Next generation human brain models: engineered flat brain organoids featuring gyrification.

Brain organoids are considered to be a highly promising in vitro model for the study of the human brain and, despite their various shortcomings, have already been used widely in neurobiological studies. Especially for drug screening applications, a highly reproducible protocol with simple tissue culture steps and consistent output, is required. Here we present an engineering approach that addresses several existing shortcomings of brain organoids. By culturing brain organoids with a polycaprolactone scaffold, we were able to modify their shape into a flat morphology. Engineered flat brain organoids (efBOs) possess advantageous diffusion conditions and thus their tissue is better supplied with oxygen and nutrients, preventing the formation of a necrotic tissue core. Moreover, the efBO protocol is highly simplified and allows to customize the organoid size directly from the start. By seeding cells onto 12 by 12 mm scaffolds, the brain organoid size can be significantly increased. In addition, we were able to observe folding reminiscent of gyrification around day 20, which was self-generated by the tissue. To our knowledge, this is the first study that reports intrinsically caused gyrification of neuronal tissue in vitro. We consider our efBO protocol as a next step towards the generation of a stable and reliable human brain model for drug screening applications and spatial patterning experiments.

Zebrafish embryo as a replacement model for initial biocompatibility studies of biomaterials and drug delivery systems.

The development of new biomaterials and drug delivery systems necessitates animal experimentation to demonstrate biocompatibility and therapeutic efficacy. Reduction and replacement of the requirement to conduct experiment using full-grown animals has been achieved through utilising zebrafish embryos, a promising bridge model between in vitro and in vivo research. In this review, we consider how zebrafish embryos have been utilised to test both the biocompatibility of materials developed to interact with the human body and drug release studies. Furthermore, we outline the advantages and limitations of this model and review legal and ethical issues. We anticipate increasing application of the zebrafish model for biomaterial evaluation in the near future. STATEMENT OF SIGNIFICANCE: This review aims to evaluate the potential application and suitability of the zebrafish model in the development of biomaterials and drug delivery systems. It creates scientific impact and interest because replacement models are desirable to the society and the scientific community. The continuous development of biomaterials calls for the need to provide solutions for biological testing. This review covers the topic of how the FET model can be applied to evaluate biocompatibility. Further, it explores the zebrafish from the wild-type to the mutant form, followed by a discussion about the ethical considerations and concerns when using the FET model.