Bone Tissue Regeneration Research Articles

Electrospun Biomimetic Periosteum Promotes Diabetic Bone Defect Regeneration through Regulating Macrophage Polarization and Sequential Drug Release.

The inadequate vascularization and abnormal immune microenvironment in the diabetic bone defect region present a significant challenge to osteogenic regulation. Inspired by the distinctive characteristics of healing staged in diabetic bone defects and the structure-function relationship in the natural periosteum, we fabricated an electrospun bilayer biomimetic periosteum (Bilayer@E) to promote regeneration of diabetic bone defects. Here, the inner layer of biomimetic periosteum was fabricated using coaxial electrospinning fibers, with a shell incorporating zinc oxide nanoparticles (ZnO NPs) and a core containing silicon dioxide nanoparticles (SiO2 NPs) mimicking the cambium of periosteum; the outer layer consisted of randomly aligned electrospun fibers loaded with deferoxamine (DFO), simulating the fibrous layer of periosteum; finally, epigallocatechin-3-gallate (EGCG) was coated onto the bilayer membrane to obtain Bilayer@E. The presence of EGCG on the Bilayer@E surface efficiently triggers a phenotypic transition in macrophages, shifting them from an M1 proinflammatory state to an M2 anti-inflammatory state. Moreover, the sequential release of ZnO NPs, DFO, and SiO2 NPs exhibits antimicrobial characteristics while coordinating angiogenesis and promoting osteogenic mineralization in cells. Importantly, the biomimetic periosteum shows strong in vivo bone tissue and periosteal regeneration properties in diabetic rats. The integration of sequential drug release and immunomodulation, tailored to meet the specific healing requirements during bone regeneration, offers new insights for advancing the application of biomaterials in this field.

Bovine hydroxyapatite for biomedical applications: A review of the effects of crosslinker and Secretome

Bovine Hydroxyapatite (BHA), a naturally derived material with a composition similar to human bone, has emerged as a promising candidate for biomedical applications, particularly in bone tissue engineering and regeneration. This review systematically explores the role of crosslinkers and secretomes in enhancing the properties of BHA scaffolds. Crosslinkers, such as glutaraldehyde, improve the mechanical stability and structural integrity of BHA, while secretomes from Mesenchymal Stem Cells (MSCs) contribute to cellular differentiation, angiogenesis, and tissue regeneration. In vitro and in vivo studies were analyzed to assess the osteoconductivity, biocompatibility, and regenerative potential of BHA scaffolds, particularly in combination with crosslinkers and MSC-derived secretomes. Findings suggest that crosslinkers significantly enhance the mechanical performance of BHA, although their concentration must be carefully optimized to prevent cytotoxicity. Secretomes, on the other hand, amplify the biological activity of BHA scaffolds by promoting angiogenesis and immune modulation, which are essential for tissue integration and healing. The synergistic application of crosslinkers and secretomes offers a promising strategy to optimize BHA scaffolds for bone regeneration. This review highlights the current advancements in the field and identifies future research directions to further refine these approaches for clinical applications in bone and dental tissue engineering.

Retraction: Growth factors regional patterned and photoimmobilized scaffold applied to bone tissue regeneration.

Retraction of 'Growth factors regional patterned and photoimmobilized scaffold applied to bone tissue regeneration' by Ling-Kun Zhang et al., J. Mater. Chem. B, 2020, 8, 10990-11000, https://doi.org/10.1039/D0TB02317E.

Enhanced Bone Orthopedic Dental Implants: Integrating Reduced Graphene Oxide with Chitosan and Hydroxyapatite

This study aimed to develop and evaluate chitosan (CH) and hydroxyapatite (HA)-based bone orthopedic implants (BOIs) incorporated with reduced graphene oxide (rGO) for wound healing and dental bone tissue regeneration applications. CH-HA–rGO composites were synthesized and characterized to assess their physicochemical, morphological, thermal, mechanical and bioactivity properties. Compressive strength and elongation at break were measured to evaluate mechanical properties. The morphology of the BOI was examined to confirm the pore structure. Bioactivity was assessed via calcium/phosphorus (Ca/P) content analysis, while biodegradation and biocompatibility were tested using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays on MG63 osteoblast cells. Fish waste was utilized in the preparation of BOI to explore its potential as a sustainable resource. The CH–HA–rGO BOI demonstrated excellent mechanical properties, including a compressive strength of 48.34 ± 0.74 MPa and an elongation at a break of 41.82 ± 0.24%. The implant displayed a well-developed pore structure and enhanced bioactivity with a high Ca/P content. Biocompatibility studies revealed significant cell viability of MG63 cells on the BOI, confirming its potential for biological applications. The CH–HA–rGO BOI showed superior mechanical strength, biocompatibility and bone mineralization potential, indicating its suitability for implant applications in large animals. The innovative use of fish waste in BOI preparation further highlights its sustainability and potential for tissue regeneration studies.

PH-Responsive Polyglycerol Nanogels for Periodontitis Treatment through Antibacterial and Pro-Angiogenesis Action.

Periodontitis is a microbe-driven inflammatory disease leading to bone resorption and tissue destruction. We propose a dual-functional nanogel complex armed with the antimicrobial drug triclosan (TCS) and the pro-angiogenesis medication deferoxamine (DFO) for combating microbial pathogens and promoting tissue regeneration. The nanogel system (NG-TCS-DFO) that we fabricated from linear polyglycerol exhibits well-defined spherical morphology and a positively charged surface for bacteria adhesion. The rapid and sustained degradation of NG-TCS-DFO in the acidic environment of an infection site induces the on-demand release of TCS and DFO. The NG-TCS-DFO shows potent bacteria elimination of the gingivitis-causing bacteria Porphyromonas gingivalis in both planktonic (99.9 %) and biofilm (99 %) states. Furthermore, the NG-TCS-DFO can promote vascularization and migration of human umbilical vein endothelial cells (HUVECs). Contributing to the synergistic effect of TCS and DFO, the NG-TCS-DFO demonstrates significant bone tissue regeneration and accelerated healing of periodontitis in vivo. This polyglycerol-based nanogel may therefore offer smart combined delivery of multiple therapeutics against bacteria-driven diseases.

Induced mesenchymal stem cells generated from periodontal ligament fibroblast for regenerative therapy

Bone fractures and bone loss represent significant global health challenges, with their incidence rising due to an aging population. Despite autologous bone grafts remain the gold standard for treatment, challenges such as limited bone availability, immune reactions, and the risk of infectious disease transmission have driven the search for alternative cell-based therapies for bone regeneration. Stem cells derived from oral tissues and umbilical cord mesenchymal stem cells (MSCs) have shown potential in both preclinical and clinical studies for bone tissue regeneration. However, their limited differentiation capacity and wound healing abilities necessitate the exploration of alternative cell sources. In this study, we generated induced pluripotent stem cells (iPSCs) using a safe, nonviral and mRNA-based approach from human periodontal ligament fibroblasts (PDLF), an easily accessible cell source. These iPSCs were subsequently differentiated into MSCs, referred to as induced MSCs (iMSCs). The resulting iMSCs were homogeneous, highly proliferative, and possessed anti-inflammatory properties, suggesting their potential as a superior alternative to traditional MSCs for regenerative therapy. These iMSCs demonstrated trilineage differentiation potential, giving rise to osteocytes, chondrocytes, and adipocytes. The iMSC-derived osteocytes (iOSTs) were homogeneous, patient-specific and showed excellent attachment and growth on commercial collagen-based membranes, highlighting their suitability for bone tissue regeneration applications. Given their promising characteristics compared to traditional MSCs, PDLF-derived iMSCs are strong candidates for future clinical studies in bone regeneration and other regenerative dental therapies.

Evaluation and optimization of physical, mechanical, and biological characteristics of 3D printed Whitlockite/calcium silicate composite scaffold for bone tissue regeneration using response surface methodology.

Calcium phosphate-based bioscaffolds are used for bone tissue regeneration because of their physical and chemical resemblance to human bone. Calcium, phosphate, sodium, potassium, magnesium, and silicon are important components of human bone. The successful biomimicking of human bone characteristics involves incorporating all the human bone elements into the scaffold material. In this work, Mg-Whitlockite (WH) and Calcium Silicate (CS) were selected as matrix and reinforcement respectively, because of their desirable elemental composition and regenerative properties. The magnesium in WH increases mineralization in bone, and the silicon ions in CS support vascularization. The Mg-WH was synthesized using the wet chemical method, and powder characterization tests were performed. Response surface methodology (RSM) is used to design the experiments with a combination of material compositions, infill ratios (IFs), and sintering temperatures (STs). The WH/CS bioceramic composite is 3D printed in three different compositions: 100/0, 75/25, and 50/50 wt%, with IFs of 50%, 75%, and 100%. The physical and mechanical characterization study of printed samples is conducted and the result is optimized using RSM. ANOVA (Analysis of Variance) is used to establish the relationship between input parameters and responses. The optimized input parameters were the WH/CS composition of 50/50 wt%, IF of 50%, and ST of 1150 °C, which bring out the best possible combination of physical and mechanical characteristics. The RSM optimized response was a density of 2.27 g cm-3, porosity of 36.74%, wettability of 45.79%, shrinkage of 25.13%, compressive strength of 12 MPa, and compressive modulus of 208.49 MPa with 92% desirability. The biological characterization studies were conducted for the scaffold samples prepared with optimized input parameters. The biological studies confirmed the capabilities of the WH/CS composite scaffolds in bone regenerative applications.

Piezoelectric scaffold based on polycaprolactone/thermoplastic polyurethane/barium titanate/cellulose nanocrystal for bone tissue engineering.

This study presents the development of a novel piezoelectric scaffold for bone tissue engineering composed of poly(ε-caprolactone) (PCL), thermoplastic polyurethane (TPU), barium titanate (BT), and cellulose nanocrystals (CNC). PCL and TPU are considered advantageous materials because of their ease of processing, versatility in design, and ability to degrade over time; however, their inherent immiscibility poses challenges to achieving optimal porous structures. In this study, porous scaffolds were produced using gas foaming and salt leaching techniques, resulting in highly porous interconnected scaffolds exhibiting considerable elasticity that is suitable for dynamic cell culture while avoiding the use of toxic solvents. Given the piezoelectric nature of bone tissue, incorporating electric biosignals into scaffolds is essential to enhance bone regeneration. Therefore, BT was incorporated as a piezoelectric material. CNC, derived from cotton, assisted in BT distribution and acted as a reinforcing agent, imparting mechanoelectrical signaling properties to the scaffolds. The optimized scaffolds PCL/TPU (75/25) featuring 100 μm pores were integrated with varying BT and CNC ratios and were subjected to multiple analyses. The results showed a measurable electrical output of 1.2 mV and enhanced cell adhesion, viability, and proliferation under dynamic culture conditions, underscoring their potential for bone tissue regeneration.

3D printing of bacterial poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/poly(lactide-co-glycolide) blend loaded with β-tricalcium phosphate for the development of scaffolds to support human mesenchymal stromal cell proliferation.

Polyhydroxyalkanoates (PHAs) are microbially produced aliphatic polyesters investigated for tissue engineering thanks to their biocompatibility, processability, and suitable mechanical properties. Taking advantage of these properties, the present study investigates the development by 3D printing of bacterial poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) scaffolds loaded with β-tricalcium phosphate (β-TCP) for bone tissue regeneration. PHBV blending with poly(lactide-co-glycolide) (PLGA) (30wt%) was exploited to enhance material processability via an optimized computer-aided wet-spinning approach. In particular, PHBV/PLGA blends were loaded with different β-TCP percentages (up to 15wt%) by suspending the ceramic particles into the polymeric solution. The composite materials were successfully fabricated into 3D scaffolds with a fully interconnected porous architecture, as demonstrated by scanning electron microscopy. The ceramic phase had a significant effect on PHBV crystallization as shown by differential scanning calorimetry, as well as on scaffold mechanical properties with a significant increase of compressive modulus in the case of 5wt% β-TCP loading. In addition, in vitro cell culture experiments demonstrated that β-TCP loading led to a significant increase of the viability of human mesenchymal stem/stromal cells grown on the scaffolds. Taken together, our data suggest that microbial PHBV processability, biomechanical performance, and bioactivity can be improved through combined PLGA blending and β-TCP loading.

Engineering advanced hierarchical nanoparticle surfaces via pulsed laser ablation for enhanced bone tissue regeneration

Engineering advanced hierarchical nanoparticle surfaces via pulsed laser ablation for enhanced bone tissue regeneration

Advances in the application and research of biomaterials in promoting bone repair and regeneration through immune modulation.

With the ongoing development of osteoimmunology, increasing evidence indicates that the local immune microenvironment plays a critical role in various stages of bone formation. Consequently, modulating the immune inflammatory response triggered by biomaterials to foster a more favorable immune microenvironment for bone regeneration has emerged as a novel strategy in bone tissue engineering. This review first examines the roles of various immune cells in bone tissue injury and repair. Then, the contributions of different biomaterials, including metals, bioceramics, and polymers, in promoting osteogenesis through immune regulation, as well as their future development directions, are discussed. Finally, various design strategies, such as modifying the physicochemical properties of biomaterials and integrating bioactive substances, to optimize material design and create an immune environment conducive to bone formation, are explored. In summary, this review comprehensively covers strategies and approaches for promoting bone tissue regeneration through immune modulation. It offers a thorough understanding of current research trends in biomaterial-based immune regulation, serving as a theoretical reference for the further development and clinical application of biomaterials in bone tissue engineering.

A new approach to overcome cytotoxic effects of Cu by delivering dual therapeutic ions (Sr, Cu)

IntroductionThe incorporation of trace elements such as strontium (Sr) and copper (Cu) in the composition of mesoporous bioactive glass (MBG) is widely known to enhance its biological functionality for bone tissue regeneration MethodsTwo MBG powders with the composition 80SiO2-11CaO-5P2O5-XCuO/SrO, one doped with 4mol.% of CuO, the second with 4mol.% of SrO were blended in the weight ratios of Cu-MBG: Sr-MBG; 100:0, 70: 30, 50: 50, 30: 70 and 0:100 aiming at minimizing Cu to minimize the cytotoxicity of Cu while preserving its antimicrobial activity. The synergistic effects of Sr and Cu ions on bioactivity, cytotoxicity, and antimicrobial activity were studied. ResultsTransmission electron microscopy (TEM) examination of Cu-MBG and Sr-MBG showed fringes related to the development of a mesoporous structure. The specific surface area values of the Cu-MBG and Sr-MBG powders were 287 and 349 m2/g, respectively. A characteristic compact layer consisting of particles with platelet-like morphology commonly associated with HAp crystals was confirmed after 7 days soaking in simulated body fluid (SBF). Mouse preosteoblast cells (MC3T3-E1) exhibited higher cell viability when exposed to a 1% w/v eluate from blended Cu-MBG powders compared to pure Cu-MBG. Notably, the Cu-MBG: Sr-MBG ratio of 30:70 exhibited cell viability of around 85% at this concentration. A higher cell viability (above 100%) towards MC3T3-E1 cells was observed for all powders when tested with the 0.1% w/v eluate. With progressive increase in the amount of Cu-MBG in the blended system the bacterial inhibitory effects were more pronounced. The Cu ions releases from Cu-MBG generate hydroxyl ions and increase the pH leading to disruption of the cellular membrane of microbes, resulting in enhanced antimicrobial activity. ConclusionThis newly developed blended system composed of Cu and Sr doped MBGs is expected to be more effective as bioactive filler in comparison to single ion doped MBGs for bone tissue engineering applications.

Exosomal miR-122 derived from M2 macrophages induces osteogenic differentiation of bone marrow mesenchymal stem cells in the treatment of alcoholic osteonecrosis of the femoral head

Alcoholic osteonecrosis of the femoral head (AIONFH) is caused by long-term heavy drinking, which leads to abnormal alcohol and lipid metabolism, resulting in femoral head tissue damage, and then pathological necrosis of femoral head tissue. If not treated in time in clinical practice, it will seriously affect the quality of life of patients and even require hip replacement to treat alcoholic femoral head necrosis. This study will confirm whether M2 macrophage exosome (M2-Exo) miR-122 mediates alcohol-induced BMSCs osteogenic differentiation, ultimately leading to the inhibition of femoral head necrosis. M2 macrophages were identified by flow cytometry, and the isolated exosomes were characterized by transmission electron microscopy (TEM) and Nanoparticle Tracking Analysis (NTA). Next, miR-122 was overexpressed by transfecting miR-122 mimic, and the expression of miR-122 in M2 macrophages and their exosomes was evaluated. Subsequently, the effect of exosomal miR-122 on the osteogenic differentiation ability of BMSCs was detected, including cell proliferation, expression of osteogenic-related genes (RUNX2, BMP2, OPN, ALP), and calcium nodule formation. Finally, the therapeutic effect of M2-Exo was analyzed in a rat model of AIONFH, and bone repair and pathological damage were evaluated by Micro-CT, RT-qPCR, HE, Masson staining, and immunohistochemistry (COL I). The results showed that M2 macrophages were successfully polarized, with an average M2-Exo particle size of 156.4 nm and a concentration of 3.2E + 12 particles/mL. The expression of miR-122 in M2 macrophages is significantly higher than that in M0 macrophages, and miR-122 mimic can increase the content of miR-122 in M2-Exo. miR-122 in M2-Exo can promote osteogenic differentiation of rat bone marrow BMSCs, enhance cell viability, and increase the expression of osteogenesis-related genes. After being applied to the AIONFH rat model, the injection of M2-exo and miR-122 mimics significantly improved the repair effect of articular cartilage, alleviated pathological changes, and promoted the regeneration of bone tissue. M2-macrophage-derived exosomal miR-122 induces osteogenic differentiation of bone mesenchymal stem cells in treating AIONFH.

NEAT1 regulates BMSCs aging through disruption of FGF2 nuclear transport

BackgroundThe aging of bone marrow mesenchymal stem cells (BMSCs) impairs bone tissue regeneration, contributing to skeletal disorders. LncRNA NEAT1 is considered as a proliferative inhibitory role during cellular senescence, but the relevant mechanisms remain insufficient. This study aims to elucidate how NEAT1 regulates mitotic proteins during BMSCs aging.MethodsBMSCs were isolated from alveolar bone of human volunteers aged 26–33 (young) and 66–78 (aged). NEAT1 expression and distribution changes during aging process were observed using fluorescence in situ hybridization (FISH) in young (3 months) and aged (18 months) mice or human BMSCs. Subsequent RNA pulldown and proteomic analyses, along with single-cell analysis, immunofluorescence, RNA immunoprecipitation (RIP), and co-immunoprecipitation (Co-IP), were conducted to investigate that NEAT1 impairs the nuclear transport of mitotic FGF2 and contributes to BMSCs aging.ResultsWe reveal that NEAT1 undergoes significant upregulated and shifts from nucleus to cytoplasm in bone marrow and BMSCs during aging process. In which, the expression correlates with nuclear DNA content during karyokinesis, suggesting a link to mitogenic factor. Within NEAT1 knockdown, hallmarks of cellular aging, including senescence-associated secretory phenotype (SASP), p16, and p21, were significantly downregulated. RNA pulldown and proteomic analyses further identify NEAT1 involved in osteoblast differentiation, mitotic cell cycle, and ribosome biogenesis, highlighting its role in maintaining BMSCs differentiation and proliferation. Notably, as an essential growth factor of BMSCs, Fibroblast Growth Factor 2 (FGF2) directly abundant binds to NEAT1 and the sites enriched with nuclear localization motifs. Importantly, NEAT1 decreased the interaction between FGF2 and Karyopherin Subunit Beta 1 (KPNB1), influencing the nuclear transport of mitogenic FGF2.ConclusionsOur findings position NEAT1 as a critical regulator of mitogenic protein networks that govern BMSC aging. Targeting NEAT1 might offer novel therapeutic strategies to rejuvenate aged BMSCs.

Multifunctional DNA-Collagen Biomaterials: Developmental Advances and Biomedical Applications.

The complexation of nucleic acids and collagen forms a platform biomaterial greater than the sum of its parts. This union of biomacromolecules merges the extracellular matrix functionality of collagen with the designable bioactivity of nucleic acids, enabling advances in regenerative medicine, tissue engineering, gene delivery, and targeted therapy. This review traces the historical foundations and critical applications of DNA-collagen complexes and highlights their capabilities, demonstrating them as biocompatible, bioactive, and tunable platform materials. These complexes form structures across length scales, including nanoparticles, microfibers, and hydrogels, a process controlled by the relative amount of each component and the type of nucleic acid and collagen. The broad distribution of different types of collagen within the body contributes to the extensive biological relevance of DNA-collagen complexes. Functional nucleic acids can form these complexes, such as siRNA, antisense oligonucleotides, DNA origami nanostructures, and, in particular, single-stranded DNA aptamers, often distinguished by their rapid self-assembly at room temperature and formation without external stimuli and modifications. The simple and seamless integration of nucleic acids within collagenous matrices enhances biomimicry and targeted bioactivity, and provides stability against enzymatic degradation, positioning DNA-collagen complexes as an advanced biomaterial system for many applications including angiogenesis, bone tissue regeneration, wound healing, and more.

Neuroregulation during Bone Formation and Regeneration: Mechanisms and Strategies.

The skeleton is highly innervated by numerous nerve fibers. These nerve fibers, in addition to transmitting information within the bone and mediating bone sensations, play a crucial role in regulating bone tissue formation and regeneration. Traditional bone tissue engineering (BTE) often fails to achieve satisfactory outcomes when dealing with large-scale bone defects, which is frequently related to the lack of effective reconstruction of the neurovascular network. In recent years, increasing research has revealed the critical role of nerves in bone metabolism. Nerve fibers regulate bone cells through neurotransmitters, neuropeptides, and peripheral glial cells. Furthermore, nerves also coordinate with the vascular and immune systems to jointly construct a microenvironment favorable for bone regeneration. As a signaling driver of bone formation, neuroregulation spans the entire process of bone physiological activities from the embryonic formation to postmaturity remodeling and repair. However, there is currently a lack of comprehensive summaries of these regulatory mechanisms. Therefore, this review sketches out the function of nerves during bone formation and regeneration. Then, we elaborate on the mechanisms of neurovascular coupling and neuromodulation of bone immunity. Finally, we discuss several novel strategies for neuro-bone tissue engineering (NBTE) based on neuroregulation of bone, focusing on the coordinated regeneration of nerve and bone tissue.

Preparation and Characterization of Mg-Based Biomaterials with Bioactive Surfaces Functionalized with EU/Gd NPs for Bone Tissue Regeneration Obtained via PEO Process

Preparation and Characterization of Mg-Based Biomaterials with Bioactive Surfaces Functionalized with EU/Gd NPs for Bone Tissue Regeneration Obtained via PEO Process

Low-Intensity Pulsed Ultrasound Responsive Scaffold Promotes Intramembranous and Endochondral Ossification via Ultrasonic, Thermal, and Electrical Stimulation.

Multiple physical stimuli are expected to produce a synergistic effect to promote bone tissue regeneration. Low-intensity pulsed ultrasound (LIPUS) has been clinically used in bone repair for the mechanical stimulation that it provides. In addition, LIPUS can also excite the biomaterials to generate other physical stimuli such as thermal or electrical stimuli. In this study, a scaffold based on decellularized adipose tissue (DAT) is established by incorporating polydopamine-modified multilayer black phosphorus nanosheets (pDA-mBP@DAT). Their effect on bone repair under LIPUS stimulation and the potential mechanisms are further investigated. This scaffold possesses piezoelectric properties and generates a mild thermogenic stimulus when stimulated by LIPUS. With superior properties, this scaffold is demonstrated to have good cytocompatibility in vitro and in vivo. Simultaneously, LIPUS promotes cell attachment, migration, and osteogenic differentiation in the pDA-mBP@DAT scaffold. Furthermore, the combined use of pDA-mBP@DAT and LIPUS significantly affects the regenerative effect in rat models of critical-sized calvarial defects. The possible mechanisms include promoting osteogenesis and neovascularization and activating the Piezo1. This study presents insight into speeding up bone regeneration by the synergistic combination of LIPUS and pDA-mBP@DAT scaffolds.

Bioinspired artificial antioxidases for efficient redox homeostasis and maxillofacial bone regeneration

Reconstructing large, inflammatory maxillofacial defects using stem cell-based therapy faces challenges from adverse microenvironments, including high levels of reactive oxygen species (ROS), inadequate oxygen, and intensive inflammation. Here, inspired by the reaction mechanisms of intracellular antioxidant defense systems, we propose the de novo design of an artificial antioxidase using Ru-doped layered double hydroxide (Ru-hydroxide) for efficient redox homeostasis and maxillofacial bone regeneration. Our studies demonstrate that Ru-hydroxide consists hydroxyls-synergistic monoatomic Ru centers, which efficiently react with oxygen species and collaborate with hydroxyls for rapid proton and electron transfer, thus exhibiting efficient, broad-spectrum, and robust ROS scavenging performance. Moreover, Ru-hydroxide can effectively sustain stem cell viability and osteogenic differentiation in elevated ROS environments, modulating the inflammatory microenvironment during bone tissue regeneration in male mice. We believe this Ru-hydroxide development offers a promising avenue for designing antioxidase-like materials to treat various inflammation-associated disorders, including arthritis, diabetic wounds, enteritis, and bone fractures.

Lipopeptide 01 from Staphylococcus Epidermidis Resists Pathogenic Bacteria and Promotes Bone Healing in Implant‐Associated Infections

AbstractImplant‐associated infections (IAI) present a significant clinical challenge. Effective prevention of and recovery from IAI is complex, involving antibacterial treatment and the promotion of bone integration. However, the current artificial implants used in clinics often lack effective antibacterial properties and have limited functionality. In this study, Lipopeptide 01 (LP01), a lipopeptide derived from the skin commensal Staphylococcus epidermidis is successfully immobilized, onto the porous surface of sulfonated Poly (ether‐ether‐ketone) (SPEEK) to create a novel artificial implant, LP01‐PS. Both in vivo and in vitro experiments demonstrates that LP01‐PS displays favorable material properties, biocompatibility, outstanding antibacterial characteristics, and the ability to promote bone formation. Mechanistically, LP01‐PS enhances antibacterial activities by triggering TLR2/P65 signaling, upregulating the expression of LL37 and β‐defensins in macrophages. Furthermore, it can boost the osteogenic differentiation capability of bone marrow mesenchymal stem cells (BMSCs) through the β‐catenin signaling pathway, thereby facilitating bone formation. The discovery of LP01‐PS with dual antibacterial and osteogenic effects, coupled with insights into its mode of action, suggests that LP01‐PS can serve as a promising implant material to enhance the success rates of total joint replacement surgeries, mitigate the risks of infection and prosthetic loosening, and foster the repair and regeneration of bone tissue.