bims-ecemfi 2026-01-11 papers

bims-ecemfi

Biomed News

on ECM and fibroblasts

Issue of 2026–01–11
fifteen papers selected by
Badri Narayanan Narasimhan, University of California, San Diego

Human Progenitor T-Cell Differentiation Regulated by the Mechanical Resistance of Thymus-Mimetic Extracellular Matrices.
Dependence of mesenchymally transitioned tumor niche fitness on cell-cell and cell-matrix adhesions.
Osteoarthritic chondrocytes exert higher contractile forces and exhibit enhanced protrusive activity when cultured in 3D degradable hydrogels.
Fibrotic substrate stiffness enhances endometriotic epithelial cell motility.
Tunable Enhancement of T Cell Expansion Through Modulation of Stiffness and Adhesion Receptor Engagement in an Engineered Hydrogel Platform.
Effects of adhesion pattern of 2D substrate on cell morphology and migration.
Single-cell chiral symmetry breaking under confinement.
An Opto-Actuated Hydrogel for Cell Mechanoactuation and Real-Time Force Monitoring.
Decoding collagen cues: the interplay of integrins and discoidin domain receptors in health and disease.
Boundary-shape driven transitions in vortex and oscillatory dynamics of confined epithelial cells.
The mechanical strain as a cross-linking agent for skeletal muscle ECM-derived hydrogels.
Designing highly tunable laminin-inspired bioactive peptide hydrogel-based biomaterials for directing cellular response.
A Water-Soluble PVA Macrothiol Enables Two-Photon Microfabrication of Cell-Interactive Hydrogel Structures at 400 mm s-1.
A human pathophysiological 3D-bone marrow model reveals immune and stromal cell heterogeneity.
Modulating Integrin and Growth Factor Signaling With Peptides: Strategies to Synergistically Enhance Bone Tissue Regeneration.

Adv Healthc Mater. 2026 Jan 04. e04316

Human Progenitor T-Cell Differentiation Regulated by the Mechanical Resistance of Thymus-Mimetic Extracellular Matrices.

Nicholas Jeffreys, Kyle T Ruark, Joshua M Price, Ella M Serrano-Wu, Blake Hanan, Andrew S Khalil, Wei-Hung Jung, Nuria Lafuente-Gómez, Christina M Tringides, Ann Gao, Joshua M Brockman, Andrew Lu, Izabela Zmirska, Kyle H Vining, Junzhe Lou, Kwasi Adu-Berchie, Siyoon Kwon, Hamza Ijaz, Azeem Sharda, David T Scadden, David J Mooney.

  T-cell-based immunotherapies have revolutionized cancer treatment, yet their reliance on patient-derived T-cells limits scalability and accessibility. Engineering functional T-cells de novo from human hematopoietic stem cells (HSCs) represents a promising alternative toward a renewable and customizable source of therapeutic lymphocytes. Successful HSC-derived T-cell generation requires recapitulation of key signaling and adhesion cues of the thymic microenvironment, particularly Notch1-DLL-4 and α4β1-integrin-VCAM-1 interactions within ex vivo engineered thymic niche (ETN) systems. Notch1-DLL-4 and α4β1-integrin-VCAM-1 interactions are known to respond to mechanical forces that regulate their bond dissociation behaviors and downstream signal transduction, yet manipulating the mechanosensitive features of these key receptor-ligand interactions in thymopoiesis has been largely ignored in current ETN designs. Here, we demonstrate that human T-cell development from cord blood-derived CD34+ HSCs is regulated via molecular cooperativity in notch1 and integrin-mediated mechanotransduction. Mechanically confining interpenetrating network (IPN) hydrogel-based 3D cell culture, comprised of collagen type I and alginate polysaccharides functionalized with DLL-4 and VCAM-1 is used as a model viscoelastic 3D ETN to manipulate human progenitor (pro)T-cell differentiation. This ETN enables orthogonal control of the mechanical properties of the thymic niche, including storage modulus, and viscoelastic properties (e.g., stress relaxation kinetics). We identify that soft, viscous matrices that enhance activation of the notch1-pathway, and subsequently notch1 intracellular domain (NICD) nuclear import, sustain the T-cell development gene regulatory network during proT-cell differentiation. Conversely, stiff, elastic matrices inhibit HSC commitment to the T-lineage, and rather promotes Myeloid-cell differentiation. Our observations indicate mechanical reciprocity in signaling pathways indispensable to thymopoiesis and highlight extracellular matrix mechanics as a variable in controlling hematopoietic stem cell fate decisions.

Keywords:  extracellular matrix; hematopoietic stem cell; mechanotransduction; notch1; progenitor T‐cell; thymus; viscoelasticity; α4β1‐integrin

DOI:  https://doi.org/10.1002/adhm.202504316
Biophys J. 2026 Jan 08. pii: S0006-3495(26)00002-0. [Epub ahead of print]

Dependence of mesenchymally transitioned tumor niche fitness on cell-cell and cell-matrix adhesions.

C Venkata Sai Prasanna, Mohit Kumar Jolly, Ramray Bhat.

  Invasion of cancer cells is often characterized by a transition in phenotype of cells or their niches from an epithelial to a mesenchymal state (EMT). Under what conditions do transitioned niches acquire greater fitness than, and outcompete, their parental un-transitioned niches, is not well-understood. Here, we use a Cellular Potts model-based multiscale computational framework to investigate this question. Inducing an EMT in a single cell at the edge of an early-growing tumor surrounded by a fibrillar extracellular matrix (ECM) allows us to temporally trace inter-niche competitions. We observe that the transitioned niche dominates the population it arises from and invades better when surrounded by dense ECM. An increase in cell-ECM adhesion by itself drives domination at 50% probability, such that the transitioned population invades faster and contributes further to collective invasion of the whole tumor. Decrease in inter- and intra-niche cell-cell adhesion by itself is not sufficient to achieve domination. However, added to high cell-ECM adhesion, loss of intra-niche (but not inter-niche adhesion) restores the probability, but not the extent, with which domination by the mesenchymally transitioned niche is achieved by attenuating its confinement by its parental population. Our simulations reveal the forces regulating such confinement and how cell-cell and cell-ECM adhesions, stochastic invasion dynamics, and ECM density contribute nuancedly to distinct aspects of inter-niche competitions within tumor populations and their fitness.

Keywords:  Epithelial-Mesenchymal Transition (EMT); cell-ECM adhesion; collective cancer invasion (CCI); niche domination; niche fitness; tumor niche

DOI:  https://doi.org/10.1016/j.bpj.2026.01.002
Acta Biomater. 2026 Jan 03. pii: S1742-7061(26)00001-2. [Epub ahead of print]

Osteoarthritic chondrocytes exert higher contractile forces and exhibit enhanced protrusive activity when cultured in 3D degradable hydrogels.

Maxim Vovchenko, Nele Vaes, Jorge Barrasa-Fano, Apeksha Shapeti, Rocío CastroViñuelas, Laurens Kimps, Christ Glorieux, Ilse Jonkers, Hans Van Oosterwyck.

  Osteoarthritis (OA) induces phenotypic changes in chondrocytes as well as alterations in matrix composition and mechanics. Yet, its impact on active cell-generated forces, a key indicator of cell-matrix interaction, remains poorly characterized. In this study, we systematically compared the force generation capacity and associated proteins of interest between human OA and non-OA articular chondrocytes and how they are affected by cell culture dimensionality (2D versus 3D) and matrix degradability. Using traction force microscopy (TFM) combined with high-resolution immunostainings we show that OA alters the expression and organization of proteins involved in force exertion and transmission across both 2D and 3D cultures, but only in a 3D degradable hydrogel environment do these changes translate into higher cell-generated contractile forces This increased force generation correlates with elevated protrusive activity, higher actomyosin content and engagement, as well as altered localization of adhesion and matrix proteins, all of which could contribute to increased cell-matrix interaction in OA chondrocytes. In contrast, OA chondrocytes display no increase in cell tractions when cultured on 2D hydrogel substrates. These findings demonstrate that the detection and interpretation of OA-related alterations in chondrocyte mechanobiology are strongly dependent on the dimensionality and degradable properties of the culture system. Our results highlight the critical role of 3D degradable environments in revealing disease-associated changes in chondrocyte force generation and emphasize the necessity of carefully selecting model systems when investigating OA mechanobiology. STATEMENT OF SIGNIFICANCE: Chondrocytes, cells essential for cartilage maintenance, are disrupted in osteoarthritis (OA) through mechanisms that remain poorly understood. We developed an in vitro 3D degradable hydrogel system that mimics chondrocyte physiological environment better than traditional 2D cultures, allowing to study OA-driven changes in cell-matrix interactions. Using this system, we applied computational techniques to compare the ability of patient-derived non-OA and OA articular chondrocytes to generate forces on their environment. Our results revealed that OA chondrocytes exert higher contractile forces and exhibit enhanced protrusive activity in 3D, but not in 2D. This combination of techniques provides new insight into OA-driven changes in cell-matrix interactions and facilitates the design of more predictive in vitro models for cartilage research.

Keywords:  Cell-matrix interaction; Chondrocyte mechanobiology; Hydrogel systems; Osteoarthritis; Traction force microscopy

DOI:  https://doi.org/10.1016/j.actbio.2026.01.001
bioRxiv. 2026 Jan 01. pii: 2025.12.31.697209. [Epub ahead of print]

Fibrotic substrate stiffness enhances endometriotic epithelial cell motility.

Shohini Banerjee, Nane Manukyan, Kimberly M Stroka.

Fibrosis is a common pathological feature of inflammatory conditions across various organ systems, leading to a marked increase in matrix stiffness. Although substrate stiffness is known to increase cell migration in cancer and stromal cell populations, it is not well understood how it affects benign epithelial cell motility, particularly within the pelvic cavity. We used an endometriotic epithelial cell line and polyacrylamide hydrogels with tunable stiffness--with glass as an extreme stiffness reference--to model mechanically driven single-cell and multicellular migration. We found that stiff substrates promoted cell speed, actin stress fiber formation, focal adhesion presentation, and spheroid expansion compared to the soft substrate. Increasing cellular contractility on the soft substrate and decreasing contractility on the stiff substrate led to an increase and decrease in cell speed, respectively. These findings provide mechanistic insight on how fibrosis as a biomechanical state regulates epithelial cell migration, with additional relevance to the pathogenesis of benign yet invasive conditions.

DOI: https://doi.org/10.64898/2025.12.31.697209
Adv Mater. 2026 Jan 08. e05965

Tunable Enhancement of T Cell Expansion Through Modulation of Stiffness and Adhesion Receptor Engagement in an Engineered Hydrogel Platform.

Niroshan Anandasivam, Rabia Ali, Lordean Gustinvil, Matthew J Rosenwasser, Iain E Dunlop, Derfogail Delcassian.

  Adoptive T cell therapies (ACT) are an important class of oncology treatments that require ex vivo T cell expansion for clinical success. Technologies that can control both phenotype and yield in expanded cell products are highly desired. Here, we develop a new hydrogel scaffold for controlled T cell expansion with yields of up to 2000× fold in two weeks, compared to other hydrogel constructs (≈250×) and Dynabeads (≈1200×). Our 2D polyethylene glycol diacrylate (PEGDA) hydrogel scaffold is cross-linked with streptavidin moieties to present various biotinylated ligands to cells with controlled hydrogel stiffness (PEGDA-Strep). Using this platform, we demonstrate that combining substrate stiffness with adhesion receptor ligands (aLFA-1 or aCD2) dictates T cell activation and proliferation. On stiff substrates, these ligands drove expansions 49% (aLFA-1) and 68% (aCD2) greater than Dynabeads with comparable T cell products, preceded by elevated metabolic and transcriptional activity. Notably, while stiff substrates increased yield, soft substrates produced T cells with superior antigen-specific killing selectivity. These findings highlight the role of mechanical sensing in T cell-APC interactions and suggest improved manufacturing methods for adoptive T cell therapy (ACT).

Keywords:  CD2; LFA‐1; T cell; adhesion receptor; expansion; hydrogels; mechanosensing

DOI:  https://doi.org/10.1002/adma.202505965
Biophys J. 2026 Jan 02. pii: S0006-3495(25)03504-0. [Epub ahead of print]

Effects of adhesion pattern of 2D substrate on cell morphology and migration.

Jieling Zhao, Jie Liang.

Focal adhesions play critical roles in a variety of cellular behaviors and physiological processes, including cell migration, proliferation, wound healing, and tumor invasion. While focal adhesions are recognized as key protein signaling and mechanosensory hubs that mediate interactions between the cell and the extracellular matrix (ECM), the mechanisms by which cells sense and respond to ECM geometry at the subcellular level, and how these cues are translated into cell-scale behaviors, remain unclear. In this study, we develop a computational cell model to investigate the effects of adhesion pattern of 2D substrate on cell morphology and migration. The model has several advancements over existing approaches, including the incorporation of cellular viscoelasticity, dynamic cell-substrate communication, and a mechano-chemical feedback loop between cell adhesion and protrusion. The simulation results are directly compared with the experimental data and show remarkable agreement. Based on both simulations and validated experiments involving cells on substrate with directional patterns under Y-27632 and sh-βPix treatments, we propose that line tension along the cell boundary, driven by contractility, plays a dominant role in driving directed cell migration. Additionally, focal adhesion-mediated protrusion through chemical signaling supplement to maintain the migration directionality. These findings provide useful insights into the underlying mechanism of the effects of cell-ECM regulated mechano-chemical interactions on cell morphology and migration.

DOI: https://doi.org/10.1016/j.bpj.2025.12.026
bioRxiv. 2025 Dec 26. pii: 2025.12.23.696323. [Epub ahead of print]

Single-cell chiral symmetry breaking under confinement.

Sebastián Echeverría-Alar, Badri Narayanan Narasimhan, Stephanie I Fraley, Wouter-Jan Rappel.

Single cells confined by the extracellular matrix can exhibit persistent rotational motion, yet the physical mechanisms underlying this chiral symmetry breaking remain unclear. Here, we address this gap with a cellular phase field model that couples cell deformation, cell polarization governed by stochastic excitable dynamics, and confinement. We identify the confinement strength as a bifurcation parameter determining three regimes: strong confinement prevents rotation through spatial constraints, intermediate confinement induces stochastic transitions between chiral and non-chiral states, and weak confinement allows persistent rotational motion. For the intermediate regime, we develop a semi-Markovian renewal process framework that characterizes the stochastic dynamics through dwell time statistics, transition probabilities and first-passage times. For the weak confinement regime, we reveal that a mechanochemical feedback enables coherent rotations despite internal noise through the reduction of local excitability mediated by mechanical contraction. We formalize this feedback analytically using Kramers escape theory. Experiments on epithelial MCF10A cells in Matrigel validate predictions for the weak confinement regime. Our results establish a theoretical approach for understanding single-cell chiral symmetry breaking under confinement, with implications for controlling single-cell dynamics by tuning extracellular matrix properties.

DOI: https://doi.org/10.64898/2025.12.23.696323
Adv Sci (Weinh). 2026 Jan 04. e11538

An Opto-Actuated Hydrogel for Cell Mechanoactuation and Real-Time Force Monitoring.

Rinku Kumar, Marc A Fernandez-Yague, Adrien Bessaguet, Hosoowi Lee, Nicolas Giuseppone, Andrés J García, Aránzazu Del Campo.

  Cellular force sensing and transduction are fundamental processes in development, homeostasis, and disease. To understand how cells detect and integrate mechanical forces, we need non-invasive methods to apply forces at the molecular scale while monitoring cellular responses within physiological contexts. Here, we present a mechanoactuated hydrogel interface that can exert forces on integrin adhesion receptors and allows monitoring of traction force responses in real time. The actuation is achieved by light excitation of a rotary molecular motor presenting an adhesion peptide to bind integrins at the cell membrane and to a hydrogel surface via flexible polymer chains. Illumination results in chain twisting and an applied pulling force on the linked integrin receptors within subcellular illuminated areas. Fluorescent particles in the hydrogel allow parallel quantification of cellular forces by traction force microscopy. With this methodology, we monitored talin recruitment, actin organization, and traction force generation and their reversibility in response to applied forces by the rotary motor-interface. We demonstrate reversible talin recruitment, enhanced F-actin polymerization, and a reduction in cell traction force when force is applied to focal adhesions. This research expands the application of nano machine-based actuation within soft hydrogels and showcases its capabilities.

Keywords:  cell forces; hydrogel; mechanoactuation; mechanotransduction; molecular motor; talin

DOI:  https://doi.org/10.1002/advs.202511538
J Biomed Sci. 2026 Jan 06. 33(1): 8

Decoding collagen cues: the interplay of integrins and discoidin domain receptors in health and disease.

Paola Trono, Ilenia Masi, Flavia Ottavi, Laura Rosanò.

  The extracellular matrix (ECM) provides critical biochemical and biophysical cues that regulate cell behavior in health and disease. Collagens dominate in abundance and structural importance, shaping tissue-specific ECM signatures that guide cellular behavior. Two major and distinct transmembrane receptor families, integrins and discoidin domain receptors (DDRs), serve as primary sensors for collagens, yet they employ fundamentally distinct binding mechanisms and signaling kinetics. While both can activate shared downstream pathways, their functional interplay remains complex and context-dependent, with the potential to fine-tune cellular responses to ECM cues. This review deciphers the nuanced crosstalk between integrin β1 and DDRs, with a particular focus on the understudied DDR2, across physiological and pathological processes. We discuss how this interplay, which evolves from cooperative to compensatory or even antagonistic signaling, is influenced by variables, such as tissue specificity, developmental timing, and pathological context, dictating cell adhesion, migration, and ECM remodeling. Key examples include DDRs acting as allosteric regulators to license integrin activation, their partnership in mechanotransduction during development, and their divergent roles in aging tissues, where altered collagen mechanics shift the receptor hierarchy. In pathology, the DDR-integrin axis is pivotal in fibrosis and cancer, influencing fibroblast activation, drug resistance, metastatic outgrowth, and immune suppression within the tumor microenvironment. Notably, the receptors can function both independently and synergistically; for instance, DDR2 in cancer-associated fibroblasts regulates integrin-mediated mechanosignaling to promote metastasis, while in other contexts, both receptors activate distinct survival pathways. Understanding the signaling dynamics and mechanisms of these receptors is necessary for deciphering how cells interpret ECM signals and how these mechanisms contribute to disease progression, especially in those diseases marked by collagen remodeling. This comprehension is crucial for developing novel therapeutic strategies. Emerging evidence suggests that combined targeting DDRs and integrins can synergistically overcome ECM-mediated therapy resistance, enhance immune infiltration, and reprogram pathological microenvironments, offering a promising approach for treating fibrosis and collagen-rich cancers.

Keywords:  Aging; Cancer; Collagen; Discoidin domain receptor (DDR) 1 and 2; Extracellular matrix (ECM); Fibrosis; Integrins; Targeted therapies; Tyrosine kinase receptor (TKR)

DOI:  https://doi.org/10.1186/s12929-025-01211-0
Soft Matter. 2026 Jan 05.

Boundary-shape driven transitions in vortex and oscillatory dynamics of confined epithelial cells.

Ryo Ienaga, Kazuyuki Shigeta, Tatsuya Fukuyama, Kazusa Beppu, Yusuke T Maeda.

Controlling the collective motion of epithelial cell populations is fundamental for understanding multicellular self-organization and for advancing tissue engineering. Under spatial confinement, cells are known to exhibit either vortex rotation or oscillatory motion depending on boundary geometry, but the mechanisms governing transitions between these states remain unclear. Here, we investigate the collective motion of MDCK cells confined within a doublet circular boundary, where the confinement aspect ratio, defined as the distance between the centers of two circles relative to their radius, can be tuned by varying the degree of overlap. When the overlap is large, cells form a stable vortex. Increasing the confinement aspect ratio destabilizes this vortex and induces oscillatory motion characterized by periodic reversals of migration direction, ultimately transitioning into disordered dynamics. To elucidate the underlying mechanism, we developed simulations of self-propelled particles incorporating local alignment (LA) and contact inhibition of locomotion (CIL). The model successfully reproduced the experimentally observed transitions from vortices to oscillatory motion and further revealed that an appropriate balance between LA and CIL is critical for stabilizing vortex pairs with velocity reversals. Our findings demonstrate that the confinement aspect ratio serves as a minimal control parameter governing transitions in the collective dynamics of epithelial monolayers.

DOI: https://doi.org/10.1039/d5sm00913h
Mater Today Bio. 2026 Feb;36 102678

The mechanical strain as a cross-linking agent for skeletal muscle ECM-derived hydrogels.

Elena Merotto, Edoardo Maghin, Lucrezia Bettella, Andrea Roberto Calore, Monica Giomo, Gioele Pagot, Matteo Nifosì, Nicola Elvassore, Vito Di Noto, Silvia Todros, Piero Giovanni Pavan, Martina Piccoli.

  Our research focuses on utilising decellularised extracellular matrix (ECM)-derived hydrogels to develop implants for repairing skeletal muscle defects. We investigate whether applying mechanical stimuli during the hydrogel reticulation phase enhances its biomechanical properties, aiming to achieve surface stiffness values closer to those of physiological tissue compared to conventional chemical cross-linking methods. The ECM-derived hydrogel is prepared and characterised in terms of surface stiffness and gelation kinetics. Before polymerisation, the ECM-derived solution is embedded with myogenic cells, and the final constructs are then obtained through a temperature-induced self-assembling mechanism. Two different modifications are alternatively added: genipin, a natural cross-linker, and a nearly-uniaxial mechanical strain using an in-house developed bioreactor. Both modifications of the ECM-derived hydrogel result in a two-fold increase in surface stiffness compared to the self-assembled samples. However, only the mechanical stimulus promotes the alignment of ECM components, which may facilitate the subsequent orientation of skeletal muscle cells and leads to a significant increase in cell proliferation after 5 days of culture. These findings indicate that mechanical stimulation functions as a physical cross-linker, positively affecting both the biomechanical properties of ECM-derived hydrogels and the subsequent behaviour of incorporated cells.

Keywords:  Extracellular matrix; Hydrogel; Mechanical strain; Skeletal muscle

DOI:  https://doi.org/10.1016/j.mtbio.2025.102678
J Mater Chem B. 2026 Jan 08.

Designing highly tunable laminin-inspired bioactive peptide hydrogel-based biomaterials for directing cellular response.

Ranit Bhandary, Sourav Sen, Sweta Mohanty, Sangita Roy.

The extracellular matrix (ECM) plays a crucial role in regulating cellular interactions and cell signaling pathways through several biochemical cues. In this context, designing bioinspired ECM mimics, particularly supramolecular hydrogels derived from major ECM components, has gained great attention owing to their biocompatibility, diverse biofunctionalities and biodegradability. Additionally, the employment of non-conventional approaches to control self-assembly and access diverse properties in a single molecular domain is emerging as a powerful strategy to fabricate tunable biomaterials. Therefore, by combining these two strategies, we explored one of the crucial basal membrane proteins of the ECM, i.e., laminin. In the present work, we mainly focus on the α5β1 laminin protein-derived peptide sequence, IVVSIVNGR. The gelation in this short, newly identified peptide sequence was induced through a solvent-mediated self-assembly approach. To our knowledge, this is the first report exploring the hydrogelation behavior and biological applications of this ECM-derived bioactive peptide sequence. Interestingly, by varying the concentration of the peptide, we were able to access diverse gels with differential nanofibrous morphologies, mechanical behaviors, and cellular responses. Biocompatibility and cellular proliferation studies on the hydrogels were performed using both neuronal (SH-SY5Y) and fibroblast (L929) cell lines. The results demonstrated that as the peptide concentration increases, more entangled networks of nanofibers were formed that offered a more uniform and suitable interface for cellular adhesion and interactions than the loosely bound, wider fibrous structures formed at lower concentration, as evident from the 2D and 3D cell culture studies. Thus, this study highlights the potential of these newly designed laminin-inspired cell-instructive scaffolds for possible futuristic applications in tissue engineering.

DOI: https://doi.org/10.1039/d5tb01989c
Adv Mater. 2026 Jan 08. e10834

A Water-Soluble PVA Macrothiol Enables Two-Photon Microfabrication of Cell-Interactive Hydrogel Structures at 400 mm s-1.

Wanwan Qiu, Margherita Bernero, Muja Emilie Ye, Xianjun Yang, Philipp Fisch, Ralph Müller, Xiao-Hua Qin.

  Two-photon polymerization (2PP) has garnered increasing attention for engineering hydrogels with tailored architectures and controlled cellular responses. However, current 2PP strategies typically rely on (meth)acrylated proteins and inefficient chain-growth crosslinking mechanisms. Although thiol-ene photo-click reactions can enhance 2PP efficiency, commercial water-soluble thiol crosslinkers (e.g., DTT-dithiothreitol) tend to form intramolecular loops and introduce structural defects due to their short molecular length. As a result, high polymer concentrations (often up to 20%-50%) are required to achieve satisfactory print fidelity. Here, we develop a series of water-soluble, polyvinyl alcohol macromolecular thiol (PVASH, bearing 10-35 thiol groups) for fast high-fidelity hydrogel microfabrication via 2PP. A two-step synthesis yields PVASH with tunable degrees of substitution and excellent water-solubility. Compared to DTT and polyethylene glycol di-thiol, PVASH-based hydrogels exhibit reduced swelling, enhanced mechanical properties, and significantly improved printing fidelity. Notably, several complex hydrogel structures are fabricated at laser power as low as 20 mW and high scanning speeds of up to 400 mm s-1, achieving sub-micron feature size at 3% polymer concentration. After biofunctionalization with RGD motifs, the micro-scaffolds support cell infiltration, adhesion, proliferation, and osteogenic differentiation. Altogether, this work reports a new strategy for 2PP microfabrication of cell-interactive hydrogel structures with unprecedented printing efficiency and precision.

Keywords:  3D printing; biomaterials; hydrogels; polyvinyl alcohol; thiol‐ene reactions; two‐photon polymerization

DOI:  https://doi.org/10.1002/adma.202510834
Commun Biol. 2026 Jan 03.

A human pathophysiological 3D-bone marrow model reveals immune and stromal cell heterogeneity.

Mariette Giannini, Giulia Campione, Lea Torcq, Sylvain Donadelli, Maroua Bencheikh, Sophia Bounaud, Sandrine Jeanpierre, Kevin Geistlich, Veronique Maguer-Satta, Sylvain Lefort, Julie Leca.

The bone marrow niche is a complex microenvironment composed of stromal, endothelial, immune and hematopoietic cells. Dysregulated interactions within this niche can contribute to hematological malignancies and also occur in the context of solid cancer metastases. Here, we present a standardized three-dimensional human bone marrow (3D-BOM) model that recapitulates key features of the human niche. Indeed, we show that monocytes/macrophages from different sources acquire enhanced pro-inflammatory phenotype in 3D compared to 2D cultures. Hematopoietic progenitor cells are also influenced by this 3D niche while maintaining stemness characteristics over extended serial culture. Single-cell transcriptomics analysis highlighted human-like stromal and endothelial cells heterogeneity. In addition, we observed monocyte/macrophage and endothelial cell remodeling in the context of acute myeloid leukemia, suggesting dynamic interactions within the 3D-BOM. These findings highlight the potential of this model to investigate cellular dynamics underlying human bone marrow physiology and pathology.

DOI: https://doi.org/10.1038/s42003-025-09433-6
Adv Sci (Weinh). 2026 Jan 05. e14782

Modulating Integrin and Growth Factor Signaling With Peptides: Strategies to Synergistically Enhance Bone Tissue Regeneration.

Lluís Oliver-Cervelló, Elisabetta Ada Cavalcanti-Adam, Carlos Mas-Moruno.

  Providing biomaterials with cell-instructive cues represents a major goal in tissue engineering to tailor cell-material interactions and guide tissue regeneration. For bone tissue regeneration, this has been classically addressed by integrating integrin-binding proteins and peptides on different substrates, aiming at mimicking the bone extracellular matrix. However, it has become evident that integrin signaling alone is not sufficient to fully recreate the cellular microenvironment required to effectively drive bone healing, and that growth factors (GFs), such as bone morphogenetic proteins (BMPs), are essential for bone development and growth. Indeed, recent research has demonstrated that integrins engage in synergistic signaling with GF receptors (GFRs). For instance, it is now well established that the osteogenic activity of BMPs can be regulated, and often enhanced, by integrins. These findings have thus encouraged the study of novel multifunctional systems that combine integrin-binding ligands with osteoinductive cues to exploit integrin-GF crosstalk and regenerate bone. This review aims to provide a comprehensive overview of the different mechanisms of signaling between integrins and GFRs, and the existing strategies to harness synergistic effects. A particular focus is put on the recent developments using the well-known integrin-binding RGD peptide and its co-presentation with BMP-derived peptides.

Keywords:  BMP; RGD; growth factor; integrin; synergy

DOI:  https://doi.org/10.1002/advs.202514782