An injectable hydrogel dressing for controlled release of hydrogen sulfide pleiotropically mediates the wound microenvironment.

The healing of scalded wounds faces many challenges such as chronic inflammation, oxidative stress, wound infection, and difficulties in vascular and nerve regeneration. Treating a single problem cannot effectively coordinate the complex regenerative microenvironment of scalded wounds, limiting the healing and functional recovery of the skin. Therefore, there is a need to develop a multi-effect treatment plan that can adaptively address the issues at each stage of wound healing. In this study, we propose a scheme for on-demand release of hydrogen sulfide (H2S) based on the concentration of reactive oxygen species (ROS) in the wound microenvironment. This is achieved by encapsulating peroxythiocarbamate (PTCM) in the ROS-responsive polymer poly(ethylene glycol)-poly(L-methionine) (PMet) to form nanoparticles, which are loaded into a thermosensitive injectable hydrogel, F127-poly(L-aspartic acid-N-hydroxysuccinimide) (F127-P(Asp-NHS)), to create a scald dressing. The H2S released by the hydrogel dressing on demand regulates the wound microenvironment by alleviating infection, reducing oxidative stress, and remodeling inflammation, thereby accelerating the healing of full-thickness scalded wounds. This hydrogel dressing for the adaptive release of H2S has great potential in addressing complex scalded wounds associated with infection and chronic inflammation.

Mg-gallate metal-organic framework-based sprayable hydrogel for continuously regulating oxidative stress microenvironment and promoting neurovascular network reconstruction in diabetic wounds.

Chronic diabetic wounds are the most common complication for diabetic patients. Due to high oxidative stress levels affecting the entire healing process, treating diabetic wounds remains a challenge. Here, we present a strategy for continuously regulating oxidative stress microenvironment by the catalyst-like magnesium-gallate metal-organic framework (Mg-GA MOF) and developing sprayable hydrogel dressing with sodium alginate/chitosan quaternary ammonium salts to treat diabetic wounds. Chitosan quaternary ammonium salts with antibacterial properties can prevent bacterial infection. The continuous release of gallic acid (GA) effectively eliminates reactive oxygen species (ROS), reduces oxidative stress, and accelerates the polarization of M1-type macrophages to M2-type, shortening the transition between inflammation and proliferative phase and maintaining redox balance. Besides, magnesium ions adjuvant therapy promotes vascular regeneration and neuronal formation by activating the expression of vascular-associated genes. Sprayable hydrogel dressings with antibacterial, antioxidant, and inflammatory regulation rapidly repair diabetic wounds by promoting neurovascular network reconstruction and accelerating re-epithelialization and collagen deposition. This study confirms the feasibility of catalyst-like MOF-contained sprayable hydrogel to regulate the microenvironment continuously and provides guidance for developing the next generation of non-drug diabetes dressings.

Corrigendum to "Design and fabrication of high-performance self-setting trimagnesium phosphate" [Bioact. Mater. 28 (2023) 348-357].

[This corrects the article DOI: 10.1016/j.bioactmat.2023.05.019.].

Metabolic Control During Macrophage Polarization by a Citrate-Functionalized Scaffold for Maintaining Bone Homeostasis.

Metabolites, as markers of phenotype at the molecular level, can regulate the function of DNA, RNA, and proteins through chemical modifications or interactions with large molecules. Citrate is an important metabolite that affects macrophage polarization and osteoporotic bone function. Therefore, a better understanding of the precise effect of citrate on macrophage polarization may provide an effective alternative strategy to reverse osteoporotic bone metabolism. In this study, a citrate functional scaffold to control the metabolic pathway during macrophage polarization based on the metabolic differences between pro-inflammatory and anti-inflammatory phenotypes for maintaining bone homeostasis, is fabricated. Mechanistically, only outside M1 macrophages are accumulated high concentrations of citrate, in contrast, M2 macrophages consume massive citrate. Therefore, citrate-functionalized scaffolds exert more sensitive inhibitory effects on metabolic enzyme activity during M1 macrophage polarization than M2 macrophage polarization. Citrate can block glycolysis-related enzymes by occupying the binding-site and ensure sufficient metabolic flux in the TCA cycle, so as to turn the metabolism of macrophages to oxidative phosphorylation of M2 macrophage, largely maintaining bone homeostasis. These studies indicate that exogenous citrate can realize metabolic control of macrophage polarization for maintaining bone homeostasis in osteoporosis.

A double-network porous hydrogel based on high internal phase emulsions as a vehicle for potassium sucrose octasulfate delivery accelerates diabetic wound healing.

Diabetic wounds are a difficult medical challenge. Excessive secretion of matrix metalloproteinase-9 (MMP-9) in diabetic wounds further degrades the extracellular matrix and growth factors and causes severe vascular damage, which seriously hinders diabetic wound healing. To solve these issues, a double-network porous hydrogel composed of poly (methyl methacrylate-co-acrylamide) (p(MMA-co-AM)) and polyvinyl alcohol (PVA) was constructed by the high internal phase emulsion (HIPE) technique for the delivery of potassium sucrose octasulfate (PSO), a drug that can inhibit MMPs, increase angiogenesis and improve microcirculation. The hydrogel possessed a typical polyHIPE hierarchical microstructure with interconnected porous morphologies, high porosity, high specific surface area, excellent mechanical properties and suitable swelling properties. Meanwhile, the p(MMA-co-AM)/PVA@PSO hydrogel showed high drug-loading performance and effective PSO release. In addition, both in vitro and in vivo studies showed that the p(MMA-co-AM)/PVA@PSO hydrogel had good biocompatibility and significantly accelerated diabetic wound healing by inhibiting excessive MMP-9 in diabetic wounds, increasing growth factor secretion, improving vascularization, increasing collagen deposition and promoting re-epithelialization. Therefore, this study provided a reliable therapeutic strategy for diabetic wound healing, some theoretical basis and new insights for the rational design and preparation of wound hydrogel dressings with high porosity, high drug-loading performance and excellent mechanical properties.

Healing with precision: A multi-functional hydrogel-bioactive glass dressing boosts infected wound recovery and enhances neurogenesis in the wound bed.

Chronic skin wounds, especially infected ones, pose a significant clinical challenge due to their increasing incidence and poor outcomes. The deteriorative microenvironment in such wounds, characterized by reduced extracellular matrix, impaired angiogenesis, insufficient neurogenesis, and persistent bacterial infection, has prompted the exploration of novel therapeutic strategies. In this study, we developed an injectable multifunctional hydrogel (GEL/BG@Cu + Mg) incorporating Gelatin-Tannic acid/ N-hydroxysuccinimide functionalized polyethylene glycol and Bioactive glass doped with copper and magnesium ions to accelerate the healing of infected wounds. The GEL/BG@Cu + Mg hydrogel composite demonstrates good biocompatibility, degradability, and rapid formation of a protective barrier to stop bleeding. Synergistic bactericidal effects are achieved through the photothermal properties of BG@Cu + Mg and sustained copper ions release, with the latter further promoting angiogenesis. Furthermore, the hydrogel enhances neurogenesis by stimulating axons and Schwann cells in the wound bed through the beneficial effects of magnesium ions. Our results demonstrate that the designed novel multifunctional hydrogel holds tremendous promise for treating infected wounds and allowing regenerative neurogenesis at the wound site, which provides a viable alternative for further improving clinical outcomes.

An Antibacterial Bionic Periosteum with Angiogenesis-Neurogenesis Coupling Effect for Bone Regeneration.

The periosteum, rich in neurovascular networks, bone progenitor cells, and stem cells, is vital for bone repair. Current artificial periosteal materials face challenges in mechanical strength, bacterial infection, and promoting osteogenic differentiation and angiogenesis. To address these issues, we adjusted the electrospinning ratio of poly-ε-caprolactone and chitosan and incorporated Zn doping whitlockite with polydopamine coating into a nanofiber membrane. After a series of characterizations, optimal results were achieved with a poly-ε-caprolactone: chitosan ratio of 8:1 and 5% nanoparticle content. In vitro cell experiments and in vivo calvarial defect models, the sustained release of Mg2+ and Ca2+ promoted vascularization and new bone formation, respectively, while the release of Zn2+ was conducive to antibacterial and cooperated with Mg2+ to promote neurovascularization. Consequently, this antibacterial bionic periosteum with an angiogenesis-neurogenesis coupling effect demonstrates a promising potential for bone repair applications.

One Stone Three Birds: Silver Sulfadiazine Modulates the Stability and Dynamics of Hydrogels for Infected Wound Healing.

Dynamic covalent bond hydrogels have demonstrated significant application potential in biomedical fields for their dynamic reversibility. However, the contradiction between the stability and dynamics of the hydrogel restricts its application. Here, utilizing silver sulfadiazine (AgSD) as a catalyst, hyaluronic acid-based hydrogels are constructed through imine bond crosslinking and incorporated disulfide bonds within the same crosslinking chain. It is found that AgSD can accelerate the formation of imine crosslinking bonds to improve the stability of hydrogels, thereby shortening the gelation time by ≈36.9 times, enhancing compression strength and adhesion strength by ≈2.4 times and 1.7 times, respectively, while inhibiting swelling and degradation rates to ≈2.1 times and 3.7 times. Besides, AgSD can coordinate with disulfide bonds to enhance the dynamics of hydrogel, enhancing the hydrogel self-healing efficiency by ≈2.3 times while reducing the relaxation time by ≈25.1 times. Significantly, AgSD imparts remarkable antibacterial properties to the hydrogel, thereby effectively facilitating the healing of bacterial infected wounds. Consequently, introducing AgSD enables hydrogels to possess concurrent stability, dynamics, and antibacterial properties. This strategy of regulating hydrogels by introducing AgSD provides a valuable reference for the application of dynamic covalent bonds.

Sonodynamic-chemotherapy synergy with chlorin e6-based carrier-free nanoparticles for non-small cell lung cancer.

Sonodynamic therapy (SDT), an emerging cancer treatment with significant potential, offers the advantages of non-invasiveness and deep tissue penetrability. The method involves activating sonosensitizers with ultrasound to generate reactive oxygen species (ROS) capable of eradicating cancer cells, addressing the challenge faced by photodynamic therapy (PDT) where conventional light sources struggle to penetrate deep tissues, impacting treatment efficacy. This study addresses prevalent challenges in numerous nanodiagnostic and therapeutic agents, such as intricate synthesis, poor repeatability, low stability, and high cost, by introducing a streamlined one-step assembly method for nanoparticle preparation. Specifically, the sonosensitizer Chlorin e6 (Ce6) and the chemotherapy drug erlotinib are effortlessly combined and self-assembled under sonication, yielding carrier-free nanoparticles (EC-NPs) for non-small cell lung cancer (NSCLC) treatment. The resulting EC-NPs exhibit optimal drug loading capacity, a simplified preparation process, and robust stability both in vitro and in vivo, owing to their carrier-free characteristics. Under the synergistic treatment of sonodynamic therapy and chemotherapy, EC-NPs induce an excess of reactive oxygen in tumor tissue, prompting apoptosis of cancer cells and reducing their proliferative capacity. Both in vitro and in vivo experiments demonstrate superior therapeutic effects of EC-NPs under ultrasound conditions compared to free Ce6. In summary, our research findings highlight that the innovatively designed carrier-free sonosensitizer EC-NPs present a therapeutic option with commendable efficacy and minimal side effects.

Strontium-Doped Hydroxyapatite Coating Improves Osteo/Angiogenesis for Ameliorative Graft-Bone Integration via the Macrophage-Derived Cytokines-Mediated Integrin Signal Pathway.

Polyethylene terephthalate (PET) artificial ligaments, renowned for their superior mechanical properties, have been extensively adopted in anterior cruciate ligament (ACL) reconstruction surgeries. However, the inherent bio-inertness of PET introduces formidable barriers to graft-bone integration, a critical aspect of rehabilitation. Previous interventions, ranging from surface roughening to chemical modifications, have aimed to address this challenge; however, consistently effective techniques for inducing graft-bone integration remain scarce. Our study employed advanced surface-coating methodologies to introduce strontium-doped hydroxyapatite (SrHA) onto PET ligaments. Detailed scanning electron microscopy (SEM) examinations revealed a uniform and integrative coating of SrHA on PET fibers. Furthermore, spectroscopic analysis confirmed the steady release of strontium ions from the coated surface under physiological conditions. In-depth cellular studies proved that extracellular strontium emanating from SrHA-coated PET (PET@SrHA) ligaments actively steers the M2 macrophage polarization. Additionally, macrophages (Mφs) manifested a heightened secretion of prohealing cytokines when exposed to PET@SrHA. Subsequent investigations showed that these cytokines acted as mediators, activating integrin signaling pathways among macrophages, vascular endothelial cells, and osteoblasts. As a direct consequence, an increased rate of angiogenesis and osteogenic differentiation was observed, vital for graft-bone integration following ACL reconstruction with PET@SrHA ligaments. From a biochemical standpoint, our results pinpoint strontium ions as influential immunomodulators, sculpting the graft-bone interface's immune environment. This insight presents the SrHA-coating technique as a viable therapeutic strategy, holding sound promise for improving angiogenesis and osseointegration outcomes during ACL reconstruction using PET-based grafts.

An Adaptable Drug Delivery System Facilitates Peripheral Nerve Repair by Remodeling the Microenvironment.

The multifaceted process of nerve regeneration following damage remains a significant clinical issue, due to the lack of a favorable regenerative microenvironment and insufficient endogenous biochemical signaling. However, the current nerve grafts have limitations in functionality, as they require a greater capacity to effectively regulate the intricate microenvironment associated with nerve regeneration. In this regard, we proposed the construction of a functional artificial scaffold based on a "two-pronged" approach. The whole system was developed by encapsulating Tazarotene within nanomicelles formed through self-assembly of reactive oxygen species (ROS)-responsive amphiphilic triblock copolymer, all of which were further loaded into a thermosensitive injectable hydrogel. Notably, the hydrogel exhibits obvious temperature sensitivity at a concentration of 6 wt %, and the nanoparticles possess concentration-dependent H2O2-response capability with a controlled release profile in 48 h. The combined strategy promoted the repair of injured peripheral nerves, attributed to the dual role of the materials, which mainly involved providing structural support, modulating the immune microenvironment, and enhancing angiogenesis. Overall, this study opens up intriguing prospects in tissue engineering.

Supramolecular Assembly Based on Calix(4)arene and Aggregation-Induced Emission Photosensitizer for Phototherapy of Drug-Resistant Bacteria and Skin Flap Transplantation.

Photodynamic therapy as a burgeoning and non-invasive theranostic technique has drawn great attention in the field of antibacterial treatment but often encounters undesired phototoxicity of photosensitizers during systemic circulation. Herein, a supramolecular substitution strategy is proposed for phototherapy of drug-resistant bacteria and skin flap repair by using macrocyclic p-sulfonatocalix(4)arene (SC4A) as a host, and two cationic aggregation-induced emission luminogens (AIEgens), namely TPE-QAS and TPE-2QAS, bearing quaternary ammonium group(s) as guests. Through host-guest assembly, the obtained complex exhibits obvious blue fluorescence in the solution due to the restriction of free motion of AIEgens and drastically inhibits efficient type I ROS generation. Then, upon the addition of another guest 4,4'-benzidine dihydrochloride, TPE-QAS can be competitively replaced from the cavity of SC4A to restore its pristine ROS efficiency and photoactivity in aqueous solution. The dissociative TPE-QAS shows a high bacterial binding ability with an efficient treatment for methicillin-resistant Staphylococcus aureus (MRSA) in dark and light irradiation. Meanwhile, it also exhibits an improved survival rate for MRSA-infected skin flap transplantation and largely accelerates the healing process. Thus, such cascaded host-guest assembly is an ideal platform for phototheranostics research.

Bioactive citrate-based polyurethane tissue adhesive for fast sealing and promoted wound healing.

As a superior alternative to sutures, tissue adhesives have been developed significantly in recent years. However, existing tissue adhesives struggle to form fast and stable adhesion between tissue interfaces, bond weakly in wet environments and lack bioactivity. In this study, a degradable and bioactive citrate-based polyurethane adhesive is constructed to achieve rapid and strong tissue adhesion. The hydrophobic layer was created with polycaprolactone to overcome the bonding failure between tissue and adhesion layer in wet environments, which can effectively improve the wet bonding strength. This citrate-based polyurethane adhesive provides rapid, non-invasive, liquid-tight and seamless closure of skin incisions, overcoming the limitations of sutures and commercial tissue adhesives. In addition, it exhibits biocompatibility, biodegradability and hemostatic properties. The degradation product citrate could promote the process of angiogenesis and accelerate wound healing. This study provides a novel approach to the development of a fast-adhering wet tissue adhesive and provides a valuable contribution to the development of polyurethane-based tissue adhesives.

Injectable Hydrogel System Incorporating Black Phosphorus Nanosheets and Tazarotene Drug for Enhanced Vascular and Nerve Regeneration in Spinal Cord Injury Repair.

Spinal cord injury (SCI) often leads to cell death, vascular disruption, axonal signal interruption, and permanent functional damage. Currently, there are no clearly effective therapeutic options available for SCI. Considering the inhospitable SCI milieu typified by ischemia, hypoxia, and restricted neural regeneration, a novel injectable hydrogel system containing conductive black phosphorus (BP) nanosheets within a lipoic acid-modified chitosan hydrogel matrix (LAMC) is explored. The incorporation of tannic acid (TA)-modified BP nanosheets (BP@TA) into the LAMC hydrogel matrix significantly improved its conductivity. Further, by embedding a bicyclodextrin-conjugated tazarotene drug, the hydrogel showcased amplified angiogenic potential in vitro. In a rat model of complete SCI, implantation of LAMC/BP@TA hydrogel markedly improved the recovery of motor function. Immunofluorescence evaluations confirmed that the composite hydrogel facilitated endogenous angiogenesis and neurogenesis at the injury site. Collectively, this work elucidates an innovative drug-incorporated hydrogel system enriched with BP, underscoring its potential to foster vascular and neural regeneration.

Photothermal antibacterial MoS2 composited chitosan hydrogel for infectious wound healing.

Pathological bacterial infection poses a serious threat to public health security. The excessive use of antibiotics has resulted in a serious decline in treatment effect and bacterial resistance. For the treatment of infected wounds, we compounded dopamine-assisted exfoliated molybdenum disulfide (MoS2@PDA) into lipoic acid modified chitosan (LAMC) to obtain a composite hydrogel dressing (LAMC-MoS2@PDA). LAMC-MoS2@PDA hydrogels exhibited excellent photothermal conversion ability and the LAMC-MoS2@PDA2 group (0.3 wt%) has a photothermal conversion efficiency of 26.29 %. Meanwhile, they showed good biocompatibility and ROS scavenging activity in vitro. Photothermal therapy usually utilizes photothermal agents to convert near-infrared light into heat energy for bacterial cell membrane destruction and bacterial protein inactivation. Under the near-infrared light irradiation, the antibacterial ratio of LAMC-MoS2@PDA hydrogels against Staphylococcus aureus and Escherichia coli reached nearly 100 %, and the morphology of the bacteria showed obvious contraction and cleavage. The hydrogels also showed an excellent antibacterial effect and wound healing promotion in the infected wound of rats. In particular, the LAMC-MoS2@PDA2 (+) group (with NIR) showed almost complete wound closure after 14 days, indicating that the LAMC-MoS2@PDA hydrogels have great potential in clinical anti-infected treatment.

3D Printed Photothermal Scaffold Sandwiching Bacteria Inside and Outside Improves The Infected Microenvironment and Repairs Bone Defects.

Bone infection is one of the most devastating orthopedic outcomes, and overuse of antibiotics may cause drug-resistance problems. Photothermal therapy(PTT) is a promising antibiotic-free strategy for treating infected bone defects. Considering the damage to normal tissues and cells caused by high-temperature conditions in PTT, this study combines the antibacterial property of Cu to construct a multi-functional Cu2 O@MXene/alpha-tricalcium phosphate (α-TCP) scaffold support with internal and external sandwiching through 3D printing technology. On the "outside", the excellent photothermal property of Ti3 C2 MXene is used to carry out the programmed temperature control by the active regulation of 808 nm near-infrared (NIR) light. On the "inside", endogenous Cu ions gradually release and the release accumulates within the safe dose range. Specifically, programmed temperature control includes brief PTT to rapidly kill early bacteria and periodic low photothermal stimulation to promote bone tissue growth, which reduces damage to healthy cells and tissues. Meanwhile, Cu ions are gradually released from the scaffold over a long period of time, strengthening the antibacterial effect of early PTT, and promoting angiogenesis to improve the repair effect. PTT combined with Cu can deliver a new idea forinfected bone defects through in vitro and vivo application.

An injectable and adaptable hydrogen sulfide delivery system for modulating neuroregenerative microenvironment.

Peripheral nerve regeneration is a complex physiological process. Single-function nerve scaffolds often struggle to quickly adapt to the imbalanced regenerative microenvironment, leading to slow nerve regeneration and limited functional recovery. In this study, we demonstrate a "pleiotropic gas transmitter" strategy based on endogenous reactive oxygen species (ROS), which trigger the on-demand H2S release at the defect area for transected peripheral nerve injury (PNI) repair through concurrent neuroregeneration and neuroprotection processing. This H2S delivery system consists of an H2S donor (peroxyTCM) encapsulated in a ROS-responsive polymer (mPEG-PMet) and loaded into a temperature-sensitive poly (amino acid) hydrogel (mPEG-PA-PP). This multi-effect combination strategy greatly promotes the regeneration of PNI, attributed to the physiological effects of H2S. These effects include the inhibition of inflammation and oxidative stress, protection of nerve cells, promotion of angiogenesis, and the restoration of normal mitochondrial function. The adaptive release of pleiotropic messengers to modulate the tissue regeneration microenvironment offers promising peripheral nerve repair and tissue engineering opportunities.

IKVAV peptide-containing hydrogel decreases fibrous scar after spinal cord injury by inhibiting fibroblast migration and activation.

Fibrous scar is one of the major factors that hinder functional recovery in patients with spinal cord injury (SCI). Studies have shown that the laminin α1 peptide chain ile-les-val-ala-Val (IKVAV) promoted axonal growth and motor function recovery in rats after SCI. However, whether IKVAV could ameliorate SCI via reducing the formation of fibrous scar was not clear. A SCI model was constructed by transecting the rat spinal cord with a scalpel and implanting poly (N-propan-2-ylprop-2-enamide) (PNIPAM)-b-poly (AC-PEG-COOH) (PNPP) or PNIPAM-b-poly (AC-PEG-IKVAV) (PNPP-IKVAV) hydrogel. 14 days later hematoxylin-eosin staining and immunohistochemical staining were used to assess the effect of PNPP-IKVAV on scar formation. The effect of PNPP-IKVAV on endoplasmic reticulum (ER) stress was investigated by immunohistochemical staining. NIH-3T3 cells were used for in vitro scratching experiments and a transforming growth factor 1 (TGF-ß1) activation model was constructed to assess the role of PNPP-IKVAV. In this study, PNPP-IKVAV inhibited fibroblast migration and suppressed TGF-ß1 activation and ER stress (ERS) to reduce the extracellular matrix secretion by fibroblasts.

Multifunctional magnetocaloric bone cement with a time-varying alkaline microenvironment for sequential bacterial inhibition, angiogenesis and osteogenesis.

Repairing infected bone defects remains a severe challenge due to antibiotic abuse and recurrence. Hence, we modified magnetocaloric Fe3O4 nanoparticles and added them to magnesium calcium phosphate bone cement (MCPC) to fabricate multifunctional magnetic composites for sequential bacterial inhibition, angiogenesis and osteogenesis. Nevertheless, high doses of Mg ions and Fe ions were released from MCPC, which adversely affected osteogenesis. Thus, Fe3O4 was modified using gelatin according to the emulsification crosslinking method, which exhibited a controllable magnetocaloric effect and degradation behavior, and favorable anti-bacterial ability under the action of an alternating magnetic field (AMF). In the early stage, the residual MgO created a local strong alkaline microenvironment by hydrolysis, which inhibited the function and activity of S. aureus and E. coli. At the later stage, the MCPC composites were controllably degraded under the function of gelatin and maintained a long-term local slight alkaline microenvironment that promoted the osteogenic differentiation and mineralization of BMSCs. In vivo subcutaneous implantation experiments further indicated that MCPC composites showed good biocompatibility and facilitated angiogenesis, presenting a promising future in magnetic materials design and infectious bone defect repair.

Design and fabrication of high-performance injectable self-setting trimagnesium phosphate.

Magnesium phosphate bone cement has become a widely used orthopedic implant due to the advantages of fast-setting and high early strength. However, developing magnesium phosphate cement possessing applicable injectability, high strength, and biocompatibility simultaneously remains a significant challenge. Herein, we propose a strategy to develop high-performance bone cement and establish a trimagnesium phosphate cement (TMPC) system. The TMPC exhibits high early strength, low curing temperature, neutral pH, and excellent injectability, overcoming the critical limitations of recently studied magnesium phosphate cement. By monitoring the hydration pH value and electroconductivity, we demonstrate that the magnesium-to-phosphate ratio could manipulate the components of hydration products and their transformation by adjusting the pH of the system, which will influence the hydration speed. Further, the ratio could regulate the hydration network and the properties of TMPC. Moreover, in vitro studies show that TMPC has outstanding biocompatibility and bone-filling capacity. The facile preparation properties and these advantages of TMPC render it a potential clinical alternative to polymethylmethacrylate and calcium phosphate bone cement. This study will contribute to the rational design of high-performance bone cement.