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.

All-in-one strategy to develop a near-infrared triggered multifunctional bioactive magnesium phosphate bone cement for bone repair.

Bone cement is widely used in clinical with optimistic filling and mechanical properties. However, the setting time of bone cement is difficult to accurately control, and the existing bone cements exhibit limited therapeutic functionalities. In response to these challenges, we designed and synthesized Nd-doped whitlockite (Nd-WH), endowing bone cement with photothermal-responsive and fluorescence imaging capabilities. The doping amount and photothermal properties of Nd-doped whitlockite were studied, and the composite bone cement was prepared. The results showed that the setting time of bone cement could be regulated by near infrared irradiation, and the multiple functions of promoting osteogenic differentiation, antibacterial and anti-tumor could be realized by adjusting the power and irradiation time of near infrared. By incorporating Nd-doped whitlockite and bone cement, we developed an all-in-one strategy to achieve setting time control, enhanced osteogenic ability, tumor cell clearance, bacterial clearance, and bone tissue regeneration. The optimized physical and mechanical properties of composite bone cement ensure adaptability and plasticity. In vitro and in vivo experiments validated the effectiveness of this bone cement platform for bone repair, tumor cell clearance and bacterial clearance. The universal methods to regulate the setting time and function of bone cement by photothermal effect has potential in orthopedic surgery and is expected to be a breakthrough in the field of bone defect repair. Further research and clinical validation are needed to ensure its safety, efficacy and sustainability. STATEMENT OF SIGNIFICANCE: Bone cement is a valuable clinical material. However, the setting time of bone cement is difficult to control, and the therapeutic function of existing bone cement is limited. Various studies have shown that the bone repair capacity of bone cements can be enhanced by synergistic stimulatory effects in vivo and ex vivo. Unfortunately, most of the existing photothermal conversion materials are non-degradable and poorly biocompatible. This study provides a bone-like photothermal conversion material with photothermal response and fluorescence imaging properties, and constructed a platform for integrated regulation of the setting time of bone cement and diversification of its functions. Therefore, it helps to design multi-functional bone repair materials that are more convenient and effective in clinical operation.

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.

LncRNA XIST regulates osteoclast formation and promotes orthodontically induced inflammatory root resorption through miR-130b-3p/PTEN axis.

The long non-coding RNA (LncRNA) X-inactive specific transcript (XIST) regulates the biological process of osteoclasts and the process of related diseases. This study was attempted to investigate the mechanism of LncRNA XIST acting in osteoclast formation and orthodontic induced inflammatory root resorption (OIIRR). The compression force (CF) -induced cell model and the orthodontic tooth movement (OTM) rat model were designed and established in this study. The expression of LncRNA XIST, miR-130b-3p, phosphatase and tensin homolog deleted on chromosome 10 (PTEN) as well as osteoclast related marker genes and inflammatory factors level were measured in this study. The interaction among LncRNA XIST, microRNA-130b-3p (miR-130b-3p) and PTEN were researched through luciferase activity and western blot assay. Pathological sections were used to analyze root resorption and osteoclast formation. The OTM rat model was successfully constructed, which was characterized by increased tooth spacing and increased root resorption pits. PTEN and LncRNA XIST was overexpressed in OTM group. Mechanism analysis showed that the overexpression of LncRNA XIST enhanced the PTEN level by sponging miR-130b-3p. The overexpression of LncRNA XIST increased the secretion of inflammatory factors and positive osteoclasts number, but inhibited the differentiation of osteoclasts by sponging miR-130b-3p and promoting the level of PTEN. This finding demonstrates that LncRNA XIST regulates osteoclast formation and aggravated OIIRR through miR-130b-3p/PTEN axis, suggesting that LncRNA XIST may be used as potential targets for OIIRR therapy.

Multifunctional Scaffold for Osteoporotic Pathophysiological Microenvironment Improvement and Vascularized Bone Defect Regeneration.

Osteoporosis is a degenerative bone disease resulting from bone homeostasis imbalance regulated by osteoblasts and osteoclasts. Treating osteoporotic bone defects tends to be more difficult due to suppressed osteogenic differentiation, hyperactive osteoclastogenesis, and impaired angiogenesis. Hence, a drug carrier system composed of gelatin-coated hollow mesoporous silica nanoparticles (HMSNs/GM) loaded with pro-osteogenic parathyroid (PTH) and anti-osteoclastogenic alendronate (ALN) is constructed and compounded into calcium magnesium phosphate cement (MCPC). The spatial-temporal release of ions and drugs, controllable degradation rate, and abundant pore structure of MCPC composites enhance osteoporotic bone regeneration in ovariectomized rats by accelerating vascularization, promoting osteogenic differentiation and mineralization, and inhibiting osteoclastogenesis and bone resorption. The MCPC/HMSNs@ALN-PTH/GM demonstrates a synergistic threefold effect on osteogenesis, osteoclastogenesis, and angiogenesis. It improves the osteoporotic pathophysiological microenvironment and promotes osteoporotic vascularized bone defect regeneration, holding huge potential for other functional biomaterials design and clinical management.

A premixed magnesium phosphate-based sealer with anti-biofilm ability for root canal filling.

The complex structure of the root canal system and microbial resistance increase the difficulty of endodontic treatment and the development of root canal sealers with good antibacterial and physicochemical properties is the key to treat refractory root canal infection. In the present study, a novel premixed root canal sealer containing trimagnesium phosphate (TMP), potassium dihydrogen phosphate (KH2PO4), magnesium oxide (MgO), zirconium oxide (ZrO2), and a bioactive oil phase was developed, and the physicochemical properties, radiopacity, antibacterial activity in vitro, anti-biofilm ability and cytotoxicity were investigated. MgO significantly improved the anti-biofilm ability and ZrO2 enhanced the radiopacity of the premixed sealer, and they had an obvious adverse effect on other properties. In addition, this sealer has advantages such as easy-to-use design, storabality, good sealing ability and biocompatibility. Therefore, this sealer has high potential for use in treating root canal infection.

Citric acid cross-linked chitosan for inhibiting oxidative stress after nerve injury.

Scaffold design is particularly important and necessary for soft tissue repair such as nerve tissue repair. In this article, we designed and manufactured a macroporous chitosan-based hydrogel with excellent cell compatibility and antioxidant properties. Here, the chitosan (CS) based hydrogel is obtained by repeated freezing and thawing using citric acid (CA) as a cross-linking agent. We have evaluated the effects of citric acid content on the physical and chemical properties of hydrogels through mechanical properties and scanning electron microscopy. CA-CS hydrogel shows a macroporous structure, as the citric acid increases, the mechanical strength increases and the pore size decreases. In vitro cell experiments show that CA-CS hydrogel partakes positive effects on cell survival, adhesion and proliferation, as well as antioxidant properties. All results provide a basis for the construction of porous chitosan-based hydrogels, while demonstrating a promising approach to deal with oxidative stress in nerve injury.

Effects of bioactive strontium-substituted hydroxyapatite on osseointegration of polyethylene terephthalate artificial ligaments.

The insufficient bioactivity of polyethylene terephthalate (PET) artificial ligaments severely weakens the ligament-bone healing in anterior cruciate ligament (ACL) reconstruction, while osteogenic modification is a prevailing method to enhance osseointegration of PET artificial ligaments. In the present study, strontium-substituted hydroxyapatite (SrHA) nanoparticles with different strontium (Sr) contents were synthesized via microwave-hydrothermal method and subsequently were coated on the surface of PET artificial ligaments. The results of XRD, FT-IR, TEM and ICP-OES revealed that the doping of Sr ions had no great influences on the phase composition, morphology and particle size of HA, but affected its chemical compositions and crystallinity. The SEM images showed that nanoparticles were successfully deposited on the surface of PET grafts, the surface hydrophilicity of which was significantly improved by the prepared coatings. The in vitro study revealed that the osteogenic activity of rat bone marrow mesenchymal stem cells (rBMSCs) was affected by varying concentrations of Sr ions in coatings and the optimal osteogenic differentiation was observed in the 2SrHA-PET group, which significantly up-regulated the expression of BMP-2, OCN, Col-I and VEGF. The enhanced osteogenic ability of the 2SrHA-PET group was further demonstrated through an in vivo study, which obviously promoted ligament-bone integration compared with that of PET and HA-PET groups, thus improving the biomechanical strength of the graft-bone complex. This study confirms that SrHA coatings can facilitate osseointegration in the repair of ligament injury in rabbits and thus offers a prospective method for ACL reconstruction by using Sr-containing biomaterial-modified PET artificial ligaments.

Magnesium Calcium Phosphate Cement Incorporating Citrate for Vascularized Bone Regeneration.

The development of bioactive bone cement is still a challenge for vascularized bone regeneration. Citrate participated in multiple biological processes, such as energy metabolism, osteogenesis, and angiogenesis. However, it is difficult to obtain a thorough and comprehensive understanding on osteogenic effects of exogenous citrate from different experimental conditions and treatment methods. In this study, by using a magnesium calcium phosphate cement (MCPC) matrix, we investigated the dual effect of exogenous citrate on osteogenesis and angiogenesis. Our studies show that citrate elevates the osteogenic function of osteoblasts under low doses and the angiogenic function of vascular endothelial cells under a broader dose range. These findings furnish a new strategy for regulating angiogenesis and osteogenic differentiation by administration of citrate in MCPC, driving the development of bioactive bone repair materials.

Enhanced proliferation and differentiation of neural stem cells by peptide-containing temperature-sensitive hydrogel scaffold.

Hydrogel has attracted great attention in the past few years as a widely used material for repairing central nerve damage. However, conventional hydrogel bio-scaffold, such as chitosan, gelatin, and sodium alginate, lack sufficient biological activity and have limited nerve repair capabilities. Therefore, to explore biologically active and intelligent hydrogel materials is particularly important and necessary for central nerve repair. Herein, we developed a temperature-sensitive hydrogel grafted with a bioactive peptide IKVAV (Ile-Lys-Val-Ala-Val, IKVAV). The hydrogel was prepared by copolymerization of N-propan-2-ylprop-2-enamide (NIPAM) and AC-PEG-IKVAV copolymers via reversible addition-fracture chain transfer (RAFT) polymerization, using polyethylene glycol (PEGDA) and N, N'-Methylenebisacrylamide (BISAM) as cross-linking agents. The prepared hydrogel scaffold demonstrates a series of excellent properties such as rapid (de)swelling performance, good biocompatibility, regular three-dimensional porous structure, and in particular good biological activity, which can guide cell fate and mediate neuron's differentiation. Therefore, the developed peptide hydrogel scaffold provides a new strategy for designing biomaterials that are widely used in tissue engineering for central nervous system injury.

Citric acid modification of a polymer exhibits antioxidant and anti-inflammatory properties in stem cells and tissues.

Biomaterials can be used as carriers of antioxidant or drug to the oxidative injury site of tissue and decrease intracellular oxidative stress levels, however, low dosage delivery or unstable molecular structure of antioxidant or drug limited the long-term sustained release. A chemically stable antioxidant molecule is essential to serve as antioxidant structure components of biomaterials that may provide the relatively high antioxidant content and persisting local antioxidant release with the degradation of materials. In this study, we used citric acid modified polyvinyl alcohol (PVA-C) as a model biomaterial to investigate the role of citric acid on the material stimulated antioxidant and anti-inflammatory effects. In cellular-based assays, PVA-C extracts showed a protective effects on bone marrow mesenchymal stem cells (BMSCs) under oxidative stress. It could enhance the antiapoptotic ability of stem cells by inhibiting reactive oxygen species. Further studies revealed that PVA-C extracts upregulated the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) and superoxide dismutase [Mn] (SOD2). in vivo animal assays, PVA-C extracts showed significant inhibitory effects on the oxidative stress and inflammatory reaction which were induced by lipopolysaccharide (LPS). These findings suggest that the citric acid modified polymer can regulate the redox signaling of stem cells and tissues by the release of citric acid from materials, leading to enhanced oxidative stress-induced degenerative diseases and inflammatory diseases therapy.

Citric acid enhances the physical properties, cytocompatibility and osteogenesis of magnesium calcium phosphate cement.

In recent years, the magnesium phosphate cements showed impressive advantages for their setting property, mechanical strength, and resorption rate in laboratory investigation. While it remained a big challenge to develop the magnesium phosphate cements with ideal self-setting properties, sufficient mechanical strength, excellent biocompatibility, and osteoinductivity for clinical application. In our work, we prepared the magnesium calcium phosphate cement (MCPC) using the MgO, KH2P2O4, and Ca(H2PO4)2 particles with the citric acid added. The citric acid was adopted to modify the setting time and compressive strength of the MCPC, which were investigated by the X-ray diffractometer and scanning electron microscopy. The cytocompatibility and osteoinductivity of the modified cements were evaluated by the MC3T3-E1 cells proliferation and morphology, alkaline phosphatase assay, alizarin red staining and western blot assay. The results demonstrated that the citric acid modified MCPC was featured of satisfactory setting time, ideal mechanical strength, good cytocompatibility and osteoinductivity, indicating its potential application for bone regeneration.

Influence of different divalent ions cross-linking sodium alginate-polyacrylamide hydrogels on antibacterial properties and wound healing.

Hydrogels are widely used as debriding agents on account of providing a moist environment for wound healing, however the lack of mechanical strength, angiogenesis and antibacterial property limits their applications. In this study, we synthesized novel divalent ion cross-liking hydrogels (copper, zinc, strontium and calcium) and compared the mechanical performance, swelling ratio, antibacterial properties and biocompatibility in vitro and vivo. Thereinto, among the four divalent ions cross-linked hydrogels, copper ion crosslinking exhibited the maximum breaking strength, while strontium and zinc ion cross-linked hydrogels exhibited an excellent mechanical strength. In addition, the swelling ratio and pore size of no-ion cross-linked hydrogels was larger than ion cross-kinked hydrogels. In vitro, the improvements on wound healing after hydrogel application were evaluated by histological and molecular assays by detecting VEGF and TGF-ß expression. In vitro and in vivo study results showed that zinc cross-kinked hydrogel had a spectrum of antibacterial activities, cell viability, mechanical strength and the ability of wound closure by promoting fibroblasts migration, vascularization, collagen deposition and the formation of granulation tissue.