompatibility characteristics. Despite this, many natural hydrogels do not possess the necessary mechanical properties to allow a simple and immediate application in the 3D printing process. In this review, we focus on the bioactive and mechanical characteristics that natural hydrogels may possess to allow efficient production of organs and tissues for biomedical applications, emphasizing the reinforcement techniques to improve their biomechanical properties.
    Keywords:  3D bioprinting; hydrogel crosslinking; naturally derived hydrogel; tissue engineering
    DOI:  https://doi.org/10.3390/biomedicines11061742
  3. Bioengineering (Basel). 2023 Jun 10. pii: 705. [Epub ahead of print]10(6):
    Bioinks of Natural Biomaterials for Printing Tissues.
    Girdhari Rijal.
      Bioinks are inks-in other words, hydrogels-prepared from biomaterials with certain physiochemical properties together with cells to establish hierarchically complex biological 3D scaffolds through various 3D bioprinting technologies [...].
    DOI:  https://doi.org/10.3390/bioengineering10060705
  4. Bioengineering (Basel). 2023 May 25. pii: 644. [Epub ahead of print]10(6):
    Tissue Engineering Strategies Applied in Bone Regeneration and Bone Repair.
    Alexis Delpierre, Guillaume Savard, Matthieu Renaud, Gael Y Rochefort.
      Bone regeneration and repair present significant challenges in the field of regenerative medicine [...].
    DOI:  https://doi.org/10.3390/bioengineering10060644
  5. Pharmaceutics. 2023 Jun 09. pii: 1700. [Epub ahead of print]15(6):
    Review on Additives in Hydrogels for 3D Bioprinting of Regenerative Medicine: From Mechanism to Methodology.
    Wenzhuo Fang, Ming Yang, Meng Liu, Yangwang Jin, Yuhui Wang, Ranxing Yang, Ying Wang, Kaile Zhang, Qiang Fu.
      The regeneration of biological tissues in medicine is challenging, and 3D bioprinting offers an innovative way to create functional multicellular tissues. One common way in bioprinting is bioink, which is one type of the cell-loaded hydrogel. For clinical application, however, the bioprinting still suffers from satisfactory performance, e.g., in vascularization, effective antibacterial, immunomodulation, and regulation of collagen deposition. Many studies incorporated different bioactive materials into the 3D-printed scaffolds to optimize the bioprinting. Here, we reviewed a variety of additives added to the 3D bioprinting hydrogel. The underlying mechanisms and methodology for biological regeneration are important and will provide a useful basis for future research.
    Keywords:  3D bioprinting; bioink; bionic scaffold; hydrogel; tissue engineering
    DOI:  https://doi.org/10.3390/pharmaceutics15061700
  6. Int J Biol Macromol. 2023 Jun 25. pii: S0141-8130(23)02464-9. [Epub ahead of print] 125570
    Photocrosslinked methacrylated natural macromolecular hydrogels for tissue engineering: A review.
    Xiaoli Yang, Xiaojing Li, Zhaoping Wu, Lingling Cao.
      A hydrogel is a three-dimensional (3D) network structure formed through polymer crosslinking, and these have emerged as a popular research topic in recent years. Hydrogel crosslinking can be classified as physical, chemical, or enzymatic, and photocrosslinking is a branch of chemical crosslinking. Compared with other methods, photocrosslinking can control the hydrogel crosslinking initiation, crosslinking time, and crosslinking strength using light. Owing to these properties, photocrosslinked hydrogels have important research prospects in tissue engineering, in situ gel formation, 3D bioprinting, and drug delivery. Methacrylic anhydride modification is a common method for imparting photocrosslinking properties to polymers, and graft-substituted polymers can be photocrosslinked under UV irradiation. In this review, we first introduce the characteristics of common natural polysaccharide- and protein-based hydrogels and the processes used for methacrylate group modification. Next, we discuss the applications of methacrylated natural hydrogels in tissue engineering. Finally, we summarize and discuss existing methacrylated natural hydrogels in terms of limitations and future developments. We expect that this review will help researchers in this field to better understand the synthesis of methacrylate-modified natural hydrogels and their applications in tissue engineering.
    Keywords:  Hydrogel; Methacrylic anhydride; Polysaccharide; Protein; Tissue engineering
    DOI:  https://doi.org/10.1016/j.ijbiomac.2023.125570
  7. Carbohydr Polym. 2023 Oct 01. pii: S0144-8617(23)00511-8. [Epub ahead of print]317 121046
    3D bioprinting of complex tissue scaffolds with in situ homogeneously mixed alginate-chitosan-kaolin bioink using advanced portable biopen.
    Amitava Bhattacharyya, Hyeong-Wook Ham, JiAe Sonh, Marla Gunbayar, R Jeffy, R Nagarajan, Mst Rita Khatun, Insup Noh.
      Control of in situ 3D bioprinting of hydrogel without toxic crosslinker is ideal for tissue regeneration by reinforcing and homogeneously distributing biocompatible reinforcing agent during fabrication of large area and complex tissue engineering scaffolds. In this study, homogeneous mixing, and simultaneous 3D bioprinting of a multicomponent bioink based on alginate (AL)-chitosan (CH), and kaolin was obtained by an advanced pen-type extruder to ensure structural and biological homogeneity during the large area tissue reconstruction. The static, dynamic and cyclic mechanical properties as well as in situ self-standing printability significantly improved with the kaolin concentration for AL-CH bioink-printed samples due to polymer-kaolin nanoclay hydrogen bonding and cross-linking with less amount of calcium ions. The Biowork pen ensures better mixing effectiveness for the kaolin-dispersed AL-CH hydrogels (evident from computational fluid dynamics study, aluminosilicate nanoclay mapping and 3D printing of complex multilayered structures) than the conventional mixing process. Two different cell lines (osteoblast and fibroblast) introduced during large area multilayered 3D bioprinting have confirmed the suitability of such multicomponent bioinks for in vitro even tissue regeneration. The effect of kaolin to promote uniform growth and proliferation of the cells throughout the bioprinted gel matrix is more significant for this advanced pen-type extruder processed samples.
    Keywords:  3D bioprinting; Alginate; Chitosan; Hydrogels; Kaolin; Tissue engineering
    DOI:  https://doi.org/10.1016/j.carbpol.2023.121046
  8. Met Mater Int. 2023 Jun 03. 1-29
    Science and Technology of Additive Manufacturing Progress: Processes, Materials, and Applications.
    Vahid Monfared, Seeram Ramakrishna, Navid Nasajpour-Esfahani, Davood Toghraie, Maboud Hekmatifar, Sadegh Rahmati.
      As a special review article, several significant and applied results in 3D printing and additive manufacturing (AM) science and technology are reviewed and studied. Which, the reviewed research works were published in 2020. Then, we would have another review article for 2021 and 2022. The main purpose is to collect new and applied research results as a useful package for researchers. Nowadays, AM is an extremely discussed topic and subject in scientific and industrial societies, as well as a new vision of the unknown modern world. Also, the future of AM materials is toward fundamental changes. Which, AM would be an ongoing new industrial revolution in the digital world. With parallel methods and similar technologies, considerable developments have been made in 4D in recent years. AM as a tool is related to the 4th industrial revolution. So, AM and 3D printing are moving towards the fifth industrial revolution. In addition, a study on AM is vital for generating the next developments, which are beneficial for human beings and life. Thus, this article presents the brief, updated, and applied methods and results published in 2020.
    Graphical Abstract:
    Keywords:  3D printing; Additive manufacturing; Medical sciences; Tissue engineering
    DOI:  https://doi.org/10.1007/s12540-023-01467-x
  9. Bioengineering (Basel). 2023 Jun 04. pii: 684. [Epub ahead of print]10(6):
    Long-Term Follow-Up of a Novel Surgical Option Combining Fibula Free Flap and 3D-Bioprinted, Patient-Specific Polycaprolactone (PCL) Implant for Mandible Reconstruction.
    Bo-Yeon Hwang, Kwantae Noh, Jung-Woo Lee.
      As the fibula free flap became the gold standard in mandibular reconstruction that required both hard tissue and soft tissue, various methods have been sought to solve the height discrepancy between the mandible and fibula. The purpose of this paper was to propose a surgical option that combined the microvascular fibula free flap with a 3D-bioprinted, patient-specific polycaprolactone (PCL) implant as a safe and simple novel method that achieved the best functional and aesthetic results in mandibular reconstruction surgery for young patients with malignant tumors. The patient's reconstructed mandible maintained volume symmetry without any deformation or complications for over 6 years. Computer-aided design/computer-aided manufacturing (CAD/CAM) and 3D printing technology enabled accurate and safe surgical results.
    Keywords:  CAD/CAM; PCL; bioprinting; mandible reconstruction; patient-specific implant (PSI); surgical guides
    DOI:  https://doi.org/10.3390/bioengineering10060684
  10. Adv Healthc Mater. 2023 Jun 27. e2300801
    Three-dimensional Functional Neuronal Networks in Free-Standing Bioprinted Hydrogel Constructs.
    Yue Yao, Harold A Coleman, Laurence Meagher, John S Forsythe, Helena C Parkington.
      The composition, elasticity and organization of the extracellular matrix within the central nervous system contribute to the architecture and function of the brain. From an in vitro modelling perspective, soft biomaterials are needed to mimic the three-dimensional (3D) neural microenvironments. While many studies have investigated 3D culture and neural network formation in bulk hydrogel systems, these approaches have limited ability to position cells to mimic sophisticated brain architectures. In this study, cortical neurons and astrocytes acutely isolated from the brains of rats are bioprinted in a hydrogel to form 3D neuronal constructs. Successful bioprinting of cellular and acellular strands in a multi-bioink approach allow the subsequent formation of gray- and white-matter tracts reminiscent of cortical structures. Immunohistochemistry shows the formation of dense, 3D axon networks. Calcium signalling and extracellular electrophysiology in these 3D neuronal networks confirm spontaneous activity in addition to evoked activities under pharmacological and electrical stimulation. Our system and bioprinting approaches are capable of fabricating soft, free-standing neuronal structures of different bioink and cell types with high resolution and throughput, which provides a promising platform for understanding fundamental questions of neural networks, engineering neuromorphic circuits and for in vitro drug screening. This article is protected by copyright. All rights reserved.
    Keywords:  bioprinting; calcium imaging; electrophysiology; neuronal network; three-dimensional
    DOI:  https://doi.org/10.1002/adhm.202300801
  11. Molecules. 2023 Jun 07. pii: 4616. [Epub ahead of print]28(12):
    The Role of Extracellular Matrix (ECM) Adhesion Motifs in Functionalised Hydrogels.
    Anna J Morwood, Ikhlas A El-Karim, Susan A Clarke, Fionnuala T Lundy.
      To create functional tissue engineering scaffolds, biomaterials should mimic the native extracellular matrix of the tissue to be regenerated. Simultaneously, the survival and functionality of stem cells should also be enhanced to promote tissue organisation and repair. Hydrogels, but in particular, peptide hydrogels, are an emerging class of biocompatible scaffolds which act as promising self-assembling biomaterials for tissue engineering and regenerative therapies, ranging from articular cartilage regeneration at joint defects, to regenerative spinal cord injury following trauma. To enhance hydrogel biocompatibility, it has become imperative to consider the native microenvironment of the site for regeneration, where the use of functionalised hydrogels with extracellular matrix adhesion motifs has become a novel, emerging theme. In this review, we will introduce hydrogels in the context of tissue engineering, provide insight into the complexity of the extracellular matrix, investigate specific adhesion motifs that have been used to generate functionalised hydrogels and outline their potential applications in a regenerative medicine setting. It is anticipated that by conducting this review, we will provide greater insight into functionalised hydrogels, which may help translate their use towards therapeutic roles.
    Keywords:  biocompatibility; biomimetic peptide; bone; dental pulp; lung; tissue engineering
    DOI:  https://doi.org/10.3390/molecules28124616
  12. Macromol Biosci. 2023 Jun 26. e2300143
    Thoroughly Hydrophilized Electrospun Poly(L-Lactide)/ Poly(ε-Caprolactone) Sponges for Tissue Engineering Application.
    Chengzhang Xu, Jun Young Cheong, Xiumei Mo, Valérie Jérôme, Ruth Freitag, Seema Agarwal, Reza Gharibi, Andreas Greiner.
      Biodegradable electrospun sponges are of interest for various applications including tissue engineering, drug release, dental therapy, plant protection, and plant fertilization. Biodegradable electrospun poly (L-lactide)/poly(ε-caprolactone) (PLLA/PCL) blend fiber-based sponge with hierarchical pore structure is inherently hydrophobic, which is disadvantageous for application in tissue engineering, fertilization, and drug delivery. We report contact angles and model studies for staining with a hydrophilic dye for untreated, plasma-treated, and surfactant treated PLLA/PCL sponges. Thorough hydrophilization of PLLA/PCL sponges was found only with the surfactant treated sponges. The MTT assay on the leachates from the sponges did not indicate any cell incompatibility. Furthermore, the cell proliferation and penetration of the hydrophilized sponges were verified by in vitro cell culture studies using MG63 and human fibroblast cells. This article is protected by copyright. All rights reserved.
    Keywords:  electrospun sponges; human cell tests; hydrophilization; polylactide
    DOI:  https://doi.org/10.1002/mabi.202300143
  13. Biotechnol J. 2023 Jun 27. e2200554
    Design and evaluation of a 3D-printed, lab-scale perfusion bioreactor for novel biotechnological applications.
    Manuel Merkel, Philipp Noll, Lars Lilge, Rudolf Hausmann, Marius Henkel.
      3D-printing increased in significance for biotechnological research as new applications like lab-on-a-chip systems, cell culture devices or 3D-printed foods were uncovered. Besides mammalian cell culture, only few of those applications focus on the cultivation of microorganisms and none of these make use of the advantages of perfusion systems. One example for applying 3D-printing for bioreactor development is the microbial utilization of alternative substrates derived from lignocellulose, where dilute carbon concentrations and harmful substances present a major challenge. Furthermore, quickly manufactured and affordable 3D-printed bioreactors can accelerate early development phases through parallelization. In this work, a novel perfusion bioreactor system consisting of parts manufactured by fused filament fabrication is presented and evaluated. Hydrophilic membranes are used for cell retention to allow the application of dilute substrates. Oxygen supply is provided by membrane diffusion via hydrophobic polytetrafluoroethylene membranes. An exemplary cultivation of Corynebacterium glutamicum ATCC 13032 supports the theoretical design by achieving competitive biomass concentrations of 18.4 g/L after 52 h. As a proof-of-concept for cultivation of microorganisms in perfusion mode, the described bioreactor system has application potential for bioconversion of multi-component substrate-streams in a lignocellulose-based bioeconomy, for in-situ product removal or design considerations of future applications for tissue cultures. Furthermore, this work provides a template-based toolbox with instructions for creating reference systems in different application scenarios or tailor-made bioreactor systems. This article is protected by copyright. All rights reserved.
    Keywords:  3D-printing; Corynebacterium glutamicum; bioeconomy; membrane bioreactor; perfusion bioreactor process
    DOI:  https://doi.org/10.1002/biot.202200554
  14. Adv Healthc Mater. 2023 Jun;12(16): e2301336
    Advanced Biomaterials Research in China.
    Yanglong Hou, Zhen Gu.
      
    DOI:  https://doi.org/10.1002/adhm.202301336
  15. Materials (Basel). 2023 Jun 08. pii: 4267. [Epub ahead of print]16(12):
    Resorbable Biomaterials Used for 3D Scaffolds in Tissue Engineering: A Review.
    Sara Vach Agocsova, Martina Culenova, Ivana Birova, Leona Omanikova, Barbora Moncmanova, Lubos Danisovic, Stanislav Ziaran, Dusan Bakos, Pavol Alexy.
      This article provides a thorough overview of the available resorbable biomaterials appropriate for producing replacements for damaged tissues. In addition, their various properties and application possibilities are discussed as well. Biomaterials are fundamental components in tissue engineering (TE) of scaffolds and play a critical role. They need to exhibit biocompatibility, bioactivity, biodegradability, and non-toxicity, to ensure their ability to function effectively with an appropriate host response. With ongoing research and advancements in biomaterials for medical implants, the objective of this review is to explore recently developed implantable scaffold materials for various tissues. The categorization of biomaterials in this paper includes fossil-based materials (e.g., PCL, PVA, PU, PEG, and PPF), natural or bio-based materials (e.g., HA, PLA, PHB, PHBV, chitosan, fibrin, collagen, starch, and hydrogels), and hybrid biomaterials (e.g., PCL/PLA, PCL/PEG, PLA/PEG, PLA/PHB PCL/collagen, PCL/chitosan, PCL/starch, and PLA/bioceramics). The application of these biomaterials in both hard and soft TE is considered, with a particular focus on their physicochemical, mechanical, and biological properties. Furthermore, the interactions between scaffolds and the host immune system in the context of scaffold-driven tissue regeneration are discussed. Additionally, the article briefly mentions the concept of in situ TE, which leverages the self-renewal capacities of affected tissues and highlights the crucial role played by biopolymer-based scaffolds in this strategy.
    Keywords:  3D scaffolds; bioceramics; biomaterials; biopolymers; foreign body response; hybrid biomaterials; immunoengineering; tissue engineering
    DOI:  https://doi.org/10.3390/ma16124267
  16. Int J Mol Sci. 2023 Jun 14. pii: 10128. [Epub ahead of print]24(12):
    Silica Aerogel-Polycaprolactone Scaffolds for Bone Tissue Engineering.
    Ana Dora Rodrigues Pontinha, Beatriz Barbosa Moreira, Bruna Lopes Melo, Duarte de Melo-Diogo, Ilídio Joaquim Correia, Patrícia Alves.
      Silica aerogel is a material composed of SiO2 that has exceptional physical properties when utilized for tissue engineering applications. Poly-ε-caprolactone (PCL) is a biodegradable polyester that has been widely used for biomedical applications, namely as sutures, drug carriers, and implantable scaffolds. Herein, a hybrid composite of silica aerogel, prepared with two different silica precursors, tetraethoxysilane (TEOS) or methyltrimethoxysilane (MTMS), and PCL was synthesized to fulfil bone regeneration requirements. The developed porous hybrid biocomposite scaffolds were extensively characterized, regarding their physical, morphological, and mechanical features. The results showed that their properties were relevant, leading to composites with different properties. The water absorption capacity and mass loss were evaluated as well as the influence of the different hybrid scaffolds on osteoblasts' viability and morphology. Both hybrid scaffolds showed a hydrophobic character (with water contact angles higher than 90°), low swelling (maximum of 14%), and low mass loss (1-7%). hOB cells exposed to the different silica aerogel-PCL scaffolds remained highly viable, even for long periods of incubation (7 days). Considering the obtained results, the produced hybrid scaffolds may be good candidates for future application in bone tissue engineering.
    Keywords:  hybrid composites; poly-ε-caprolactone (PCL); silica aerogel; tissue engineering
    DOI:  https://doi.org/10.3390/ijms241210128
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