Background:Excessive inflammation and exacerbated oxidative stress are significant hallmarks of the diabetic bone microenvironment, which give rise to dysregulated immune reactions and impaired bone homeostasis, thereby hindering bone defect healing and increasing the incidence of bone nonunion. Methods:A biodegradable photothermal hybrid (SC/MTZ) was developed through the in situ self-assembly of zeolitic imidazolate framework-8 (ZIF-8) nanoparticles on tannic acid (TA)-functionalized Ti3C2Tx MXene nanosheets, which were then integrated into a methacrylated silk fibroin/carboxymethyl chitosan methacryloyl matrix. The integration of in situ photopolymerization and chelation coordination for double crosslinking, along with the incorporation of heterojunction MXene@TA/ZIF-8 (MTZ) nanosheets, enhances the physicochemical properties and biological activity of the hydrogels, providing optimal mechanical support and prolonged retention at the defect site. Results:The hydrogel platform demonstrated outstanding antibacterial properties and effectively reprogrammed macrophages from the proinflammatory M1 phenotype to the anti-inflammatory M2 phenotype. This was achieved through the combined effects of localized mild hyperthermia and stimuli-responsive release of bioactive agents (TA and Zn2+), which also enhanced mitochondrial function and inhibited RANKL-induced osteoclast formation and bone resorption. In situ injection of the photoactivated SC/MTZ hydrogel markedly accelerated cranial defect healing in diabetic rats by synergistically enhancing immune homeostasis, osteogenesis, and angiogenesis while suppressing osteoclast activity. Conclusions:In summary, this study proposes an innovative method for developing multifunctional photothermal nanosheet-encapsulated hybrid hydrogels aimed at effectively managing diabetic bone defects.

Diabetes-induced osteoporosis significantly elevates the risk of fracture-related disability and mortality. Developing effective therapeutic strategies for diabetic-related bone defects has become a pressing concern in both clinical and research domains. This study innovatively constructs a near-infrared light-responsive (NIR) intelligent hydrogel system (carboxymethyl chitosan/gelatin/black phosphorus@bFGF, CG/BPb), utilizing carboxymethyl chitosan and gelatin as the matrix while integrating polydopamine (PDA)-functionalized black phosphorus nanosheets (BP@PDA) as a controlled-release carrier for basic fibroblast growth factor (bFGF). The CG/BPb hydrogel demonstrated remarkable mechanical strength (up to 25 kPa compressive stress at 55

Despite significant advancements in biomaterial-guided in situ bone regeneration, treating osteoporotic bone defects remains a substantial challenge in clinical practice. The imbalance in osteoblast/osteoclast function, coupled with attenuated vascularization, leads to delayed bone repair or even nonunion, whereas the acidic, hydrogen peroxide (H2O2)-rich osteoporotic microenvironment dampens macrophage immunological responses, creating a vicious cycle of inflammation and oxidative stress that inhibits bone regeneration. To address these challenges, a versatile coordination chemistry-driven tannic acid-functionalized calcium carbonate microsphere (TCM) was tailored and incorporated into 3,4-dihydroxyphenylalanine-modified hyaluronic acid (HA-DOPA)/phenylboronic acid-modified alginate (Alg-PBA)-based dynamically crosslinked hydrogel (HDAP/TCM) to promote the reconstruction of osteoporotic bone defects through integrated immune regulation, osteoblast/osteoclast homeostasis, and revascularization. Owing to the dual-crosslinking strategy of dynamic boronate bonds and metal coordination bonds, the resulting hydrogel exhibited an interconnected porous structure, injectability, tissue adhesion, self-healing behavior, enhanced mechanical properties, and pH/ROS-responsive degradation and release under the tested conditions. The TCM incorporated into the hydrogel functions as a naturally derived photothermal stimulator to induce osteogenesis, vascular network reconstruction, and M2 macrophage polarization, as well as to neutralize acidic inflammatory conditions in the osteoporotic bone microenvironment. Moreover, the developed HDAP/TCM hydrogel platform can respond intelligently to the pathological microenvironment (pH and ROS) of osteoporosis for the on-demand release of bioactive agents (i.e., polyphenols and Ca2+), combine spatiotemporally controlled mild local hyperthermia with synergistic free-radical scavenging, alleviate inflammation, protect osteoblasts and endothelial cells from oxidative stress damage, and inhibit excessive osteoclast activation in the alkaline microenvironment generated by TCM degradation. Transcriptomic analysis revealed that HDAP/TCM improved the inflammatory microenvironment by inhibiting NF-κB signaling and altering inflammation- and macrophage polarization-related gene expression in LPS-stimulated RAW264.7 cells, thereby significantly accelerating the repair and functional reconstruction of osteoporotic bone defects. In conclusion, these findings suggest that injectable microenvironment-responsive HDAP/TCM hydrogels can be promising alternative materials for the treatment of osteoporotic bone defects.

Functional self-assembling peptides prepared by linking short functional peptides to basic self-assembling peptides via solid-phase synthesis are often single-function and insufficient for preventing complex diseases, including noise-induced hearing loss (NIHL). Herein, a strategy to design multifunctional self‑assembling peptides (NPR36) for preventing NIHL is presented. Compared to the conventional approach of constructing multifunctional self-assembling peptide systems through co-assembling distinct functional peptides, this strategy integrates multiple functions into a single self-assembling peptide by conjugating multifunctional hormone-derived peptides with extended basic self-assembling peptides. This monolithic integration eliminates the need to balance concentration ratios and prevents efficacy loss that occurs when the concentration of any component drops below its therapeutic threshold, while also ensuring that each peptide possesses complete multifunctionality, thereby enhancing therapeutic effects. Benefiting from the non-covalent interactions of the extended assembly motif, NPR36 self‑assembling peptides can form nanofibers and achieve sustained release during disassembly, maintaining an effective concentration at the treatment site. Furthermore, a fiber-microalgae complex was formed by combining NPR36 with Spirulina platensis. This fiber-microalgae-based system synergistically exerted antioxidant and anti-apoptotic effects, markedly reducing hair cell loss and restoring hearing. Overall, preventive interventions based on multifunctional self-assembling peptides could overcome the clinical translation challenges in the prevention of inner ear disorders.

The development of an intelligent, responsive therapeutic system capable of orchestrating highly ordered tissue regeneration has emerged as a promising strategy for the treatment of diabetic bone defects. Herein, natural polyphenol-derived black phosphorus (BP)-based multifunctional hydrogels are elaborately designed to work in conjunction with mild photothermal therapy for programmed regulation of the bone regeneration microenvironment through on-demand antioxidation, anti-inflammation, immunomodulation, and angiogenesis-osteogenesis coupling. Inspired by metal-phenol coordination chemistry, we constructed a novel metal-phenolic network system as a "multifunctional armor" for traditional BP nanosheets. In vitro biological experiments and RNA sequencing analysis demonstrated that polyphenol-derived BP nanosheets with remarkable osteogenic, reactive oxygen species (ROS)-scavenging, and anti-inflammatory properties could remodel the immune microenvironment and alleviate oxidative stress by regulating multiple inflammation-related signaling pathways. Upon uniform cross-linking with biocompatible hydrogels, the resulting hybrids exhibited a porous microstructure resembling that of a bone extracellular matrix, along with outstanding injectability, biodegradability, improved mechanical properties, and excellent photothermal effects. Moreover, the combined effects of polyphenol functionalization and mild heat stimulation enable exceptional performance in fostering anti-inflammation, angiogenesis, and osteogenesis in a spatial and temporal manner. Collectively, these findings highlight the promising application prospects of such polyphenol-derived multifunctional hydrogel platforms for complex bone defect healing and reconstruction.

The repair and reconstruction of large-scale bone defects face enormous challenges because of the failure to reconstruct the osteo-vascularization network. Herein, a near-infrared (NIR) light-responsive hydrogel system is reported to achieve programmed tissue repair and regeneration through the synergetic effects of on-demand drug delivery and mild heat stimulation. The spatiotemporal hydrogel system (HG/MPa) composed of polydopamine-coated Ti3C2Tx MXene (MP) nanosheets decorated with acidic fibroblast growth factor (aFGF, a potent angiogenic drug) and hydroxypropyl chitosan/gelatin (HG) hydrogel is developed to orchestrate the reconstruction of the osteo-vascularization network and boost bone regeneration. Upon exposure to NIR light irradiation, the engineered HG/MPa hydrogel can achieve the initial complete release of aFGF to induce rapid angiogenesis and provide sufficient blood supply, maximizing its biofunction in the defect area. This integrated hydrogel system demonstrated good therapeutic efficacy in promoting cell adhesion, proliferation, migration, angiogenesis, and osteogenic differentiation through periodic NIR irradiation. In vivo, animal experiments further revealed that the spatiotemporalized hydrogel platform synergized with mild photothermal treatment significantly accelerated critical-sized bone defect healing by increasing the osteo-vascularization network density, recruiting endogenous stem cells, and facilitating the production of osteogenesis/angiogenesis-related factors. Overall, smart-responsive hydrogel could enhance the reconstruction of the osteo-vascularization network in bone regeneration.

Background: The comprehensive management of diabetic bone defects remains a substantial clinical challenge due to the hostile regenerative microenvironment characterized by aggravated inflammation, excessive reactive oxygen species (ROS), bacterial infection, impaired angiogenesis, and unbalanced bone homeostasis. Thus, an advanced multifunctional therapeutic platform capable of simultaneously achieving immune regulation, bacterial elimination, and tissue regeneration is urgently designed for augmented bone regeneration under diabetic pathological milieu. Methods and Results: Herein, a photoactivated soft -hard combined scaffold system (PGCZ) was engineered by introducing polydopamine-modified zeolitic imidazolate framework -8 -loaded double -network hydrogel (soft matrix component) into 3D -printed poly( epsilon -caprolactone) (PCL) scaffold (hard matrix component). The versatile PGCZ scaffold based on double -network hydrogel and 3D -printed PCL was thus prepared and features highly extracellular matrix -mimicking microstructure, suitable biodegradability and mechanical properties, and excellent photothermal performance, allowing long-term structural stability and mechanical support for bone regeneration. Under periodic near -infrared (NIR) irradiation, the localized photothermal effect of PGCZ triggers the on -demand release of Zn 2+ , which, together with repeated mild hyperthermia, collectively accelerates the proliferation and osteogenic differentiation of preosteoblasts and potently inhibits bacterial growth and biofilm formation. Additionally, the photoactivated PGCZ system also presents outstanding immunomodulatory and ROS scavenging capacities, which regulate M2 polarization of macrophages and drive functional cytokine secretion, thus leading to a pro -regenerative microenvironment in situ with enhanced vascularization. In vivo experiments further demonstrated that the PGCZ platform in conjunction with mild photothermal therapeutic activity remarkably attenuated the local inflammatory cascade, initiated endogenous stem cell recruitment and neovascularization, and orchestrated the osteoblast/osteoclast balance, ultimately accelerating diabetic bone regeneration. Conclusions: This work highlights the potential application of a photoactivated soft -hard combined system that provides long-term biophysical (mild photothermal stimulation) and biochemical (on -demand ion delivery) cues for accelerated healing of diabetic bone defects.

Background: Factor-free biomaterial scaffolds play an increasingly important role in promoting in situ bone reconstruction and regeneration. However, the complicated and variable pathophysiological microenvironments of the injury sites under diabetic conditions, including the vicious cycle of oxidative stress and inflammatory response, impaired osteo/angiogenesis function and hyperactive osteoclastogenesis, as well as increased susceptibility to bacterial infection, may largely weaken the therapeutic potential of implanted scaffolds, leading to uncontrolled and poor outcomes of bone defect healing. Methods and Results: To tackle the aforementioned challenges, a mild photothermal-assisted multifunctional therapeutic platform (denoted as GAD/MC) that integrates copper-containing two-dimensional Ti3C2Tx MXene nanosheets, gelatin methacrylate, and alginate-graft-dopamine was proposed to achieve efficient and synergistic therapy for diabetic bone defects. Thereinto, copper-decorated MXene (MC) nanosheets were employed as both functional crosslinkers and nanofillers to participate in the construction of an interpenetrating polymer network structure through multiple covalent and noncovalent bonds, which conferred the hydrogel with advantageous traits like enhanced mechanical properties, injectability and moldability, strong bone tissue adhesion and self-healing ability, as well as excellent anti-swelling and near-infrared (NIR) photothermal conversion capabilities. On account of the NIR/pH dual-responsive properties, the resulting hydrogel system was capable of achieving the controlled and stimuli-responsive release of bioactive Cu2+, allowing on-demand delivery at the site of injury. Moreover, with the assistance of mild photothermal effects, this integrated hydrogel system demonstrated remarkable antibacterial and antioxidant properties. It effectively scavenged excessive reactive oxygen species (ROS), inhibited inflammatory responses, and promoted macrophage polarization towards the pro-healing M2 phenotype. Such characteristics were beneficial for recreating an optimized microenvironment that supported the adhesion, proliferation, migration, and differentiation of osteoblasts and endothelial cells, while concurrently inhibiting osteoclast function. In a critical-sized cranial defect model using diabetic rats, the injectable GAD/MC hydrogel system combined with on-demand mild hyperthermia further synergistically accelerated new bone formation and bone healing processes by eliminating intracellular ROS, ameliorating inflammation, orchestrating M2 macrophage polarization, promoting osteo/angiogenesis, and suppressing osteoclastogenesis. Conclusions: Overall, the constructed multifunctional injectable hydrogel system has emerged as a promising therapeutic candidate for addressing complex bone-related challenges by remodeling the disordered immune microenvironment and expediting the bone healing process.

The repair of osteoporotic bone defects, particularly those with irregular shapes, remains a significant challenge due to insufficient bone regeneration and an abnormal level of reactive oxygen species (ROS), which impairs the balance of bone remodeling. Materials that intrinsically regulate ROS to rebalance the activation of osteoblasts and osteoclasts represent a highly desirable alternative to current grafting strategies for the management of osteoporotic defects. Inspired by the tea polyphenols and natural extracellular matrix of bone tissue, a novel biomimetic composite scaffold, the epichlorohydrin-crosslinked hydroxyethyl cellulose/soy protein isolate/polydopamine-coated hydroxyapatite composite sponge (EHSS/PHA) scaffold was designed to orchestrate bone-forming bone marrow mesenchymal stem cells (BMSCs) and bone-resorbing osteoclasts for the rejuvenation of osteoporotic bone defect repair. Benefiting from the distinctive capabilities of the EHSS/PHA, including scavenging active oxygen and osteoinduction, we found that the EHSS/PHA could inhibit the formation of osteoclasts and promote osteogenesis of BMSCs by up-regulating the ratio of Opg/Rankl and activating the β-catenin signaling pathway in an oxidative stress environment. With its antioxidant ability, osteogenic, and self-deploying capability, EHSS/PHA effectively promoted the repair of tibial defects in osteoporotic rats by removing excess reactive oxygen species at the defect site. Taken together, this work presents the EHSS/PHA with multifunctional properties that provide new insight into osteoporotic bone defects.

BackgroundMost bone-related injuries to grassroots troops are caused by training or accidental injuries. To establish preventive measures to reduce all kinds of trauma and improve the combat effectiveness of grassroots troops, it is imperative to develop new strategies and scaffolds to promote bone regeneration.MethodsIn this study, a porous piezoelectric hydrogel bone scaffold was fabricated by incorporating polydopamine (PDA)-modified ceramic hydroxyapatite (PDA-hydroxyapatite, PHA) and PDA-modified barium titanate (PDA-BaTiO3, PBT) nanoparticles into a chitosan/gelatin (Cs/Gel) matrix. The physical and chemical properties of the Cs/Gel/PHA scaffold with 0-10 wt% PBT were analyzed. Cell and animal experiments were performed to characterize the immunomodulatory, angiogenic, and osteogenic capabilities of the piezoelectric hydrogel scaffold in vitro and in vivo.ResultsThe incorporation of BaTiO3 into the scaffold improved its mechanical properties and increased self-generated electricity. Due to their endogenous piezoelectric stimulation and bioactive constituents, the as-prepared Cs/Gel/PHA/PBT hydrogels exhibited cytocompatibility as well as immunomodulatory, angiogenic, and osteogenic capabilities; they not only effectively induced macrophage polarization to M2 phenotype but also promoted the migration, tube formation, and angiogenic differentiation of human umbilical vein endothelial cells (HUVECs) and facilitated the migration, osteo-differentiation, and extracellular matrix (ECM) mineralization of MC3T3-E1 cells. The in vivo evaluations showed that these piezoelectric hydrogels with versatile capabilities significantly facilitated new bone formation in a rat large-sized cranial injury model. The underlying molecular mechanism can be partly attributed to the immunomodulation of the Cs/Gel/PHA/PBT hydrogels as shown via transcriptome sequencing analysis, and the PI3K/Akt signaling axis plays an important role in regulating macrophage M2 polarization.ConclusionThe piezoelectric Cs/Gel/PHA/PBT hydrogels developed here with favorable immunomodulation, angiogenesis, and osteogenesis functions may be used as a substitute in periosteum injuries, thereby offering the novel strategy of applying piezoelectric stimulation in bone tissue engineering for the enhancement of combat effectiveness in grassroots troops.

Natural hazards not only have great contribution to fatality but also economic loss. Although government has proposed well developed polices to rapidly handle emergencies and systematically organized recovery actions, failures of emergency relief, such as ineffective rescue, can significantly increase the post-hazard death rate. With the advance of artificial intelligence, the use of robots for disaster management applications is a new trend in managing and accessing natural disasters. Disaster response robotics is capable of assisting and replacing rescue teams working in dangerous scenarios, which not only alleviates labor-intensity but also reduces the potential risks associated with rescue personnel. Research on construction automation has advanced, but extensive development is required to reach fully autonomous construction in disaster management and post-disaster recovery. Instead, human robotics collaboration is promising and able to effectively alleviate the knowledge deficit and confusion. In the article, different functions of disaster response robotics are introduced, and technical challenges and future improvements are described.

The reconstruction of large bone defects by bioactive materials without exogenous cells, cytokines or growth factors remains a substantial clinical challenge. Herein, we present the rational design of injectable and adhesive (GMAD/LP) hydrogels composed of gelatin-methacryloyl (GelMA), dopamine-grafted alginate (AD), and polydopamine-functionalized Laponite (Lap@PDA) nanosheets that can act as osteoimmune regulators to engineer the pro-regenerative microenvironment for personalized bone regeneration. The as-fabricated GMAD/LP hydrogel with excellent tissue adhesion, self-healing, injectability, and improved mechanical strength can fill irregular bone defects in a minimally invasive manner. Moreover, the hydrogel exhibited outstanding osteogenic potential and osteoimmunomodulatory functions in vitro, significantly promoting the adhesion, proliferation, spreading, and osteogenic differentiation of bone mesenchymal stem cells (BMSCs), which was further augmented by hydrogel-induced macrophage M2-phenotype polarization and effective M2 macrophage-BMSC crosstalk. In vivo experiments in a cranial defect model demonstrated that the GMAD/LP hydrogel induced a reparative microenvironment similar to that in normal cranium, as characterized by an increased percentage of antiinflammatory M2 macrophages and endogenous stem cells and high-level neovascularization, consequently accelerating bone healing. This strategy not only achieves a bioactive hydrogel for bone defect reconstruction but also provides a feasible methodology to recover injured bone tissue through integrated design with diverse functions. (c) 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Painful neuroma, as one of the complications of nerve injury from disease or trauma, results in instinctive neuropathic pain that adversely affects a patient's quality of life. To intercept neuroma development, capping strategies have been performed as effective therapies. Nonetheless, the most appropriate biocompatible material to shield the nerves is an urgent clinical requirement. Herein, a compatible hydroxyethyl cellulose (HEC)/soy protein isolate (SPI) sponge capping conduit (HSSC) is used to prevent neuroma in vivo. Following capping on the sciatic nerve stump in vivo, the behavior of the rats and the structure of tissues are compared through histological assessment and autotomy scoring. The HSSCs gained a dismal autotomy score and enhanced the amelioration, where inflammatory invasions and overdeposition of collagen are defeated. The expression of myelin growth linked genes (Krox20, MPZ, and MAG) in the HSSC group at the eighth week was almost 2 times higher than that of the no capping group. The HSSC conduit served as a physical barrier to repress the infiltration of inflammation as well as provided an optimum microenvironment for facilitating nerve rejuvenation and intercepting neuroma development during nerve amelioration.

The treatment of bone defects remains a substantial clinical challenge due to the lack of spatiotemporal management of the immune microenvironment, revascularization, and osteogenic differentiation. Herein, deferoxamine (DFO)-loaded black phosphorus nanosheets decorated by polydopamine layer are prepared (BPPD) and compounded into gelatin methacrylate/sodium alginate methacrylate (GA) hybrid hydrogel as a smart-responsive therapeutic system (GA/BPPD) for accelerated bone regeneration. The BPPD nanocomposites served as bioactive components and near-infrared (NIR) photothermal agents, which conferred the hydrogel with excellent NIR/pH dual-responsive properties, realizing the stimuli-responsive release of DFO and PO4 3 - during bone regeneration. Under the action of NIR-triggered mild photothermal therapy, the GA/BPPD hydrogel exhibited a positive effect on promoting osteogenesis and angiogenesis, eliminating excessive reactive oxygen species, and inducing macrophage polarization to the M2 phenotype. More significantly, through macrophage M2 polarization-induced osteoimmune microenvironment, this hydrogel platform could also drive functional cytokine secretion for enhanced angiogenesis and osteogenesis. In vivo experiments further demonstrated that the GA/BPPD system could facilitate bone healing by attenuating the local inflammatory response, increasing the secretion of pro-healing factors, stimulating endogenous cell recruitment, and accelerating revascularization. Collectively, the proposed intelligent photothermal hydrogel platform provides a promising strategy to reshape the damaged tissue microenvironment for augmented bone regeneration.

Ideal periosteum materials are required to participate in a sequence of bone repair-related physiological events, including the initial immune response, endogenous stem cell recruitment, angiogenesis, and osteogenesis. However, conventional tissue-engineered periosteal materials have difficulty achieving these functions by simply mimicking the periosteum via structural design or by loading exogenous stem cells, cytokines, or growth factors. Herein, we present a novel biomimetic periosteum preparation strategy to comprehensively enhance the bone regeneration effect using functionalized piezoelectric materials. The resulting biomimetic periosteum possessing an excellent piezoelectric effect and improved physicochemical properties was prepared using a biocompatible and biodegradable poly(3-hydroxybutyric acid-co-3-hydrovaleric acid) (PHBV) polymer matrix, antioxidized polydopamine-modified hydroxyapatite (PHA), and barium titanate (PBT), which were further incorporated into the polymer matrix to fabricate a multifunctional piezoelectric periosteum by a simple one-step spin-coating method. The addition of PHA and PBT dramatically enhanced the physicochemical properties and biological functions of the piezoelectric periosteum, resulting in improved surface hydrophilicity and roughness, enhanced mechanical performance, tunable degradation behavior, and stable and desired endogenous electrical stimulations, which is conducive to accelerating bone regeneration. Benefiting from endogenous piezoelectric stimulation and bioactive components, the as-fabricated biomimetic periosteum demonstrated favorable biocompatibility, osteogenic activity, and immunomodulatory functions in vitro, which not only promoted adhesion, proliferation, and spreading as well as osteogenesis of mesenchymal stem cells (MSCs) but also effectively induced M2 macrophage polarization, thereby suppressing reactive oxygen species (ROS)-induced inflammatory reactions. Through in vivo experiments, the biomimetic periosteum with endogenous piezoelectric stimulation synergistically accelerated the formation of new bone in a rat critical-sized cranial defect model. The whole defect was almost completely covered by new bone at 8 weeks post treatment, with a thickness close to that of the host bone. Collectively, with its favorable immunomodulatory and osteogenic properties, the biomimetic periosteum developed here represents a novel method to rapidly regenerate bone tissue using piezoelectric stimulation.

Diabetic wound treatment poses significant global challenges in clinical work and research, alternative treatment approaches need to be developed urgently. Exudate management and angiogenic function are critical to improve diabetic wound healing. In this work, a Janus bilayer electrospun dressing is fabricated via modified electrospinning technologies. The outer layer of dressing is hydrophilic deferoxamine (DFO)-loaded polycaprolactone (PCL) and polyethylene glycol (PEG) random nanofiber, while the inner layer is hydrophobic PCL nanofiber with mesh-like structure and patterns, and the bilayer layers are fabricated via layer-by-layer assembly. The mechanical properties, wettability, and drug release performance of the Janus dressing were studied. Difference in wettability between the two layers enables excess biological fluid to drain away from the wound, and simultaneously trigger the cascade release of DFO in the outer layer. The in vitro data evidenced that the Janus dressing had good biocompatibility. The mesh-like inner surface is considered favorable for attachment and proliferation of fibroblast, and the controlled release of DFO significantly enhanced tube formation. In vivo results from a diabetic full-thickness cutaneous wound model showed that the Janus dressing created a unique microenvironment that accelerates the wound healing process through effective biofluid draining and stimulation of angiogenesis process. The findings indicated that the Janus dressing presented a potentially valuable method for the management and treatment of diabetic wound in clinical applications.

Ferroptosis regulators have been found to affect tumor progression. However, studies focusing on ferroptosis and soft tissue sarcoma (STS) are rare. Somatic mutation, copy number variation, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis, consensus clustering, differentially expressed genes analysis (DEGs), principal component analysis (PCA) and gene set enrichment analysis (GSEA) were used to identify and explore different ferroptosis modifications in STS. A nomogram was constructed to predict the prognosis of STS. Moreover, three immunotherapy datasets were used to assess the Fescore. Western blotting, siRNA transfection, EdU assay and reactive oxygen species (ROS) measurement were performed. 16 prognostic ferroptosis regulators were screened and significant differences were observed in somatic mutation, copy number variation (CNV) and RT-qPCR among these ferroptosis regulators. 2 different ferroptosis modification patterns were found (Fe cluster A and B). Fe cluster A with higher Fescore was correlated with p53 pathway and had better prognosis of STS (p = 0.002) while Fe cluster B with lower Fescore was correlated with angiogenesis and MYC pathway and showed a poorer outcome. Besides, the nomogram effectively predicted the outcome of STS and the Fescore could also well predict the prognosis of other 16 tumors and immunotherapy response. Downregulation of LOX also inhibited growth and increased ROS production in sarcoma cells. The molecular characterization of ferroptosis regulators in STS was explored and an Fescore was constructed. The Fescore quantified ferroptosis modification in STS patients and effectively predicted the prognosis of a variety of tumors, providing novel insights for precision medicine.

A photoactivated bone scaffold integrated with minimally invasive implantation and mild thermal-stimulation capability shows great promise in the repair and regeneration of irregularly damaged bone tissues. Developing multifunctional photothermal biomaterials that can simultaneously serve as both controllable thermal stimulators and biodegradable engineering scaffolds for integrated immunomodulation, infection therapy, and impaired bone repair remains an enormous challenge. Herein, an injectable and photocurable hydrogel therapeutic platform (AMAD/MP) based on alginate methacrylate, alginate-graft-dopamine, and polydopamine (PDA)-functionalized Ti3C2 MXene (MXene@PDA) nanosheets is rationally designed for near-infrared (NIR)-mediated bone regeneration synergistic immunomodulation, osteogenesis, and bacterial elimination. The optimized AMAD/MP hydrogel exhibits favorable biocompatibility, osteogenic activity, and immunomodulatory functions in vitro. The proper immune microenvironment provided by AMAD/MP could further modulate the balance of M1/M2 phenotypes of macrophages, thereby suppressing reactive oxygen species-induced inflammatory status. Significantly, this multifunctional hydrogel platform with mild thermal stimulation efficiently attenuates local immune reactions and further promotes new bone formation without the addition of exogenous cells, cytokines, or growth factors. This work highlights the potential application of an advanced multifunctional hydrogel providing photoactivated on-demand thermal cues for bone tissue engineering and regenerative medicine.

Hemorrhage, infection, and frequent replacement of dressings bring great clinical challenges to wound healing. In this work, Flammulina velutipes extract (FV) and hydroxyethyl cellulose (HEC) were chemically cross-linked and freeze-dried to obtain novel HFV cryogels (named HFVn, with n = 10, 40, or 70 corresponding to the weight percentage of the FV content), which were constructed for wound hemostasis and full-thickness skin defect repair. Systematic characterization experiments were performed to assess the morphology, mechanical properties, hydrophilic properties, and degradation rate of the cryogels. The results indicated that HFV70 showed a loose interconnected-porous structure and exhibited the highest porosity (95%) and water uptake ratio (over 2,500%) with a desirable degradation rate and shape memory properties. In vitro cell culture and hemocompatibility experiments indicated that HFV70 showed improved cytocompatibility and hemocompatibility. It can effectively mimic the extracellular matrix microenvironment and support the adhesion and proliferation of L929 cells, and its hemolysis rate in vitro was less than 5%. Moreover, HFV70 effectively induced tube formation in HUVEC cells in vitro. The results of the bacteriostatic annulus confirmed that HFV70 significantly inhibited the growth of Gram-negative E. coli and Gram-positive S. aureus. In addition, HFV70 showed ideal antioxidant properties, with the DPPH scavenging rate in vitro reaching 74.55%. In vivo rat liver hemostasis experiments confirmed that HFV70 showed rapid and effective hemostasis, with effects comparable to those of commercial gelatin sponges. Furthermore, when applied to the repair of full-thickness skin defects in a rat model, HFV70 significantly promoted tissue regeneration. Histological analysis further confirmed the improved pro-angiogenic and anti-inflammatory activity of HFV70 in vivo. Collectively, our results demonstrated the potential of HFV70 in the treatment of full-thickness skin defects and rapid hemostasis.

Osteogenesis and osteoclastogenesis are closely associated during the bone regeneration process. The development of multifunctional bone repair scaffolds with dual therapeutic actions (pro-osteogenesis and anti-osteoclastogenesis) is still a challenging task for bone tissue engineering applications. Herein, through a facile surface coating process, mussel-inspired polydopamine (PDA) is adhered to the surface of a biocompatible porous scaffold followed by the immobilization of a small-molecule activator (LYN-1604 (LYN)) and the subsequent in situ coprecipitation of hydroxyapatite (HA) nanocrystals. PDA, acting as an intermediate bridge, can provide strong LYN immobilization and biomineralization ability, while LYN targets osteoclast precursor cells to inhibit osteoclastic differentiation and functional activity, which endows LYN/HA-coated hybrid scaffolds with robust anti-osteoclastogenesis ability. Due to the synergistic effects of the LYN and HA components, the obtained three-dimensional hybrid scaffolds exhibited the dual effects of osteoclastic inhibition and osteogenic stimulation, thereby promoting bone tissue repair. Systematic characterization experiments confirmed the successful fabrication of LYN/HA-coated hybrid scaffolds, which exhibited an interconnected porous structure with nanoroughened surface topography, favorable hydrophilicity, and improved mechanical properties, as well as the sustained sequential release of LYN and Ca ions. In vitro experiments demonstrated that LYN/HA-coated hybrid scaffolds possessed satisfactory cytocompatibility, effectively promoting cell adhesion, spreading, proliferation, alkaline phosphatase activity, matrix mineralization, and osteogenesis-related gene and protein secretion, as well as stimulating angiogenic differentiation of endothelial cells. In addition to osteogenesis, the engineered scaffolds also significantly reduced osteoclastogenesis, such as tartrate-resistant acid phosphatase activity, F-actin ring staining, and osteoclastogenesis-related gene and protein secretion. More importantly, in a rat calvarial defect model, the newly developed hybrid scaffolds significantly promoted bone repair and regeneration. Microcomputed tomography, histological, and immunohistochemical analyses all revealed that the LYN/HA-coated hybrid scaffolds possessed not only reliable biosafety but also excellent osteogenesis-inducing and osteoclastogenesis-inhibiting effects, resulting in faster and higher-quality bone tissue regeneration. Taken together, this study offers a powerful and promising strategy to construct multifunctional nanocomposite scaffolds by promoting osteo/angiogenesis and suppressing osteoclastogenesis to accelerate bone regeneration.