bims-ecemfi 2025-11-09 papers

bims-ecemfi

Biomed News

on ECM and fibroblasts

Issue of 2025–11–09
ten papers selected by
Badri Narayanan Narasimhan, University of California, San Diego

Mechano-induced patterned domain formation by monocytes.
Zwitterionic Microgel Scaffolds Support Matrix Accumulation by Regulating Protein Adsorption.
Interfacial Energy Balance Governs Initial Cell Spreading Dynamics.
Advancing Organ-on-Chip Models With a Sacrificial Granular Hydrogel Strategy for Enhanced Permeability and Biomimicry.
Vector-stimuli-responsive magnetorheological fibrous materials.
Extracellular matrix and proteolysis: mechanisms driving irreversible changes and shaping cell behavior.
α‑Ketoglutaric Acid as a Sustainable and Universal Photoinitiator for Hydrogels.
Fibrillar Bundles as Fibrous Filler Materials for Attaining Cell Anisotropy in Bioprinting.
Mechanotyping of Organoids for Assessing Drug-Induced Injuries.
Hairy Gels: Mimicking the Hair-Covered Architecture and Responses of Animal and Plant Tissues.

Nat Mater. 2025 Nov 05.

Mechano-induced patterned domain formation by monocytes.

Wenxuan Du, Jingyi Zhu, Yufei Wu, Hongyi Liu, Ashley L Kiemen, Zeqi Wan, Eban Andrew Hanna, Hui Zhang, Sean X Sun, Denis Wirtz.

Matrix stiffness and the corresponding mechanosignalling play indispensable roles in cellular phenotypes and functions. How tissue stiffness influences the behaviour of monocytes, a major circulating leukocyte of the innate system, and how it may promote the emergence of collective cell behaviour is less understood. Here we show that human primary monocytes, uniquely among key immune cells, undergo a dynamic local phase separation to form highly regular, reversible, multicellular, multilayered domains on soft collagen-coated hydrogels of physiological stiffnesses. Local activation of the β2 integrin-ICAM-1 complex initiates intercellular adhesion, while global soluble inhibitory factors maintain the steady-state domain pattern over days. While inhibiting their phagocytic capability, domain formation promotes the survival of monocytes. A computational model incorporating the Cahn-Hilliard equation of phase separation with the Turing mechanism of local activation and global inhibition suggests that cell seeding density and chemotactic and random cell migration contribute to domain pattern formation, which is experimentally validated. This work reveals that cells can generate complex phases by exploiting their mechanosensing abilities and combined short-range interactions and long-range signals to enhance their survival.

DOI: https://doi.org/10.1038/s41563-025-02397-2
Adv Healthc Mater. 2025 Nov 07. e03483

Zwitterionic Microgel Scaffolds Support Matrix Accumulation by Regulating Protein Adsorption.

Erika E Wheeler, Ayla N Apsey, J Kent Leach.

  Substrate charge influences protein adsorption, cell adhesion, and biocompatibility. Hydrogels formed from zwitterionic polymers, which possess balanced cationic and anionic groups, are advantageous due to their high levels of hydration, ability to resist non-specific protein adsorption, high biocompatibility, and non-immunogenicity. Compared to bulk hydrogels, microgel-based scaffolds enhance cell proliferation, migration, cell-matrix interaction, and nutrient transport. However, previous studies using zwitterionic microgel scaffolds have not fully characterized how substrate charge influences cell behaviors such as viability, spreading, and extracellular matrix (ECM) deposition. In this study, microgels using polymers with various functional groups that imbue distinct substrate charges and emulsion-based microfluidics are fabricated. Charged proteins adsorbed more to substrates with an opposing charge. When seeding human mesenchymal stromal cells (MSCs) into microgel annealed scaffolds, we observed differences in cell viability and cell spreading as a function of substrate charge, with zwitterionic polymers best promoting viability and spreading. Lastly, it is found that zwitterionic microgel scaffolds maintained ECM accumulation in inflammatory conditions, while ECM deposition decreased in scaffolds formed from nonionic or negatively charged polymers. These data demonstrate that substrate charge influences protein adsorption, MSC adhesion, and subsequent ECM deposition, highlighting its importance in designing macroporous scaffolds for tissue engineering.

Keywords:  Zwitterionic hydrogels; extracellular matrix; mesenchymal stromal cells; microgels; protein adsorption

DOI:  https://doi.org/10.1002/adhm.202503483
Langmuir. 2025 Nov 02.

Interfacial Energy Balance Governs Initial Cell Spreading Dynamics.

Jifeng Ren, Shuhuan Hu, Yi Liu, Siping Huang, Jingqian Zhang, Qi Gao, King Wai Chiu Lai, Raymond H W Lam.

Cell spreading is a fundamental process in physiological and pathological contexts, including tissue formation, wound healing, and cancer cell extravasation. Previous studies have examined biophysical mechanisms governing early spreading (around 1-10 min) while biomolecular processes also begin to emerge, yet initial spreading in an even earlier stage (<1 min) remains largely unexplored. Here, we present a deterministic model based on interfacial energy balance─integrating strain energy, surface adhesion energy, and viscous dissipation─to quantitatively describe initial spreading dynamics. Using interference reflection microscopy (IRM), we characterize spreading behaviors of three breast cell lines (MCF-10A, MCF-7, and MDA-MB-231) on extracellular matrix-coated substrates. Model predictions, incorporating biomechanical and biochemical parameters measured through IRM and atomic force microscopy (AFM), show strong agreements with experimental observations. This work provides a universal framework for understanding initial spreading and offers insights into strategies to regulate initial cell spreading, with potential applications in cancer treatment and tissue engineering.

DOI: https://doi.org/10.1021/acs.langmuir.5c03250
Small Methods. 2025 Nov 05. e00652

Advancing Organ-on-Chip Models With a Sacrificial Granular Hydrogel Strategy for Enhanced Permeability and Biomimicry.

Hugo R Caires, Óscar Castillo-Fernández, Núria Sima, Mariana V Magalhães, Andreu Benavent-Claró, Nil Masó-Castro, Wanlapa Roobsoong, Carmen Fernandez-Becerra, Aurora Hernández-Machado, Hernando A Del Portillo, Cristina C Barrias.

  Infectious diseases such as malaria, leishmaniasis, and human immunodeficiency virus (HIV) involve pathogens with complex life cycles that span multiple organs, including the bone marrow (BM), a niche for latent or cryptic infections. Studying these hidden stages in patients presents significant technical and ethical challenges, underscoring the need for advanced in vitro models such as organ-on-chip (OoC) platforms. While cell-laden hydrogels can replicate tissue-like 3D-microenvironments, their small mesh size may restrict pathogen migration and cell-pathogen interactions, both critical for establishing infection on-chip. To overcome this limitation, this work develops a "reversed" granular hydrogel strategy that creates interconnected microporosity in hydrogels incorporated into organ-on-chip compartments. Sacrificial alginate (ALG) µgels are embedded as porogens in a fibrin-collagen (FIB-COL) precursor inside a custom BM-on-chip and, after crosslinking, are selectively removed by in situ enzymatic/chemical leaching to yield highly porous hydrogels (pFIB-COL). The pFIB-COL supports 3D-cultures of mesenchymal stromal cells, endothelial cells, and erythroblasts. Physical and cellular analyses show reduced flow resistance, enhanced particle and cell permeation, more uniform cell distribution and improved endothelial network formation compared with native FIB-COL. This versatile strategy is readily adaptable to other hydrogel systems, providing a valuable tool for the faithful modeling of infection processes in biomimetic 3D-microenvironments within OoC devices.

Keywords:  3D model; infection model; microporogen‐structured hydrogel; porous hydrogel; sacrificial microparticles

DOI:  https://doi.org/10.1002/smtd.202500652
Nature. 2025 Nov 05.

Vector-stimuli-responsive magnetorheological fibrous materials.

Junhong Pu, Haiqiong Li, Jin Liu, Ke Li, Xiaoming Tao.

Fibrous materials that provide reversible actuation1,2 or adapt mechanical properties3,4 in response to external stimuli hold great promise for smart textiles5, soft robotics6 and wearable technologies7. Although considerable progress has been made in creating fibrous materials responsive to scalar stimuli such as voltage8, temperature6, humidity2 and ion concentration9, these technologies often lack directional controllability and functional diversity10-14. Here we report a class of vector-stimuli-responsive magnetorheological fibrous materials, guided by our engineering model integrating the structural mechanics of textiles with the magnetics of soft magnetic materials. We mass-produced soft magnetic polymer composite fibres with optimized mechanical and magnetic properties, which we then assembled into concentric helical yarns. These yarns exhibited pronounced bending and stiffening properties controlled by the direction and magnitude of magnetic fields, allowing for customized fabrics with various actuation and stiffening functionalities. We demonstrated innovative smart textiles derived from those fabrics, including an active ventilation fabric for personal moisture management, an integrated conformable gripper for handling objects of varying shapes and stiffness, and a compact remote-controllable haptic finger glove that replicates the sensation of fabric hardness and smoothness. Our work provides insights into stimuli-responsive fibrous materials, elevating them from scalar to sophisticated vector control, heralding an era of smart textile innovation.

DOI: https://doi.org/10.1038/s41586-025-09706-4
FEBS J. 2025 Nov 03.

Extracellular matrix and proteolysis: mechanisms driving irreversible changes and shaping cell behavior.

Inna Solomonov, Orit Kollet, Irit Sagi.

  The extracellular matrix (ECM) provides structural support and dynamic signaling cues, governing cellular behavior and tissue integrity. ECM remodeling, critically regulated by irreversible proteolysis, profoundly impacts development, homeostasis, and disease. This review examines the major families of ECM-degrading proteases-matrix metalloproteinases (MMPs), serine proteases, a disintegrin and metalloproteinases (ADAMs), metalloproteinase with thrombospondin motifs (ADAMTSs), and cysteine proteases-emphasizing their shared regulatory mechanisms and proteolytic activity in reshaping the tissue microenvironment. These proteases exhibit functional redundancy, particularly in the generation of matrikines, growth factors, and cytokines from common ECM substrates, all contributing to ECM softening. These overlaps in substrates and the resulting bioactive molecules amplify proteolysis within the tissue. The generated matrikines, growth factors, and cytokines further drive ECM remodeling through feedback loops, influencing the expression and activation of proteolytic enzymes. Despite these shared mechanisms, protease families demonstrate cell-specific functional specialization shaped by transcriptional programs, microenvironmental signals, and subcellular targeting, ensuring precise spatiotemporal proteolysis during processes such as development, wound healing, and immune responses. Dysregulation of this intricate proteolytic network contributes to chronic pathologies and cancer. Thus, understanding and targeting these processes is crucial for therapeutic intervention and the improved regulation of biological functions. Collectively, these insights reveal how irreversible ECM proteolysis orchestrates complex, context-dependent biological responses in both health and disease.

Keywords:  extracellular matrix; matrix metalloproteinases; mechanisms of proteolysis; proteases; proteolysis

DOI:  https://doi.org/10.1111/febs.70292
ACS Omega. 2025 Oct 28. 10(42): 49506-49521

α‑Ketoglutaric Acid as a Sustainable and Universal Photoinitiator for Hydrogels.

Yawei Zhao, Yuqing Liu, Tailai Yan, Malcolm Xing, Wen Zhong.

Hydrogels have acquired numerous attentions in biomedicine and smart bioelectronics due to similar properties to our tissues. Initiators are crucial in vinyl polymerization for hydrogel preparation which can influence mechanical properties and physical/chemical structures. We report α-ketoglutaric acid (αKG), an intermediate in the citric acid cycle, as an ecofriendly photoinitiator for vinyl polymerization. We comprehensively investigated the mechanical properties of hydrogels initiated by comparing αKG with Irgacure 2959 (I-2959) and ammonium persulfate (APS). We found that αKG successfully initiated the polymerization in both synthetic and natural hydrogels (polyethylene glycol, polyacrylamide, gelatin, alginate, and chitosan). Meanwhile, the interactions between αKG and functional groups of macromolecules make αKG a potential additive in hydrogels, which could influence the hydrogel mechanics. In contrast to the potential toxicity of unreacted APS and the limited water solubility of I-2959, αKG proves to be a more versatile and sustainable option in gelation than the other two. This work throws new light on hydrogel fabrication with the initiator alteration for potential biomedical applications.

DOI: https://doi.org/10.1021/acsomega.5c03346
Adv Healthc Mater. 2025 Nov 07. e03767

Fibrillar Bundles as Fibrous Filler Materials for Attaining Cell Anisotropy in Bioprinting.

Sven Heilig, Zan Lamberger, Lys Sprenger, Vivien Priebe, Camilla Mussoni, Denitsa Docheva, Kristina Andelovic, Jürgen Groll, Sahar Salehi, Gregor Lang, Matthias Ryma.

  Cellular alignment is essential for the function of anisotropic tissues such as skeletal muscle, tendon, cardiac, or neuronal tissues, where cell polarization governs mechanical integrity and signal transduction. However, engineering 3D tissue constructs with anisotropic extracellular microenvironments remains challenging, especially in larger constructs, which are commonly fabricated using extrusion-based bioprinting of cell-laden hydrogels, also known as bioinks. Here, a new class of bioprintable fibrous filler materials, fibrillar bundles, is presented that can be incorporated into bioinks and harness shear forces during extrusion bioprinting to achieve in situ alignment without the need for additional processing steps. These fibril bundles consist of multiple submicrometer fibrils fused into a larger bundle. They support robust cell adhesion and effectively promote polarization and alignment across multiple cell types. When incorporated into bioinks and printed with muscle cells, the fibrillar bundles enhance cellular alignment, and quantitative analysis confirms the directional growth of multinuclear myotubes and their morphological maturation. This approach offers a scalable and integrative solution for inducing anisotropy within 3D biofabricated tissues, holding promise for applications in muscle tissue engineering and beyond.

Keywords:  bioprinting; fibers; filler materials; melt electrofibrillation; muscle alignment

DOI:  https://doi.org/10.1002/adhm.202503767
Adv Mater. 2025 Nov 05. e09675

Mechanotyping of Organoids for Assessing Drug-Induced Injuries.

Murat Kaynak, Mehmet D Aşık, Elif E Inan, Maksymilian Prondzynski, Hamzeh Ghasemzadeh, Amir Poorghani, Yashasvi Tharani, Matilda Holtz, Daryush D Mehta, William T Pu, Orhun K Muratoglu, Martin L Yarmush, Alexander Alexeev, O Berk Usta.

  Changes in the mechanical properties, i.e., mechanotypes, of tissues are powerful indicators of disease states and drug-induced injuries. Although differential mechanotyping has emerged as a valuable tool for non-invasive disease diagnostics, it remains particularly underutilized for drug safety and efficacy screening in preclinical studies. This is largely due to the lack of scalable mechanotyping methods compatible with modern 3D organoid models. Here, the Centrifugal Mechanical Testing (CeMeT) platform is presented, which enables rapid, robust, and label-free mechanotyping of 3D organoids. Utilizing centrifugal mechanical principles and high-speed imaging, this platform achieves high accuracy and precision and can assess a wide range of tissue stiffness. It is demonstrated that the CeMeT platform distinguishes mechanical properties, i.e., stiffness and elastic recovery, among various hydrogel bead formulations and hiPSC-derived cardiac organoids, successfully detecting pathological changes in mechanotype with high sensitivity. Through experiments on organoids treated with drugs like pergolide and Cytochalasin-D, it is established that changes in organoid mechanotypes can serve as reliable indicators of drug-induced tissue injuries in vitro. These findings position the CeMeT platform as a potentially transformative tool for early-stage drug safety assessment through mechanotyping, with immediate applications extending to fundamental disease pathology research and drug efficacy testing using organoid models.

Keywords:  drug‐induced injuries; mechanical drug testing; mechanotyping; organoids; tissue biomechanics

DOI:  https://doi.org/10.1002/adma.202509675
ACS Appl Mater Interfaces. 2025 Nov 05.

Hairy Gels: Mimicking the Hair-Covered Architecture and Responses of Animal and Plant Tissues.

Brady C Zarket, Hanchu Wang, Faraz A Burni, Srinivasa R Raghavan.

  Many animal and plant tissues are covered with slender hairs or filaments (called cilia, villi, tentacles, etc.). The hairs have important functions, which include protection from external elements, adhesion to prey, or increased absorption of nutrients. Here, we present a technique to create soft materials covered by hairs. Both the base and the hairs are hydrogels (i.e., aqueous polymer networks). The hairs are grown from the base by an "inside-out" polymerization guided by a template. By carefully selecting the monomers and cross-linkers for the polymerization, we control the chemistry as well as the mechanical properties of the base and the hairs. Moreover, we can tune all geometric parameters, including the hair diameter, length, and spacing. Hairs increase the surface area of the base gel by 10-fold, allowing a hairy gel to absorb solutes much faster than a bare gel. We also create patterns of different hairs on the same surface, including hairs that respond to stimuli such as magnetic fields. Lastly, we induce hair-covered gels to fold into tubes upon exposure to a stimulus (viz. a change in solvent quality). In the folded tube, the hairs can decorate the outer or inner surface. Folding of hairy gels mimics the folding of sundew plant leaves to trap prey.

Keywords:  Biomimetic materials; gel folding; nature-inspired materials; stimuli-responsive materials

DOI:  https://doi.org/10.1021/acsami.5c14817