Biomaterials and Porous Scaffolds for Tissue Engineering and Regenerative Medicine

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Guest Editor
Department of Mechanical Engineering, The University of Hong Kong, Hong Kong, China
Interests: biomedical materials; tissue engineering; materials and systems for the controlled release of drugs/biomolecules/genes; surface engineering; nanotechnologies; electrospinning; additive manufacturing ("3D printing"); biomanufacturing
School of Mechanical Engineering, Dongguan University of Technology, Dongguan, China
Interests: 3D/4D printing; biofabrication; tissue regeneration; biomaterials; organoid
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Guest Editor
Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences (CAS), Shenzhen, China
Interests: biointerfaces; stimuli-responsive biomaterials; tissue engineering; biomanufacturing; electrospinning; electrospraying

Special Issue Information

Dear Colleagues,

Tissue engineering emerged more than three decades ago. It has attracted great attention because it holds great promise for solving many difficult medical problems that current treatments cannot deal with or cannot achieve satisfactory clinical outcomes for. Worldwide efforts over the past few decades have led to remarkable progresses in regenerating human body tissues such as skin, blood vessels, and bone. However, there are still great challenges in tissue engineering and regenerative medicine. Recent advances in materials science and engineering, nanoscience and nanotechnology, manufacturing technologies, biological science, clinical sciences, etc., can significantly move the field forward and greatly assist us to tackle the challenges and regenerate complex body tissues/organs such as the gastrointestinal tract, liver, and uterus.

There are different strategies for human body tissue regeneration. Many researchers have successfully used scaffold-, growth factor (GF)-, or cell-based tissue engineering for regenerating human skin, bone, articular cartilage, etc. In scaffold-based tissue engineering, scaffolds provide conducive microenvironments for cells and play vital roles for cell adhesion, proliferation, differentiation, and new tissue formation. Many biocompatible materials, including polymers, metals, ceramics, and composites/hybrids, have been used/developed as tissue engineering materials and have achieved their successes. However, different materials have their advantages and shortcomings. For example, hydrogels have seen their increasing use in the tissue engineering field because of their particular attractiveness, but they are weak materials. Strong and highly resilient hydrogels are now being investigated/developed for targeted applications by research groups in different continents. For the regeneration of a specific body tissue, the material/materials should be carefully selected and evaluated. There are also many scaffold fabrication technologies, including electrospinning and additive manufacturing (i.e., “3D printing”). Electrospinning is attractive because it can produce nanofibrous structures that mimic the extracellular matrix structure. However, there are limitations in electrospinning, so significant improvements for electrospun products are also required. 3D-printing technologies have significantly raised our ability to create complex scaffolds or cell-scaffold constructs for regenerating complex body tissues. Bioprinting has shown great promise in a number of areas, including tissue engineering. However, there many scientific and technological issues that need to be addressed for 3D printing in tissue engineering and for bioprinting. Additionally, stem cells are increasingly used in tissue engineering investigations. Again, there are fundamental and technical questions that need to be answered for their wide use in the field. Designing scaffolds and scaffold simulation (mechanical, fluidic, etc.) are gaining increasing attention with the aim to achieve the best clinical performance for scaffolds. Biomimicking scaffolds are becoming popular for tissue regeneration. Guidelines on scaffold design, which are tissue specific, should therefore be established. Even though there are already numerous investigations on cell‒scaffold interactions, scaffold‒tissue interactions, and biochemical and/or biomechanical cues on cell behaviour and tissue formation, great efforts are still needed to gain further understanding and new insights in these areas. Furthermore, developing multifunctional scaffolds that can also perform other functions (anti-inflammatory, anti-cancer, etc.) provides much wider scope for our R&D activities.

This Special Issue provides a forum for sharing new research findings and new insights in different areas mentioned above from people, both experienced workers and newcomers, involved in tissue engineering and regenerative medicine. These people include biomaterials scientists and engineers, tissue engineers, biological scientists, clinicians, and industrialists. Submissions presenting new ideas/approaches, new materials, new scaffold designs, new fabrication technologies, novel scaffolds, new testing techniques, and new assessment methods are very welcome. The materials and porous scaffolds that are presented in these submissions are/will be used for regenerating different body tissues/organs, including skin, blood vessels, bone, tendon/ligament, articular cartilage, osteochondral tissue, gastrointestinal tract, liver, uterus, etc. Articles of excellent quality in this Special Issue will be selected as Feature Papers of the Journal of Functional Biomaterials.

Prof. Dr. Min Wang
Dr. Chong Wang
Dr. Qilong Zhao
Guest Editors

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Keywords

  • tissue engineering
  • regenerative medicine
  • natural polymer
  • synthetic polymer
  • hydrogel
  • metal
  • ceramic
  • composite
  • hybrid
  • porous scaffold
  • scaffold design
  • biomimicking
  • graded scaffold
  • multifunctional scaffold
  • cell‒scaffold construct
  • scaffold fabrication
  • electrospinning
  • 3D printing
  • bioprinting
  • structure
  • performance
  • biodegradation
  • scaffold simulation
  • biochemical cue
  • biomechanical cue
  • bioreactor
  • mature cell
  • stem cell
  • cell‒scaffold interaction
  • scaffold‒tissue interaction
  • in vitro evaluation
  • in vivo evaluation

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Published Papers (8 papers)

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Research

21 pages, 5285 KiB  
Article
Three-Dimensional Printing of Hydrogel Blend Tissue Engineering Scaffolds with In Situ Delivery of Anticancer Drug for Treating Melanoma Resection-Induced Tissue Defects
by Xiao-Die Chen, Xin-Yang Zhang, Han-Qi Zhu, Helen H. Lu and Min Wang
J. Funct. Biomater. 2024, 15(12), 381; https://doi.org/10.3390/jfb15120381 - 18 Dec 2024
Viewed by 791
Abstract
Surgery is considered the gold standard for treating melanoma, but the high recurrence rate after surgery still remains as a major challenge. Therefore, using doxorubicin (DOX) as a model drug, this study investigated the 3D printing of anticancer drug-loaded hydrogel blend scaffolds for [...] Read more.
Surgery is considered the gold standard for treating melanoma, but the high recurrence rate after surgery still remains as a major challenge. Therefore, using doxorubicin (DOX) as a model drug, this study investigated the 3D printing of anticancer drug-loaded hydrogel blend scaffolds for inhibiting post-operation melanoma recurrence and for promoting tissue regeneration. Three-dimensional printing could successfully produce methacrylate-modified chitosan (CSMA) and methylcellulose (MC) hydrogel blend scaffolds. Polymer blend inks exhibited satisfactory printability, and the printed porous scaffolds showed good biocompatibility and mechanical properties. Three-dimensionally printed DOX-loaded hydrogel scaffolds displayed controlled drug release, which may effectively prevent/impede tumor recurrence after surgery. Furthermore, combining 3D printing and bioprinting, DOX-loaded and rat bone marrow mesenchymal stem cell (rBMSC)-laden scaffolds were created for assessing local DOX delivery on healthy tissues. Within the 14-day culture period, rBMSCs encapsulated in multilayered scaffolds that were incorporated with DOX displayed rejuvenated cell viability. The 3D printed and bioprinted dual purpose hydrogel scaffolds have the promise of combating tumor recurrence and providing structural support for tissue regeneration. Full article
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20 pages, 4201 KiB  
Article
Impact of Particle Size and Sintering Temperature on Calcium Phosphate Gyroid Structure Scaffolds for Bone Tissue Engineering
by Romina Haydeé Aspera-Werz, Guanqiao Chen, Lea Schilonka, Islam Bouakaz, Catherine Bronne, Elisabeth Cobraiville, Grégory Nolens and Andreas Nussler
J. Funct. Biomater. 2024, 15(12), 355; https://doi.org/10.3390/jfb15120355 - 21 Nov 2024
Cited by 1 | Viewed by 1250
Abstract
Due to the chemical composition and structure of the target tissue, autologous bone grafting remains the gold standard for orthopedic applications worldwide. However, ongoing advancements in alternative grafting materials show that 3D-printed synthetic biomaterials offer many advantages. For instance, they provide high availability, [...] Read more.
Due to the chemical composition and structure of the target tissue, autologous bone grafting remains the gold standard for orthopedic applications worldwide. However, ongoing advancements in alternative grafting materials show that 3D-printed synthetic biomaterials offer many advantages. For instance, they provide high availability, have low clinical limitations, and can be designed with a chemical composition and structure comparable to the target tissue. This study aimed to compare the influences of particle size and sintering temperature on the mechanical properties and biocompatibility of calcium phosphate (CaP) gyroid scaffolds. CaP gyroid scaffolds were fabricated by 3D printing using powders with the same chemical composition but different particle sizes and sintering temperatures. The physicochemical characterization of the scaffolds was performed using X-ray diffractometry, scanning electron microscopy, and microtomography analyses. The immortalized human mesenchymal stem cell line SCP-1 (osteoblast-like cells) and osteoclast-like cells (THP-1 cells) were seeded on the scaffolds as mono- or co-cultures. Bone cell attachment, number of live cells, and functionality were assessed at different time points over a period of 21 days. Improvements in mechanical properties were observed for scaffolds fabricated with narrow-particle-size-distribution powder. The physicochemical analysis showed that the microstructure varied with sintering temperature and that narrow particle size distribution resulted in smaller micropores and a smoother surface. Viable osteoblast- and osteoclast-like cells were observed for all scaffolds tested, but scaffolds produced with a smaller particle size distribution showed less attachment of osteoblast-like cells. Interestingly, low attachment of osteoclast-like cells was observed for all scaffolds regardless of surface roughness. Although bone cell adhesion was lower in scaffolds made with powder containing smaller particle sizes, the long-term function of osteoblast-like and osteoclast-like cells was superior in scaffolds with improved mechanical properties. Full article
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10 pages, 1007 KiB  
Article
Core–Shell Microspheres with Encapsulated Gold Nanoparticle Carriers for Controlled Release of Anti-Cancer Drugs
by Lin Guo, Qilong Zhao and Min Wang
J. Funct. Biomater. 2024, 15(10), 277; https://doi.org/10.3390/jfb15100277 - 24 Sep 2024
Viewed by 1139
Abstract
Cancer is one of the major threats to human health and lives. However, effective cancer treatments remain a great challenge in clinical medicine. As a common approach for cancer treatment, chemotherapy has saved the life of millions of people; however, patients who have [...] Read more.
Cancer is one of the major threats to human health and lives. However, effective cancer treatments remain a great challenge in clinical medicine. As a common approach for cancer treatment, chemotherapy has saved the life of millions of people; however, patients who have gone through chemotherapy often suffer from severe side effects owing to the inherent cytotoxicity of anti-cancer drugs. Stabilizing the blood concentration of an anti-cancer drug will reduce the occurrence or severity of side effects, and relies on using an appropriate drug delivery system (DDS) for achieving sustained or even on-demand drug delivery. However, this is still an unmet clinical challenge since the mainstay of anti-cancer drugs is small molecules, which tend to be diffused rapidly in the body, and conventional DDSs exhibit the burst release phenomenon. Here, we establish a class of DDSs based on biodegradable core–shell microspheres with encapsulated doxorubicin hydrochloride-loaded gold nanoparticles (DOX@Au@MSs), with the core–shell microspheres being made of poly(lactic-co-glycolic acid) in the current study. By harnessing the physical barrier of the biodegradable shell of core–shell microspheres, DOX@Au@MSs can provide a sustained release of the anti-cancer drug in the test duration (which is 21 days in the current study). Thanks to the photothermal properties of the encapsulated gold nanoparticle carriers, the core–shell biodegradable microspheres can be ruptured through remotely controlled near-infrared (NIR) light, thereby achieving an NIR-controlled triggered release of the anti-cancer drug. Furthermore, the route of the DOX-Au@MS-enabled controlled release of the anti-cancer drug can provide durable cancer cell ablation for the long period of 72 h. Full article
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11 pages, 3519 KiB  
Article
Cell Proliferation, Chondrogenic Differentiation, and Cartilaginous Tissue Formation in Recombinant Silk Fibroin with Basic Fibroblast Growth Factor Binding Peptide
by Manabu Yamada, Arata Nakajima, Kayo Sakurai, Yasushi Tamada and Koichi Nakagawa
J. Funct. Biomater. 2024, 15(8), 230; https://doi.org/10.3390/jfb15080230 - 17 Aug 2024
Viewed by 1238
Abstract
Regeneration of articular cartilage remains a challenge for patients who have undergone cartilage injury, osteochondritis dissecans and osteoarthritis. Here, we describe a new recombinant silk fibroin with basic fibroblast growth factor (bFGF) binding peptide, which has a genetically introduced sequence PLLQATLGGGS, named P7. [...] Read more.
Regeneration of articular cartilage remains a challenge for patients who have undergone cartilage injury, osteochondritis dissecans and osteoarthritis. Here, we describe a new recombinant silk fibroin with basic fibroblast growth factor (bFGF) binding peptide, which has a genetically introduced sequence PLLQATLGGGS, named P7. In this study, we cultured a human mesenchymal cell line derived from bone marrow, UE6E7-16, in wild-type fibroin sponge (FS) and recombinant silk fibroin sponge with P7 peptide (P7 FS). We compared cell proliferation, chondrogenic differentiation and cartilaginous tissue formation between the two types of sponge. After stimulation with bFGF at 3 ng/mL, P7 FS showed significantly higher cell growth (1.2-fold) and higher cellular DNA content (5.6-fold) than did wild-type FS. To promote chondrogenic differentiation, cells were cultured in the presence of TGF-β at 10 ng/mL for 28 days. Immunostaining of P7 FS showed SOX9-positive cells comparable to wild-type FS. Alcian-Blue staining of P7 FS also showed cartilaginous tissue formation equivalent to wild-type FS. A significant increase in cell proliferation in P7 FS implies future clinical application of this transgenic fibroin for regeneration of articular cartilage. To produce cartilaginous tissue efficiently, transgenic fibroin sponges and culture conditions must be improved. Such changes should include the selection of growth factors involved in chondrogenic differentiation and cartilage formation. Full article
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22 pages, 6821 KiB  
Article
Design of Laser Activated Antimicrobial Porous Tricalcium Phosphate-Hydroxyapatite Scaffolds for Orthopedic Applications
by Emil Filipov, Ridvan Yildiz, Anna Dikovska, Lamborghini Sotelo, Tharun Soma, Georgi Avdeev, Penka Terziyska, Silke Christiansen, Anne Leriche, Maria Helena Fernandes and Albena Daskalova
J. Funct. Biomater. 2024, 15(2), 36; https://doi.org/10.3390/jfb15020036 - 30 Jan 2024
Cited by 1 | Viewed by 2287
Abstract
The field of bone tissue engineering is steadily being improved by novel experimental approaches. Nevertheless, microbial adhesion after scaffold implantation remains a limitation that could lead to the impairment of the regeneration process, or scaffold rejection. The present study introduces a methodology that [...] Read more.
The field of bone tissue engineering is steadily being improved by novel experimental approaches. Nevertheless, microbial adhesion after scaffold implantation remains a limitation that could lead to the impairment of the regeneration process, or scaffold rejection. The present study introduces a methodology that employs laser-based strategies for the development of antimicrobial interfaces on tricalcium phosphate–hydroxyapatite (TCP-HA) scaffolds. The outer surfaces of the ceramic scaffolds with inner porosity were structured using a femtosecond laser (λ = 800 nm; τ = 70 fs) for developing micropatterns and altering local surface roughness. The pulsed laser deposition of ZnO was used for the subsequent functionalization of both laser-structured and unmodified surfaces. The impact of the fs irradiation was investigated by Raman spectroscopy and X-ray diffraction. The effects of the ZnO-layered ceramic surfaces on initial bacterial adherence were assessed by culturing Staphylococcus aureus on both functionalized and non-functionalized scaffolds. Bacterial metabolic activity and morphology were monitored via the Resazurin assay and microscopic approaches. The presence of ZnO evidently decreased the metabolic activity of bacteria and led to impaired cell morphology. The results from this study have led to the conclusion that the combination of fs laser-structured surface topography and ZnO could yield a potential antimicrobial interface for implants in bone tissue engineering. Full article
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19 pages, 8907 KiB  
Article
Fibronectin Conformations after Electrodeposition onto 316L Stainless Steel Substrates Enhanced Early-Stage Osteoblasts’ Adhesion but Affected Their Behavior
by Séverine Alfonsi, Pithursan Karunathasan, Ayann Mamodaly-Samdjee, Keerthana Balathandayutham, Sarah Lefevre, Anamar Miranda, Olivier Gallet, Damien Seyer and Mathilde Hindié
J. Funct. Biomater. 2024, 15(1), 5; https://doi.org/10.3390/jfb15010005 - 21 Dec 2023
Cited by 1 | Viewed by 2183
Abstract
The implantation of metallic orthopedic prostheses is increasingly common due to an aging population and accidents. There is a real societal need to implement new metal implants that combine durability, good mechanical properties, excellent biocompatibility, as well as affordable costs. Since the functionalization [...] Read more.
The implantation of metallic orthopedic prostheses is increasingly common due to an aging population and accidents. There is a real societal need to implement new metal implants that combine durability, good mechanical properties, excellent biocompatibility, as well as affordable costs. Since the functionalization of low-cost 316L stainless steel substrates through the successive electrodeposition of a polypyrrole film (PPy) and a calcium phosphate deposit doped with silicon was previously carried out by our labs, we have also developed a bio-functional coating by electrodepositing or oxidating of fibronectin (Fn) coating. Fn is an extracellular matrix glycoprotein involved in cell adhesion and differentiation. Impacts of either electrodeposition or oxidation on the structure and functionality of Fn were first studied. Thus, electrodeposition is the technique that permits the highest deposition of fibronectin, compared to adsorption or oxidation. Furthermore, electrodeposition seems to strongly modify Fn conformation by the formation of intermingled long fibers, resulting in changes to the accessibility of the molecular probes tested (antibodies directed against Fn whole molecule and Fn cell-binding domain). Then, the effects of either electrodeposited Fn or oxidized Fn were validated by the resulting pre-osteoblast behavior. Electrodeposition reduced pre-osteoblasts’ ability to remodel Fn coating on supports because of a partial modification of Fn conformation, which reduced accessibility to the cell-binding domain. Electrodeposited Fn also diminished α5 integrin secretion and clustering along the plasma membrane. However, the N-terminal extremity of Fn was not modified by electrodeposition as demonstrated by Staphylococcus aureus attachment after 3 h of culture on a specific domain localized in this region. Moreover, the number of pre-osteoblasts remains stable after 3 h culture on either adsorbed, oxidized, or electrodeposited Fn deposits. In contrast, mitochondrial activity and cell proliferation were significantly higher on adsorbed Fn compared with electrodeposited Fn after 48 h culture. Hence, electro-deposited Fn seems more favorable to pre-osteoblast early-stage behavior than during a longer culture of 24 h and 48 h. The electrodeposition of matrix proteins could be improved to maintain their bio-activity and to develop this promising, fast technique to bio-functionalize metallic implants. Full article
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18 pages, 7377 KiB  
Article
Nanostructured Porous Silicon for Bone Tissue Engineering: Kinetics of Particle Degradation and Si-Controlled Release
by Naveen Fatima, Hamideh Salehi, Eduardo J. Cueto-Díaz, Alban Desoutter, Frédéric Cuisinier, Frédérique Cunin and Pierre-Yves Collart-Dutilleul
J. Funct. Biomater. 2023, 14(10), 493; https://doi.org/10.3390/jfb14100493 - 30 Sep 2023
Viewed by 2434
Abstract
Nanostructured porous silicon (pSi) is a synthetic silicon-based material. Its biocompatibility and bioresorbability in body fluids make pSi an appealing biomaterial for tissue engineering, with surfaces characteristics facilitating human cell adhesion and differentiation. The resorption kinetics of such porous biomaterials is crucial for [...] Read more.
Nanostructured porous silicon (pSi) is a synthetic silicon-based material. Its biocompatibility and bioresorbability in body fluids make pSi an appealing biomaterial for tissue engineering, with surfaces characteristics facilitating human cell adhesion and differentiation. The resorption kinetics of such porous biomaterials is crucial for in vivo bone regeneration, in order to adapt biomaterial resorption to tissue formation, and to control the release of loaded bioactive molecules. We investigated pSi as a bioactive scaffold for bone tissue engineering, with an emphasis on kinetics of pSi resorption and silicon release. PSi particles and chips were fabricated from crystalline silicon, and functionalized by oxidation and chemical grafting of amine groups to mimic biological structures. Materials resorption over time was investigated with Raman spectroscopy, infrared spectroscopy, and Scanning Electron Microscopy. Silicon release was followed by mass spectrometry. Particle degradation and inclusion in newly formed bone were studied in vivo. The in vitro experiments revealed that non-oxidized pSi had an accelerated initial dissolution in ddH2O and an inhibition of initial Si release in SBF. This high reactivity also led to transformation towards amorphous non-resorbable silica when incubated in SBF. PSi resorption started immediately with a maximal dissolution in the first 24 h. Later, the dissolution rate decreased over time. In comparison, the resorption process of oxidized pSi seemed delayed, but more continuous. This delayed dissolution increased the bioactivity and stability, leading to enhanced bone formation in vivo. Delayed pSi degradation provided a constant surge of silicic acid over time and promoted bone regeneration, demonstrating the high potential of pSi for bone tissue engineering: Oxidized pSi were almost completely resorbed after 2 months of healing, with remaining partially dissolved particles surrounded by newly formed bone. On the contrary, non-oxidized particles were still obviously present after 2 months with limited bone regeneration. This delayed resorption is consistent with the in vitro observations in SBF, and particles’ transformation towards silica. Full article
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15 pages, 10647 KiB  
Article
Cryo-Electrospinning Generates Highly Porous Fiber Scaffolds Which Improves Trabecular Meshwork Cell Infiltration
by Devon J. Crouch, Carl M. Sheridan, Julia G. Behnsen, Raechelle A. D’Sa and Lucy A. Bosworth
J. Funct. Biomater. 2023, 14(10), 490; https://doi.org/10.3390/jfb14100490 - 22 Sep 2023
Cited by 8 | Viewed by 2615
Abstract
Human trabecular meshwork is a sieve-like tissue with large pores, which plays a vital role in aqueous humor outflow. Dysfunction of this tissue can occur, which leads to glaucoma and permanent vision loss. Replacement of trabecular meshwork with a tissue-engineered device is the [...] Read more.
Human trabecular meshwork is a sieve-like tissue with large pores, which plays a vital role in aqueous humor outflow. Dysfunction of this tissue can occur, which leads to glaucoma and permanent vision loss. Replacement of trabecular meshwork with a tissue-engineered device is the ultimate objective. This study aimed to create a biomimetic structure of trabecular meshwork using electrospinning. Conventional electrospinning was compared to cryogenic electrospinning, the latter being an adaptation of conventional electrospinning whereby dry ice is incorporated in the fiber collector system. The dry ice causes ice crystals to form in-between the fibers, increasing the inter-fiber spacing, which is retained following sublimation. Structural characterization demonstrated cryo-scaffolds to have closer recapitulation of the trabecular meshwork, in terms of pore size, porosity, and thickness. The attachment of a healthy, human trabecular meshwork cell line (NTM5) to the scaffold was not influenced by the fabrication method. The main objective was to assess cell infiltration. Cryo-scaffolds supported cell penetration deep within their structure after seven days, whereas cells remained on the outer surface for conventional scaffolds. This study demonstrates the suitability of cryogenic electrospinning for the close recapitulation of trabecular meshwork and its potential as a 3D in vitro model and, in time, a tissue-engineered device. Full article
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