Journal: Bioactive Materials

Article Title: Dynamic modelling of liver–bone axis: A microphysiological approach to hepatic osteodystrophy

doi: 10.1016/j.bioactmat.2025.12.011

Figure Lengend Snippet: Perfusion micro-physiological devices (MPDs) support long-term bone culture. (A) Schematics elucidating the 3D bone co-culture in HAP containing scaffolds in a perfusion-based single MPDs for addressing challenges during long-term bone co-cultures, (B) Schematics for single organ perfusion-based MPD construction having a single well volume of 2.26 cm 3 for housing a cylindrical 3D scaffold (0.16 cm 3 ) and connected with microchannels (500 μm in diameter) for maintaining the flow, (C – D) Flow velocity and pressure simulations within the single chambered compartment, (E) Quantification of metabolic activity (resazurin assay) of hMSCs and THP-1 co-cultured cells on 3D scaffolds/cryogels within the perfusion-based MPDs (n = 3), ( F ) Live (CAM-green)/dead (PI- red) staining of bone co-culture 3D scaffolds/cryogels revealed the efficiency of perfusion systems over static system over a period of 21-day culture (green = live cells; red = dead cells) (n = 6), ( G ) cell apoptosis (lactate dehydrogenase assay- LDH) (n = 3), ( H ) Osteoblastic activity (alkaline phosphatase assay- ALP) (n = 3) and ( I ) osteoclastic activity (tartarate resistant acid phosphatase assay-TRAP) (n = 3) of bone co-culture scaffolds revealed significant improvement in the day 14 and 21 functional activity. All data presented as Mean ± S.D., where ∗p ≤ 0.05, ∗∗p ≤ 0.01, ∗∗∗p ≤ 0.001 were considered as significant and ns: as non-significant.

Article Snippet: Hepatic osteodystrophy (HOD), chronic liver disease (CLD), micro-physiological devices (MPDs), carbon tetrachloride (CCl4), metabolic dysfunction associated steatotic liver disease (MASLD), bone mineral density (BMD), insulin-like growth factor-1 (IGF-1), fibroblast growth factor 21 (FGF-21), Hepatocyte nuclear factor-α (HNF-α), organ-on-chip (OoC), Dimethyl sulfoxide (DMSO), Hydroxyethyl methacrylate (HEMA), Bisacrylamide (BAA), phorbol 12-myristate 13-acetate (PMA), nano-hydroxyapatite (HAP), ammonium persulphate (APS), N,N,N′,N′-Tetramethylethylenediamine (TEMED), hexamethyldisilazane (HMDS), paraformaldehyde (PFA), diclofenac sodium salt, Alkaline Phosphatase (ALP), Tartrate-resistant acid phosphatase (TRAP), bovine serum albumin (BSA), Hematoxylin & Eosin (H&E), Picrosirius Red (PSR), Alizarin Red S (ARS) and Massons's Trichrome (MT) stain, Fetal Bovine Serum (FBS), RPMI 1640 media, Dulbecco's Modified Eagle Medium (DMEM), Human umbilical vein endothelial cells (HUVEC), Human umbilical cord derived mesenchymal stem cells (hMSCs), Sprague Dawley (SD) rats, Phosphate buffer saline (PBS), solvent uptake (SU), swelling ratio (SR), degree of degradation (DD), human hepatic progenitor cells (HepaRG) and/or carcinoma cell line (Huh-7), human hepatic stellate cells (LX-2), Scanning electron microscopy (SEM), Deoxy ribonucleic acid (DNA), ribonucleic acid (RNA), micro-physiological device (MPD), polymerase chain reaction (PCR) smooth muscle actin (α-SMA), transforming growth factor (TGF-β), tumour necrosis Factor (TNF-α), peroxisome proliferator-activated receptor (PPAR), tartrate-Resistant acid phosphatase (TRAP), Alkaline Phosphatase (ALP), parathyroid hormone (PTH), interleukins (IL), bone morphogenetic protein (BMP), osteocalcin (OCN), lecithin-cholesterol acyltransferase (LCAT), apolipoprotein E (APOE), Reverse Cholesterol Transport (RCT).

Techniques: Co-Culture Assay, Activity Assay, Resazurin Assay, Cell Culture, Staining, Lactate Dehydrogenase Assay, ALP Assay, Acid Phosphatase Assay, Functional Assay