Biology subjects

Ang, N.

Publications and source records attributed to Ang, N..

4 recordsLinked to original sources

bioRxiv2026

Off-the-Shelf Multilayer Vascular Grafts with Damage-Resistant Hydrogel Coatings Incorporating Integrin Targeting

Synthetic grafts remain ineffective for small-caliber vascular applications due to thrombosis and intimal hyperplasia. To address these limitations, our lab designed a multilayer graft consisting of a hydrogel coating that promotes post-implantation endothelialization and an electrospun mesh that matches arterial mechanical properties. Damage-resistant hydrogels were engineered using a double-network system composed of polyether urethane diacrylamide and N-acryloyl glycinamide to enhance fracture resistance through hydrogen bonding. In this study, we utilized redox initiation to apply conformal, durable hydrogels to electrospun grafts. Bioactivity wa introduced using streptococcal collagen-like proteins containing 1{beta}1 and 2{beta}1 integrin-binding motifs, enabling selective cell-material interactions that support endothelialization while preserving acute thromboresistance. To establish the feasibility of these grafts as off-the-shelf devices, we evaluated coating integrity and bioactivity retention following sterilization and dynamic physiological loading. Sterilized composites exhibited surgically-associated damage resistance, indicating that sterilization did not compromise hydrogel durability. Coating integrity and bioactivity were also preserved after six weeks of physiological loading. Acut thromboresistance was supported by both static platelet adhesion assays and dynamic whole-blood bioreactor studies using heparinized blood, with low platelet adhesion observed relative to ePTFE. Finally, a pilot ovine carotid model demonstrated successful surgical handling and sustained graft patency. Collectively, these results highlight the promise of multilayer vascular grafts as durable, thromboresistant conduits for small-diameter vascular applications. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=60 SRC="FIGDIR/small/741222v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@14ec910org.highwire.dtl.DTLVardef@17259e8org.highwire.dtl.DTLVardef@6cb611org.highwire.dtl.DTLVardef@1251d7d_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2025

Direct contact between iPSC-derived macrophages and hepatocytes drives reciprocal acquisition of Kupffer cell identity and hepatocyte maturation

Hepatic macrophages play central roles in liver homeostasis, injury, and immune-mediated hepatotoxicity through dynamic crosstalk with hepatocytes. While monocyte-derived macrophages have been widely used in vitro, they do not fully recapitulate the biology of liver-resident Kupffer cells (KCs), which are embryonically derived and maintained locally. Recent advances suggest that induced pluripotent stem cell (iPSC)-derived macrophages (iMacs) more closely resemble embryonic macrophages and may therefore serve as a relevant platform to model KC biology. Here, we developed a human iPSC-based co-culture system by combining iMacs with iPSC-derived hepatocytes (iHeps) derived from the same donor, enabling direct cell-cell interactions. We hypothesized that such interactions would both enhance hepatocyte maturation and promote KC-like differentiation of iMacs. Indeed, co-culture induced KC-like phenotypes in iMacs and improved functional maturation of iHeps, highlighting the importance of bidirectional cellular communication. Comparative analyses with iMacs cultured in hepatocyte-conditioned media revealed that direct contact provides additional signals beyond soluble factors in driving hepatic macrophage specialization. Functionally, this co-culture system demonstrated improved physiological relevance, particularly in modeling immune-mediated drug responses, as evidenced by enhanced cytokine production profiles upon exposure to a panel of test compounds. Overall, this study establishes a novel human iPSC-derived platform that captures key aspects of hepatocyte-macrophage crosstalk, providing a more physiologically relevant model to investigate liver biology and assess immune-mediated drug toxicity.

immunology↗

bioRxiv2025

Characterization of Sex-Based Differences in Integrin-Mediated Endothelial Cel Adhesion to Bioactive Hydrogels

Endothelialization promotes thromboresistance in blood-contacting devices, but biomaterial designs often overlook sex differences in endothelialization processes. In this study, we elucidated sex differences in endothelial cell-material interactions through investigation of the integrin-ligand interplay with biomaterial substrates and the corollary effects on cell adhesion and spreading. First, integrin expression of human coronary artery endothelial cells (HCAECs) was characterized for age-matched donors (3 male, 3 female). Sex-based differences in integrin expression were identified, with notably higher 2{beta}1, 5{beta}1, and V{beta}3 expression in female cells and higher 1{beta}1 expression in male cells. On polyethylene glycol (PEG)-based hydrogel incorporating collagen or gelatin, female cells showed increased attachment on stiff substrates as compared to male HCAECs, likely driven by increased 2{beta}1, 5{beta}1, and V{beta}3 expression in female cells. Collectively, these results demonstrate sex-biased endothelial cell responses to bioactive hydrogels mediated by integrin interactions and highlight the importance of incorporating biological sex as a design variable in the development of blood-contacting biomaterials. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=72 SRC="FIGDIR/small/656802v2_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@41bfb9org.highwire.dtl.DTLVardef@921619org.highwire.dtl.DTLVardef@e8df4corg.highwire.dtl.DTLVardef@9c0faa_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2025

Creatine synthesis is a tumor suppressor pathway hypostatic to one-carbon metabolism

Methylene tetrahydrofolate reductase 2 (MTHFD2), the rate-limiting enzyme of mitochondrial one-carbon metabolism, is one of the most highly expressed metabolic enzymes across diverse cancers and lymphoproliferative disorders. However, its exact roles in oncogenic metabolism remain poorly defined. We show that MTHFD2 is a key regulator of mitochondrial energetics in Epstein-Barr virus-transformed B lymphoblastoid cell lines (LCLs), an in vitro model of post-transplant lymphoproliferative disorder (PTLD). We also delineate a role for MTHFD2 in fueling de novo creatine synthesis; MTHFD2 mediates the production of glycine, a necessary substrate for creatine synthesis, through serine catabolism. Aminomethyltransferase (AMT) suppression short-circuits the glycine cleavage system (GCS) to augment LCL mitochondrial glycine levels. Creatine synthesis is hypostatic to mitochondrial one-carbon metabolism; inhibition of creatine synthesis improves LCL fitness only when MTHFD2 is lost. Our findings emplace MTHFD2 at the nexus of amino acid and energy metabolism pathways in LCLs, with potential clinical ramifications for PTLD. Highlights* Complete activation of creatine synthesis in an in vitro cellular model of PTLD * Creatine synthesis is a major sink for mitochondrial 1C-derived glycine * Reverse GCS activity due to AMT deficiency in lymphoblastoid cells * Epistasis between mitochondrial 1C metabolism and creatine synthesis eTOC BlurbLeung et al. demonstrate that MTHFD2 is crucial for creatine synthesis in lymphoproliferative disorders. MTHFD2 supports forward 1C flux through SHMT and drives reverse GCS activity to augment mitochondrial glycine, a substrate for creatine synthesis. Tumor-suppressive effects of creatine synthesis are unmasked with MTHFD2 loss, exhibiting metabolic epistasis.

molecular biology↗