The mechanical effects of chemical stimuli on neurospheres.

The formulation of more accurate models to describe tissue mechanics necessitates the availability of tools and instruments that can precisely measure the mechanical response of tissues to physical loads and other stimuli. In this regard, neuroscience has trailed other life sciences owing to the unavailability of representative live tissue models and deficiency of experimentation tools. We previously addressed both challenges by employing a novel instrument called the cantilevered-capillary force apparatus (CCFA) to elucidate the mechanical properties of mouse neurospheres under compressive forces. The neurospheres were derived from murine stem cells, and our study was the first of its kind to investigate the viscoelasticity of living neural tissues in vitro. In the current study, we demonstrate the utility of the CCFA as a broadly applicable tool to evaluate tissue mechanics by quantifying the effect that oxidative stress has on the mechanical properties of neurospheres. We treated mouse neurospheres with non-cytotoxic levels of hydrogen peroxide and subsequently evaluated the storage and loss moduli of the tissues under compression and tension. We observed that the neurospheres exhibit viscoelasticity consistent with neural tissue and show that elastic modulus decreases with increasing size of the neurosphere. Our study yields insights for establishing rheological measurements as biomarkers by laying the groundwork for measurement techniques and showing that the influence of a particular treatment may be misinterpreted if the size dependence is ignored.

Brain Organoids: A New, Transformative Investigational Tool for Neuroscience Research.

Brain organoids are self-assembled, three-dimensionally structured tissues that are typically derived from pluripotent stem cells. They are multicellular aggregates that more accurately recapitulate the tissue microenvironment compared to the other cell culture systems and can also reproduce organ function. They are promising models for evaluating drug leads, particularly those that target neurodegeneration, since they are genetically and phenotypically stable over prolonged durations of culturing and they reasonably reproduce critical physiological phenomena such as biochemical gradients and responses by the native tissue to stimuli. Beyond drug discovery, the use of brain organoids could also be extended to investigating early brain development and identifying the mechanisms that elicit neurodegeneration. Herein, the current state of the fabrication and use of brain organoids in drug development and medical research is summarized. Although the use of brain organoids represents a quantum leap over existing investigational tools used by the pharmaceutical industry, they are nonetheless imperfect systems that could be greatly improved through bioengineering. To this end, some key scientific challenges that would need to be addressed in order to enhance the relevance of brain organoids as model tissue are listed. Potential solutions to these challenges, including the use of bioprinting, are highlighted thereafter.

A review of fibrin and fibrin composites for bone tissue engineering.

Tissue engineering has emerged as a new treatment approach for bone repair and regeneration seeking to address limitations associated with current therapies, such as autologous bone grafting. While many bone tissue engineering approaches have traditionally focused on synthetic materials (such as polymers or hydrogels), there has been a lot of excitement surrounding the use of natural materials due to their biologically inspired properties. Fibrin is a natural scaffold formed following tissue injury that initiates hemostasis and provides the initial matrix useful for cell adhesion, migration, proliferation, and differentiation. Fibrin has captured the interest of bone tissue engineers due to its excellent biocompatibility, controllable biodegradability, and ability to deliver cells and biomolecules. Fibrin is particularly appealing because its precursors, fibrinogen, and thrombin, which can be derived from the patient's own blood, enable the fabrication of completely autologous scaffolds. In this article, we highlight the unique properties of fibrin as a scaffolding material to treat bone defects. Moreover, we emphasize its role in bone tissue engineering nanocomposites where approaches further emulate the natural nanostructured features of bone when using fibrin and other nanomaterials. We also review the preparation methods of fibrin glue and then discuss a wide range of fibrin applications in bone tissue engineering. These include the delivery of cells and/or biomolecules to a defect site, distributing cells, and/or growth factors throughout other pre-formed scaffolds and enhancing the physical as well as biological properties of other biomaterials. Thoughts on the future direction of fibrin research for bone tissue engineering are also presented. In the future, the development of fibrin precursors as recombinant proteins will solve problems associated with using multiple or single-donor fibrin glue, and the combination of nanomaterials that allow for the incorporation of biomolecules with fibrin will significantly improve the efficacy of fibrin for numerous bone tissue engineering applications.