Regenerative Biomaterials最新文献

[This corrects the article DOI: 10.1093/rb/rbaf003.].

Bioadhesives are being increasingly used in clinical practice, but pose significant health risks due to their uncontrollable intraoperative leakage. Nevertheless, there is currently a critical lack of effective solutions. Herein, we propose a second near-infrared window (NIR-II) fluorescence-visible indocyanine green (ICG)-BioGlue adhesive for precision surgical adhesion with intraoperative leakage prevention. The fabricated ICG-BioGlue adhesive based on the non-covalent interaction exhibits nearly 100% fluorescence labeling efficiency and maintains long-term stable NIR-II fluorescence for up to 3 months. During surgery, ICG-BioGlue adhesive enables real-time visualization of wound adhesion in various fields such as aortic dissection adhesion and liver or kidney wound hemostasis, preventing leakage into surrounding tissues. Moreover, the stable fluorescence of ICG-BioGlue adhesive allows effective imaging-guided removal of long-term adhesive fragments in the body when they cause compression symptoms after surgery. Considering it consists solely of Food and Drug Administration-approved drugs ICG and BioGlue, with a straightforward synthesis method and versatile applicability, ICG-BioGlue adhesive holds excellent potential for clinical translation. Our study provides a leakage-preventing strategy to enhance biosafety and promote the widespread application of bioadhesives in clinical settings.

Immune factors secreted by immune cells play a pivotal role in orchestrating inflammatory responses and facilitating tissue regeneration. Fiber dressings, owing to their extracellular matrix-like architecture and tunable physical properties, have emerged as promising candidates in regenerative medicine. Beyond serving as passive structural supports, fibers are increasingly recognized as active modulators of cell behavior through their inherent physical characteristics. However, how fiber diameter at the micro- and nanoscale influences the immune factor secretion profile of immune cells remains poorly defined. In this study, three types of fibers with distinct diameter scales were fabricated to systematically assess their immunomodulatory effects. In vitro analyses revealed that microscale fibers markedly enhanced the secretion of pro-regenerative and anti-inflammatory factors, such as VEGF, EGF, IL-10 and TGF-β1, while suppressing pro-inflammatory factors including TNF-α and IL-6. Mechanistic investigations indicated that this size-dependent immunomodulation may be driven by activation of the FAK-Wnt signaling pathway triggered by topographical cues. In vivo, microscale fibers significantly promoted neovascularization, attenuated inflammatory responses and accelerated tissue repair, further corroborating their immunoregulatory potential in a physiological setting. These findings establish fiber diameter as a critical physical cue for shaping the immune microenvironment and present a new strategy for immunoregulation through structural design. This work provides a conceptual framework for the development of biomaterials with intrinsic immunomodulatory properties and offers new therapeutic insights for the treatment of chronic inflammation-associated disorders.

Cellular receptors serve as central hubs that translate external signals into intracellular programs governing cell fate, function and behavior. Achieving precise and reversible control over receptor activity has long been a major challenge in both fundamental biology and translational medicine. Optogenetic receptor engineering provides a transformative solution by integrating photosensitive domains into natural receptor frameworks. This strategy enables light-dependent modulation of signaling with high spatial and temporal precision while maintaining minimal disturbance to endogenous pathways. Unlike chemogenetic systems or classical photoreceptive ion channels, this approach preserves endogenous ligand specificity and avoids slow ligand diffusion/clearance-associated artifacts. Through such systems, researchers can dissect causal relationships in dynamic signaling events, finely manipulate neuromodulatory and immune circuits and program cellular activities involved in development and tissue regeneration. The approach also allows quantitative control of signaling intensity and duration, offering new opportunities for linking molecular design to physiological outcomes. By combining optogenetic principles with advances in materials science and bioelectronics, future designs may achieve improved optical fidelity, enhanced light penetration and better signal amplification within complex biological environments. Integration with AI-guided protein engineering may also accelerate the discovery of optimized photosensory-receptor pairings. Together, these developments point to an emerging field where light-responsive receptors function as programmable interfaces between photonic control and cellular computation. In summary, the engineering of optogenetic receptors establishes a conceptual and technological framework for reversible, accurate and tunable regulation of cellular communication. This review summarizes current progress, outlines key design principles and provides conceptual guidelines for advancing next-generation light-responsive receptors and their biomedical applications. However, key translational challenges-including immunogenicity of non-human photoreceptors, limited gene-delivery efficiency and long-term biosafety-remain to be addressed through nonviral delivery strategies, autologous cell engineering and de-immunized or humanized photoreceptor design.

Brain pathologies such as ischemic stroke or traumatic brain injury (TBI) are among the most impactful diseases worldwide. In ischemic stroke, we currently lack truly effective treatments capable of delaying infarct progression, limiting lesion size or stimulating endogenous brain repair mechanisms to promote neurovascular remodeling and functional recovery. Two main barriers continue to limit the clinical translation of therapeutic molecules: the highly restrictive nature of the blood-brain barrier and that many bioactive molecules exhibit low stability at the target site, with half-lives shorter than the therapeutic window. In this study, we developed tunable silk fibroin (SF) films of variable concentration, fabricated via water annealing, that effectively preserve the functional activity of the chemokine CXCL12 (SDF-1α). The 2% SF formulation provided sustained release of SDF-1α for at least 7 days, promoting the in vitro migration of mesenchymal stem cells (MSCs) and low-density bone marrow mononuclear cells (LDBM), the latter containing hematopoietic stem cells. When implanted on the cortical surface, the SDF-1α-SF films successfully stimulated the guided migration of exogenously administered MSCs and LDBM from subcortical regions into the cerebral cortex. Furthermore, co-implantation of SDF-1α-SF films with MSCs or LDBM enhanced cell retention at the cortical site, effectively minimizing off-target dispersion. In a photothrombotic model of cortical ischemia, allowing precise control of lesion location and size, SDF-1α-SF films significantly reduced lesion volume and preserved neuronal function in the somatosensory cortex, as assessed by electrophysiology. Our findings provide proof of concept for using chemokine-releasing biomaterials to actively modulate stem cell migration and retention within the brain, offering strong potential for neuroprotection and tissue remodeling in areas at risk or already affected by damage.

Oxidative stress in the periodontal microenvironment intensifies inflammation and accelerates alveolar bone destruction. Consequently, strategies that effectively suppress oxidative stress while promoting osteogenesis are central to the management of periodontitis. Here, we present an in situ injectable antioxidant nanoparticle system designed to initiate a sequential chemico-biological cascade, achieving dual therapeutic outcomes of inflammation suppression and bone regeneration. The engineered nanoparticles were fabricated by encapsulating 4-octyl itaconate (4OI) within mesoporous polydopamine nanoparticles [4OI-loaded mesoporous dopamine (MDAI)]. Following cellular uptake, MDAI activates a two-step antioxidant mechanism. First, the mesoporous polydopamine scaffold undergoes ROS-triggered degradation within inflammatory macrophages, directly scavenging excessive ROS. Subsequently, the released 4OI activates the Nrf-2/HO-1 signaling axis, leading to robust antioxidant and cytoprotective effects, as evidenced by the pronounced upregulation of Nrf-2 and modulation of HO-1 activity. This signaling cascade shifts macrophage polarization toward the anti-inflammatory M2 phenotype and suppresses pro-inflammatory cytokines such as tumor necrosis factor alpha and interleukin 6. Transcriptome sequencing further confirmed broad downregulation of inflammatory pathways and associated genes. Moreover, the ROS-scavenging activity of MDAI indirectly enhanced osteoblast differentiation and bone formation. When incorporated into a thermosensitive hydrogel for localized administration, MDAI exhibited prolonged retention and sustained bioactivity within periodontal pockets. In a murine periodontitis model, this formulation effectively reduced inflammatory infiltration, decreased cytokine expression, modulated macrophage polarization and enhanced alveolar bone regeneration. Collectively, these findings establish MDAI-mediated chemico-biological cascade therapy as a potent and integrative platform for treating periodontitis and restoring periodontal tissue homeostasis.

The microenvironment of diabetic wounds is at risk of slow recovery, scarring and infection in medical treatment. Although many hydrogel dressings combine photothermal and gas therapies, few use CO₂'s Bohr effect to enhance oxygen release while offering precise, in situ control over gas and drug release. To address this, we designed an injectable multifunctional hydrogel dressing with photothermal, antibacterial, and near-infrared (NIR) - induced CO₂ properties. In this work, we developed carboxymethyl chitosan-alginate-black tea carbon conjugated with CO₂-precursors (CMCS/Alginate/BTC-CO₂) dressing. The black tea hydrothermal carbon nanoparticles attached CO₂ precursors on the surface, thermally decomposed under near-infrared irradiation to release CO₂ gas. Meanwhile, the excellent photothermal conversion efficiency enabled the hydrogel complex to demonstrate antimicrobial function. The high absorption in the UV range prevents the deposition of melanin. The CMCS/Alginate/BTC-CO₂ hydrogels exhibited good cytocompatibility and synergistically promoted NIH/3T3 cell migration. In vivo experiments in diabetic model mice verified that treatment of NIR-conjugated CMCS/Alginate/BTC-CO₂ hydrogels accelerated wound recovery, angiogenesis, and collagen deposition. Overall, we designed and verified the combination of stimuli-responsive photothermal CO₂ release from NIR, antimicrobial, and injectable multifunctional hydrogels, providing an effective solution for promoting diabetic wound healing both in vivo and in vitro. Such multifunctional dressing is expected to accelerate the process of wound treatment and alleviate the adverse reactions after recovery.

The development of biodegradable scaffolds with improved mechanical and biological performance is a pressing challenge in bone tissue engineering. Poly(lactic acid) (PLA), widely used in fused deposition modelling (FDM) due to its processability and biocompatibility, lacks sufficient bioactivity and strength for demanding applications. In this study, we fabricated and evaluated zinc-reinforced PLA composite filaments (5-30 wt% Zn) via melt extrusion and FDM to define a practical printability window and establish process-structure-function relationships aimed at enhancing osteointegration and stability. Microstructure, density, and crystallinity were characterized by optical microscopy/scanning electron microscope, Archimedes' principle, X-ray diffraction, and differential scanning calorimetry. Mechanical performance was quantified by tensile testing of standardized samples and compression of gyroid lattices. In vitro performance was evaluated using human osteoblasts through viability assays, adhesion quantification, and Alizarin Red S staining. Composites incorporating ≤10 wt% Zn showed uniform particle dispersion without impairing printability. Zn10 (10 wt% Zn) recovered PLA-like tensile strength with the highest strain-at-fracture among groups and exhibited significantly higher compressive strength and modulus than PLA and Zn5 (5 wt% Zn). All groups were found to be non-cytotoxic (∼100% viability) and supported osteoblast adhesion. Notably, zinc-containing scaffolds promoted significantly higher calcium deposition after 28 days, demonstrating enhanced late-stage osteogenic differentiation. These findings demonstrate that low-level Zn reinforcement can improve both structural integrity and biological performance of PLA-based scaffolds, supporting Zn-reinforced PLA as a scalable, extrusion-ready platform for the biofabrication of patient-specific bone-regenerative implants.

Mandibular radiation-induced bone injury (RIBI) is a common, severe complication of radiotherapy with no effective treatment. The early course is clinically subtle yet pathologically complex: ionizing radiation (IR) rapidly induces microvascular dysfunction, amplifies immune-mediated inflammation and disrupts bone homeostasis. This complexity, together with safety considerations, hampers therapeutic translation. Magnesium (Mg²⁺) is an essential bone component whose pro-osteogenic activity is well established; nevertheless, irradiation may remodel the multi-target effects of bioactive ions, and the integrated mechanisms of Mg²⁺ in bone radiation injury remain to be clarified. Here, we compared local delivery of an Mg²⁺- crosslinked alginate hydrogel (Mg@Alg) under irradiated versus non-irradiated conditions in rats and combined macrophage and endothelial cell models to evaluate radioprotective effects and mechanisms. In our study, Mg@Alg attenuated bone loss and apoptosis within 14 days after IR, promoted M2-like macrophage polarization, and improved microvascular density and maturation, thereby contributing to inflammatory microenvironment remodeling. Mechanistically, Mg²⁺ intervention was accompanied by decreased ferritin, downregulation of prolyl hydroxylase domain-2 (PHD2), and stabilization of hypoxia-inducible factor-1α (HIF-1α), together with vascular endothelial growth factor A upregulation; these changes were partly reversed by Fe²⁺, suggesting an iron-dependent, PHD2/HIF-1α-biased modulation that coordinates immune homeostasis and vascular regeneration to improve immune-vascular coupling. Notably, while Mg²⁺ efficacy appeared enhanced under IR, the effective concentration window narrowed. In sum, peri-radiotherapy, localized, short-term Mg²⁺ delivery may improve bone tolerance to radiation and mitigate early RIBI. These findings provide an experimental basis for low-risk, clinically translatable bone radioprotective strategies and expand the application paradigm of magnesium-based materials in radiotherapy protection contexts.

Decellularized extracellular matrix (dECM), a promising tissue engineering scaffold for cardiovascular applications, might exhibit enhanced durability when endowed with anticalcification and antithrombotic properties. Herein, we present a biomimetic bilayer hydrogel coating applied to acellular swim bladders (ASBs). First, we designed an endothelium-mimicking (HCT) hydrogel coating, comprising alternately assembled endothelial glycocalyx macromolecule hyaluronic acid, copper ions, and tannic acid. Subsequently, a hydrophilic methacrylated silk fibroin (SilMA) hydrogel was incorporated as the outer coating layer. Notably, the HCT hydrogel penetrated and anchored into the ASB matrix, forming an interpenetrating network that enhanced the biostability and mechanical properties of the ASB matrix. Additionally, the SilMA hydrogel enhanced the hydrophilicity and antifouling properties of the HCT coating. In vitro experiments and subcutaneous implantation further revealed that the bilayer hydrogel (H/S) coating exhibited excellent biocompatibility, hemocompatibility, antibacterial activity, and anticalcification properties. Furthermore, a blood circulation model and rabbit shunt assay confirmed the great anticoagulation properties of the H/S coating. Moreover, in an in vivo rat carotid aorta replacement model, the H/S coating effectively promoted endothelialization, enhanced vascular remodeling, prevented calcification and thrombosis, and ultimately improved ASB durability. Based on these findings, our endothelium-mimicking hydrophilic bilayer hydrogel coating holds great promise as a surface modification strategy for tissue engineering scaffolds.