Huang Y, Liang H, Zhu C
… +7 more, Fang Z, Zhou J, Qian J, Mayo KH, Zhu C, Li P, Li J
Biomaterials
· 2026 Nov · PMID 42160952
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Zinc (Zn)-based metals are promising materials for guided bone regeneration due to their controllable degradation and bioactivity. However, the immunomodulatory processes by which Zn influences angiogenesis during bone r...Zinc (Zn)-based metals are promising materials for guided bone regeneration due to their controllable degradation and bioactivity. However, the immunomodulatory processes by which Zn influences angiogenesis during bone regeneration remain incompletely understood. This study investigated the role of Zn-based metals in the early osteoimmune microenvironment and its association with angiogenic responses involving macrophage-derived extracellular vesicles (EVs). Compared to the control, Zn membranes were associated with enhanced osteogenesis and angiogenesis during bone defect repair. Single-cell RNA sequencing identified Arg1 macrophages as a prominent cell population in the early osteoimmune microenvironment. This subset appeared to function as intermediate communication and showed extensive interactions with endothelial cells after implantation. Functional enrichment analysis demonstrated increased metabolic activity and enrichment of pathways associated with vesicle transport in this subset. Conditioned media from Zn-stimulated macrophages enhanced endothelial migration and tube formation, whereas inhibition of EVs release significantly attenuated these effects. The expression of P2Y11 was increased in endothelial cells exposed to the media from Zn-treated macrophages. These findings provided significant information regarding EV-mediated communication between macrophages and endothelial cells for Zn-based implant response.
Cai J, Hu J, Zhang Z
… +6 more, Ma S, Dou H, Pan D, Geng B, Li P, Shen L
Biomaterials
· 2026 Nov · PMID 42160951
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The treatment of osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA) infection is severely hindered by the challenges of bacterial infection, excessive inflammation, and impaired osteogenesis. To a...The treatment of osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA) infection is severely hindered by the challenges of bacterial infection, excessive inflammation, and impaired osteogenesis. To address these challenges, we first develop an integrated nanoplatform (Se-CD@Cu-EGC) with concurrent anti-inflammatory, antibacterial, and osteogenic activities based on metal-phenolic networks (MPNs) and selenium-doped carbon dots (Se-CDs). Initially, a systematic investigation into the structure-activity relationship of MPNs is conducted using five polyphenol compounds with different numbers of phenolic hydroxyl groups. This reveals that Cu-EGC, assembled from Cu and (-)-epigallocatechin (EGC), possesses suitable pH-responsive degradation behaviors and exhibits strongest antibacterial activity owing to the synergistic membrane disruption and cuproptosis-like death. To further endow Cu-EGC with anti-inflammatory and osteogenic activities, Se-CDs with both immune regulation and osteogenic activity are loaded on Cu-EGC to form Se-CD@Cu-EGC nanoplatforms. The doping of Se element in CDs not only endows CDs with ROS scavenging performance and anti-inflammatory ability through reprogramming macrophages from pro-inflammatory M1 phenotype to anti-inflammatory M2 phenotype, but also optimizes the surface charge state of CDs to activate BMP/Smad pathway for promoting osteogenic differentiation of BMSCs. Se-CD@Cu-EGC is then incorporated into GelMA hydrogel for the eradicating biofilms, mitigating inflammation, and promoting bone repair in a MRSA-induced osteomyelitis model. This work not only elucidates the precise influence of polyphenol structure on the antibacterial activity of MPNs but also presents a novel strategy for the rational design of multifunctional biomaterials against infectious osteomyelitis.
Gray LT, Raczy MM, Briquez PS
… +25 more, Marchell TM, Alpar AT, Wallace RP, Volpatti LR, Sasso MS, Cao S, Nguyen M, Mansurov A, Budina E, Watkins EA, Solanki A, Mitrousis N, Reda JW, Yu SS, Tremain AC, Wang R, Nicolaescu V, Furlong K, Dvorkin S, Manicassamy B, Randall G, Wilson DS, Kwissa M, Swartz MA, Hubbell JA
Biomaterials
· 2026 May · PMID 42156299
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Zhu A, Liu J, Song Z
… +4 more, Zhan Y, Liu S, Su Y, Li J
Biomaterials
· 2026 Nov · PMID 42155176
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Immunotherapy offers a promising opportunity for cancer treatment; while only a subset of patients derive substantial benefits because of its low response efficacy and potential off-target side effects. Unlike convention...Immunotherapy offers a promising opportunity for cancer treatment; while only a subset of patients derive substantial benefits because of its low response efficacy and potential off-target side effects. Unlike conventional immunotherapy, we herein report an X-ray programmable interleukin-12 (IL-12) expression via a calcium ion (Ca) signaling-gated nanoplasmid (SPN) system for cancer immunotherapy. Such SPN are designed to be destructible upon reactive oxygen species (ROS) respond, composing of a semiconducting polymer core as a radiosensitizer, transient receptor potential vanilloid 1 (TRPV1) agonist capsaicin and engineering plasmid containing Ca-responsive c-fos promoter and IL-12 as the target gene. SPN are responded to produce ROS with low-dose X-ray activation by radiosensitization effect, which leads to the on-demand release of capsaicin and plasmid. As such, capsaicin turns on TRPV1 ion channel to facilitate extracellular Ca influx and subsequent activation of MAPK/ERK signaling pathway. This signaling cascade then initiates the Ca-responsive c-fos promoter to drive IL-12 expression of the engineering plasmids, thereby allowing for potent IL-12-based immunotherapy. This X-ray programmable immunotherapy strategy shows obvious antitumor effects in TRPV1-positive orthotopic glioblastoma and metastatic breast cancer murine models. This current study highlights the potential and application of X-ray programmable immunotherapy strategy for renovating cancer treatments.
Gao H, Wu W, Chen X
… +7 more, Shi P, Zhang A, Wu W, Yu Z, Yang C, Cheng Z, Zhang Y
Biomaterials
· 2026 Nov · PMID 42155175
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Mitochondrial dysfunction in nucleus pulposus (NP) cells is a key driver of intervertebral disc degeneration (IDD), leading to metabolic imbalance and cellular senescence. To address this, we developed an injectable "son...Mitochondrial dysfunction in nucleus pulposus (NP) cells is a key driver of intervertebral disc degeneration (IDD), leading to metabolic imbalance and cellular senescence. To address this, we developed an injectable "sono-electrical coupling" hydrogel (GBC@PNA) based on a thermosensitive P(NIPAM-AAM) network loaded with gallic acid, barium titanate and carbon nanotubes. Upon ultrasound exposure, the scaffold generates a localized micro-electric field and controllably releases gallic acid. This combined stimulation significantly enhanced the viability of degenerated NP cells, promoted extracellular matrix synthesis, and reduced inflammation and senescence in vitro. Mechanistically, the sono-electrical effect activated intracellular calcium signaling, leading to CaMKII-dependent mitochondrial translocation and phosphorylation of Parkin, thereby restarting PINK1/Parkin-mediated mitophagy to clear damaged mitochondria and restore energy metabolism. This pathway was systematically validated through transcriptomics, protein interaction and functional inhibition studies. In a rat IDD model, the intervention effectively maintained disc height, improved histology and delayed degeneration, demonstrating good biosafety. This work pioneers a strategy that couples external physical energy with intracellular mitochondrial quality control, offering a novel "sono-electro-chemical" therapy for IDD and a new paradigm for "energy-biology"-based tissue engineering.
Choi W, RuizdelRio J, Embrione V
… +5 more, Agarwal D, Blecke K, Gaffey AC, Wahlin KJ, Eliceiri BP
Biomaterials
· 2026 Nov · PMID 42155174
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Small extracellular vesicles (EVs) deliver nucleic acid and protein therapeutics that promote tissue repair, however, there are few approaches to direct the tropism of EVs to specific tissues. Here, we address this chall...Small extracellular vesicles (EVs) deliver nucleic acid and protein therapeutics that promote tissue repair, however, there are few approaches to direct the tropism of EVs to specific tissues. Here, we address this challenge by engineering EVs to display a peptide library on the surface of EVs that is linked to barcoded guide RNA payloads (gRNAs). We show how these EVs can be administered systemically into mouse models and the cellular uptake of these gRNA-bearing EVs assessed by recovery of the small RNAs followed by PCR amplification and barcode sequencing. Since the design of the peptide library was linked to specific barcodes encoded on the same plasmid, subsequent sequencing of barcode sequences recovered from tissues revealed profiles of EV uptake associated with the display of specific peptide sequences on the surface of EVs. Therefore, candidate peptide motifs were cloned for validation using in vivo and in vitro readouts. In addition to the barcode-based tissue profiling, gRNA-laded EVs mediated functional gene editing in the Cre-loxP R26 LSL-tdTomato reporter mouse model in vivo. These studies demonstrated how EV display linked with barcoded gRNA payloads can address barriers to EV-based delivery of gene editing therapies.
Liu M, Zhou Y, Kang H
… +3 more, Wang J, Xu B, Cui W
Biomaterials
· 2026 Nov · PMID 42155173
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Inflammation-mediated progesterone resistance, driven by the sustained acidification of the inflammatory microenvironment from V-type H-ATPase overexpression in inflammatory cells, critically impedes the treatment of end...Inflammation-mediated progesterone resistance, driven by the sustained acidification of the inflammatory microenvironment from V-type H-ATPase overexpression in inflammatory cells, critically impedes the treatment of endometrial hyperplasia (EH). Herein, a smart short-fiber scaffold (PGCL) was innovatively fabricated by covalently conjugating levonorgestrel (LNG) to poly (lactic acid)/gelatin nanofibers via a two-step click chemistry approach. The fibers recruit inflammatory fluid and respond intelligently to the acidic inflammatory microenvironment through triazole bond cleavage, enabling targeted LNG release for estrogen antagonism and microenvironment regulation. Specifically, within the mildly acidic lesion site, hydrogen ions trigger the rupture of triazole bonds, resulting in the controlled release of LNG to precisely treat EH. Meanwhile, the highly absorbent and self-expanding properties of PGCL enable adaptation to the complex uterine architecture, while its porous structure (>85% porosity) facilitates inflammatory exudate recruitment. Transcriptomic analysis revealed that PGCL alleviates progesterone resistance by inhibiting the PI3K/AKT/NF-κB pathway, which modulates macrophage polarization and reduces V-type H-ATPase expression, thereby suppressing proliferation through DNA synthesis blockade and downregulating VEGF and pro-inflammatory factors. In EH model rats, PGCL treatment reduced endometrial thickness by 32.45%, gland density by 41.24%, and inflammatory factor expression by 38.22-55.58% in EH model rats. Short fibers that recruit inflammatory exudate enable a novel strategy for endometrial repair through smart-responsive estrogen antagonism.
Yu Z, Li Y, Zhang S
… +9 more, Cao R, Liu K, Deng J, Yang Z, Wang H, Wang Q, Miao L, Hu B, Pan Y
Biomaterials
· 2026 Nov · PMID 42150243
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Periodontitis leads to alveolar bone resorption, driven by persistent periodontal pathogen infection. Such persistent infection creates a unique microenvironment conducive to sustained reactive oxygen species (ROS) produ...Periodontitis leads to alveolar bone resorption, driven by persistent periodontal pathogen infection. Such persistent infection creates a unique microenvironment conducive to sustained reactive oxygen species (ROS) production. Therefore, further investigation into approaches that simultaneously combat bacteria and improve the local microenvironment is needed. In the present study, a hydrogel drug delivery system was proposed, which employed an in-situ synthesis strategy of zeolitic imidazole frameworks 90 (ZIF90) encapsulating tungsten (W)-based polyoxometalate nanoparticles (ZIF90-W) to increase the W ratio and confer ATP responsiveness. ZIF90-W was incorporated into phenylboronic acid-modified quaternary ammonium salt chitosan hydrogel (QPT hydrogel), forming QPT@ZIF90-W hydrogel with responsive release properties in the periodontal pocket. Results demonstrated that QPT@ZIF90-W hydrogel exhibited over 90% antibacterial efficacy against periodontal pathogens. Besides, QPT@ZIF90-W significantly promoted osteogenic differentiation of MC3T3-E1 cells after scavenging mitochondrial ROS and total ROS. Mechanistically, the pro-osteogenic effect of QPT@ZIF90-W hydrogel was associated with the significant upregulation of Plagl1, following oxidative stress elimination and subsequent activating the Wnt signaling pathway, according to the transcriptome sequencing results. Concurrently, in vivo experiments demonstrated that QPT@ZIF90-W hydrogel treatment, compared with other groups, reduced inflammatory cell infiltration, upregulated Plagl1 and osteogenesis related proteins, and partially ameliorated alveolar bone resorption. In summary, QPT@ZIF90-W is characterized by synergistic antibacterial effect and ROS scavenging capability. These dual activities reshape the oxidative microenvironment and then activate Plagl1/Wnt pathway to promote osteogenesis, which offer a novel and potential strategy for the precise treatment of periodontitis-induced bone defects.
Biomaterials
· 2026 Nov · PMID 42150242
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The development of physiologically relevant three-dimensional (3D) cell culture platforms is essential for advancing tissue engineering, disease modeling, and drug screening. However, conventional spheroid fabrication me...The development of physiologically relevant three-dimensional (3D) cell culture platforms is essential for advancing tissue engineering, disease modeling, and drug screening. However, conventional spheroid fabrication methods face persistent challenges in reproducibility, architectural control, and biocompatibility. Here, we present a modular spheroid assembly strategy based on magnetic RNA building blocks (RBBs) and azide-presenting cell building blocks (CBBs), enabling programmable and bioorthogonal construction of 3D multicellular architectures. RBBs were synthesized via rolling circle transcription in the presence of Mn, forming magnetically responsive RNA-based nanostructures. Incorporation of DBCO-modified nucleotides enabled strain-promoted azide-alkyne cycloaddition (SPAAC) with CBBs, yielding highly selective and rapid spheroid formation. The resulting spheroids exhibited uniform 3D organization, high viability, and robust biocompatibility across multiple cell types. Furthermore, modular assembly via secondary click chemistry allowed for heterotypic spheroid integration and magnetic spatial control, mimicking complex tissue microenvironments. Importantly, the magnetic scaffolds were fully degradable under physiological reductive conditions, permitting residue-free removal post-assembly. This versatile, tunable, and biodegradable RNA-based platform offers a powerful solution for constructing magnetically controllable, heterocellular spheroids, advancing next-generation 3D culture systems.
Zhang H, Zhou CH, Shi P
… +7 more, Wang T, Xue K, Yang J, Xie X, Chu LY, Ju XJ, Wang J
Biomaterials
· 2026 Nov · PMID 42150241
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Periodontitis is characterized by a self-sustaining pathophysiological cycle in which bacterial infection propagates destructive inflammation and oxidative stress, compromises tissue repair capacities, and facilitates re...Periodontitis is characterized by a self-sustaining pathophysiological cycle in which bacterial infection propagates destructive inflammation and oxidative stress, compromises tissue repair capacities, and facilitates recurrent infection. Current monotherapeutic strategies exhibit limited efficacy against this multifactorial pathology. Although resveratrol (RSV) exhibits significant anti-inflammatory and antioxidant activities, its clinical application is limited by poor solubility and suboptimal bioavailability. Herein, we fabricate a kind of injectable composite microspheres (RSV@Lipo@PMS) that encapsulate RSV-loaded cationic liposomes into polydopamine-modified alginate microspheres. This design leverages the synergistic interplay among the therapeutic bioactivity of RSV, the inherent antibacterial function of cationic liposomes, and the sustained retention afforded by the adhesive microcarriers. The composite system demonstrates robust reactive oxygen species (ROS) scavenging capacity, effectively suppresses lipopolysaccharide-induced inflammation in macrophages, and potently enhances bactericidal efficacy against key periodontal pathogens in vitro. In an experimental rat model of periodontitis, local administration significantly inhibits alveolar bone resorption and promotes functional tissue regeneration. Furthermore, to elucidate the underlying mechanisms of the composite system in alleviating periodontitis, we apply integrated transcriptomic and metabolomic profiling, which indicates a coordinated restoration of lipid metabolic homeostasis and mitochondrial energy metabolism. This multi-targeted strategy not only presents a promising therapeutic platform but also provides a mechanistic framework for the management of complex inflammatory conditions.
Yao S, Lv Y, Pang M
… +14 more, Lai X, Xie Z, Lin Y, Di J, Yu Y, Kang J, Huang X, Du C, Qiu Y, Guan Y, Wang J, Liu B, Peng Xiang A, Rong L
Biomaterials
· 2026 Nov · PMID 42150240
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Mesenchymal stromal cells (MSCs) hold great promise for spinal cord injury (SCI) repair owing to their potent immunomodulatory and neuroprotective properties, yet their therapeutic efficacy collapses in the chronic phase...Mesenchymal stromal cells (MSCs) hold great promise for spinal cord injury (SCI) repair owing to their potent immunomodulatory and neuroprotective properties, yet their therapeutic efficacy collapses in the chronic phase. We identify a critical, overlooked barrier: the pathological stiffening of the fibrotic scar microenvironment hijacks the mechanotransduction machinery of transplanted MSCs, driving them toward a maladaptive fibroblast-like phenotype that compromises their immunomodulatory and regenerative functions, ultimately blunting their overall therapeutic potential. Here, we reveal that stiff substrates enforce MSCs into a pro-fibrotic state via a YAP/Smad-dependent mechanism. To overcome this, we developed a "soft-priming" strategy that effectively erases this fibrotic mechanical memory of MSCs. Mechanistically, soft priming does not merely prevent YAP nuclear translocation but promotes its cytoplasmic retention and subsequent lysosomal degradation, effectively dismantling the pro-fibrotic YAP signaling axis and rendering MSCs refractory to future stiffness challenges in vivo. Transplantation of these mechanically-reset MSCs into a SCI mouse model resulted in reduced scar formation, sustained immunomodulation and robust functional recovery by the early chronic stage, compared to standard-culture MSCs. By identifying soft mechanical priming as a scalable, chemical-free manufacturing step to insulate cells against hostile host environments, our findings provide a pragmatic translational pathway to revitalize MSC therapies for fibrosis-associated central nervous system (CNS) disorders.
Li Y, Ye Y, Zhang Y
… +7 more, Guo J, Tian W, Yin R, Yan J, Gao Q, Dai J, Zhu L
Biomaterials
· 2026 Nov · PMID 42150239
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The regeneration of functional cervical tissue for congenital or acquired defects remains an unmet clinical challenge. While decellularized extracellular matrix scaffolds offer structural support, their regenerative capa...The regeneration of functional cervical tissue for congenital or acquired defects remains an unmet clinical challenge. While decellularized extracellular matrix scaffolds offer structural support, their regenerative capacity is inherently limited for critical-sized, full-thickness cervical defects. Here, we developed a composite graft by seeding human umbilical cord-derived mesenchymal stem cells (UC-MSCs) onto a biomimetic, bilayer collagen scaffold (CS). In a rabbit model of complete ectocervical excision, both the CS and UC-MSCs/CS construct promoted organized, full-thickness regeneration of epithelium, vascularized stroma, and smooth muscle layers. The regenerated cervix exhibited physiological hormone receptor expression and mucus production. Notably, compared with the scaffold alone, the composite yielded a smaller cervical diameter and denser morphology, and improved biomechanical strength over six months. These results demonstrate that UC-MSCs synergize with a decellularized collagen scaffold to support structural cervical regeneration, offering a clinically translatable, "off-the-shelf" strategy for reconstructing severe cervical defects.
Li M, Li XL, Fu T
… +4 more, Xiong K, Zhou Z, Tian W, Huang B
Biomaterials
· 2026 Nov · PMID 42143992
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Diabetic wounds are characterized by a persistent pathological imbalance between infection and regeneration, in which bacterial colonization and impaired tissue repair synergistically hinder the healing process. However,...Diabetic wounds are characterized by a persistent pathological imbalance between infection and regeneration, in which bacterial colonization and impaired tissue repair synergistically hinder the healing process. However, most existing wound dressings focus on a single therapeutic function, limiting their capacity to orchestrate both antimicrobial defense and tissue regeneration within the multifactorial wound microenvironment. Inspired by the spatially hierarchical architecture of natural honeycombs, we developed a biomimetic bidirectional membrane (PYS) fabricated via a breath figure patterning technique and biomass-derived polyester materials to achieve integrated structural and functional stratification. The dense and smooth outer layer serves as an effective physical antimicrobial barrier, while the inner layer features a downward-opening honeycomb structure that enables high-efficiency loading and sustained release of epidermal growth factor (EGF), providing a favorable three-dimensional microenvironment for cell migration and angiogenesis. In a diabetic mouse wound model, PYS-EGF significantly suppressed bacterial adhesion, promoted neovascularization, and accelerated wound closure. This study demonstrates that synergistic integration of structural biomimicry and functional stratification can achieve coordinated antimicrobial and regenerative effects in diabetic wounds, offering a promising strategy for the design of next-generation wound healing materials.
Yang H, Zhao T, Zhao P
… +3 more, Cao C, Fang F, Liu X
Biomaterials
· 2026 Nov · PMID 42143991
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Extracellular vesicles (EVs) are nanoscale membrane structures secreted by cells and play a key mediating role in intercellular communication. Their biosynthesis and function are profoundly modulated by mechanical signal...Extracellular vesicles (EVs) are nanoscale membrane structures secreted by cells and play a key mediating role in intercellular communication. Their biosynthesis and function are profoundly modulated by mechanical signals from the cellular microenvironment. Mechanical forces, including shear stress, tensile strain, and matrix stiffness, exert fundamental effects on cellular behavior and disease progression by regulating the biogenesis, composition, and function of EVs. This review summarizes current knowledge on how biomechanical cues regulate EV-mediated intercellular communication in diseases such as atherosclerosis, osteoarthritis, and cancer. Specifically, we explore the mechanisms by which abnormal mechanical forces alter the cargo of EVs, such as miRNAs, proteins, and lipids, thereby driving disease progression through pathways like plaque instability, metastatic niche formation, and bone metabolism imbalance. Additionally, this review evaluates the therapeutic potential of mechanically regulated EVs, with a focus on their roles as diagnostic biomarkers and targeted drug delivery vehicles. By integrating cutting-edge perspectives from mechanobiology and EV research, this review lays a theoretical foundation for developing novel precision medicine strategies targeting biomechanically driven diseases.
Ferraresso M, Ali-Mohamad N, Cau MF
… +12 more, Seadler M, Turner H, Ferraresso F, Zhang Y, Carver TW, Nagaswami C, Beckett A, Peng HT, Litvinov RI, Weisel JW, Bacca M, Kastrup CJ
Biomaterials
· 2026 Nov · PMID 42143432
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Hemorrhage is a leading cause of mortality in humans, responsible for approximately two million deaths annually worldwide. The contraction of blood clots is a robust process that occurs intravascularly to reduce the size...Hemorrhage is a leading cause of mortality in humans, responsible for approximately two million deaths annually worldwide. The contraction of blood clots is a robust process that occurs intravascularly to reduce the size of pathological thrombi. However, it is not clear if clot contraction contributes to hemostasis. Here we show that blood clots in laceration wounds contract, and the forces can decrease the size of wounds by up to 80%. Clots contracted after penetrating injuries in swine, as revealed by scanning electron microscopy. Contraction was robust throughout hemorrhagic shock in two swine models, with ex vivo clots becoming 20-40% of their initial volume (60-80% contraction) at sustained rates of ∼1.5% of clot volume min. In two models of laceration, one using a synthetic gel and the other using ex vivo lacerated livers, contraction decreased the size of wounds in a platelet-dependent response, generating forces up to approximately 0.5 N. A ten-fold increase in platelet count increased the closure by ∼22%. A mechanics-based computational model representing the clot as a tunable biomaterial composed of fibrin fibers and platelet motors replicated and confirmed this phenomenon. Thus, platelet-driven clot contraction is an important component of the hemostatic response to severe injury, and contraction is a tunable process that may be useful for improving biomaterials for hemostasis.
Xu W, Li X, Hu W
… +7 more, Zhou J, Liu X, Yu J, Zhang F, Nie W, Lu G, Zhao Y
Biomaterials
· 2026 Nov · PMID 42143431
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Owing to the reticular structure and dense lymphocyte concentration within the spleen, spleen-targeted vaccines can overcome the challenges faced by conventional vaccines, such as inefficient antigen delivery and delayed...Owing to the reticular structure and dense lymphocyte concentration within the spleen, spleen-targeted vaccines can overcome the challenges faced by conventional vaccines, such as inefficient antigen delivery and delayed immune activation. However, the existing spleen-targeted vaccines are ineffective in preventing and treating immunologically cold tumors. Herein, we develop a spleen/tumor dual-target hybrid vaccine that combines red blood cell membrane-derived vesicles (RBCVs) and bacterial outer membrane vesicles (OMVs) to deliver tumor antigens. This hybrid vaccine utilizes RBCVs to enhance the biosafety of OMVs and endows them with a spleen-targeting ability. Co-delivery of OMVs as adjuvants with tumor antigens to the spleen triggers rapid and robust immune responses, promoting immune memory formation to prevent the development and metastasis of immunologically cold tumors. In addition to acting as vaccine adjuvants, OMVs can target and remodel the immunosuppressive tumor microenvironment by reprogramming tumor-associated macrophages and downregulating regulatory T cells, thereby enhancing the immune responses induced by vaccines and immune checkpoint inhibitors. Because of their antigen-loading flexibility, these versatile vesicles can be used for the spleen-targeted delivery of various protein- or nucleic acid-based antigens, offering a safe and promising strategy for the prevention and treatment of diverse tumors and pathogens.
An Y, Zhang H, Zhang Y
… +10 more, Zhang S, Zheng L, Shao H, Du W, Cheng L, Sun W, Ma J, Ruan Y, Xu J, Qin L
Biomaterials
· 2026 Nov · PMID 42143430
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Long-term bisphosphonates (BPs) are widely used to treat osteoporosis, however, they are paradoxically associated with the development of atypical femoral fractures (AFFs), which often characterized by impaired healing....Long-term bisphosphonates (BPs) are widely used to treat osteoporosis, however, they are paradoxically associated with the development of atypical femoral fractures (AFFs), which often characterized by impaired healing. In this study, we induced an AFF model using zoledronate (ZOL) administration in ovariectomized (OVX) osteoporotic rats, following a unilateral femoral fracture. Here we identified that a local pro-senescent microenvironment causes persistent inflammation and impairs effective regeneration in rat AFFs. Molecular hydrogen has demonstrated anti-senescence and anti-inflammatory properties, yet its effects on AFF healing remain unexplored. Therefore, we treated the AFF rats with hydrogen rich water (HRW). The outcomes were assessed by radiographs, histology, micro-CT, and biomechanical tests. The fracture microenvironment was analyzed based on the indicators of senescence, fibrosis, macrophage polarization, cytokine expression, and angiogenesis. We found that HRW significantly promoted callus bridging and resolved the non-union gap in ZOL-induced AFFs, whereas the ZOL group exhibited persistent fibrous tissue. Micro-CT and biomechanical tests confirmed that HRW did not compromise the mechanical strength of the bone mass elevated by BPs. Instead, HRW specifically attenuated the local senescent microenvironment, with a reduction in both SA-β-gal activity and the expression of p16, p21 within the fracture gap. This was accompanied by clearance of pathological fibroblasts, a shift from pro-inflammatory M1 to anti-inflammatory M2 macrophages, a rebalanced cytokine profile, and restored formation of osteogenesis-coupled type-H vessels. Our findings confirm that molecular hydrogen facilitates AFFs healing by locally reversing the senescent microenvironment, rather than boosting systemic bone formation. This creates a favorable niche for callus bridging, representing a novel therapeutic strategy for fracture delayed union or non-union.
Qiao Z, Shang X, Lv Q
… +10 more, Liu Y, Zheng X, Chen W, Wang R, Wu Y, Li Y, Si C, Chang J, Luo X, Yang C
Biomaterials
· 2026 Nov · PMID 42143429
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Myocardial patches, particularly collagen-based systems, have emerged as promising therapeutic platforms for repairing injured cardiac tissue after myocardial infarction (MI). However, their clinical translation remains...Myocardial patches, particularly collagen-based systems, have emerged as promising therapeutic platforms for repairing injured cardiac tissue after myocardial infarction (MI). However, their clinical translation remains constrained by insufficient wet-tissue adhesion, mechanical mismatch with the native myocardium, and limited regenerative bioactivity. Inspired by the interpenetrating rigid-flexible architecture of deep-sea glass sponge spicules, we developed a biomimetic hydrogel cardiac patch (PCH@D) designed to address these challenges in an integrated manner. The patch is constructed as a multi-component interpenetrating network, in which diatom-derived biosilica serves as a rigid skeletal framework and silicate ion reservoir, while a dual-network matrix of acrylated collagen and poly(acrylic acid), reinforced by catechol-functionalized hyperbranched polymers, forms a flexible organic phase that mediates wet-tissue adhesion through cooperative hydrophobic-catechol interactions by actively displacing interfacial water and forming stable covalent bonds with tissues. As a result, the PCH@D patch achieves rapid and robust adhesion to wet myocardium (40.59 ± 3.30 kPa), exhibits mechanical properties well matched to native myocardium, and offers sustained silicate ion release over 28 days. In a murine MI model, implantation of the PCH@D patch reduced cardiomyocyte apoptosis, promoted M2 macrophage polarization, enhanced angiogenesis, and effectively mitigated adverse ventricular remodeling, leading to improved cardiac function. This work highlights a bioinspired materials design strategy for cardiac patches that integrates mechanical compatibility with active biological regulation.
Zhang Y, Huang W, Zhu K
… +3 more, Si Q, Wang T, Qin Y
Biomaterials
· 2026 Nov · PMID 42143428
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Ferroptosis, a regulated cell death (RCD) process driven by iron-dependent lipid peroxidation, has emerged as a pivotal focus in recent therapeutic research for lung diseases. This comprehensive review synthesizes the la...Ferroptosis, a regulated cell death (RCD) process driven by iron-dependent lipid peroxidation, has emerged as a pivotal focus in recent therapeutic research for lung diseases. This comprehensive review synthesizes the latest breakthroughs in ferroptosis-based therapy development, highlighting the transformative potential of nanomedicine in the precise regulation of this cell death pathway-with particular emphasis on the critical role of immune remodeling in achieving optimal therapeutic outcomes. The ferroptosis execution cascade is first delineated, alongside its mechanistic differences from disulfidptosis: a novel RCD modality that shares key regulatory nodes with ferroptosis, yet possesses distinct execution mechanisms centered on sulfur metabolism and unique translational value in lung cancer. Central to this discussion is the lung-specific ferroptosis paradox: while targeted ferroptosis induction effectively eradicates therapy-resistant lung tumors, uncontrolled activation in alveolar epithelial cells (AECs) may initiate and exacerbate interstitial lung disease (ILD). Lung cancer-specific ferroptosis vulnerabilities are further characterized, including differential sensitivity between major non-small cell lung cancer (NSCLC) subtypes and unique therapeutic windows in high-frequency mutant subtypes (e.g., KEAP1-mutant lung adenocarcinoma). Promising therapeutic strategies focus on nanomedicine-driven approaches, including tumor-targeted nanocarriers, stimuli-responsive systems, and biomimetic vesicles, that enable spatiotemporally precise control of ferroptosis, thereby maximizing antitumor efficacy while mitigating the risks of immune dysregulation and off-target pulmonary toxicity. The mechanisms by which nanomedicines overcome the core clinical bottlenecks of ferroptosis therapy are elaborated, alongside a systematic comparison of intravenous, intratumoral, and inhalation administration routes tailored for lung disease interventions. The bidirectional crosstalk between ferroptosis and antitumor immunity within the lung tumor microenvironment (TME) is systematically dissected, with detailed characterization of how nanomedicine-mediated ferroptosis modulation optimizes this crosstalk to drive therapeutic pulmonary immune remodeling. Finally, key future directions for the advancement of precision ferroptosis medicine are outlined, including spatiotemporally controlled ferroptosis activation, biomarker-driven patient stratification panels, and rational strategies to balance therapeutic efficacy and pulmonary safety throughout clinical translation.