Anisotropy Properties of Tissues: A Basis for Fabrication of Biomimetic Anisotropic Scaffolds for Tissue Engineering

Datta, Pallab; Vyas, Veena; Dhara, Santanu; Chowdhury, Amit Roy; Barui, Ananya

doi:10.1007/s42235-019-0101-9

Cited by 51 publications

(52 citation statements)

References 187 publications

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“…Biomimetic scaffolds have shown great promise in the field of tissue engineering, as their structure can be tailored to recreate microenvironments suitable for tissue formation 45 – 47 . While significant efforts have been devoted to promoting anisotropic mechanical properties of tissue engineering scaffolds, accurate characterization of scaffold 3D diffusion properties is needed to confirm their functional performance and further enhance their biological relevance 48 , 49 . Moreover, a standard tool for 3D diffusion measurement is in great need to assure quality control in the industrial scaffold fabrication process.…”

Section: Resultsmentioning

confidence: 99%

“…By enabling accurate quantification of 3D diffusion behavior in scaffolds, LiFT-FRAP serves to augment current tissue engineering approaches. Like endogenous tissues, biomimetic scaffolds must possess several types of highly direction-dependent organization, including structural, mechanical, and diffusion anisotropy 49 . Although numerous studies have been devoted to mimic the structural and mechanical anisotropy of native tissues, diffusion anisotropy has not been well studied due to the lack of tools capable of examining 3D diffusion in tissues and scaffolds 45 – 49 .…”

Section: Discussionmentioning

confidence: 99%

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A noninvasive fluorescence imaging-based platform measures 3D anisotropic extracellular diffusion

Chen

Hepfer

et al. 2021

Nat Commun

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Diffusion is a major molecular transport mechanism in biological systems. Quantifying direction-dependent (i.e., anisotropic) diffusion is vitally important to depicting how the three-dimensional (3D) tissue structure and composition affect the biochemical environment, and thus define tissue functions. However, a tool for noninvasively measuring the 3D anisotropic extracellular diffusion of biorelevant molecules is not yet available. Here, we present light-sheet imaging-based Fourier transform fluorescence recovery after photobleaching (LiFT-FRAP), which noninvasively determines 3D diffusion tensors of various biomolecules with diffusivities up to 51 µm2 s−1, reaching the physiological diffusivity range in most biological systems. Using cornea as an example, LiFT-FRAP reveals fundamental limitations of current invasive two-dimensional diffusion measurements, which have drawn controversial conclusions on extracellular diffusion in healthy and clinically treated tissues. Moreover, LiFT-FRAP demonstrates that tissue structural or compositional changes caused by diseases or scaffold fabrication yield direction-dependent diffusion changes. These results demonstrate LiFT-FRAP as a powerful platform technology for studying disease mechanisms, advancing clinical outcomes, and improving tissue engineering.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A noninvasive fluorescence imaging-based platform measures 3D anisotropic extracellular diffusion

Chen

Hepfer

et al. 2021

Nat Commun

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“…However, the control over the microscopic architecture has been mostly overlooked. Mechanical and biological properties of animal tissues depend not only on the chemical composition, but also on the specific spatial arrangement of structural molecules and biological factors [10]. For example, cartilage is composed of a glycosaminoglycan-based matrix containing Col fibers with specific orientation, parallel to the surface on the superficial zone and perpendicular in deeper layers [28].…”

Section: Discussionmentioning

confidence: 99%

“…Despite impressive advances, the field still lacks reliable methods to mimic tissue architectures at shorter scale lengths [9] and (macro)molecular organization within the biomaterial ink. However, it is wellknown how microarchitectural features provide specific and unique properties to every natural tissue [10]. Collagen (Col) is the most abundant protein in the extracellular matrix (ECM), where it is found with a hierarchical fibrillar structure ranging from the triple helix at the molecular level, up to the fibrils and fibers on the microscopic level.…”

Section: Introductionmentioning

confidence: 99%

Tissue mimetic hyaluronan bioink containing collagen fibers with controlled orientation modulating cell morphology and alignment

Schwab

Hélary

Richards

et al. 2020

Preprint

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Biofabrication is providing scientists and clinicians the ability to produce engineered tissues with desired shapes, chemical and biological gradients. Typical resolutions achieved with extrusion-based bioprinting are at the macroscopic level. However, for capturing the fibrillar nature of the extracellular matrix (ECM), it is necessary to arrange ECM components at smaller scales, down to the sub-micron and the molecular level. In this study, we introduce a (bio)ink containing hyaluronan (HA) as tyramine derivative (THA) and collagen (Col). Similarly to other connective tissues, in this (bio)ink Col is present in fibrillar form and HA as viscoelastic space filler. THA was enzymatically crosslinked under mild conditions allowing simultaneous Col fibrillogenesis, thus achieving a homogeneous distribution of Col fibrils within the viscoelastic HA-based matrix. THA-Col composite displayed synergistic properties in terms of storage modulus and shear-thinning, translating into good printability. Shear-induced alignment of the Col fibrils along the printing direction was achieved and quantified via immunofluorescence and second harmonic generation. Cell-free and cell-laden constructs were printed and characterized, analyzing the influence of the controlled microscopic anisotropy on cell behavior and chondrogenic differentiation. THA-Col showed cell instructive properties modulating hMSC adhesion, morphology and sprouting from spheroids stimulated by the presence and the orientation of Col fibers. Actin filament staining showed that hMSCs embedded into aligned constructs displayed increased cytoskeleton alignment along the fibril direction. Based on gene expression of cartilage/bone markers and matrix production, hMSCs embedded into the bioink displayed chondrogenic differentiation comparable or superior to standard pellet culture by means of proteoglycan production (Safranin O staining and proteoglycan quantification) as well as increase in cartilage related genes. The possibility of printing matrix components with control over microscopic alignment brings biofabrication one step closer to capturing the complexity of native tissues.

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“…The intensive research on meniscus anisotropy of the last decades has boosted technological approaches that exploit this knowledge to develop novel therapeutic solutions 77 . In this context, modern techniques capable of designing scaffolds at the micro-and nanoscale are expected to make a huge impact in the field.…”

Section: Recent Advances In Meniscal Zonal Reconstructionmentioning

confidence: 99%

Engineering Anisotropic Meniscus: Zonal Functionality and Spatiotemporal Drug Delivery

Abbadessa

Crecente‐Campo

Alonso

2021

Tissue Engineering Part B: Reviews

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Human meniscus is a fibrocartilaginous structure that is crucial for an adequate performance of the human knee joint. Degeneration of the meniscus is often followed by partial or total meniscectomy, which enhances the risk of developing knee osteoarthritis. The lack of a satisfactory treatment for this condition has triggered a major interest in drug delivery and tissue engineering strategies intended to restore a bioactive and fully functional meniscal tissue. The aim of this review is to critically discuss the most relevant studies on spatiotemporal drug delivery and tissue engineering, aiming for a multi-zonal meniscal reconstruction. Indeed, the development of meniscal tissue implants should involve a provision for adequate active molecules and scaffold features that take into account the anisotropic ultrastructure of human meniscus. This zonal differentiation is reflected in the meniscus biochemical composition, collagen fiber arrangement and cell distribution. In this sense, it is expected that a proper combination of advanced drug delivery and zonal tissue engineering strategies will play a key-role in the future trends in meniscus regeneration.

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Anisotropy Properties of Tissues: A Basis for Fabrication of Biomimetic Anisotropic Scaffolds for Tissue Engineering

Cited by 51 publications

References 187 publications

A noninvasive fluorescence imaging-based platform measures 3D anisotropic extracellular diffusion

A noninvasive fluorescence imaging-based platform measures 3D anisotropic extracellular diffusion

Tissue mimetic hyaluronan bioink containing collagen fibers with controlled orientation modulating cell morphology and alignment

Engineering Anisotropic Meniscus: Zonal Functionality and Spatiotemporal Drug Delivery

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