Tissue Engineering 3D Neurovascular Units: A Biomaterials and Bioprinting Perspective

Potjewyd, Geoffrey; Moxon, Samuel R.; Wang, Tao; Domingos, Marco; Hooper, Nigel M.

doi:10.1016/j.tibtech.2018.01.003

Cited by 91 publications

(63 citation statements)

References 111 publications

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“…Further studies are warranted to dissect molecular mechanisms and test this idea of leveraging the potentially beneficial effects of biomaterial‐shifted astrocytes in vivo. The ultimate therapeutic goal should then be the development of biomaterial approaches that optimize the multicellular microenvironment of the entire neurovascular unit in order to facilitate CNS reconstruction after injury and disease .…”

Section: Resultsmentioning

confidence: 99%

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Promoting Neuro-Supportive Properties of Astrocytes with Epidermal Growth Factor Hydrogels

Chan

Niu

Hayakawa

et al. 2019

Stem Cells Translational Medicine

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Biomaterials provide novel platforms to deliver stem cell and growth factor therapies for central nervous system (CNS) repair. The majority of these approaches have focused on the promotion of neural progenitor cells and neurogenesis. However, it is now increasingly recognized that glial responses are critical for recovery in the entire neurovascular unit. In this study, we investigated the cellular effects of epidermal growth factor (EGF) containing hydrogels on primary astrocyte cultures. Both EGF alone and EGF-hydrogel equally promoted astrocyte proliferation, but EGF-hydrogels further enhanced astrocyte activation, as evidenced by a significantly elevated Glial fibrillary acidic protein (GFAP) gene expression. Thereafter, conditioned media from astrocytes activated by EGF-hydrogel protected neurons against injury and promoted synaptic plasticity after oxygen-glucose deprivation. Taken together, these findings suggest that EGF-hydrogels can shift astrocytes into neuro-supportive phenotypes. Consistent with this idea, quantitative-polymerase chain reaction (qPCR) demonstrated that EGF-hydrogels shifted astrocytes in part by downregulating potentially negative A1-like genes (Fbln5 and Rt1-S3) and upregulating potentially beneficial A2-like genes (Clcf1, Tgm1, and Ptgs2). Further studies are warranted to explore the idea of using biomaterials to modify astrocyte behavior and thus indirectly augment neuroprotection and neuroplasticity in the context of stem cell and growth factor therapies for the CNS. STEM CELLS

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Section: Resultsmentioning

confidence: 99%

“…Recently, there has been an emerging move toward combining cell and growth factor therapies with biomaterials in order to enhance bioavailability and delivery . The majority of efforts thus far have focused on repairing or reconstituting neurons.…”

Section: Introductionmentioning

confidence: 99%

Promoting Neuro-Supportive Properties of Astrocytes with Epidermal Growth Factor Hydrogels

Chan

Niu

Hayakawa

et al. 2019

Stem Cells Translational Medicine

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“…Animal-or human-derived neurons cultured in regular culture dishes lack the 3D cellular organization that regulates neuronal function and many key cellular processes in vivo. Importantly, it has become clear in the last decade that cells sense and respond to the dimensionality and rigidity of their environment, and these qualities cannot be modeled using regular tissue culture methods 31 . Multicellular spheroid systems consisting of human primary or iPSC-derived EC, pericytes, astrocytes and neurons are cultured into multicellular BBB-and/or brain-organoid structures [32][33][34][35][36] .…”

Section: Discussionmentioning

confidence: 99%

An in vitro bioengineered model of the human arterial neurovascular unit to study neurodegenerative diseases

Robert

Weilinger

Zao

et al. 2020

Preprint

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Introduction: The neurovascular unit (NVU) – the interaction between the neurons and the cerebrovasculature – is increasingly important to interrogate through human-based experimental models. Although advanced models of cerebral capillaries have been developed in the last decade, there is currently noin vitro3-dimensional (3D) perfusible model of the human cortical arterial NVU. Method: We used a tissue-engineering technique to develop a scaffold-directed, perfusible, 3D human NVU that is cultured in native-like flow conditions that mimics the anatomy and physiology of cortical penetrating arteries. Results: This system, composed of primary human vascular cells (endothelial cells, smooth muscle cells and astrocytes) and induced pluripotent stem cell (iPSC) derived neurons, demonstrates a physiological multilayer organization of the involved cell types. It also reproduces key characteristics of cortical neurons and astrocytes, as well as the formation of a selective and functional endothelial barrier. We further provide proof-of-principle that our in vitro human arterial NVU may be suitable to study neurodegenerative diseases such as Alzheimer’s disease (AD), as we report both phosphorylated tau and beta-amyloid accumulation in our model over time. Finally, we show that our arterial NVU model enables the study of neuronal and glial fluid biomarkers. Conclusion: This model is a suitable tool to investigate arterial NVU functions such as neuronal electrophysiology in health and disease. Further the design of platform allows culture under native-like flow conditions for extended periods of time and yields sufficient tissue and media for downstream immunohistochemistry and biochemistry analyses.

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“…Tissue engineering paradigm has several components: a scaffold that mimics the tissue that needs to be regenerated; cells to lay down the ECM; morphogenic signs so cells can differentiate. Tissue engineering can be applied to all types of tissues that constitutes human body such as bone tissue [35,36], osteochondral [37,38], cartilage [39,40], neural tissue [41,42]; skeletal tissue [43,44]; skin [45,46]; meniscus [47,48]; or even blood vessels [49]. Bone tissue engineering strategies aim to achieve bone regeneration which is required in several clinical conditions including but not limited to osteoporosis [15,50], bone infection [15] and resection of musculoskeletal sarcoma which usually results in large bone defects [51].…”

Section: Scaffolds-based Tissue Engineeringmentioning

confidence: 99%

Scaffolds and coatings for bone regeneration

Pereira

Cengiz

Silva

et al. 2020

J Mater Sci: Mater Med

109

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Bone tissue has an astonishing self-healing capacity yet only for non-critical size defects (<6 mm) and clinical intervention is needed for critical-size defects and beyond that along with non-union bone fractures and bone defects larger than critical size represent a major healthcare problem. Autografts are, still, being used as preferred to treat large bone defects. Mostly, due to the presence of living differentiated and progenitor cells, its osteogenic, osteoinductive and osteoconductive properties that allow osteogenesis, vascularization, and provide structural support. Bone tissue engineering strategies have been proposed to overcome the limited supply of grafts. Complete and successful bone regeneration can be influenced by several factors namely: the age of the patient, health, gender and is expected that the ideal scaffold for bone regeneration combines factors such as bioactivity and osteoinductivity. The commercially available products have as their main function the replacement of bone. Moreover, scaffolds still present limitations including poor osteointegration and limited vascularization. The introduction of pores in scaffolds are being used to promote the osteointegration as it allows cell and vessel infiltration. Moreover, combinations with growth factors or coatings have been explored as they can improve the osteoconductive and osteoinductive properties of the scaffold. This review focuses on the bone defects treatments and on the research of scaffolds for bone regeneration. Moreover, it summarizes the latest progress in the development of coatings used in bone tissue engineering. Despite the interesting advances which include the development of hybrid scaffolds, there are still important challenges that need to be addressed in order to fasten translation of scaffolds into the clinical scenario. Finally, we must reflect on the main challenges for bone tissue regeneration. There is a need to achieve a proper mechanical properties to bear the load of movements; have a scaffolds with a structure that fit the bone anatomy. Graphical Abstract* Helena Filipa Pereira

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Tissue Engineering 3D Neurovascular Units: A Biomaterials and Bioprinting Perspective

Cited by 91 publications

References 111 publications

Promoting Neuro-Supportive Properties of Astrocytes with Epidermal Growth Factor Hydrogels

Promoting Neuro-Supportive Properties of Astrocytes with Epidermal Growth Factor Hydrogels

An in vitro bioengineered model of the human arterial neurovascular unit to study neurodegenerative diseases

Scaffolds and coatings for bone regeneration

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