Promotion Of Osteogenesis Research Articles

Osteogenesis promotion on MC3T3 by micro-area potential difference (MAPD) on titanium alloy.

The ability of osseointegration of implants is an important factor in ensuring the long-term stability of bone implants in their recipient sites. In this paper, Ti-M titanium alloys with different surface micro-area potential difference (MAPD) were prepared and the adhesion, proliferation, spreading, and differentiation behavior of osteoblasts (MC3T3) on the surface of Ti-M alloy were investigated in detail to reveal the effect of MAPD on cell compatibility and osteogenic differentiation. The results showed that the alloy with high MAPD exhibited facilitated bone differentiation, demonstrating that MAPD significantly enhanced the alkaline phosphatase activity and mineralization ability of osteoblasts, and upregulated the expression of osteogenic differentiation-related factors. It is suggested that it might be a strategy to promote the surface bioactivity of titanium alloy by adjusting the surface MAPD.&#xD.

Biological and structural properties of curcumin-loaded graphene oxide incorporated collagen as composite scaffold for bone regeneration.

To address the challenges related to bone defects, including osteoinductivity deficiency and post-implantation infection risk, this study developed the collagen composite scaffolds (CUR-GO-COL) with multifunctionality by integrating the curcumin-loaded graphene oxide with collagen through a freeze-drying-cross-linking process. The morphological and structural characteristics of the composite scaffolds were analyzed, along with their physicochemical properties, including water absorption capacity, water retention rate, porosity, in vitro degradation, and curcumin release. To evaluate the biocompatibility, cell viability, proliferation, and adhesion capabilities of the composite scaffolds, as well as their osteogenic and antimicrobial properties, in vitro cell and bacterial assays were conducted. These assays were designed to assess the impact of the composite scaffolds on cell behavior and bacterial growth, thereby providing insights into their potential for promoting osteogenesis and inhibiting infection. The CUR-GO-COL composite scaffold with a CUR-GO concentration of 0.05% (w/v) exhibits optimal biological compatibility and stable and slow curcumin release rate. Furthermore, in vitro cell and bacterial tests demonstrated that the prepared CUR-GO-COL composite scaffolds enhance cell viability, proliferation and adhesion, and offer superior osteogenic and antimicrobial properties compared with the CUR-GO composite scaffold, confirming the osteogenesis promotion and antimicrobial effects. The introduction of CUR-GO into collagen scaffold creates a bone-friendly microenvironment, and offers a theoretical foundation for the design, investigation and utilization of multifunctional bone tissue biomaterials.

Using chondroitin sulfate lithium hydrogel for diabetic bone regeneration via regulation of macrophage polarization

Bone regeneration in a diabetic environment remains a clinical challenge because of the proinflammatory microenvironment and malfunction of osteogenesis. Traditional therapy for bone defects doesn't work out in diabetes. Therefore, we introduced lithium (Li) into chondroitin sulfate (CS) and developed a crosslinked hydrogel composed of gelatin methacryloyl (GelMA) and chondroitin sulfate lithium (CS-Li) which could release Li in a sustained manner. This crosslinked hydrogel has a porous microstructure, excellent biocompatibility, and osteogenesis properties. With the synergetic effects of CS and Li, this crosslinked hydrogel regulates macrophage polarization to anti-inflammatory phenotype in the high glucose microenvironment and alleviates the inhibition of angiogenesis and osteogenesis caused by diabetes both in vitro and in vivo. The relationship between macrophage polarization and the promotion of angiogenesis and osteogenesis in diabetic microenvironments may be attributed to the activation of Glycogen synthase kinase-3β/β-catenin pathways. Overall, significant results in this study present that CS-Li was a potential therapy for bone defects in diabetic patients.

Interleukin-4-Loaded Heparin Hydrogel Regulates Macrophage Polarization to Promote Osteogenic Differentiation.

In bone tissue engineering, biological scaffolds are designed with structural and functional properties that closely resemble the extracellular environment, aiming to establish a microenvironment conducive to osteogenesis. Macrophages hold significant potential for promoting osteogenesis and modulating the biological behavior of tumor cells. Multiple coculture experiments of macrophages and osteoblasts have demonstrated that macrophage polarization significantly impacts osteogenesis. Therefore, exploring bone biomaterials that can modulate macrophage polarization holds great clinical significance. In this study, heparin was modified with maleimide and was used as a raw material to form a hydrogel with 4-am-PEG-SH. The compound was used to polarize macrophages and promote osteogenesis after combining with interleukin 4 (IL-4) by taking advantage of the electronegativity of heparin. The results revealed overexpressed M2 macrophage-related phenotypic genes and cocultivation with MC3T3-E1 cells demonstrated the osteogenesis-promoting effect of the loaded IL-4 heparin hydrogel. Previous research reported that hydrogel loaded with IL-4 can be used as a biomaterial for osteogenesis promotion. Heparin materials used in this paper are derived from clinically anticoagulant drugs and feature a simple operation. The synthesized hydrogel effectively binds cytokines, regulates macrophages to induce osteogenesis and has many potential clinical applications.

Zinc finger-inspired peptide-metal-phenolic nanointerface enhances bone-implant integration under bacterial infection microenvironment through immune modulation and osteogenesis promotion

Orthopedic and dental implantations under bacterial infection microenvironment face significant challenges in achieving high-quality bone-implant integration. Designing implant coatings that incorporate both immune defense and anti-inflammation is difficult in conventional single-functional coatings. We introduce a multifunctional nanointerface using a zinc finger-inspired peptide-metal-phenolic nanocoating, designed to enhance implant osseointegration under such conditions. Abaloparatide (ABL), a second-generation anabolic drug for treating osteoporosis, can be integrated into the design of a zinc-phenolic network constructed on the implant surface (ABL@ZnTA). Importantly, the phenolic-coordinated Zn2+ ions in ABL@ZnTA can act as zinc finger motif to co-stabilize the configuration of ABL through multiple molecular interactions, enabling high bioactivity, high loading capacity (1.36 times), and long-term release (>7 days) of ABL. Our results showed that ABL@ZnTA can modulate macrophage polarization from the pro-inflammatory M1 towards the anti-inflammatory M2 phenotype, promoting immune osteogenesis with increased OCN, ALP, and SOD 1 expression. Furthermore, the ABL@ZnTA significantly reduces inflammatory fibrous tissue encapsulation and enhances the long-term stability of the implants, indicated by enhanced binding strength (6 times) and functional connectivity (1.5−3 times) in the rat bone defect model infected by S. aureus. Overall, our research offers a nano-enabled synergistic strategy that balances infection defense and osteogenesis promotion in orthopedic and dental implantations.

Polyaptamer-Driven Crystallization of Alendronate for Synergistic Osteoporosis Treatment through Osteoclastic Inhibition and Osteogenic Promotion.

Osteoclastic inhibition using antiresorptive bisphosphonates and osteogenic promotion using antisclerostin agents represent two distinct osteoporosis treatments in clinical practice, each individual treatment suffers from unsatisfactory therapeutic efficacy due to its indirect intervention in osteoclasis and promotion of osteogenesis simultaneously. Although this issue is anticipated to be resolved by drug synergism, a tempting carrier-free dual-medication nanoassembly remains elusive. Herein, we prepare such a nanoassembly made of antiresorptive alendronate (ALN) crystal and antisclerostin polyaptamer (Apt) via a nucleic acid-driven crystallization method. This nanoparticle can protect Apt from rapid nuclease degradation, avoid the high cytotoxicity of free ALN, and effectively concentrate in the cancellous bone by virtue of the bone-binding ability of DNA and ALN. More importantly, the acid microenvironment of cancellous bone triggers the disassociation of nanoparticles for sustained drug release, from which ALN inhibits the osteoclast-mediated bone resorption while Apt promotes osteogenic differentiation. Our work represents a pioneering demonstration of nucleic acid-driven crystallization of a bisphosphonate into a tempting carrier-free dual-medication nanoassembly. This inaugural advancement augments the antiosteoporosis efficacy through direct inhibition of osteoclasis and promotion of osteogenesis simultaneously and establishes a paradigm for profound understanding of the underlying synergistic antiosteoporosis mechanism of antiresorptive and antisclerostin components. It is envisioned that this study provides a highly generalizable strategy applicable to the tailoring of a diverse array of DNA-inorganic nanocomposites for targeted regulation of intricate pathological niches.

3D-printed HA15-loaded β-Tricalcium Phosphate/Poly (Lactic-co-glycolic acid) Bone Tissue Scaffold Promotes Bone Regeneration in Rabbit Radial Defects.

In this study, a β-tricalcium phosphate (β-TCP)/poly (lactic-co-glycolic acid) (PLGA) bone tissue scaffold was loaded with osteogenesis-promoting drug HA15 and constructed by three-dimensional (3D) printing technology. This drug delivery system with favorable biomechanical properties, bone conduction function, and local release of osteogenic drugs could provide the basis for the treatment of bone defects. The biomechanical properties of the scaffold were investigated by compressive testing, showing comparable biomechanical properties with cancellous bone tissue. Furthermore, the microstructure, pore morphology, and condition were studied. Moreover, the drug release concentration, the effect of anti-tuberculosis drugs in vitro and in rabbit radial defects, and the ability of the scaffold to repair the defects were studied. The results show that the scaffold loaded with HA15 can promote cell differentiation into osteoblasts in vitro, targeting HSPA5. The micro-computed tomography scans showed that after 12 weeks of scaffold implantation, the defect of the rabbit radius was repaired and the peripheral blood vessels were regenerated. Thus, HA15 can target HSPA5 to inhibit endoplasmic reticulum stress which finally leads to promotion of osteogenesis, bone regeneration, and angiogenesis in the rabbit bone defect model. Overall, the 3D-printed β-TCP/PLGA-loaded HA15 bone tissue scaffold can be used as a substitute material for the treatment of bone defects because of its unique biomechanical properties and bone conductivity.

Global research trends of nanomaterials application in periodontitis and peri-implantitis: A bibliometric analysis

BackgroundThe application of nanomaterials (NMs) in the treatment of periodontitis and peri-implantitis has shown multifunctional benefits, such as antibacterial properties, immune regulation, and promotion of osteogenesis. However, a comprehensive bibliometric analysis to evaluate global scientific production in this field has not yet been conducted. MethodWe searched for publications related to nanomaterials in periodontitis and peri-implantitis using the WOSCC database. The contributions from institutions, journals, countries, and authors were assessed using VOSviewer, the bibliometrix R package, and Microsoft Excel 2019. ResultsWe identified 2275 publications from 66 countries/regions focusing on nanomaterials in periodontitis and peri-implantitis, published between 1993 and 2023. China and the USA were the top contributors in this field, with 653 and 221 publications, respectively. Key topics include antibacterial properties, delivery systems, nanoparticles, and regeneration. The research focus has evolved from traditional treatments to advanced applications of multifunctional nanomaterials. ConclusionSignificant progress has been made in the application of NMs in periodontitis and peri-implantitis from 1993 to 2023. Future research hotspots will likely focus on multifunctional nanomaterials and those adhering to good manufacturing practices (GMP).

Unlocking the potential of stimuli-responsive biomaterials for bone regeneration.

Bone defects caused by tumors, osteoarthritis, and osteoporosis attract great attention. Because of outstanding biocompatibility, osteogenesis promotion, and less secondary infection incidence ratio, stimuli-responsive biomaterials are increasingly used to manage this issue. These biomaterials respond to certain stimuli, changing their mechanical properties, shape, or drug release rate accordingly. Thereafter, the activated materials exert instructive or triggering effects on cells and tissues, match the properties of the original bone tissues, establish tight connection with ambient hard tissue, and provide suitable mechanical strength. In this review, basic definitions of different categories of stimuli-responsive biomaterials are presented. Moreover, possible mechanisms, advanced studies, and pros and cons of each classification are discussed and analyzed. This review aims to provide an outlook on the future developments in stimuli-responsive biomaterials.

Injectable hydrogel scaffold incorporating microspheres containing cobalt-doped bioactive glass for bone healing.

Injectable in situ-forming scaffolds that induce both angiogenesis and osteogenesis have been proven to be promising for bone healing applications. Here, we report the synthesis of an injectable hydrogel containing cobalt-doped bioactive glass (BG)-loaded microspheres. Silk fibroin (SF)/gelatin microspheres containing BG particles were fabricated through microfluidics. The microspheres were mixed in an injectable alginate solution, which formed an in situ hydrogel by adding CaCl2. The hydrogel was evaluated for its physicochemical properties, in vitro interactions with osteoblast-like and endothelial cells, and bone healing potential in a rat model of calvarial defect. The microspheres were well-dispersed in the hydrogel and formed pores of >100 μm. The hydrogel displayed shear-thinning behavior and modulated the cobalt release so that the optimal cobalt concentration for angiogenic stimulation, cell proliferation, and deposition of mineralized matrix was only achieved by the scaffold that contained BG doped with 5% wt/wt cobalt (A-S-G5Co). In the scaffold containing higher cobalt content, a reduced biomimetic mineralization on the surface was observed. The gene expression study indicated an upregulation of the osteogenic genes of COL1A1, ALPL, OCN, and RUNX2 and angiogenic genes of HIF1A and VEGF at different time points in the cells cultured with the A-S-G5Co. Finally, the in vivo study demonstrated that A-S-G5Co significantly promoted both angiogenesis and osteogenesis and improved bone healing after 12 weeks of follow-up. These results show that incorporation of SF/gelatin microspheres containing cobalt-doped BG in an injectable in situ-forming scaffold can effectively enhance its bone healing potential through promotion of angiogenesis and osteogenesis.

Nanofibrous Microspheres: A Biomimetic Platform for Bone Tissue Regeneration.

Bone, a fundamental constituent of the human body, is a vital scaffold for support, protection, and locomotion, underscoring its pivotal role in maintaining skeletal integrity and overall functionality. However, factors such as trauma, disease, or aging can compromise bone structure, necessitating effective strategies for regeneration. Traditional approaches often lack biomimetic environments conducive to efficient tissue repair. Nanofibrous microspheres (NFMS) present a promising biomimetic platform for bone regeneration by mimicking the native extracellular matrix architecture. Through optimized fabrication techniques and the incorporation of active biomolecular components, NFMS can precisely replicate the nanostructure and biochemical cues essential for osteogenesis promotion. Furthermore, NFMS exhibit versatile properties, including tunable morphology, mechanical strength, and controlled release kinetics, augmenting their suitability for tailored bone tissue engineering applications. NFMS enhance cell recruitment, attachment, and proliferation, while promoting osteogenic differentiation and mineralization, thereby accelerating bone healing. This review highlights the pivotal role of NFMS in bone tissue engineering, elucidating their design principles and key attributes. By examining recent preclinical applications, we assess their current clinical status and discuss critical considerations for potential clinical translation. This review offers crucial insights for researchers at the intersection of biomaterials and tissue engineering, highlighting developments in this expanding field.

An intelligent controlled release hydrogel with photothermal effect for the treatment of bone defects

To solve the difficulty of natural healing in patients with severe bone defects, and the challenges of insufficient autologous bone graft material and large incisions in conventional surgery, we were designed an intelligent co-regulated hydrogel system with NIR response. The goal is to be able to prevent inflammation and bacterial adhesion, thereby promoting repair and development of the bone defect area. The hydrogel system consisted of hyaluronic acid, carboxymethyl chitosan and Pht-loaded PDA-encapsulated ZIF-8 NPs (Pht@ZIF-8@PDA) by Schiff base reaction. Compared to high-temperature photothermal therapy (PTT), which destroyed surrounding healthy cells, the present study was based on a new strategy of mild photothermal therapy (42.5 ± 1.2 °C) and leaded to a better promotion of osteogenesis. NIR activated the photothermal properties of PDA in scaffolds, intelligently released Pht and Zn2+, inhibited Escherichia coli and Staphylococcus aureus (inhibition rate ≥ 96 %), and promoted bone regeneration in the rat model. Meanwhile, it could promote bone regeneration by upregulating osteogenic factors and stimulating the expression of proteins related to BMP/SMAD signaling pathway. The research highlights the potential applications of synergistically modulated hydrogels, which opens up a new application path for this material in bone tissue engineering, regenerative medicine, and other related fields.

Inflammatory microenvironment regulation and osteogenesis promotion by bone-targeting calcium and magnesium repletion nanoplatform for osteoporosis therapy

Osteoporosis is the most common bone metabolic disease that affects the health of middle-aged and elderly people, which is hallmarked by imbalanced bone remodeling and a deteriorating immune microenvironment. Magnesium and calcium are pivotal matrix components that participate in the bone formation process, especially in the immune microenvironment regulation and bone remodeling stages. Nevertheless, how to potently deliver magnesium and calcium to bone tissue remains a challenge. Here, we have constructed a multifunctional nanoplatform composed of calcium-based upconversion nanoparticles and magnesium organic frameworks (CM-NH2-PAA-Ald, denoted as CMPA), which features bone-targeting and pH-responsive properties, effectively regulating the inflammatory microenvironment and promoting the coordination of osteogenic functions for treating osteoporosis. The nanoplatform can efficaciously target bone tissue and gradually degrade in response to the acidic microenvironment of osteoporosis to release magnesium and calcium ions. This study validates that CMPA possessing favorable biocompatibility can suppress inflammation and facilitate osteogenesis to treat osteoporosis. Importantly, high-throughput sequencing results demonstrate that the nanoplatform exerts a good inflammatory regulation effect through inhibition of the nuclear factor kappa-B signaling pathway, thereby normalizing the osteoporotic microenvironment. This collaborative therapeutic strategy that focuses on improving bone microenvironment and promoting osteogenesis provides new insight for the treatment of metabolic diseases such as osteoporosis.

The Effect of Antibacterial-Osteogenic Surface Modification on the Osseointegration of Titanium Implants: A Static and Dynamic Strategy.

Titanium (Ti) and its alloys are widely used biomaterials in bone repair. Although these biomaterials possess stable properties and good biocompatibility, the high elastic modulus and low surface activity of Ti implants have often been associated with infection, inflammation, and poor osteogenesis. Therefore, there is an urgent need to modify the surface of Ti implants, where changes in surface morphology or coatings loading can confer specific functions to help them adapt to the osseointegration formation phase and resist bacterial infection. This can further ensure a healthy microenvironment for bone regeneration as well as the promotion of immunomodulation, angiogenesis, and osteogenesis. Therefore, in this review, we evaluated various functional Ti implants after surface modification, both in terms of static modifications and dynamic response strategies, mainly focusing on the synergistic effects of antimicrobial activities and functionalized osteogenic. Finally, the current challenges and future perspectives are summarized to provide innovative and effective solutions for osseointegration and bone defect repair.

An Injectable Black Phosphorus Hydrogel for Rapid Tooth Extraction Socket Healing.

The excess production of reactive oxygen species (ROS) will delay tooth extraction socket (TES) healing. In this study, we developed an injectable thermosensitive hydrogel (NBP@BP@CS) used to treat TES healing. The hydrogel formulation incorporated black phosphorus (BP) nanoflakes, recognized for their accelerated alveolar bone regeneration and ROS-scavenging properties, and dl-3-n-butylphthalide (NBP), a vasodilator aimed at enhancing angiogenesis. In vivo investigations strongly demonstrated that NBP@BP@CS improved TES healing due to antioxidation and promotion of alveolar bone regeneration by BP nanoflakes. The sustained release of NBP from the hydrogel promoted neovascularization and vascular remodeling. Our results demonstrated that the designed thermosensitive hydrogel provided great opportunity not only for ROS elimination but also for the promotion of osteogenesis and angiogenesis, reflecting the "three birds with one stone" concept, and has tremendous potential for rapid TES healing.

A Self-Transformed N-Chlorinated ε-Polylysine Coating Endows Titanium Implants with Programmed Integration of Robust Antibacterial and Pro-Osteogenic Abilities

Implant-associated infection and poor osseointegration are the main causes of orthopedic implantation failure. For a long-term successful implantation, simultaneously introducing prevention of infection and promotion of osteogenesis into implants is highly desired but remains a grand challenge. Inspired by the human immune mechanism of tissue repair under bacterial infection, we propose a self-transformed strategy for the modification of titanium with porous N-chlorinated ε-polylysine coating (Ti-PL-NCl) through pore-making, surface grafting and chlorination. The as-prepared Ti-PL-NCl exhibits an excellent antibacterial activity against S. aureus and E. coli in the presence of N-chloramine in the early stage, with an antibacterial rate as high as 95.8% and 99.4%, respectively. With the consumption of oxidative chlorine, the N─Cl groups of Ti-PL-NCl are transformed into N─H groups with moderate antibacterial yet strong pro-osteogenic abilities. The self-transformed N-chlorinated ε-polylysine coating enables Ti-PL-NCl to achieve long-lasting antibacterial activity as well as enhanced pro-osteogenesis, thus providing adaptive bioactivities for bone-implant integration. Rat implant-associated osteomyelitis model confirms that Ti-PL-NCl has excellent efficacy of infection prevention and osseointegration promotion. This work may provide a new paradigm of designing multifunctional implants to achieve long-term successful implantation.

Nanoparticle-Mediated Multiple Modulation of Bone Microenvironment To Tackle Osteoarthritis.

Development of nanomedicines that can collaboratively scavenge reactive oxygen species (ROS) and inhibit inflammatory cytokines, along with osteogenesis promotion, is essential for efficient osteoarthritis (OA) treatment. Herein, we report the design of a ROS-responsive nanomedicine formulation based on fibronectin (FN)-coated polymer nanoparticles (NPs) loaded with azabisdimethylphoaphonate-terminated phosphorus dendrimers (G4-TBP). The constructed G4-TBP NPs-FN with a size of 268 nm are stable under physiological conditions, can be specifically taken up by macrophages through the FN-mediated targeting, and can be dissociated in the oxidative inflammatory microenvironment. The G4-TBP NPs-FN loaded with G4-TBP dendrimer having intrinsic anti-inflammatory property and FN having both anti-inflammatory and antioxidative properties display integrated functions of ROS scavenging, hypoxia attenuation, and macrophage M2 polarization, thus protecting macrophages from apoptosis and creating designed bone immune microenvironment for stem cell osteogenic differentiation. These characteristics of the G4-TBP NPs-FN lead to their effective treatment of an OA model in vivo to reduce pathological changes of joints including synovitis inhibition and cartilage matrix degradation and simultaneously promote osteogenic differentiation for bone repair. The developed nanomedicine formulation combining the advantages of both bioactive phosphorus dendrimers and FN to treat OA may be developed for immunomodulatory therapy of different inflammatory diseases.

Porous Titanium/SF Sponge Composite Scaffold with Loads of Gentamicin and Small Extracellular Vesicles to Improve Antibacterial and Osteogenesis Properties

AbstractAdditive manufacturing has been widely used for producing porous titanium orthopedic implants. However, the higher surface area inherent to porous structures increases the risk of bacterial colonization. In this work, composite scaffolds with dual functions of the antibacterial and osteogenesis promotion properties are developed. The porous titanium is fabricated using a selective laser melting process to provide mechanical support. Silk fibrin (SF) sponge‐loading gentamicin and extracellular vesicles (EVs) are prepared in the pores of the porous titanium. The developed composite scaffolds are investigated for their antibacterial and osteogenesis effects. The samples exhibit well antibacterial activity against Escherichia coli. The samples also show good cytocompatibility, effectively promoting the adhesion and proliferation of the bone marrow mesenchymal stem cells (rBMSCs). EVs significantly promote the expression of osteogenesis‐related genes in rBMCSs and the superior extracellular matrix mineralization reveals that EVs have a remarkable role in enhancing osteogenic differentiation. Therefore, the composite scaffolds with dual functions of antibacterial and osteogenesis promotion properties have excellent potential for orthopedic implant applications.

Enhanced Bacterial Cuproptosis-Like Death via Reversal of Hypoxia Microenvironment for Biofilm Infection Treatment.

A recently emerging cell death pathway, known as copper-induced cell death, has demonstrated significant potential for treating infections. Existing research suggests that cells utilizing aerobic respiration, as opposed to those reliant on glycolysis, exhibit greater sensitivity to copper-induced death. Herein, a MnO2-loaded copper metal-organic frameworks platform is developed denoted as MCM, to enhance bacterial cuproptosis-like death via the remodeling of bacterial respiratory metabolism. The reversal of hypoxic microenvironments induced a cascade of responses, encompassing the reactivation of suppressed immune responses and the promotion of osteogenesis and angiogenesis. Initially, MCM catalyzed O2 production, alleviating hypoxia within the biofilm and inducing a transition in bacterial respiration mode from glycolysis to aerobic respiration. Subsequently, the sensitized bacteria, characterized by enhanced tricarboxylic acid cycle activity, underwent cuproptosis-like death owing to increased copper concentrations and aggregated intracellular dihydrolipoamide S-acetyltransferase (DLAT). The disruption of hypoxia also stimulated suppressed dendritic cells and macrophages, thereby strengthening their antimicrobial activity through chemotaxis and phagocytosis. Moreover, the nutritional effects of copper elements, coupled with hypoxia alleviation, synergistically facilitated the regeneration of bones and blood vessels. Overall, reshaping the infection microenvironment to enhance cuproptosis-like cell death presents a promising avenue for eradicating biofilms.

Osseointegrative and immunomodulative 3D-Printing Ti6Al4V-based implants embedded with biogenic hydroxyapatite

Although titanium-based metal implants have become a game changer in dental and orthopedic therapies, they still have several problems such as late osseointegration and immune response. In this study, we present a novel strategy to develop Ti6Al4V-based implants embedded with biogenic hydroxyapatite derived from equine bone to overcome these problems. A selective laser melting technique was employed for facile fabrication with flexible fusing feedstock and regular uniform distribution of equine bone. The physicochemical characteristics, cell attachment and proliferation, osteogenic differentiation, osseointegration, inflammatory response, and metabolomics of the developed Ti6Al4V/equine bone composite were then investigated. The Ti6Al4V-based composite integrated with equine bone at a certain concentration has improved the crystalline structure (β-Ti) suitable for implantation and exhibited higher hydrophilicity and protein adsorption. They significantly promoted cell attachment, osteogenic differentiation, and anti-inflammatory effects in vitro. In vivo study confirmed the osseointegration and alleviated inflammatory responses. Furthermore, the Ti6Al4V-based implants integrated with equine bone significantly reduced metabolites associated with inflammatory responses both in vitro and in vivo. The observed reduction in inflammatory responses suggests a subsequent promotion of osteogenesis. These promising results position the Ti6Al4V-based implant integrated with equine bone as a potential candidate for replacing conventional dental and orthopedic implants.