Engineering biomimetic intestinal topological features in 3D tissue models: retrospects and prospects

Conventional 2D intestinal models cannot precisely recapitulate biomimetic features in vitro and thus are unsuitable for various pharmacokinetic applications,development of disease models,and understanding the host-microbiome interactions.Thus,recently,efforts have been directed toward recreating in vitro models with intestine-associated unique 3D crypt-villus(for small intestine)or crypt-lumen(for large intestine)architectures.This review comprehensively delineates the current advancements in this research area in terms of the different microfabrication technologies(photolithography,laser ablation,and 3D bioprinting)employed and the physiological relevance of the obtained models in mimicking the features of native intestinal tissue.A major thrust of the manuscript is also on highlighting the dynamic interplay between intestinal cells(both the stem cells and differentiated ones)and different biophysical,biochemical,and mechanobiological cues along with interaction with other cell types and intestinal microbiome,providing goals for the future developments in this sphere.The article also manifests an outlook toward the application of induced pluripotent stem cells in the context of intestinal tissue models.On a concluding note,challenges and prospects for clinical translation of 3D patterned intestinal tissue models have been discussed.

Beneficial effects of AOS-iron supplementation on intestinal structure and microbiota in IDA rats

The objective of this study was to investigate the effects of agar oligosaccharide-iron(AOS-iron)on intestinal tissue pathology and microbiota in IDA rats induced by a low-iron diet,further to find the relationship between intestinal microbiota and iron metabolic disorders.After 4 weeks of AOS-iron supplementation,the fecal iron content of IDA rats markedly increased in a dose-dependent manner,only the damaged cecum and colon tissues in medium-dose(MD)and high-dose(HD)groups were repaired to the baseline,while the diversity of gut microbiota was improved even at low dose(LD).Furthermore,the supplementation of AOS-iron altered the composition of gut microbiota.At the genus level,the beneficial microbiota was enriched in AOS-iron groups,but the relative abundance of potential opportunistic pathogens obviously reduced compared to that in the anemia model(AM)group.Spearman’s correlation analysis revealed that biochemical parameters,including blood metabolic parameters,iron contents,body weight,GSH-PX and T-AOC activity,were positively correlated with SMB53,Anaerotruncus,Anaerostipes and Coprobacillus but negatively correlated with Morganella,Fusobacterium and Serratia.These findings indicated that AOS-iron effectively repaired the damaged intestinal tissue and ameliorated iron metabolic disorders by regulating gut microbiota desirably,which could provide references for the treatment of IDA.

Advancing intestinal organoid technology to decipher nano-intestine interactions and treat intestinal disease

With research burgeoning in nanoscience and nanotechnology,there is an urgent need to develop new biological models that can simulate native structure,function,and genetic properties of tissues to evaluate the adverse or beneficial effects of nanomaterials on a host.Among the current biological models,three-dimensional(3D)organoids have developed as powerful tools in the study of nanomaterial-biology(nano-bio)interactions,since these models can overcome many of the limitations of cell and animal models.A deep understanding of organoid techniques will facilitate the development of more efficient nanomedicines and further the fields of tissue engineering and personalized medicine.Herein,we summarize the recent progress in intestinal organoids culture systems with a focus on our understanding of the nature and influencing factors of intestinal organoid growth.We also discuss biomimetic extracellular matrices(ECMs)coupled with nanotechnology.In particular,we analyze the application prospects for intestinal organoids in investigating nano-intestine interactions.By integrating nanotechnology and organoid technology,this recently developed model will fill the gaps left due to the deficiencies of traditional cell and animal models,thus accelerating both our understanding of intestine-related nanotoxicity and the development of nanomedicines.