Biomaterials[JOURNAL]
Sun
200 papers
Advanced materials for non-alcoholic fatty liver disease and cardiovascular disease comorbidity therapeutics.
Na J, Huang L, Wang L … +4 more , Ni Y, Chen Y, Luo Q, Li Y
Biomaterials · 2026 Oct · PMID 42001540 · Publisher ↗
Non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) frequently co-occur, driven by inter-organ metabolic crosstalk that current single-target therapies fail to disrupt. This review reframes NAFLD-C...
Non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) frequently co-occur, driven by inter-organ metabolic crosstalk that current single-target therapies fail to disrupt. This review reframes NAFLD-CVD comorbidity through a materials-first lens and advances a translational design framework that couples pathophysiology with engineering principles. We synthesize three major pathological axes, including lipid overflow and impaired reverse cholesterol transport, inflammation-oxidative stress amplification driven by Kupffer cell-NLRP3 and mitochondrial ROS/MAPK signaling, as well as gut-liver-vascular dysregulation involving bile acid FXR/TGR5 pathways and microbiota-derived metabolites, and further map these mechanisms to organ-selective and stimulus-responsive therapeutic interventions. Specifically, we highlight liver-heart co-targeting via GalNAc/ASGPR and VCAM-1 ligands, HDL-mimetic and exosome platforms that restore cholesterol efflux, ROS/pH/enzyme-responsive carriers that achieve microenvironment-triggered release and mitochondria-addressed nanodevices including antioxidant nanozymes, Mito-therapeutics, and optogenetically guided CRISPR/RNA payloads that recalibrate energy/redox homeostasis. We further outline macrophage-reprogramming strategies using cytokine mRNA and miRNA modulators to resolve chronic inflammation, and propose closed-loop systems that integrate AI-guided design with synthetic biology circuits for adaptive, multi-organ control. Across platforms, we distill actionable criteria covering clinical translation, biodistribution fidelity, barrier traversal, compensation-proof multi-pathway control, and safety-by-design. This materials-anchored roadmap moves the field from single-organ symptom control to systemic metabolic reprogramming, positioning advanced materials as catalysts for durable, precision therapy in NAFLD-CVD comorbidity.
Metabolic reprogramming of human macrophages drives the formation of hybrid M1/M2 pro-regenerative extracellular vesicles.
Gorgun C, Klavina P, Martins CS … +6 more , Payet C, Cavanagh BL, Pultar M, Hackl M, Curtis AM, Hoey DA
Biomaterials · 2026 Oct · PMID 42001539 · Publisher ↗
The coordinated activity of macrophages is essential for bone repair, with pro-inflammatory M1 macrophages driving early responses and anti-inflammatory M2 macrophages supporting later tissue remodeling. While both pheno...
The coordinated activity of macrophages is essential for bone repair, with pro-inflammatory M1 macrophages driving early responses and anti-inflammatory M2 macrophages supporting later tissue remodeling. While both phenotypes are required, prolonged persistence of either subtype can impair healing, underscoring the correct transition between the two states. Macrophage polarization is closely linked to cellular metabolism, and human macrophages display distinct metabolic profiles. Macrophage-derived extracellular vesicles (EVs) carry bioactive cargo and reflect parental polarization, influencing recipient cell function. This raises critical questions about how metabolic regulation influences human macrophage function, their EVs and their effect on angiogenesis and osteogenesis. This study investigates EVs derived from polarized primary human macrophages and from macrophages exposed to DASA-58, a small molecule which activates the metabolic enzyme pyruvate kinase M2 (PKM2). Alterations in macrophage metabolism modify the molecular cargo of their EVs, including microRNAs (miRNAs), to modulate regenerative activity. These findings demonstrate that human macrophage-derived EVs exert metabolically dependent effects on angiogenesis and osteogenesis, and that metabolic modulation enables the generation of EVs with hybrid pro-regenerative properties intermediate between M1 and M2. This establishes metabolic reprogramming within human macrophages using small molecules as a strategy to engineer novel phenotypes and EVs for bone repair.
Matrix composition modulates cancer cell phenotypes and secretions in a blood-brain barrier organ-on-a-chip model: Comparison of collagen and hyaluronic acid.
Dabaja AA, Hoque Apu E, Zhao V … +10 more , Manimaran S, Slayton MD, Li H, Serhan H, Bao L, Morikawa A, Lowenstein PR, Castro MG, Merajver SD, Oliver CR
Biomaterials · 2026 Oct · PMID 41999709 · Publisher ↗
Recent advances in organ-on-a-chip (OOC) blood-brain barrier (BBB) models for oncology research have revealed key insights into the metastatic cascade. However, in most 3D BBB systems, type I collagen is commonly selecte...
Recent advances in organ-on-a-chip (OOC) blood-brain barrier (BBB) models for oncology research have revealed key insights into the metastatic cascade. However, in most 3D BBB systems, type I collagen is commonly selected as the brain-side extracellular matrix (ECM) due to its ease of use and affordability. This selection overlooks the native ECM composition of the brain, which is primarily composed of hyaluronan/hyaluronic acid (HyA). Given that the ECM occupies approximately 20% of the brain volume and actively modulates tumor progression, substrate selection is an important yet frequently under-examined component in 3D BBB systems. Using our published blood-brain barrier niche (BBN), we compared HyA and type I collagen matrices to evaluate their impact on cancer cell phenotypes and the tumor microenvironment (TME) to establish which substrate affords the greatest versatility across different lines of investigation. Using a TA DHR-3 rheometer, we examined biophysical variations of these matrices in response to oscillatory shear. We then assessed phenotypic and migratory differences in human breast cancer cells, and their brain-seeking subclones in an ECM of HyA with media versus type I collagen, within our BBN device. Finally, ELISA analysis revealed significant matrix-dependent impact on key chemokine alterations, with collagen matrices promoting CXCL5 and DKK1 secretion across all conditions relative to HyA. We conclude that ECM selection to mimic the patient's brain microenvironment in OOC systems is a critical decision due to inherent substrate differences and either can be appropriate depending on the study goals.
Ionic immune checkpoint blockade through potassium-scavenging hydrogel to potentiate CD8 T cell-mediated cancer immunotherapy.
Liu Y, Zhou X, Li W … +8 more , Feng B, Sun J, Li R, Ma H, Li L, Zhou F, Ding J, Chen X
Biomaterials · 2026 Oct · PMID 41999708 · Publisher ↗
Immunotherapy efficacy is constrained by immunosuppressive features of the tumor microenvironment (TME) beyond canonical molecular checkpoints, including emerging extracellular ionic regulatory mechanisms that remain poo...
Immunotherapy efficacy is constrained by immunosuppressive features of the tumor microenvironment (TME) beyond canonical molecular checkpoints, including emerging extracellular ionic regulatory mechanisms that remain poorly characterized. Here, we identify potassium ion (K) as a metabolically coupled ionic immune checkpoint that suppresses CD8 T cell antitumor immunity. Using a murine melanoma model with an elevated-K microenvironment, we demonstrate that excess extracellular K profoundly impairs CD8 T cell proliferation, activation, and effector function while promoting functional exhaustion without reducing T cell abundance. Mechanistically, K-mediated immunosuppression is accompanied by restricted glucose uptake, suppressed glycolytic flux, and impaired mitochondrial fitness, establishing metabolic insufficiency as a key basis for ionic checkpoint-driven T cell dysfunction. To therapeutically target this extracellular and non-molecular suppressive mechanism, we develop a localized K-depleting strategy by encapsulating the clinically approved potassium-binding agent sodium zirconium cyclosilicate (ZS-9) within a thermosensitive poly (lactide-co-glycolide)-polyethylene glycol-poly (lactide-co-glycolide) (PLGA-PEG-PLGA) hydrogel, forming a peritumoral K-scavenging depot. This biomaterial platform efficiently remodels the ionic TME, restores CD8 T cell metabolic fitness and effector function, alleviates T cell exhaustion, and significantly enhances the antitumor efficacy of adoptive cell therapy (ACT). Collectively, this work establishes extracellular ionic modulation as a metabolically grounded immune checkpoint mechanism and highlights biomaterials-based ionic remodeling as a translatable strategy to augment cancer immunotherapy.
The role of growth factors in peripheral nerve regeneration and opportunities for next-generation biological therapeutics.
Alpizar Vargas V, Shultz RB, Laimo FA … +2 more , Cullen DK, Lee HH
Biomaterials · 2026 Oct · PMID 41996898 · Publisher ↗
Regeneration after peripheral nerve injury (PNI) involves complex processes that are often insufficient to facilitate full functional recovery. In particular, PNI stimulates the release of a multitude of growth factors w...
Regeneration after peripheral nerve injury (PNI) involves complex processes that are often insufficient to facilitate full functional recovery. In particular, PNI stimulates the release of a multitude of growth factors with critical spatial and temporal specificity to aid in regeneration by affecting axons, glia, immune cells, and vasculature. Depending on the severity of the injury, however, these endogenous processes may be inadequate to support regeneration, leaving patients with life-long sensory and motor deficits. Current treatments in these cases attempt to modify the regenerative environment, and many involve direct or indirect growth factor modulations to stimulate and sustain regenerative processes. For example, surgical interventions in the case of segmental defects may involve nerve conduits, which passively sequester and concentrate local growth factors, or nerve autografts, which provide autologous Schwann cells that actively secrete growth factors to drive axonal growth. Other strategies include electrical stimulation and physical therapy, each altering growth factor release to enhance axonal regeneration and functional innervation, respectively. Next-generation biological therapeutics including biomaterial-growth factor release systems and tissue engineered nerve grafts are emerging as potential regenerative scaffolds capable of presenting both structural and trophic cues. This review describes the critical role that growth factors play in orchestrating regenerative processes after PNI while highlighting novel therapeutics that are leveraging the unique capabilities of specific growth factors to augment peripheral nerve regeneration and facilitate functional recovery. Impact statement. This review describes the critical role that growth factors play after peripheral nerve injury by detailing the primary growth factors involved, the effects of their release over time and space, and how advanced regenerative therapies are leveraging these mechanisms to enhance nerve regeneration and functional recovery.
Biomaterials-enabled revelation of sustained p-Smad signaling and abnormal adhesion of leukemia-derived bone marrow stem cells.
Arnaldos-Pérez I, Machillot P, Geistlich K … +7 more , Marchadier L, Maguer Satta V, Migliorini E, Guyon L, Lefort S, Albiges-Rizo C, Picart C
Biomaterials · 2026 Oct · PMID 41990418 · Publisher ↗
Acute myeloid leukemia (AML) is an aggressive bone marrow disease, characterized by increased levels of bone morphogenetic proteins (BMPs). In this study, the impact of the BMP-enriched leukemia environment was determine...
Acute myeloid leukemia (AML) is an aggressive bone marrow disease, characterized by increased levels of bone morphogenetic proteins (BMPs). In this study, the impact of the BMP-enriched leukemia environment was determined on surrounding cells, notably mesenchymal stem cells (MSC). BMP-2, 4, 7, 9, and TGFβ1 were presented via a biomimetic extracellular matrix to healthy and AML-MSC. We have previously shown the existence of a bidirectional cross-talk between BMP receptors and integrins, which tightly connect cell adhesion to cell differentiation. In this study, we investigated how BMPRs and integrins are regulated in the AML microenvironment, in particular in the context of MSC adhesion and differentiation. Smad phosphorylation and cell adhesive responses were assessed for MSC cultured on biomimetic materials with matrix-bound BMPs/TGFβ1 using a recently-developed high-content immunofluorescence method. The specific role of BMP receptors and of integrin beta chains in the activation of pSmad signal, cell adhesion and cell spreading was studied using silencing RNA. 33% of the AML-MSCs exhibited increased receptor levels, with higher variability for BMPR2, β1 and β5 receptors. Notably, AML-MSC exhibited an upregulated and sustained pSmad signaling, associated to ALK5, ALK6 and BMPR2 dysfunctions. AML-MSC adhesion was strongly impaired, associated with a loss of cooperation between BMPR and β integrins. Unexpectedly, β integrins inhibited AML-MSC adhesion, while BMPRI receptors promoted it, notably ALK5. Furthermore, we proved that MSCs from AML patients exhibit an impaired differentiation into osteogenic, chondrogenic and adipogenic lineage. For the first time, we proved here that MSCs present in the AML microenvironment present an altered adhesion and differentiation, due to an altered cross-talk between BMPRs and integrins. This paves the way for future therapeutic strategies taking into account ALK5 and integrin beta chains in AML disease.
Mechanical confinement balances ECM remodeling in chondrocytes via MAPK and Hedgehog signaling.
Yuan MH, Lust ST, Marciano D … +7 more , Gautrot JE, Dreiss CA, Dell'Accio F, Eldridge SE, Grigoriadis AE, Tang C, Gentleman E
Biomaterials · 2026 Oct · PMID 41985400 · Publisher ↗
Mechanical cues from the extracellular matrix (ECM) are critical regulators of chondrocyte behavior and cartilage homeostasis. Mechanical confinement, determined by the stress relaxation properties of the surrounding mat...
Mechanical cues from the extracellular matrix (ECM) are critical regulators of chondrocyte behavior and cartilage homeostasis. Mechanical confinement, determined by the stress relaxation properties of the surrounding matrix, can drive anabolic ECM production or catabolic activity. However, the intracellular signaling pathways linking confinement to ECM remodeling remain poorly defined. Here, alginate hydrogels with tunable stress relaxation properties were used to investigate how confinement regulates signaling and matrix production. Low-confinement, fast-relaxing matrices promoted ECM deposition, whereas high-confinement, slow-relaxing matrices increased inflammatory and catabolic gene expression. Kinase activity profiling identified mitogen-activated protein kinase (MAPK) signaling as a key pathway modulated by confinement, with subsequent activation of Hedgehog (Hh) signaling. Pharmacological activation of Hh signaling enhanced matrix deposition and restored chondrogenic morphology in low-confinement conditions. ECM formation negatively correlated with primary cilia length, and confinement-mediated changes in chondrocyte volume occurred even without primary cilia. These findings support a model in which confinement regulates matrix production via MAPK and Hh signaling to maintain homeostasis, with alterations in confinement, such as those in osteoarthritis or aging, linked to changes in chondrocyte phenotype. This work positions confinement as a central regulator of cartilage mechanobiology and provides design principles for viscoelastic biomaterials supporting balanced ECM remodeling.
In situ thermosensitive mRNA-loaded hydrogel modulates post-surgery tumor immune microenvironment to prevent recurrence and metastasis.
Liu X, Wang C, Wang W … +4 more , Chen Z, Luo M, Yang R, Deng H
Biomaterials · 2026 Oct · PMID 41980379 · Publisher ↗
Surgery remains the primary cancer treatment, but postoperative trauma disrupts the local immune microenvironment by altering the critical balance between M1 and M2 macrophages while simultaneously elevating reactive oxy...
Surgery remains the primary cancer treatment, but postoperative trauma disrupts the local immune microenvironment by altering the critical balance between M1 and M2 macrophages while simultaneously elevating reactive oxygen species (ROS) levels at the surgical site. The critical clinical dilemma in postoperative tumor management lies in achieving re-balancing over macrophage polarization within the post-operative niche - specifically maintaining tumor-suppressing M1 phenotype while permitting necessary wound-healing M2 function. Here, we developed an in situ thermosensitive hydrogel platform capable of co-delivering two nanoparticle systems (BCD NPs and PPS NPs) to alleviate the immunosuppressive microenvironment. Specifically, CRISPR/Cas9-loaded nanoparticles (BCD@CRISPR NPs) were incorporated into the hydrogel for addressing the high proportion of M2-type macrophages at the resection site, reprogramming the macrophages with an effective M1/M2 ratio to exert potent antitumor functions. Meanwhile, the PPS nanoparticles were employed for the clearance of ROS at the surgical site, thereby ensuring that the normal wound healing process remained unimpeded. Using an in situ tumor resection model, the synergistic effects of ROS clearance and macrophage repolarization at the postoperative site were leveraged to achieve efficient immune microenvironment modulation.
Zinc-containing biomaterials for bone disease therapy and tissue repair: Design principles, mechanistic insights, and translational pathways.
Zare I, Far MS, Tajabadi S … +10 more , Jafari Z, Heidari BS, Esmaeili Y, Davachi SM, Mirshafiei M, Rafienia M, Shen J, Ambrosio L, Raucci MG, Bigham A
Biomaterials · 2026 Oct · PMID 41980378 · Publisher ↗
Bone tissue engineering has emerged as a promising strategy not only for treating bone defects and related diseases but also for supporting bone regeneration. However, its success relies on the development of effective b...
Bone tissue engineering has emerged as a promising strategy not only for treating bone defects and related diseases but also for supporting bone regeneration. However, its success relies on the development of effective biomaterials that can simultaneously fulfill therapeutic needs and replicate the natural extracellular matrix of bone tissue. Zinc (Zn) is an essential nutrient that plays a crucial role in bone metabolism. Indeed, it is known to enhance bone formation and regeneration. Unlike conventional bioactive ions that primarily contribute to mineral deposition or antimicrobial activity, Zn plays a multifaceted regulatory role in bone regeneration by simultaneously modulating osteogenesis, angiogenesis, immune responses, and cellular enzymatic pathways, while also enabling controlled biodegradation and therapeutic functionality. Zn-containing biomaterials have shown great potential for bone tissue engineering applications due to their unique properties, including high biocompatibility, biodegradability, antibacterial activity, and osteogenic properties. This review provides an overview of the synthesis, design, and recent advancements in various types of biomaterials combined with Zn, including Zn-based metal-organic frameworks (MOFs), Zn oxide nanoparticles (ZnO NPs), Zn-doped hydroxyapatite (ZnHA), Zn-functionalized magnetic nanostructures, scaffolds/implants, hydrogels, and cements, among others, for the treatment of bone diseases and tissue regeneration. The present review also focuses on the mechanisms by which Zn-containing biomaterials promote bone regeneration, including regulation of osteoblast differentiation, stimulation of angiogenesis, and inhibition of osteoclast activity. Furthermore, we discuss the clinical translation of Zn-containing platforms, including commercially available products, ongoing clinical trials, and preclinical systems. Ultimately, Zn-containing biomaterials hold promise as therapeutic and regenerative agents with strong potential to treat bone-related diseases and induce regeneration in the near future.
A 3-N nose-to-brain urolithin a nanomotor targeting microglial mitophagy in neuroinflammation.
Fu Y, Zhao G, Zou H … +9 more , Zhu K, Zhou Y, Yang L, Zhao Y, Yang J, Niu B, Liu Z, Liu X, Lu H
Biomaterials · 2026 Oct · PMID 41980377 · Publisher ↗
Cognitive impairment is the primary manifestation of neuroinflammation-related central nervous system diseases. Intranasal administration is an effective method, bypassing the blood-brain barrier and delivering drugs to...
Cognitive impairment is the primary manifestation of neuroinflammation-related central nervous system diseases. Intranasal administration is an effective method, bypassing the blood-brain barrier and delivering drugs to the brain. Herein, we designed a biomimetic self-propelled nanomotor with an inflammation-targeting capacity. This nanomotor comprised a hollow mesoporous manganese dioxide (HMnO) core and a polydopamine (PDA) shell. HMnO effectively catalyzed the conversion of endogenous HO into HO and O, enabling the movement of the nanomotor into a wider area to reduce neuroinflammation. The nanomotor was loaded with the natural compound urolithin A (UA), which significantly improved the bioavailability of the compound and enhanced mitophagy. Furthermore, PDA modification imparted the nanomotor with strong adhesive properties, enabling them to anchor effectively to the olfactory nerve and enhancing delivery to the brain. In vitro, PDA@HMnO@UA alleviated mitochondrial dysfunction, oxidative stress, and inflammation levels by enhancing mitophagy in lipopolysaccharide (LPS)-induced BV2 cells. Following intranasal administration, PDA@HMnO@UA exerted neuroprotective effects by alleviating microglial activation, neuroinflammation, and neuronal loss, ultimately rescuing the neurocognitive function in the LPS-induced neuroinflammation model. In summary, this study presents an ideal nanomotor platform based on the 3-N strategy, which means "Nanomotor loaded with a Natural product to traverse a Natural anatomical pathway," that can alleviate cognitive impairments caused by neuroinflammation, offering a promising delivery approach for treating neuroinflammatory diseases.
Enhanced delivery of low-density lipoprotein-based nanoparticles to the mouse glioblastoma using focused ultrasound as a novel therapy.
Brambila C, Sahebi Vaighan N, Youssef I … +6 more , Chaudhary J, Anwar A, Bachoo R, Patel T, Chopra R, Corbin IR
Biomaterials · 2026 Oct · PMID 41967385 · Publisher ↗
Glioblastoma (GBM) is a highly invasive and infiltrative primary brain tumor with a poor prognosis. This tumor avidly acquires cholesterol from its environment through the low-density lipoprotein receptor (LDLR) to facil...
Glioblastoma (GBM) is a highly invasive and infiltrative primary brain tumor with a poor prognosis. This tumor avidly acquires cholesterol from its environment through the low-density lipoprotein receptor (LDLR) to facilitate their aggressive and rapid proliferative phenotype. The blood-brain barrier (BBB) remains a major challenge for drug delivery to GBM as it restricts the entry of most therapeutics limiting their treatment efficacy. Focused ultrasound (FUS) with microbubbles is a non-invasive and safe method to transiently open the BBB to improve the delivery of the therapeutic agents to the brain. In this study, we aim to establish a facile and effective drug delivery strategy to GBM that integrates FUS-mediated BBB disruption and LDLR targeted delivery. Herein, an invasive intracranial mouse model of GBM was developed with the PS5A cell line. GBM bearing mice received intravenous injection of low-density lipoprotein (LDL) nanoparticles loaded with oleic acid and carbocyanine fluorescent dye with and without pulse FUS sonication in the tumor region of the brain. Tumor bearing mice without LDL nanoparticle or FUS intervention served as untreated controls. Initial confirmation of tumor progression and BBB opening was evaluated by magnetic resonance Imaging (MRI). Fluorescent imaging of the brain tissues post treatment revealed a markedly higher fluorescent signal in the sonicated tumor area when compared to the contralateral hemisphere, groups receiving LDL nanoparticle alone or untreated controls. The combination of LDLR targeting and FUS enabled enhanced intracellular delivery of LDL nanoparticles to GBM cells in the bulk tumor and surrounding peritumor regions in the striatum. These findings indicate that drug delivery can be achieved not only to bulk tumor but also to tumor cells infiltrating surrounding brain tissue behind the BBB. In summary, the current study establishes a foundational framework for the combination of FUS and receptor-targeted delivery of LDL nanoparticles to GBM.
Extracellular matrix-associated molecules of senescent cells induce a senescence phenotype in proliferative cells via TGF-β signaling pathway.
Sá Ferreira R, Aires HR, Rebelo C … +4 more , Passos JF, Ori A, Pitrez PR, Ferreira L
Biomaterials · 2026 Oct · PMID 41967384 · Publisher ↗
Senescent cells accumulate in various tissues as we age and are characterized by growth arrest and a senescence-associated secretory phenotype (SASP). This phenotype involves the release of various factors, such as pro-i...
Senescent cells accumulate in various tissues as we age and are characterized by growth arrest and a senescence-associated secretory phenotype (SASP). This phenotype involves the release of various factors, such as pro-inflammatory molecules, reactive oxygen species (ROS) and extracellular vesicles (EVs), which can trigger senescence in neighboring cells. However, it remains unclear whether non-soluble factors produced by senescent cells, such as the extracellular matrix (ECM) or its associated molecules (collectively termed the matrisome), can induce paracrine senescence. In this study, vascular cells were used as an in vitro model system to investigate this hypothesis. These findings reveal that decellularized ECM from senescent vascular smooth muscle cells (S-ECM) or fibroblasts, but not from proliferating cells (P-ECM), robustly induces a senescence phenotype in human proliferative endothelial cells (ECs) over a two-week culture period, whereas ECM from proliferating cells (P-ECM) does not elicit this effect. This induction appears to be at least partially mediated by the transforming growth factor beta (TGF-β) signaling pathway. Notably, inhibiting TGF-β receptor 1 (TGFβR1) in proliferative ECs grown in S-ECM significantly attenuated the senescence phenotype. These results further show that one of the matrisome proteins able to mediate the pro-senescence effect of S-ECM is transforming growth factor beta 1 induced transcript 1 (TGFβ1|1). Importantly, when discs coated with S-ECM were implanted in young mice, an increase in senescence markers was observed compared to mice implanted with discs coated with P-ECM. Overall, this research demonstrates that senescent-derived ECM acts as a potent trigger of cellular senescence, both in vitro and in vivo, with the involvement of the TGF-β signaling pathway playing a crucial role.
Cardiac fibroblast anisotropy is determined by YAP-dependent cellular contractility and ECM production.
Pereira-Sousa D, Guillamat P, Niro F … +8 more , Vinarský V, Fernandes S, Cassani M, Pagliari S, Trepat X, Rasponi M, Oliver-De La Cruz J, Forte G
Biomaterials · 2026 Oct · PMID 41966554 · Publisher ↗
Cardiac fibroblasts (CFbs) determine the topological arrangement and the anisotropy of the heart tissue which maintains tissue integrity and function through the production and remodeling of the extracellular matrix (ECM...
Cardiac fibroblasts (CFbs) determine the topological arrangement and the anisotropy of the heart tissue which maintains tissue integrity and function through the production and remodeling of the extracellular matrix (ECM). Under pathological conditions, CFbs can activate into myofibroblasts and promote maladaptive ECM remodeling that may lead to heart failure. Yes-Associated Protein (YAP) - a key player in cardiac fibrosis onset - has been implicated in CFb activation but its role in coordinating the supracellular organization of CFbs and in shaping the instructive properties of the ECM remains poorly understood. We addressed these questions by generating CFbs from wild-type (WT) and YAP knockout (KO) human embryonic stem cells. YAP depletion reduced the expression of cardiogenic markers and altered the transcriptomic profile of ECM- and contractility-related genes. We further demonstrated that YAP expression is required for CFbs monolayer alignment, and its absence resulted in reduced ECM deposition, decreased anisotropy, and diminished force generation. Pharmacological inhibition of cell contractility closely mirrored YAP KO phenotype, suggesting that YAP regulates both monolayer organization and ECM structure through its control over contractility. ECM cross-seeding experiments confirmed the role of ECM as a structural guide for cellular alignment. Moreover, cardiomyocytes cultured on KO CFb-derived ECM exhibited impaired sarcomere organization and altered calcium dynamics. Together, these findings demonstrate that YAP activity in CFbs governs the structural and functional properties of the ECM, influencing both fibroblast alignment and cardiomyocyte activity. Moreover, they underscore the critical role of YAP in maintaining the supracellular organization and mechanical integrity of cardiac tissue.
Decellularized extracellular matrix enhances hydrogel printability for bioprinting functional muscle constructs in a volumetric muscle loss model.
Sabetkish S, Luo Y, Lu YZ … +3 more , Martino MM, Currie P, Meagher L
Biomaterials · 2026 Oct · PMID 41966553 · Publisher ↗
Volumetric muscle loss (VML) remains a major clinical challenge due to the limited regenerative capacity of skeletal muscle. Effective repair requires the use of biomaterials that support cell viability, promote myogenic...
Volumetric muscle loss (VML) remains a major clinical challenge due to the limited regenerative capacity of skeletal muscle. Effective repair requires the use of biomaterials that support cell viability, promote myogenic differentiation and enable vascularisation to allow the formation of structurally aligned, functional muscle. Here, we have integrated a biomimetic bioink based on gelatin methacryloyl (GelMA) and methacryloyl-modified decellularized extracellular matrix (dECM-MA) with a micropost tension-assisted bioprinting strategy to engineer skeletal muscle constructs for VML repair. We synthesized and characterized GelMA and dECM-MA bioinks, demonstrating well-preserved ECM components, reproducible gelation, mechanical properties and rheological properties suitable for extrusion bioprinting. In vitro, printed GelMA + dECM-MA scaffolds supported high cell viability, alignment and robust myogenic differentiation of C2C12 myoblasts, human satellite cells (hSkMSCs) and human umbilical vein endothelial cells (HUVECs). Co-culture of satellite cells with HUVECs enhanced endothelial network formation and improved myotube maturation. Printing around PDMS microposts provided passive mechanical tension, producing aligned fibres and greater contraction velocity and micropost displacement in co-culture constructs under electrical stimulation. To assess regenerative potential, 3-day-matured constructs were implanted in a mouse VML model. Constructs containing both hSkMSCs and HUVECs showed the greatest tissue regeneration, higher myofiber density, improved organization, and enhanced functional recovery compared with acellular or monoculture constructs. No immune response towards the presence of the human cells or porcine ECM was observed, suggesting a protective role for dECM-MA. Together, this integrated bioink-biomechanical platform resulted in the generation of vascularised, aligned, and functional muscle tissue with strong translational potential for VML therapy.
A biomimetic arsenic-based nanozyme enhances dual epigenetic regulation to improve the efficacy of immunotherapy for acute myeloid leukaemia.
Chang A, Peng H, Chen Y … +8 more , Zhang H, Xu X, Zhang K, Yang J, Li W, Wang X, Dong X, Ni J
Biomaterials · 2026 Oct · PMID 41966552 · Publisher ↗
Aberrant epigenetic modifications in acute myeloid leukaemia (AML) limit immunotherapeutic efficacy. Arsenic ions are capable of undergoing valence transformation in organisms, exhibit favourable enzyme-mimetic activity,...
Aberrant epigenetic modifications in acute myeloid leukaemia (AML) limit immunotherapeutic efficacy. Arsenic ions are capable of undergoing valence transformation in organisms, exhibit favourable enzyme-mimetic activity, and thereby play a crucial role in enhancing dual epigenetic regulation. Therefore, to achieve potent epigenetic regulation, in this study, a biomimetic arsenic-based nanozyme (As/ZIF-8@M) that exhibits leukaemia cell recognition and phagocytosis capabilities, as well as bone marrow homing effects, was engineered. Within AML cells, this nanozyme exerted peroxidase (POD)-like and glutathione oxidase (GSHOx)-like activities through the valence state conversion of arsenic (As and As), thereby achieving potent regulation of DNA methylation and arginine methylation. This further activated the cGAS-STING pathway, leading to reversal of the immunosuppressive microenvironment in AML, increased PD-L1 blockade efficacy, and subsequent improvements in immunotherapy efficacy for leukaemia. This study presents the first biomimetic arsenic-based nanozyme leveraging catalysis to remodel the AML microenvironment, thereby enhancing dual epigenetic regulation. This innovative strategy holds significant promise for improving the efficacy of immunotherapy for leukaemia.
MOF-based nanozymes: Rational design and biomedical applications.
Chen R, Bao Y, Huang R … +3 more , Liu H, Luo Y, Zhang D
Biomaterials · 2026 Oct · PMID 41966551 · Publisher ↗
Nanozymes are nanomaterials with enzyme-mimicking catalytic activities that have extraordinary potential in biotechnology. Metal‒organic frameworks (MOFs), emerging nanoporous materials with atomically defined active sit...
Nanozymes are nanomaterials with enzyme-mimicking catalytic activities that have extraordinary potential in biotechnology. Metal‒organic frameworks (MOFs), emerging nanoporous materials with atomically defined active sites and ordered porous architectures, have been established as an important subclass of nanozymes. In this review, we systematically summarize the recent advances in MOF-based nanozymes. We first comprehensively describe the diverse bioinspired nanozyme activities of pristine MOFs and subsequently provide a critical overview of activity regulation strategies and rational design principles for constructing high-performance nanozyme platforms. These MOF-based nanozymes feature well-defined active sites that effectively mimic the catalytic microenvironments of natural enzymes, displaying exceptional catalytic activity and substrate selectivity. Leveraging the superior catalytic performance and inherent advantages of MOFs, MOF-based nanozymes with microenvironmental responsiveness exhibit promising prospects in various disease therapies and multimodal synergistic treatments. We highlight their potential therapeutic applications in cancer, inflammatory diseases, and infection treatment. The challenges and prospects of MOF-based nanozymes are also presented.
CO-driven cascade disruption of outer membrane barrier: A potent strategy to enhance treatment of gram-negative bacterial infections.
Lu H, Yang Z, Zhou Q … +13 more , Li L, Jin T, Yu L, Ran Y, Ding Y, Pan Y, Zhang Y, Deng H, Zhang Z, Kang M, Wang D, Tang BZ, Cai X
Biomaterials · 2026 Oct · PMID 41962277 · Publisher ↗
The robust outer membrane (OM) barrier is a major contributor to antibiotic resistance in multidrug-resistant Gram-negative bacteria (MDR GNB). Disrupting this barrier presents a promising strategy to overcome this chall...
The robust outer membrane (OM) barrier is a major contributor to antibiotic resistance in multidrug-resistant Gram-negative bacteria (MDR GNB). Disrupting this barrier presents a promising strategy to overcome this challenge. Herein, we propose a carbon monoxide (CO)-driven cascade inhibition strategy to disrupt the OM barrier, aiming to significantly boost the antimicrobial efficacy of existing treatments. As a proof of concept, we developed AIE&CO@G3, a nanogel that combines CO-releasing molecules (CORM-401) and aggregation-induced emission (AIE) photosensitizer (PSs). CO significantly potentiated the antimicrobial activity of AIE PSs-based antimicrobial photodynamic therapy (AIE-aPDT), with similar synergistic effects observed when combined with multiple first-line antibiotics. Mechanistically, CO-induced OM disruption facilitated the penetration of AIE PSs and antibiotics, thereby substantially boosting their efficacy both in vitro (against multiple MDR GNB) and in vivo (in models of MDR P. aeruginosa-infected bacterial keratitis and pneumonia). This was achieved by inhibiting adenosine triphosphate (ATP) synthesis and disrupting the biosynthesis and transport of glycerophospholipids (GPL) and lipopolysaccharides (LPS). This pioneering study highlights CO's potential in OM disruption and provides a novel strategy for combating MDR GNB infections.
A modular design of two-pronged sub-organelle targeting strategy disrupting mitochondria-endoplasmic reticulum crosstalk for mitigating rheumatoid arthritis.
Ren J, Tang Y, Liao Z … +4 more , Wen X, Hua Y, Li Y, Wang Q
Biomaterials · 2026 Oct · PMID 41962276 · Publisher ↗
The pathological crosstalk between endoplasmic reticulum (ER) stress and mitochondria (MT) dysfunction aggravates rheumatoid arthritis (RA) process by promoting the abnormal formation of mitochondria-associated ER membra...
The pathological crosstalk between endoplasmic reticulum (ER) stress and mitochondria (MT) dysfunction aggravates rheumatoid arthritis (RA) process by promoting the abnormal formation of mitochondria-associated ER membranes (MAMs). Current single organelle-specific therapies are insufficient to halt MAMs-mediated pathological inter-organelle communication and thereby showed limited efficacy in suppressing RA. A two-pronged dual organelles regulatory strategy that concurrently inhibit ER stress and MT dysfunction, thereby suppressing the aberrant MAMs formation will be promising to achieve prolonged RA remission. Due to the multiple delivery barriers from tissue to sub-organelle level, conventional approaches involve decorating nanocarriers with multiple functional groups. However, this typically leads to increased structural complexity and unpredictable in vivo performance. Here, we adopted a minimalist modular design strategy. By fine-tuning the density and ratio of dual organelles-targeted modules, we optimized the physicochemical properties of the Res@DPGT nanoplatform for maximal sub-organelle drug delivery. The optimal two-pronged nanoplatform Res@DPGT achieve a hierarchical targeting process from the tissue level to sub-organelle level, ultimately delivering therapeutic resveratrol (Res) to ER and MT. In inflammatory cells, Res@DPGT significantly suppress ER stress and MT dysfunction by disrupting MAMs formation, eliciting potent anti-inflammatory efficacy. In arthritic rats, intravenously administrated Res@DPGT show enhanced internalization by circulating monocytes and leverage the inflammatory tropism of circulating monocytes to achieve preferential distribution and prolonged retention in inflamed joints. Ultimately, Res@DPGT remarkedly alleviate RA by disrupting the MAMs-mediated pathological ER-MT coupling.
Curvature-degradation coupling drives cellular functions and osteointegration in additively manufactured biodegradable Zn-Mg scaffolds.
Qin Y, Wang Y, Chen L … +11 more , Lan Q, Jing Z, Dai J, Zou D, Chen K, Yang H, Xu N, Cai H, Wen P, Zheng Y, Li W
Biomaterials · 2026 Oct · PMID 41962275 · Publisher ↗
Geometric curvature is a fundamental regulator of cellular functions and bone tissue regeneration, yet its interplay with degradation in biodegradable metals remains elusive due to the insufficient curvature range of exi...
Geometric curvature is a fundamental regulator of cellular functions and bone tissue regeneration, yet its interplay with degradation in biodegradable metals remains elusive due to the insufficient curvature range of existing scaffold design. Here, we introduce additively manufactured Zn-Mg scaffolds inspired by Calabi-Yau manifolds and triply periodic minimal surface, enabling a broad curvature distribution while maintaining consistent pore size and porosity. In vitro, convex regions facilitated Zn ion diffusion and Ca/P mineral deposition, whereas concave regions accumulated Zn ion and suppressed mineral formation. This spatially heterogeneous ion microenvironment reshapes cellular behaviors compared to inert Ti controls. On Ti scaffolds, osteoblasts preferentially migrate toward negatively curved regions due to curvature-driven ECM deformation and focal adhesion signaling. In contrast, on Zn scaffolds, moderate Zn release at convex regions promotes proliferation and mineralization, mediating the intrinsic negative-curvature preference. In vivo, Zn-Mg scaffolds promoted bone regeneration and demonstrated uniform osteointegration compared to Ti controls. These findings reveal curvature-degradation coupling effects and establish architectural design principles for biodegradable metal implants.
Engineering versatile nanoplatforms for calcium homeostasis modulation and broad-spectrum disease therapies.
Dong Y, Wang Y, Chen K … +7 more , Sun G, Cao X, Li X, Lu W, Dai X, Huang B, Chen Y
Biomaterials · 2026 Oct · PMID 41962274 · Publisher ↗
Calcium ions (Ca) serve as a pivotal intracellular second messenger, participating in core physiological processes including cell proliferation, neurotransmission, and apoptosis. The maintenance of calcium homeostasis de...
Calcium ions (Ca) serve as a pivotal intracellular second messenger, participating in core physiological processes including cell proliferation, neurotransmission, and apoptosis. The maintenance of calcium homeostasis depends on the precise interplay of plasma membrane channels and intracellular organelle stores. Dysregulation of calcium signaling is implicated in the pathogenesis of multiple diseases, including Alzheimer's disease, cancer, and cardiovascular disorders. Conventional pharmacological interventions are limited by off-target effects, insufficient bioavailability, and a lack of temporal and spatial control. Ca-regulated nanoplatform achieves spatiotemporally controlled drug release and responsive calcium level modulation through advanced surface engineering and stimulus-responsive design, substantially improving therapeutic precision and efficacy. Furthermore, nanoprobes permit real-time monitoring of calcium dynamics with high sensitivity and resolution. This comprehensive review systematically summarizes and highlights significant advances in engineering versatile nanoplatforms for calcium homeostasis modulation, focusing on constructed nanocarriers for drug delivery, functional nano-regulators for calcium flux intervention, and sensitive nanoprobes for real-time calcium imaging and quantification. Current challenges and future directions are also discussed to inspire the development of next-generation nanotheranostic platforms for precise diagnosis and treatment of calcium homeostasis-related diseases.
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