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生物设计与制造(英文)
生物设计与制造(英文)

季刊

2096-5524

生物设计与制造(英文)/Journal Bio-Design and Manufacturing CSCD北大核心SCI
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    Biomaterials and emerging technologies for tissue engineering and in vitro models

    J.Miguel OliveiraRui L.Reis
    237-239页

    An oxygenating colloidal bioink for the engineering of biomimetic tissue constructs

    Seol-Ha JeongJarno HiemstraPatrick V.BlokzijlRebeca Damian-Ferrara...
    240-261页
    查看更多>>摘要:Ensuring a sufficient oxygen supply is pivotal for the success of bioprinting applications since it fosters tissue integration and natural regeneration.Variation in oxygen concentration among diverse tissues necessitates the precise recreation of tissue-specific oxygen levels in imprinted constructs to support the survival of targeted cells.Although oxygen-releasing biomaterials,such as oxygen-generating microparticles(OMPs),have shown promise for enhancing the oxygen supply of microenvironments in injured tissues,whether this approach is scalable for large tissues and whether tissue-specific bioinks with varying OMP concentrations remain printable remain unknown.This study addresses this critical gap by introducing an innovative class of engineered oxygenated bioinks that combine colloidal-based microgels with OMPs.We report that incorporating nanosized calcium peroxide(nCaO2)and manganese oxide nanosheets(nMnO2)into hydrophobic polymeric microparticles enables precise modulation of oxygen release while controlling hydrogen peroxide release.Moreover,the fabrication of oxygenating and cytocompatible colloidal gels is achieved using an aqueous two-phase system.This study thoroughly evaluates the fundamental characteristics of the resulting bioink,including its rheological behaviors,printability,shape fidelity,mechanical properties,and oxygen release properties.Moreover,this study demonstrates the macroscopic scalability and cytocompatibility of printed constructs produced via cell-laden oxygenating colloidal bioinks.By showcasing the effectiveness of extrusion-based bioprinting,this study underscores how it can be used to fabricate biomimetic tissues,indicating its potential for new applications.The findings presented here advance the bioprinting field by achieving scalability with both high cell viability and the possibility of mimicking specifically oxygenated tissues.This work thereby offers a promising avenue for the development of functional tissues with enhanced physiological relevance.

    Development and characterization of 3D-printed electroconductive pHEMA-co-MAA NP-laden hydrogels for tissue engineering

    Sara De NittoAleksandra SerafinAlexandra KaradimouAchim Schmalenberger...
    262-276页
    查看更多>>摘要:Tissue engineering(TE)continues to be widely explored as a potential solution to meet critical clinical needs for diseased tissue replacement and tissue regeneration.In this study,we developed a poly(2-hydroxyethyl methacrylate-co-methacrylic acid)(pHEMA-co-MAA)based hydrogel loaded with newly synthesized conductive poly(3,4-ethylene-dioxythiophene)(PEDOT)and polypyrrole(PPy)nanoparticles(NPs),and subsequently processed these hydrogels into tissue engineered constructs via three-dimensional(3D)printing.The presence of the NPs was critical as they altered the rheological properties during printing.However,all samples exhibited suitable shear thinning properties,allowing for the development of an optimized processing window for 3D printing.Samples were 3D printed into pre-determined disk-shaped configurations of 2 and 10 mm in height and diameter,respectively.We observed that the NPs disrupted the gel crosslinking efficiencies,leading to shorter degradation times and compressive mechanical properties ranging between 450 and 550 kPa.The conductivity of the printed hydrogels increased along with the NP concentration to(5.10±0.37)×10-7 S/cm.In vitro studies with cortical astrocyte cell cultures demonstrated that exposure to the pHEMA-co-MAA NP hydrogels yielded high cellular viability and proliferation rates.Finally,hydrogel antimicrobial studies with staphylococcus epidermidis bacteria revealed that the developed hydrogels affected bacterial growth.Taken together,these materials show promise for various TE strategies.

    A facile strategy for tuning the density of surface-grafted biomolecules for melt extrusion-based additive manufacturing applications

    I.A.O.BeerenG.Dos SantosP.J.DijkstraC.Mota...
    277-291页
    查看更多>>摘要:Melt extrusion-based additive manufacturing(ME-AM)is a promising technique to fabricate porous scaffolds for tissue engi-neering applications.However,most synthetic semicrystalline polymers do not possess the intrinsic biological activity required to control cell fate.Grafting of biomolecules on polymeric surfaces of AM scaffolds enhances the bioactivity of a construct;however,there are limited strategies available to control the surface density.Here,we report a strategy to tune the surface density of bioactive groups by blending a low molecular weight poly(ε-caprolactone)5k(PCL5k)containing orthogonally reactive azide groups with an unfunctionalized high molecular weight PCL75k at different ratios.Stable porous three-dimensional(3D)scaf-folds were then fabricated using a high weight percentage(75 wt.%)of the low molecular weight PCL5k.As a proof-of-concept test,we prepared films of three different mass ratios of low and high molecular weight polymers with a thermopress and reacted with an alkynated fluorescent model compound on the surface,yielding a density of 201-561 pmol/cm2.Subsequently,a bone morphogenetic protein 2(BMP-2)-derived peptide was grafted onto the films comprising different blend compositions,and the effect of peptide surface density on the osteogenic differentiation of human mesenchymal stromal cells(hMSCs)was assessed.After two weeks of culturing in a basic medium,cells expressed higher levels of BMP receptor II(BMPRII)on films with the conjugated peptide.In addition,we found that alkaline phosphatase activity was only significantly enhanced on films contain-ing the highest peptide density(i.e.,561 pmol/cm2),indicating the importance of the surface density.Taken together,these results emphasize that the density of surface peptides on cell differentiation must be considered at the cell-material interface.Moreover,we have presented a viable strategy for ME-AM community that desires to tune the bulk and surface functionality via blending of(modified)polymers.Furthermore,the use of alkyne-azide"click"chemistry enables spatial control over bioconjugation of many tissue-specific moieties,making this approach a versatile strategy for tissue engineering applications.

    Highly sensitive ratiometric fluorescent fiber matrices for oxygen sensing with micrometer spatial resolution

    Giuliana GrassoValentina OnestoStefania ForcinitiEliana D'Amone...
    292-306页
    查看更多>>摘要:Oxygen(O2)-sensing matrices are promising tools for the live monitoring of extracellular O2 consumption levels in long-term cell cultures.In this study,ratiometric O2-sensing membranes were prepared by electrospinning,an easy,low-cost,scalable,and robust method for fabricating nanofibers.Poly(ε-caprolactone)and poly(dimethyl)siloxane polymers were blended with tris(4,7-diphenyl-1,10-phenanthroline)ruthenium(Ⅱ)dichloride,which was used as the O2-sensing probe,and rhodamine B isothiocyanate,which was used as the reference dye.The functionalized scaffolds were morphologically characterized by scanning electron microscopy,and their physicochemical profiles were obtained by Fourier transform infrared spectroscopy,thermogravimetric analysis,and water contact angle measurement.The sensing capabilities were investigated by confocal laser scanning microscopy,performing photobleaching,reversibility,and calibration curve studies toward different dissolved O2(DO)concentrations.Electrospun sensing nanofibers showed a high response to changes in DO concentrations in the physiological-pathological range from 0.5%to 20%and good stability under ratiometric imaging.In addition,the sensing systems were highly biocompatible for cell growth promoting adhesiveness and growth of three cancer cell lines,namely metastatic melanoma cell line SK-MEL2,breast cancer cell line MCF-7,and pancreatic ductal adenocarcinoma cell line Panc-1,thus recreating a suitable biological environment in vitro.These O2-sensing biomaterials can potentially measure alterations in cell metabolism caused by changes in ambient O2 content during drug testing/validation and tissue regeneration processes.

    Oxygen tension modulates cell function in an in vitro three-dimensional glioblastoma tumor model

    Sen WangSiqi YaoNa PeiLuge Bai...
    307-319页
    查看更多>>摘要:Hypoxia is a typical feature of the tumor microenvironment,one of the most critical factors affecting cell behavior and tumor progression.However,the lack of tumor models able to precisely emulate natural brain tumor tissue has impeded the study of the effects of hypoxia on the progression and growth of tumor cells.This study reports a three-dimensional(3D)brain tumor model obtained by encapsulating U87MG(U87)cells in a hydrogel containing type I collagen.It also documents the effect of various oxygen concentrations(1%,7%,and 21%)in the culture environment on U87 cell morphology,proliferation,viability,cell cycle,apoptosis rate,and migration.Finally,it compares two-dimensional(2D)and 3D cultures.For comparison purposes,cells cultured in flat culture dishes were used as the control(2D model).Cells cultured in the 3D model proliferated more slowly but had a higher apoptosis rate and proportion of cells in the resting phase(G0 phase)/gap I phase(G1 phase)than those cultured in the 2D model.Besides,the two models yielded significantly different cell morphologies.Finally,hypoxia(e.g.,1%O2)affected cell morphology,slowed cell growth,reduced cell viability,and increased the apoptosis rate in the 3D model.These results indicate that the constructed 3D model is effective for investigating the effects of biological and chemical factors on cell morphology and function,and can be more representative of the tumor microenvironment than 2D culture systems.The developed 3D glioblastoma tumor model is equally applicable to other studies in pharmacology and pathology.

    Cellular interplay to 3D in vitro microphysiological disease model:cell patterning microbiota-gut-brain axis

    Kamare AlamLakshmi NairSouvik MukherjeeKulwinder Kaur...
    320-357页
    查看更多>>摘要:The microbiota-gut-brain axis(MGBA)has emerged as a key prospect in the bidirectional communication between two major organ systems:the brain and the gut.Homeostasis between the two organ systems allows the body to function without disease,whereas dysbiosis has long-standing evidence of etiopathological conditions.The most common communication paths are the microbial release of metabolites,soluble neurotransmitters,and immune cells.However,each pathway is intertwined with a complex one.With the emergence of in vitro models and the popularity of three-dimensional(3D)cultures and Transwells,engineering has become easier for the scientific understanding of neurodegenerative diseases.This paper briefly retraces the possible communication pathways between the gut microbiome and the brain.It further elaborates on three major diseases:autism spectrum disorder,Parkinson's disease,and Alzheimer's disease,which are prevalent in children and the elderly.These diseases also decrease patients'quality of life.Hence,understanding them more deeply with respect to current advances in in vitro modeling is crucial for understanding the diseases.Remodeling of MGBA in the laboratory uses many molecular technologies and biomaterial advances.Spheroids and organoids provide a more realistic picture of the cell and tissue structure than monolayers.Combining them with the Transwell system offers the advantage of compartmentalizing the two systems(apical and basal)while allowing physical and chemical cues between them.Cutting-edge technologies,such as bioprinting and microfluidic chips,might be the future of in vitro modeling,as they provide dynamicity.

    Innovation leading development:a glimpse into three-dimensional bioprinting in Israel

    Lujing GaoZixuan LiuDaniel DikovskyJiqian Wang...
    358-382页
    查看更多>>摘要:Three-dimensional(3D)printing has attracted increasing research interest as an emerging manufacturing technology for devel-oping sophisticated and exquisite architecture through hierarchical printing.It has also been employed in various advanced industrial areas.The development of intelligent biomedical engineering has raised the requirements for 3D printing,such as flexible manufacturing processes and technologies,biocompatible constituents,and alternative bioproducts.However,state-of-the-art 3D printing mainly involves inorganics or polymers and generally focuses on traditional industrial fields,thus severely limiting applications demanding biocompatibility and biodegradability.In this regard,peptide architectonics,which are self-assembled by programmed amino acid sequences that can be flexibly functionalized,have shown promising potential as bioinspired inks for 3D printing.Therefore,the combination of 3D printing and peptide self-assembly poten-tially opens up an alternative avenue of 3D bioprinting for diverse advanced applications.Israel,a small but innovative nation,has significantly contributed to 3D bioprinting in terms of scientific studies,marketization,and peptide architectonics,including modulations and applications,and ranks as a leading area in the 3D bioprinting field.This review summarizes the recent progress in 3D bioprinting in Israel,focusing on scientific studies on printable components,soft devices,and tissue engineering.This paper further delves into the manufacture of industrial products,such as artificial meats and bioinspired supramolecular architectures,and the mechanisms,physicochemical properties,and applications of peptide self-assembly.Undoubtedly,Israel contributes significantly to the field of 3D bioprinting and should thus be appropriately recognized.