Directly coaxial bioprinting of 3D vascularized tissue using novel bioink based on decellularized human amniotic membrane.

Despite several progressions in the biofabrication of large-scale engineered tissues, direct biopri nting of perfusable three-dimensional (3D) vasculature remained unaddressed. Developing a feasible method to generate cell-laden thick tissue with an effective vasculature network to deliver oxygen and nutrient is crucial for preventing the formation of necrotic spots and tissue death. In this study, we developed a novel technique to directly bioprint 3D cell-laden prevascularized construct. We developed a novel bioink by mixing decellularized human amniotic membrane (dHAM) and alginate (Alg) in various ratios. The bioink with encapsulated human vein endothelial cells (HUVECs) and a crosslinker, CaCl2, were extruded via sheath and core nozzle respectively to directly bioprint a perfusable 3D vasculature construct. The various concentration of bioink was assessed from several aspects like biocompatibility, porosity, swelling, degradation, and mechanical characteristics, and accordingly, optimized concentration was selected (Alg 4 %w/v - dHAM 0.6 %w/v). Then, the crosslinked bioink without microchannel and the 3D bioprinted construct with various microchannel distances (0, 1.5 mm, 3 mm) were compared. The 3D bioprinted construct with a 1.5 mm microchannels distance demonstrated superiority owing to its 492 ± 18.8 % cell viability within 14 days, excellent tubulogenesis, remarkable expression of VEGFR-2 which play a crucial role in endothelial cell proliferation, migration, and more importantly angiogenesis, and neovascularization. This perfusable bioprinted construct also possess appropriate mechanical stability (32.35 ± 5 kPa Young's modulus) for soft tissue. Taking these advantages into the account, our new bioprinting method possesses a prominent potential for the fabrication of large-scale prevascularized tissue to serve for regenerative medicine applications like implantation, drug-screening platform, and the study of mutation disease.

Multimodal Brain MRI of Deep Gray Matter Changes Associated With Inflammatory Bowel Disease.

BACKGROUND: Behavioral symptoms, including mood disorders, substantially impact the quality of life of patients with inflammatory bowel disease (IBD), even when clinical remission is achieved. Here, we used multimodal magnetic resonance imaging (MRI) to determine if IBD is associated with changes in the structure and function of deep gray matter brain regions that regulate and integrate emotional, cognitive, and stress responses. METHODS: Thirty-five patients with ulcerative colitis (UC) or Crohn's disease (CD) and 32 healthy controls underwent 3 Tesla MRIs to assess volume, neural activity, functional connection strength (connectivity), inflammation, and neurodegeneration of key deep gray matter brain regions (thalamus, caudate, pallidum, putamen, amygdala, hippocampus, and hypothalamus) involved in emotional, cognitive and stress processing. Associations with sex, presence of pain, disease activity, and C-reactive protein (CRP) concentration were examined. RESULTS: Significantly increased activity and functional connectivity were observed in cognitive and emotional processing brain regions, including parts of the limbic system, basal ganglia, and hypothalamus of IBD patients compared with healthy controls. Inflammatory bowel disease patients exhibited significantly increased volumes of the amygdala and hypothalamus, as well as evidence of neurodegeneration in the putamen and pallidum. Hippocampal neural activity was increased in IBD patients with active disease. The volume of the thalamus was positively correlated with CRP concentration and was increased in females experiencing pain. CONCLUSIONS: Patients with IBD exhibit functional and structural changes in the limbic and striatal systems. These changes may be targets for assessing or predicting the response to therapeutic interventions aimed at improving comorbid emotional and cognitive symptoms.

Magnetic resonance imaging revealed structural and functional changes within the brains of inflammatory bowel disease patients, in regions known to be involved in processing brain signals associated with behavioral symptoms, anxiety, pain, stress, and cognitive deficits.