Biomaterials[JOURNAL]
Sun
200 papers
Covalently photosensitized probiotic bacteria for light-triggered tumor clearance and self-limiting immunotherapy.
Yin Y, Cheng X, Fang Y … +8 more , Zhou X, Guo H, Zhong S, Wegner SV, Sun W, Hou C, Chen F, Zeng W
Biomaterials · 2026 Nov · PMID 42105730 · Publisher ↗
Live bacterial therapy holds great promise in tumor treatment due to its inherent ability to target tumors and activate the immune system. However, its clinical translation faces significant challenges, including limited...
Live bacterial therapy holds great promise in tumor treatment due to its inherent ability to target tumors and activate the immune system. However, its clinical translation faces significant challenges, including limited antitumor efficacy and safety risks posed by bacterial residue. To address these challenges, we developed a self-limiting, light-activatable biohybrid system named OTTQ-Cl@HEcN. It consists of the probiotic Escherichia coli Nissle 1917 (EcN) covalently conjugated with a hypoxia-tolerant Type I photosensitizer (PS) OTTQ-Cl via a genetically engineered HaloTag conjugation strategy. Upon light irradiation, OTTQ-Cl@HEcN generates localized reactive oxygen species (ROS), simultaneously killing tumor cells and bacteria. This built-in bacterial self-elimination ensures effective tumor clearance and minimizes systemic exposure. In multiple tumor models, OTTQ-Cl@HEcN elicited potent local and systemic antitumor immunity, characterized by robust dendritic cells (DCs) maturation, enhanced T cells activation, and the establishment of long-term immune memory that prevented tumor recurrence and metastasis. The key features of OTTQ-Cl@HEcN include its precise tumor targeting, hypoxia compatibility, potent immune activation, and intrinsic biosafety, collectively enabling a controlled and effective antitumor response.
Decellularized matrix scaffold integrating hyaluronic acid-celecoxib modulates inflammation and promotes regenerative meniscus remodeling.
Ding Y, Zhang H, Cai P … +9 more , Yu X, Cui J, Song J, Lu C, Sun B, Mo X, Lin H, Lin J, Wu J
Biomaterials · 2026 Nov · PMID 42105729 · Publisher ↗
Meniscus injuries present dual challenges, including limited regenerative capacity due to avascularity and a persistent inflammatory microenvironment following injury. Herein, we reported a decellularized meniscus extrac...
Meniscus injuries present dual challenges, including limited regenerative capacity due to avascularity and a persistent inflammatory microenvironment following injury. Herein, we reported a decellularized meniscus extracellular matrix (dmECM) scaffold functionalized with a hyaluronic acid (HA) and celecoxib (CLX) grafted (dmECM-HC) through carbodiimide chemistry. This design integrates acute immunomodulation with long-term regenerative support. The dmECM scaffold recapitulated the ECM architecture of the native meniscus, while the HA-CLX enhanced its elasticity and immunomodulatory capacity. The dmECM-HC scaffold exhibited superior mechanical performance retention during 1000 cyclic compression cycles and demonstrated sustained release of CLX for up to 7 weeks in vitro. It promoted M2 polarization of lipopolysaccharide (LPS)-stimulated macrophages and effectively modulated acute inflammation through Toll-like receptor, tumor necrosis factor (TNF), and Nuclear factor kappa-B (NF-κB) signaling pathways. Together with its robust antioxidant capacity, the dmECM-HC scaffold provided a pro-regenerative microenvironment. Furthermore, it significantly facilitated stem cell recruitment and ECM deposition. In a rabbit meniscus defect model, the dmECM-HC scaffold promoted tissue repair by activating NF-κB and calcium signaling pathways. At 12 weeks, it significantly enhanced tissue maturation and collagen arrangement in the defect area and mitigated cartilage degeneration. This strategy guides meniscus healing with a dual function by modulating the inflammatory environment while providing biomimetic structural support.
An electrostatic co-assembled extracellular vesicles infused hydrogel for bone regeneration in aged defects.
Zhang X, Liu X, Wang Y … +7 more , Zhu C, Liu D, Zheng Y, Zhang Y, Yang H, Xu Y, Shi Q
Biomaterials · 2026 Nov · PMID 42105728 · Publisher ↗
Age-related bone defects remain challenging due to the reduced osteogenic capacity of aged bone marrow mesenchymal stem cells (A-BMSCs). An injectable hydrogel incorporating extracellular vesicles (EVs) from young BMSCs...
Age-related bone defects remain challenging due to the reduced osteogenic capacity of aged bone marrow mesenchymal stem cells (A-BMSCs). An injectable hydrogel incorporating extracellular vesicles (EVs) from young BMSCs (Y-EVs) was designed to enhance bone regeneration. The hydrogel, composed of star-PEG-KA7 and polyphosphate-gelatin (P-GA, generated by conjugating imidazole-modified polyphosphate (PolyP-Im) with gelatin (GA), encapsulates Y-EVs to form the P-GA/KA7@Y-EVs system. In vitro, Y-EVs promoted osteogenic differentiation and alleviated senescence in A-BMSCs, while the hydrogel provided injectability, biocompatibility, and sustained release. In vivo, P-GA/KA7@Y-EVs significantly improved cranial bone regeneration in aged rats, surpassing Y-EVs or hydrogel alone. Transcriptomic and microRNA analyses indicated that Y-EVs rejuvenated A-BMSCs by modulating PI3K-Akt, TGF-β, and MAPK pathways, supported by gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment. This EVs-infused bioactive hydrogel offers a minimally invasive and effective strategy for age-related bone regeneration.
Immune-instructive biomaterials in oral tissue regeneration and therapy.
Park S, Linsley CS, Zarubova J … +2 more , Wu BM, Li S
Biomaterials · 2026 Nov · PMID 42097026 · Publisher ↗
Oral diseases, including periodontitis, peri-implantitis, pulpitis, mucosal lesions, and oral squamous cell carcinoma, affect billions of people, which are increasingly recognized as immune-driven conditions with systemi...
Oral diseases, including periodontitis, peri-implantitis, pulpitis, mucosal lesions, and oral squamous cell carcinoma, affect billions of people, which are increasingly recognized as immune-driven conditions with systemic implications. Unlike other tissues, the oral cavity presents a uniquely complex immune landscape shaped by continuous microbial exposure, stratified epithelial barriers, and inductive lymphoid structures. Traditional treatments focus on mechanical repair, antimicrobial control, and tissue regeneration, but often fail to address the underlying immune dysregulation directly. This review highlights biomaterial strategies that modulate oral immunity to drive resolution of the disease, restore homeostasis, and promote regeneration. We first discuss the oral mucosal immune environment and its role in disease pathogenesis, particularly the contributions of macrophages, T cells, and tissue-resident populations. Next, we highlight five immunomodulatory approaches: (1) delivery platforms such as mucoadhesive coatings, hydrogels, particles, and microneedles for the local delivery of bioactive payloads; (2) the physicochemical properties of biomaterials such as micro/nanotopography, wettability, surface charge, and immunoactive ion release that directly program innate and adaptive responses; (3) multi-functional platforms that integrate biomaterial structural functions and delivery capability; (4) cell-based immunomodulation; and (5) delivery of cell secretome such as extracellular vesicles. Applications span periodontitis and peri-implantitis, temporomandibular joint (TMJ) inflammation, and oral squamous cell carcinoma. Finally, we discuss how mechanistic investigations, innovative technologies, emerging diagnostic and therapeutic approaches, and the integration with artificial intelligence (AI) may transform the future directions in the field. Together, immunomodulatory biomaterials enable innovative approaches in oral medicine and patient-specific therapies.
A molecularly defined polymeric platform for environmentally responsive activation of STING to enhance cancer immunotherapy.
Schulman JA, Arora K, Kwiatkowski AJ … +8 more , Chada NC, Steele JA, Pagendarm HM, Woodworth ME, Sheehy TL, Gibson-Corley K, Balko JM, Wilson JT
Biomaterials · 2026 Nov · PMID 42097025 · Publisher ↗
The stimulator of interferon genes (STING) pathway is a promising immuno-oncology target. Despite their potential, STING agonists have yielded underwhelming results in clinical trials due to pharmacological barriers that...
The stimulator of interferon genes (STING) pathway is a promising immuno-oncology target. Despite their potential, STING agonists have yielded underwhelming results in clinical trials due to pharmacological barriers that limit their safety and efficacy. Herein, we describe the design and pre-clinical evaluation of a polymeric dimeric amidobenzimidazole (diABZI) STING agonist delivery platform for cancer immunotherapy. Central to our technology is a stimuli-responsive diABZI-functionalized reversible addition-fragmentation chain transfer (RAFT) polymerization chain transfer agent (CTA) that allows well-defined polymer chains to be grown directly from a single STING agonist. Using a biocompatible poly(N,N'-dimethylacrylamide) polymer as a first-generation scaffold and a disulfide as a clinically relevant linker, we demonstrate our platform liberates a potent diABZI analog under reducing conditions to trigger STING-driven inflammatory gene expression in tumors, thereby stimulating antitumor immunity in multiple murine models and synergizing with α-PD-1 immune checkpoint blockade to eliminate tumors. This work therefore establishes a promising delivery platform for microenvironmental regulation of STING activation with promise as an immunotherapy for cancer.
Chronic alteration of Ca and hemodynamic signals induced by intracortical microstimulation in the visual cortex of awake mice.
Suematsu N, Vazquez AL, Kozai TD
Biomaterials · 2026 Nov · PMID 42097024 · Publisher ↗
Understanding the chronic effects of intracortical microstimulation (ICMS) and device implantation on cortical function is essential for the development of stable neuroprosthetics. We chronically implanted penetrating mi...
Understanding the chronic effects of intracortical microstimulation (ICMS) and device implantation on cortical function is essential for the development of stable neuroprosthetics. We chronically implanted penetrating microelectrodes into Thy1-GCaMP6s mice and conducted longitudinal mesoscopic widefield and two-photon Ca imaging alongside intrinsic optical signal recordings over 12 weeks. Six ICMS frequencies (10-500 Hz) and contralateral visual LED stimuli were delivered in repeated sessions. Oxygen extraction fraction (OEF) was estimated from dual-wavelength reflectance, and hemodynamic response functions (HRFs) were derived via regularized deconvolution. Over the chronic period, 25-Hz ICMS evoked progressively larger Ca responses with extending duration, while spatial spread remained stable after the first few days. Low-frequency ICMS preserved stable Ca depression, whereas high-frequency ICMS and visual stimulation showed partial declines in depression magnitude and spatial extent. Two-photon imaging revealed that somatic and neuropil compartments followed distinct activation and depression trajectories, with somatic ICMS responses declining then recovering while neuropil activation tracked mesoscale trends. Concurrently, OEF reductions deepened, reflecting increased relative blood supply, and the spatial extent of OEF signals contracted in the first week before expanding by day 21. Epileptiform Ca events emerged in nearly half of mice, predominantly under 25-Hz ICMS. HRF peak amplitude increased between day 0 and days 7-21, with latency decreasing. Spontaneous neural and hemodynamic activity near the probe was suppressed acutely but recovered over weeks. Chronic ICMS induces progressive potentiation of neuronal and vascular responses alongside local neurovascular uncoupling on day 0 and sustained silencing of spontaneous activity near the implant. These dynamics stabilized 6-7 weeks after implantation. The frequency-dependent epileptiform susceptibility, coupled with persistent focal neurovascular deficits, underscores the need for adaptive stimulation strategies during the pre-stabilization period and electrode designs that mitigate local suppression to ensure long-term stability of cortical neuroprostheses.
Replenishing interfacial lubrication: A cartilage-inspired polyzwitterionic dressing for spatiotemporal healing of friction-prone diabetic wound.
Yu P, Li Y, Liu Y … +5 more , Ma Z, Jiang Y, Lu B, Sun Q, Wang D
Biomaterials · 2026 Nov · PMID 42097023 · Publisher ↗
Frequent frictions and overexpressed reactive oxygen-nitrogen species are two prominent barriers to friction-prone diabetic wound healing. Current commercial dressings fail to adaptively replenish the interfacial lubrica...
Frequent frictions and overexpressed reactive oxygen-nitrogen species are two prominent barriers to friction-prone diabetic wound healing. Current commercial dressings fail to adaptively replenish the interfacial lubrication and restore immune homeostasis. By mimicking the lubrication and antioxidation properties of cartilage, we develop an engineered polyzwitterionic dressing by upcycling kitchen waste (eggshell membrane, ESM). With the sequential chemical modification of ergothioneine (EGT) and active-ester-contained zwitterionic copolymer, the resulting EP-ESM dressing replenishes interfacial lubrication (μ = 0.0204) by thickening the hydrated fluid film and thinning the tissue fluid. We quantify the mathematical correlation between time-controlled lubrication and responsive EGT release, confirming the improved efficiency of lubrication replenishment and the inherent lubricity of EP-ESM dressing. In addition, it demonstrates enhanced anti-oxidation performance by synergistic proton-transfer and electron-transfer mechanisms, thereby preserving mitochondrial energy metabolism. EP-ESM also exhibit an immunoregulatory property (2.77-fold increment in CD206 and 68.04% reduction in CD86), as analyzed using RNA-sequencing and qPCR. Consequently, in the full-thickness wound at the dorsal neck of diabetic rats, EP-ESM dressing shows a superior spatiotemporal healing performance compared with pristine ESM and commercial Tegaderm dressings, as evidenced by the increased wound closure rate, more collagen deposition and mature, and rapid angiogenesis. This study offers a promising regenerative strategy that integrates immunoregulation with dynamic lubrication replenishment for chronic wound repair and other tribological diseases.
Hide-and-seek molecular navigator targets tumor cell surface thiols by programmable disulfide exchange.
Chen P, Hu G, Yang W … +9 more , Nakashima Y, Xu Z, Yang Y, Kondo S, Chen X, Takasugi S, Kovács E, Fujiu K, Cabral H
Biomaterials · 2026 Nov · PMID 42090835 · Publisher ↗
Metabolism dysregulation induces distinct thiol profiles between cancer and healthy cells, offering an attractive therapeutic target. However, systemically targeting cancer-specific thiols remains challenging due to the...
Metabolism dysregulation induces distinct thiol profiles between cancer and healthy cells, offering an attractive therapeutic target. However, systemically targeting cancer-specific thiols remains challenging due to the widespread presence of these groups in the physiological environment. Here, we design a molecular navigator (MONA) with spatiotemporally programmable thiol-reactivity to target the thiols on cancer cells upon intravenous injection. MONA operates through a bioresponsive "Hide-and-Seek" mechanism based on tunable disulfide exchange across biological compartments. In the "Hide" phase, MONA circulates stealthily through rapid conjugation with endogenous albumin via disulfide bonding. In the "Seek" phase, albumin facilitates MONA transcytosis into tumors, where elevated glutathione levels trigger disulfide exchange, releasing MONA to multivalently engage with thiols on cancer cells. When conjugated with a photosensitizer, MONA induces cancer cell membrane disruption upon light irradiation, enabling potent phototherapy. This approach leads to complete tumor regression and systemic abscopal effects in an immunosuppressive murine breast cancer model. These findings highlight MONA as a powerful strategy for precise thiol-targeted cancer therapy.
Dynamic protein-polysaccharide hydrogels with spatiotemporal controlled delivery for brain microenvironment remodeling and neural regeneration of intracerebral hemorrhage stroke.
Wan L, Xu J, Wang X … +9 more , Wei Y, He Z, Xie Y, Cao J, Zhong R, Li J, You C, Tan H, Tian M
Biomaterials · 2026 Nov · PMID 42090834 · Publisher ↗
The treatment of intracerebral hemorrhage (ICH) remains highly challenging, primarily due to its dynamic and multifaceted pathologies, which create a hostile microenvironment at the lesion site characterized by a ROS-inf...
The treatment of intracerebral hemorrhage (ICH) remains highly challenging, primarily due to its dynamic and multifaceted pathologies, which create a hostile microenvironment at the lesion site characterized by a ROS-inflammation-glial scar feedback loop and severely impaired neural regeneration. Herein, a dynamic protein-polysaccharide hydrogel is designed, constructed by a visible light-induced thiol-disulfide exchange reaction as a general strategy, and integrated with a spatiotemporal controlled delivery of chondroitinase ABC (ChABC) and insulin-like growth factor-1 (IGF-1) loaded in mesoporous silica nanoparticles (MSNs). Thiolated gelatin and thiolated hyaluronan were chosen to formulate the hydrogel that mimics brain ECM providing structure support with cell adhesion, infiltration, and tunable degradability, but also presents anti-swelling and pro-coagulant capacities. Importantly, the thiol-disulfide chemistry endowed the hydrogel efficient ROS scavenging and ROS-responsive on-demand release of ChABC, while MSNs loading achieved a sustained release of IGF-1. In vitro studies, the hydrogel is shown to reduce cellular ROS, regulate anti-inflammation polarization of macrophages via the MAPK signaling pathway, and promote neural stem cells (NSCs) proliferation, migration, differentiation and endothelial angiogenesis. Moreover, in an ICH mouse model, the hydrogel is demonstrated not only to enable efficient tissue ROS scavenging, anti-inflammation polarization of microglial/macrophages, and dynamical self-adaptive reduction of glial scar, achieving microenvironment remodeling, but also to regulate behaviors of endogenous NSCs and enhance angiogenesis, providing neural regeneration. Consequently, these effects enhanced neurons and myelin repair, ultimately contributing to synergistic recovery of neurological function. Overall, this dynamic hydrogel represents a promising strategy for simultanously remodeling the lesion site's microenvironment and promoting neural regeneration, thereby improving the treatment efficacy of ICH.
Transforming sutures from passive tools into active immunomodulatory platforms: Prolonging corneal graft survival using reloadable tacrolimus-eluting sutures.
Xie M, Hong Y, Li A … +7 more , Zou H, Liu J, Zhang F, Tian L, Li S, Jie Y, Wang Y
Biomaterials · 2026 Nov · PMID 42090833 · Publisher ↗
Corneal allograft rejection remains a major cause of transplant failure. To address the limitations of topical immunosuppressants-such as poor bioavailability and patient non-compliance-this study introduces a transforma...
Corneal allograft rejection remains a major cause of transplant failure. To address the limitations of topical immunosuppressants-such as poor bioavailability and patient non-compliance-this study introduces a transformative strategy: engineering surgical sutures into active, reloadable immunomodulatory platforms. We developed a novel tacrolimus-eluting suture by modifying its surface with poly(dopamine) and anchoring a cyclodextrin-tacrolimus inclusion complex. This design enables sustained local drug release directly at the graft-host junction. Crucially, the system is reloadable; after initial depletion, the drug payload can be non-invasively replenished via cyclodextrin, allowing it to match the prolonged risk period of post-transplantation. In vitro studies confirmed sustained release over one week, and ex vivo corneal penetration models validated efficacy. By integrating long-term, localized immunosuppression into the standard-of-care suture, this platform offers a groundbreaking approach to prolong graft survival and personalize postoperative management.
Adhesive adjuvant protein for long-lasting immune response in vaccination.
Jung S, Woo HT, Oh YE … +3 more , Cha H, Hwang BH, Cha HJ
Biomaterials · 2026 Nov · PMID 42090832 · Publisher ↗
Subunit vaccines remain essential despite recent advances in mRNA technology, due to their lower pathogenicity risk, targeted immune responses, and superior stability profiles. However, because of their low immunogenicit...
Subunit vaccines remain essential despite recent advances in mRNA technology, due to their lower pathogenicity risk, targeted immune responses, and superior stability profiles. However, because of their low immunogenicity, effective adjuvants are required to elicit robust, long-lasting immunity comparable to that of natural infections. Conventional adjuvants, such as aluminum (alum), provide only limited cellular activation and rapid antigen clearance, thereby limiting their efficacy. Similarly, potent peptide adjuvants are hampered by short in vivo half-lives. Bioengineered mussel adhesive protein (MAP) has attracted substantial attention for its unique underwater adhesive properties and non-immunogenicity, owing to its intrinsically disordered structural nature. Here, we aim to establish a mussel-inspired adhesive adjuvant protein (AAP) that leverages the underwater adhesiveness of MAP and the immunostimulatory effect of the adjuvant peptide. AAP enables the formation of an in situ crosslinked nanoparticulate vaccine that mimics natural infection dynamics by creating an antigen depot. In vitro and in vivo evaluations confirmed that this formulation significantly prolongs retention of antigen and adjuvant compared with alum, thereby inducing robust, sustained, and balanced immune responses. This study demonstrates that the adhesive adjuvant protein-based nanoparticulate vaccine can elicit potent immune responses and finely modulate immune responses, making it a promising vaccine candidate.
Cargo-defined engineered vesicles enable targeted miRNA delivery for cardiac repair after myocardial infarction.
Zhang Y, Wei G, Wang H … +13 more , Wang J, Sun X, Cao W, Lai F, Lin Y, Zhang S, Liu N, Hu K, Su G, Huang R, Zou J, Xu T, Tong L
Biomaterials · 2026 Nov · PMID 42085858 · Publisher ↗
Myocardial infarction (MI) remains a leading cause of morbidity and mortality worldwide, and current therapeutic strategies offer limited efficacy in promoting long-term cardiac repair. miRNAs have emerged as promising t...
Myocardial infarction (MI) remains a leading cause of morbidity and mortality worldwide, and current therapeutic strategies offer limited efficacy in promoting long-term cardiac repair. miRNAs have emerged as promising therapeutic agents owing to their capacity to modulate gene networks involved in cardiomyocyte apoptosis, mitochondrial dysfunction, and extracellular matrix (ECM) remodeling. Herein, we identified miR-30d as a potential therapeutic target, exhibiting dynamic expression changes in plasma extracellular vesicles (EVs) from MI patients before and after percutaneous coronary intervention (PCI). To facilitate targeted delivery, we developed an engineered milk-derived EV-like vehicle (mELV) system in which endogenous RNAs were depleted via sonication to reduce off-target effects and improve cargo uniformity. These mELVs were further loaded with miR-30d and subsequently functionalized with an ischemic myocardium targeting peptide (IMTP). Intravenous administration of miR30d-mELVs in murine MI model conferred both acute cardioprotection and sustained improvements in cardiac function, accompanied by reduced pathological remodeling. Mechanistically, miR-30d directly targets Thbs2, leading to suppression of downstream MMP2 expression, attenuation of mitochondrial reactive oxygen species production, and inhibition of ECM degradation. Collectively, these findings underscore the therapeutic potential of miR-30d and establish programmable RNA-depleted, IMTP-conjugated mELVs as a safe, targeted, and effective platform for miRNA delivery in post-MI gene therapy.
Gene-programmed micro-nano metabolic engine drives coupled osteogenic-angiogenic regeneration.
Yang W, Ding T, Zhang Y … +7 more , Zhou W, Zhuang P, Chen Y, Viitala T, Kang H, Zhang H, Cui W
Biomaterials · 2026 Nov · PMID 42085857 · Publisher ↗
Effective bone healing is accompanied by coupled osteogenic-angiogenic regeneration, a process that critically depends on metabolic communication between bone marrow mesenchymal stem cells (BMSCs) and endothelial cells t...
Effective bone healing is accompanied by coupled osteogenic-angiogenic regeneration, a process that critically depends on metabolic communication between bone marrow mesenchymal stem cells (BMSCs) and endothelial cells through an endogenous metabolic axis in which endothelial nitric oxide synthase (eNOS) catalyzes the conversion of l-arginine into nitric oxide (NO). However, within hypoxic microenvironments such as those present in large bone defects, the restricted expression of eNOS and the depletion of its substrate synergistically suppress NO biosynthesis, thereby impairing osteogenic-angiogenic signaling coupling and subsequent tissue regeneration. Herein, we developed a gene-programmed micro-nano metabolic engine (GP-MNME) to actively reconstruct NO metabolic homeostasis. GP-MNME features a spatially hierarchical dual-module architecture: the nano-module is fabricated via a nanoprecipitation strategy and consists of amorphous calcium phosphate nanoparticles modified with l-arginine for efficient BMP-2 mRNA loading, while the micro-module is formed by microfluidic-fabricated GelMA microgels covalently conjugated with E7 peptides for BMSC targeting and encapsulation of the nano-modules. In a bone defect, the micro-module enriches BMSCs and releases the nano-modules. Upon cellular uptake, these nanoparticles concurrently upregulate eNOS expression and supply l-arginine to synergistically increase NO production (>3.1-fold). The re-established NO homeostasis serves as the central output of the metabolic engine, subsequently driving osteogenic mineralization and angiogenic sprouting (both > 3-fold), and ultimately promoting coupled osteogenic-angiogenic regeneration in rat bone defect (new bone formation >2.4-fold). Overall, this study presents a proactive metabolic modulation strategy for bone regeneration via reconstructing intracellular NO biosynthesis in situ.
A biomimetic nanotherapeutic hydrogel orchestrates multi-mechanism therapy for ischemic skin flaps.
Cheng S, Dai Z, Xi S … +10 more , Zhao J, Ding J, Wang Z, Yu H, Wang Z, Sun Y, Muhammad I, Li B, Gao W, Wang L
Biomaterials · 2026 Nov · PMID 42085856 · Publisher ↗
Despite considerable advances in nanotherapeutics, their clinical application is often limited by suboptimal monotherapy, rapid immune clearance and insufficient target-site accumulation. These limitations are particular...
Despite considerable advances in nanotherapeutics, their clinical application is often limited by suboptimal monotherapy, rapid immune clearance and insufficient target-site accumulation. These limitations are particularly pronounced in the treatment of flap necrosis because of the complex ischemic microenvironment. To address this challenge, we fabricated a multifunctional therapeutic platform by loading melanin nanoparticles (MNPs) with the PI3Kα agonist UCL-TRO-1938, coating them with membranes derived from tert-butyl hydroperoxide (TBHP)-preconditioned human umbilical vein endothelial cells (HUVECs), and embedding them within a fibrin hydrogel. The resulting CM-1938@MNP hydrogels conferred cytoprotective effects in vitro by rescuing HUVECs from TBHP induced dysfunction and shifting macrophage polarization from the M1 to M2 phenotype. In a mouse model of ischemic skin flaps, local injection of the hydrogel markedly improved flap survival by stimulating angiogenesis, alleviating oxidative stress, and suppressing inflammation; these results were confirmed by RNA-seq analysis. This work presents a biomimetic strategy that transcends conventional single target therapies, offering a promising versatile platform for treating ischemia.
Engineering lipid nanoparticle surface hydrophobicity to modulate nano-bio interface and enable tissue-selective mRNA delivery.
Xu Z, Jolly KJ, Sankara CS … +9 more , Mi K, Canchola A, Feng H, Gillen OP, Heiden KD, Basso KB, Chou WC, Lin Z, Zhang F
Biomaterials · 2026 Nov · PMID 42085855 · Full text
Predominant liver accumulation remains a major challenge for the application of lipid nanoparticle (LNP)-based gene therapies. While tuning the apparent pKa is an effective strategy for influencing endogenous proteins th...
Predominant liver accumulation remains a major challenge for the application of lipid nanoparticle (LNP)-based gene therapies. While tuning the apparent pKa is an effective strategy for influencing endogenous proteins that regulate LNP-mediated tissue-specific delivery, recent evidence suggests that alternative mechanisms may exist. Here, we reveal a new mechanism by which LNP surface hydrophobicity influences extrahepatic delivery. Using dendrimers as modular molecules and an in-house developed surface hydrophobicity assay, we show that reducing lipid grafting on the dendrimer decreases the surface hydrophobicity of dendrimer-based LNPs (dLNPs), leading to reduced stability in plasma and decreased plasma protein adsorption. This diminishes the ability of LNPs to target liver hepatocytes through endogenous mechanisms involving interactions between apolipoproteins and their cognate receptors. At the same time, we find that dLNPs with lower surface hydrophobicity exhibit enhanced targeting of granulocytes relative to monocytic cells, potentially due to complement protein interactions. Further modification of dendrimers with quaternary amines increases dLNP surface charge density and improves lung delivery by preferentially targeting lung epithelial cells. While this modification also reduces surface hydrophobicity, the enhanced lung delivery is associated with distinct protein corona compositions rather than reduced protein adsorption. These findings establish modulation of LNP surface hydrophobicity as a novel strategy for achieving extrahepatic delivery.
Genetically engineered extracellular vesicles-based collagen-targeting bioinspired scaffold for tendon regenerative repair.
Zhang YJ, Cui J, Xie XY … +11 more , Wu SS, Cao MY, Ning LJ, Li X, Wang J, Zhao LL, Zhu M, Liu HM, Zhang Y, Luo JC, Qin TW
Biomaterials · 2026 Nov · PMID 42081860 · Publisher ↗
Tendon injuries, particularly massive tendon defects, pose significant clinical challenges due to the limited regenerative capacity of tendons and suboptimal outcomes of current therapies. This study presents a bioinspir...
Tendon injuries, particularly massive tendon defects, pose significant clinical challenges due to the limited regenerative capacity of tendons and suboptimal outcomes of current therapies. This study presents a bioinspired scaffold that integrates genetically engineered extracellular vesicles (EVs) with collagen-targeting capabilities into a decellularized bovine tendon sheet (DBTS) for tendon regenerative repair. Rat tendon-derived stem cells (TDSCs) were genetically modified to overexpress biglycan (Bgn) and fibromodulin (Fmod), producing bioactive EVs that drive tenogenic differentiation via the miR-145-5p/TGFβ2 signaling pathway. The incorporation of a collagen-targeting peptide (CTP) on EVs surfaces ensured efficient attachment and sustained release at the injury site. The resulting bioinspired scaffold provided a supportive microenvironment for tendon regeneration, demonstrated in vitro by improved stem cell proliferation, migration and tenogenic differentiation, and in vivo by enhanced collagen alignment, extracellular matrix remodeling, and biomechanical performance of regenerated Achilles tendons in rats. This scaffold represents an innovative approach in cell-free regenerative strategy, offering targeted modulation of the tendon niche with translational potential for treating massive tendon injuries.
Magnesium-doped biomimetic intrafibrillar mineralized decellularized extracellular matrix cryogel with oriented microchannel for vascularized bone regeneration.
Chen A, Yang Q, Ma X … +6 more , Gao X, Zhang S, Zhang X, Liu J, Wu Z, Zhang C
Biomaterials · 2026 Nov · PMID 42070544 · Publisher ↗
Despite the significant advancements in the development of biomimetic materials for bone repair, accurately replicating the complex characteristics of natural bone tissue across multiple scales remains a challenge. Inspi...
Despite the significant advancements in the development of biomimetic materials for bone repair, accurately replicating the complex characteristics of natural bone tissue across multiple scales remains a challenge. Inspired by the intrinsic hierarchical structure of bone tissue, a multi-dimensional biomimetic strategy was developed by restoring the component composition, simulating biomineralization processes, mimicking hierarchical structures, and imparting essential biological functions to improve bone regeneration efficiency. Specifically, directional freezing technology followed by photopolymerization of a precursor solution containing methacrylated hyaluronic acid and decellularized extracellular matrix was utilized to fabricate construct with oriented microchannels, and subsequent magnesium-doped polymer induced liquid precursor mineralization to successfully fabricate scaffolds (Mg-MCG) that closely mimicked the natural bone tissue composition and structure. Studies revealed that the scaffold was fabricated with amenable mineral content (50-60%), matrix stiffness, and hierarchical structure similar to bone tissue, which in turn facilitated rapid and directed cell infiltration to create an oriented and parallel cell distribution. In vitro and in vivo studies further demonstrated the ability of the scaffold to regulate H-type vessels regeneration and promoting vascularized bone regeneration in addition to its excellent biodegradability. Based on an in-depth understanding of bone hierarchical characteristics, this strategy achieved collaborative biomimicry across compositional components, structural features, and functional attributes, significantly enhancing the adaptive regeneration between the biomimetic scaffold and bone tissue.
Retraction notice to "Stiffness memory of indirectly 3D-printed elastomer nanohybrid regulates chondrogenesis and osteogenesis of human mesenchymal stem cells" [Biomaterials 186 (2018) 18884].
Linxiao Wu, Magaz A, Wang T … +6 more , Liu C, Darbyshire A, Loizidou M, Emberton M, Birchall M, Song W
Biomaterials · 2026 May · PMID 42069483 · Publisher ↗
Abstract loading — click title to view on PubMed.
Effects of structure on the degradation behavior and osteogenic properties of 3D-printed Mg-Ti interpenetrating composites.
Cui Y, Xiong S, Chen J … +6 more , Zhang M, Cao Y, Li S, Tan Y, Zhou C, Yang B
Biomaterials · 2026 Nov · PMID 42068793 · Publisher ↗
Magnesium-titanium (Mg-Ti) composites have the potential in applications to bone repair and orthopedic implants due to their mechanical properties derived from Ti and biological functions derived from Mg. However, the de...
Magnesium-titanium (Mg-Ti) composites have the potential in applications to bone repair and orthopedic implants due to their mechanical properties derived from Ti and biological functions derived from Mg. However, the degradation rate of Mg in the composite is accelerated due to the effect of galvanic corrosion, which has affected its clinical application. In order to regulate the degradation behavior of Mg-Ti composites,3D printing technology was employed to prepare Ti scaffolds with porous structures of different pore areas and pore shapes (square, hexagonal, and triangular), then Mg was infiltrated into the porous Ti scaffold to obtain the Mg-Ti composites. The results showed that the groups with smaller pore areas had a faster initial degradation rate and could reach a stable stage earlier. The degradation of the square structure composite was more controllable compared to the other two composites, so it was selected for the subsequent study on osteogenic properties. The addition of Mg in the composite enhanced the apatite-forming ability, upregulated the expression of osteogenic-related genes such as RUNX2, ALP, and OPN, and promoted the generation of bone tissue and collage. The results indicated that the Mg-Ti composite could regulate the content and the degradation rate of Mg through structure, thereby improving the osteogenic properties by regulating the release of Mg in the surrounding microenvironment. This study explored the degradation mechanism and systematically established a relationship between structure, degradation, and osteogenesis of Mg-Ti composites, thereby providing ideas for the structural optimization of Mg-Ti composites and offering references for applications in medical bone repair.
Electrospun vascular adventitia-derived ECM/PCL fiber-co-hydrogel scaffold: A novel approach to vascular regeneration with enhanced cell affinity and tunable biomechanical properties.
Xie C, Wu Z, Wu Q … +8 more , Chen Z, Chen S, Yi L, Deng C, Yuan H, Lu T, Liu Y, Huang C
Biomaterials · 2026 Nov · PMID 42068792 · Publisher ↗
Despite advancements in small-diameter vascular grafts (SDVGs), they continue to face significant clinical challenges, including thrombosis, insufficient endothelialization, and incompatible mechanical properties. To add...
Despite advancements in small-diameter vascular grafts (SDVGs), they continue to face significant clinical challenges, including thrombosis, insufficient endothelialization, and incompatible mechanical properties. To address these limitations, this study developed a heparin-incorporated vascular adventitia extracellular matrix (vaECM)/PCL fiber-co-hydrogel vascular scaffold using electrospinning-co-electrospray technology combined with vaECM self-assembly gelation. This scaffold combines the mechanical strength of PCL fibers with the bioactivity of vaECM hydrogel, while the incorporated heparin enhances its antithrombotic properties. Material characterization reveals that the fiber-co-hydrogel scaffold possesses a biomimetic layered structure, tunable mechanical properties, self-healing ability, low swelling ratio, and hierarchical degradation. Co-culture experiments with endothelial cells and smooth muscle cells demonstrate that this scaffold significantly promotes endothelial cell adhesion, proliferation, and migration, as well as the maturation of smooth muscle cells. Blood compatibility tests confirm its superior anticoagulant and antiplatelet properties. In a rat abdominal aorta replacement model, the scaffold showed significantly enhanced endothelial coverage by week 4, and by week 16, it supported the regeneration of mature vascular smooth muscle and orderly remodeling of the extracellular matrix. These results highlight the remarkable vascular regenerative potential of this fiber-co-hydrogel scaffold, driven by its bioactive vaECM hydrogel and bio-matched material stiffness, offering a promising avenue for the clinical application of small-diameter vascular grafts.
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