Engineering in vitro immune-competent tissue models for testing and evaluation of therapeutics

(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.

Download Full-text

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.

Download Full-text

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

Download Full-text

Biomaterial-based strategies for in vitro neural models

Biomaterials Science ◽

10.1039/d1bm01361k ◽

2022 ◽

Author(s):

Alp Ozgun ◽

David Lomboni ◽

Hallie Arnott ◽

William A. Staines ◽

John Woulfe ◽

...

Keyword(s):

Neural Tissue ◽

Neural Models ◽

Tissue Models

This review provides a comprehensive compendium of commonly used biomaterials as well as the different fabrication techniques employed for the design of 3D neural tissue models.

Download Full-text

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.

Download Full-text

Easy and affordable method for rapid prototyping of tissue models in vitro using three-dimensional bioprinting

Journal of Applied Biomedicine ◽

10.1016/j.bbe.2017.12.001 ◽

2018 ◽

Vol 38 (1) ◽

pp. 158-169 ◽

Cited By ~ 17

Author(s):

Ashutosh Bandyopadhyay ◽

Vimal Kumar Dewangan ◽

Kiran Yellappa Vajanthri ◽

Suruchi Poddar ◽

Sanjeev Kumar Mahto

Keyword(s):

Rapid Prototyping ◽

Three Dimensional ◽

Tissue Models

Download Full-text

Tissue Engineering Approaches in the Design of Healthy and Pathological In Vitro Tissue Models

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2017.00040 ◽

2017 ◽

Vol 5 ◽

Cited By ~ 45

Author(s):

Silvia Caddeo ◽

Monica Boffito ◽

Susanna Sartori

Keyword(s):

Tissue Engineering ◽

Tissue Models

Download Full-text

Bioreactors as physiologicallike in vitro models

Biomedical Science and Engineering ◽

10.4081/bse.2019.94 ◽

2020 ◽

Author(s):

Sara Mantero ◽

Federica Boschetti

Keyword(s):

Culture Conditions ◽

In Vitro Models ◽

In Vivo Models ◽

In Vitro Development ◽

Culture Cells ◽

Vitro Development ◽

Tissue Models ◽

Mechanical Stretching

Bioreactors are powerful tools for in vitro development of engineered substitutes through controlled biological, physical, and mechanical culture conditions: bioreactor technology allows a closer in vitro replication of native tissues. One of bioreactors applications is the design of in vitro 3D tissue models as a bridge between 2D and in vivo models, allowing the application of 3R (replacement, reduction, refinement) principle. To this aim, bioreactors can be used to culture cells seeded on engineered scaffolds under in vivo-like conditions. Another key use of bioreactors is for perfusion decellularization of tissues and organs to be used as scaffolds. This contribution describes a dynamic stretching. bioreactor, imposing a mechanical stretching to the cultured constructs, allowing the development of skeletal muscle engineered constructs, and a decellularization bioreactor, designed for decellularization of blood vessels.

Download Full-text