Biomaterial-based strategies for in vitro neural models

Formation of tissue models in 3 dimensions is more effective in recapitulating structure and function compared to their 2-dimensional (2D) counterparts. Formation of 3D engineered tissue to control shape and size can have important implications in biomedical research and in engineering applications such as biological soft robotics. While neural spheroids routinely are created during differentiation processes, further geometric control of in vitro neural models has not been demonstrated. Here, we present an approach to form functional in vitro neural tissue mimic (NTM) of different shapes using stem cells, a fibrin matrix, and 3D printed molds. We used murine-derived embryonic stem cells for optimizing cell-seeding protocols, characterization of the resulting internal structure of the construct, and remodeling of the extracellular matrix, as well as validation of electrophysiological activity. Then, we used these findings to biofabricate these constructs using neurons derived from human embryonic stem cells. This method can provide a large degree of design flexibility for development of in vitro functional neural tissue models of varying forms for therapeutic biomedical research, drug discovery, and disease modeling, and engineering applications.

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Designing of an Advanced Compression Bioreactor with an Implementation of a Low-Cost Controlling System Connected to a Mobile Application

Processes ◽

10.3390/pr9060915 ◽

2021 ◽

Vol 9 (6) ◽

pp. 915

Author(s):

Gözde Dursun ◽

Muhammad Umer ◽

Bernd Markert ◽

Marcus Stoffel

Keyword(s):

Mobile Application ◽

Low Cost ◽

Experimental Information ◽

Raspberry Pi ◽

Tissue Constructs ◽

Cost Controlling ◽

Controlling System ◽

And Control ◽

Tissue Models

(1) Background: Bioreactors mimic the natural environment of cells and tissues by providing a controlled micro-environment. However, their design is often expensive and complex. Herein, we have introduced the development of a low-cost compression bioreactor which enables the application of different mechanical stimulation regimes to in vitro tissue models and provides the information of applied stress and strain in real-time. (2) Methods: The compression bioreactor is designed using a mini-computer called Raspberry Pi, which is programmed to apply compressive deformation at various strains and frequencies, as well as to measure the force applied to the tissue constructs. Besides this, we have developed a mobile application connected to the bioreactor software to monitor, command, and control experiments via mobile devices. (3) Results: Cell viability results indicate that the newly designed compression bioreactor supports cell cultivation in a sterile environment without any contamination. The developed bioreactor software plots the experimental data of dynamic mechanical loading in a long-term manner, as well as stores them for further data processing. Following in vitro uniaxial compression conditioning of 3D in vitro cartilage models, chondrocyte cell migration was altered positively compared to static cultures. (4) Conclusion: The developed compression bioreactor can support the in vitro tissue model cultivation and monitor the experimental information with a low-cost controlling system and via mobile application. The highly customizable mold inside the cultivation chamber is a significant approach to solve the limited customization capability of the traditional bioreactors. Most importantly, the compression bioreactor prevents operator- and system-dependent variability between experiments by enabling a dynamic culture in a large volume for multiple numbers of in vitro tissue constructs.

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The Role of Biomimetic Hypoxia on Cancer Cell Behaviour in 3D Models: A Systematic Review

Cancers ◽

10.3390/cancers13061334 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1334

Author(s):

Ye Liu ◽

Zahra Mohri ◽

Wissal Alsheikh ◽

Umber Cheema

Keyword(s):

Systematic Review ◽

Cellular Response ◽

3D Culture ◽

3D Models ◽

In Vitro Models ◽

Research Findings ◽

Tissue Models

The development of biomimetic, human tissue models is recognized as being an important step for transitioning in vitro research findings to the native in vivo response. Oftentimes, 2D models lack the necessary complexity to truly recapitulate cellular responses. The introduction of physiological features into 3D models informs us of how each component feature alters specific cellular response. We conducted a systematic review of research papers where the focus was the introduction of key biomimetic features into in vitro models of cancer, including 3D culture and hypoxia. We analysed outcomes from these and compiled our findings into distinct groupings to ascertain which biomimetic parameters correlated with specific responses. We found a number of biomimetic features which primed cancer cells to respond in a manner which matched in vivo response.

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A Review of Three-Dimensional In Vitro Tissue Models for Drug Discovery and Transport Studies

Journal of Pharmaceutical Sciences ◽

10.1002/jps.22257 ◽

2011 ◽

Vol 100 (1) ◽

pp. 59-74 ◽

Cited By ~ 300

Author(s):

Nelita T. Elliott ◽

Fan Yuan

Keyword(s):

Drug Discovery ◽

Three Dimensional ◽

Transport Studies ◽

Tissue Models

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Aligned Chitosan-Gelatin Cryogel-Filled Polyurethane Nerve Guidance Channel for Neural Tissue Engineering: Fabrication, Characterization, and In Vitro Evaluation

Biomacromolecules ◽

10.1021/acs.biomac.8b01308 ◽

2018 ◽

Vol 20 (2) ◽

pp. 662-673 ◽

Cited By ~ 23

Author(s):

Anamika Singh ◽

Parvaiz A. Shiekh ◽

Mainak Das ◽

Jukka Seppälä ◽

Ashok Kumar

Keyword(s):

Tissue Engineering ◽

Neural Tissue ◽

Neural Tissue Engineering ◽

In Vitro Evaluation

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Transcriptional response of Hoxb genes to retinoid signalling is regionally restricted along the neural tube rostrocaudal axis

Royal Society Open Science ◽

10.1098/rsos.160913 ◽

2017 ◽

Vol 4 (4) ◽

pp. 160913 ◽

Cited By ~ 4

Author(s):

Nicoletta Carucci ◽

Emanuele Cacci ◽

Paola S. Nisi ◽

Valerio Licursi ◽

Yu-Lee Paul ◽

...

Keyword(s):

Neural Tube ◽

Neural Development ◽

Transcriptional Response ◽

Neural Tissue ◽

Positional Information ◽

Multiple Roles ◽

Chromatin Activation ◽

Neural Stem Progenitor Cells ◽

Rostrocaudal Axis

During vertebrate neural development, positional information is largely specified by extracellular morphogens. Their distribution, however, is very dynamic due to the multiple roles played by the same signals in the developing and adult neural tissue. This suggests that neural progenitors are able to modify their competence to respond to morphogen signalling and autonomously maintain positional identities after their initial specification. In this work, we take advantage of in vitro culture systems of mouse neural stem/progenitor cells (NSPCs) to show that NSPCs isolated from rostral or caudal regions of the mouse neural tube are differentially responsive to retinoic acid (RA), a pivotal morphogen for the specification of posterior neural fates. Hoxb genes are among the best known RA direct targets in the neural tissue, yet we found that RA could promote their transcription only in caudal but not in rostral NSPCs. Correlating with these effects, key RA-responsive regulatory regions in the Hoxb cluster displayed opposite enrichment of activating or repressing histone marks in rostral and caudal NSPCs. Finally, RA was able to strengthen Hoxb chromatin activation in caudal NSPCs, but was ineffective on the repressed Hoxb chromatin of rostral NSPCs. These results suggest that the response of NSPCs to morphogen signalling across the rostrocaudal axis of the neural tube may be gated by the epigenetic configuration of target patterning genes, allowing long-term maintenance of intrinsic positional values in spite of continuously changing extrinsic signals.

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Biophysical stimulation for in vitro engineering of functional cardiac tissues

Clinical Science ◽

10.1042/cs20170055 ◽

2017 ◽

Vol 131 (13) ◽

pp. 1393-1404 ◽

Cited By ~ 14

Author(s):

Anastasia Korolj ◽

Erika Yan Wang ◽

Robert A. Civitarese ◽

Milica Radisic

Keyword(s):

Cardiac Tissue ◽

Culture Media ◽

Culture Conditions ◽

Lineage Specification ◽

Cardiac Tissues ◽

Cardiac Lineage ◽

And Function ◽

Tissue Models

Engineering functional cardiac tissues remains an ongoing significant challenge due to the complexity of the native environment. However, our growing understanding of key parameters of the in vivo cardiac microenvironment and our ability to replicate those parameters in vitro are resulting in the development of increasingly sophisticated models of engineered cardiac tissues (ECT). This review examines some of the most relevant parameters that may be applied in culture leading to higher fidelity cardiac tissue models. These include the biochemical composition of culture media and cardiac lineage specification, co-culture conditions, electrical and mechanical stimulation, and the application of hydrogels, various biomaterials, and scaffolds. The review will also summarize some of the recent functional human tissue models that have been developed for in vivo and in vitro applications. Ultimately, the creation of sophisticated ECT that replicate native structure and function will be instrumental in advancing cell-based therapeutics and in providing advanced models for drug discovery and testing.

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Experiments on the Development of the Head of the Chick Embryo

Journal of Experimental Biology ◽

10.1242/jeb.13.2.219 ◽

1936 ◽

Vol 13 (2) ◽

pp. 219-236

Author(s):

C. H. WADDINGTON ◽

A. COHEN

Keyword(s):

Thin Sheet ◽

Neural Tissue ◽

Primitive Streak ◽

Neural Plate ◽

Head Region ◽

Process Stage ◽

Optic Vesicles ◽

Lens Formation ◽

Embryonic Ectoderm

1. Experiments were made on the development of the head of chicken embryos cultivated in vitro. 2. Defects in the presumptive head region of primitive streak embryos are regulated completely if the wound fills up before the histogenesis of neural tissue begins in the head-process stage. Different methods by which the hole is filled are described. 3. No repair occurs in the head-process and head-fold stages, and in this period two masses of neural tissue cannot heal together. 4. Median defects, even if repaired as regards neural tissue, cause a failure of the ventral closure of the foregut. The lateral evaginations of the gut develop typically in atypical situations. The headfold may break through and join up with the endoderm in such a way that the gut acquires an anterior opening. 5. The paired heart rudiments may develop separately. The separate vesicles begin to contract at a time appropriate to the development of the embryo as a whole. The two hearts are mirror images, the left one having the normal curvature, but the embryos do not survive long enough for the hearts to acquire a very definite shape. 6. The forebrain has a considerable capacity for repair in the early somite stages (five to twenty-five somites). One-half of the forebrain can remodel itself into a complete forebrain. In some cases the neural plate and epidermis grow together over the wound, in others the epidermis and mesenchyme make the first covering, leaving a space along the inside of which the neural tissue grows. The neural tissue may become a very thin sheet. 7. The repaired forebrain may induce the formation of a nasal placode from the non-presumptive nasal epidermis which covers the wound. 8. If the optic vesicle is entirely removed, a new one is not formed, but parts of the vesicle can regulate to complete eye-cups, either when still attached to the forebrain or after being isolated in the extra-embryonic regions of another embryo. 9. Injured optic vesicles induce lenses from the non-presumptive epidermis which grows over the wound. Transplanted optic neural tissue from embryos of about five somites induces the formation of lentoids from extra-embryonic ectoderm, but only in a small proportion of cases. 10. The presumptive lens epidermis can produce a slight thickening even when contact with the optic cup is prevented. 11. The significance of periods of minimum regulatory power for the concept of determination is discussed. 12. The data concerning lens formation are discussed in terms of the field concept.

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