ABSTRACT
Here, we present a physiologically relevant model of the human pulmonary alveoli. This alveolar lung-on-a-chip platform is composed of a three-dimensional porous hydrogel made of gelatin methacryloyl with an inverse opal structure, bonded to a compartmentalized polydimethylsiloxane chip. The inverse opal hydrogel structure features well-defined, interconnected pores with high similarity to human alveolar sacs. By populating the sacs with primary human alveolar epithelial cells, functional epithelial monolayers are readily formed. Cyclic strain is integrated into the device to allow biomimetic breathing events of the alveolar lung, which, in addition, makes it possible to investigate pathological effects such as those incurred by cigarette smoking and severe acute respiratory syndrome coronavirus 2 pseudoviral infection. Our study demonstrates a unique method for reconstitution of the functional human pulmonary alveoli in vitro, which is anticipated to pave the way for investigating relevant physiological and pathological events in the human distal lung.
Subject(s)
Lab-On-A-Chip Devices , Models, Biological , Pulmonary Alveoli/physiology , Alveolar Epithelial Cells , Antiviral Agents/pharmacology , Cigarette Smoking/adverse effects , Dimethylpolysiloxanes/chemistry , Gelatin/chemistry , Humans , Hydrogels/chemistry , Methacrylates/chemistry , Porosity , Pulmonary Alveoli/cytology , Pulmonary Alveoli/pathology , Respiration , Respiratory Mucosa/cytology , Respiratory Mucosa/physiology , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicityABSTRACT
Lymphatic vessels, as a means to metastasize, are frequently recruited by tumor tissues during their progression. However, reliable in vitro models to dissect the intricate crosstalk between lymphatic vessels and tumors are still in urgent demand. Here, we describe a tissue-engineering method based on sacrificial bioprinting, to develop an enabling model of the human breast tumor with embedded multiscale lymphatic vessels, which is compatible with existing microscopy to examine the processes of lymphatic vessel sprouting and breast tumor cell migration in a physiologically relevant volumetric microenvironment. This platform will potentially help shed light on the complex biology of the tumor microenvironment, tumor lymphangiogenesis, lymphatic metastasis, as well as tumor anti-lymphangiogenic therapy in the future. We further anticipate wide adoption of the method to the production of various tissues and their models with incorporation of lymphatics vessels towards relevant applications.
Subject(s)
Breast Neoplasms , Lymphangiogenesis , Lymphatic Vessels , Breast , Endothelial Cells , Female , Humans , Lymphatic Vessels/diagnostic imaging , Tumor MicroenvironmentABSTRACT
Layered double hydroxides (LDHs), when incorporated into biomaterials, provide a tunable composition, controllable particle size, anion exchange capacity, pH-sensitive solubility, high-drug loading efficiency, efficient gene and drug delivery, controlled release and effective intracellular uptake, natural biodegradability in an acidic medium, and negligible toxicity. In this review, we study potential applications of LDH-based nanocomposite scaffolds for tissue engineering. We address how LDHs provide new solutions for nanostructure stability and enhance in vivo studies' success.