Water-triggered shape memory cellulose / sodium alginate / montmorillonite composite sponges for rapid hemostasis.

Uncontrollable bleeding caused by severe trauma is life-threatening. Therefore, it is of great significance to develop hemostatic materials that meet the rapid hemostasis of wounds. In this study, a water-triggered shape memory carboxylated cellulose nanofiber/sodium alginate/montmorillonite (CNSAMMTCa) composite hemostatic sponge was prepared, which can promote coagulation by concentrating the blood and activating intrinsic pathway. The anisotropic three-dimensional porous structure formed by directional freeze-drying technology improved the performance of composite sponges which showed good prospects in rapid hemostasis. The results showed that CNSAMMTCa composite sponge had good porous structure, water absorption ability, cytocompatibility and blood cell aggregation capacity. Simultaneously, we confirmed that CNSA3MMT2Ca has best coagulation performance in the mouse censored bleeding model and liver rupture bleeding model. Therefore, CNSAMMTCa composite hemostatic sponge is a safe and efficient rapid hemostatic material which is expected to become an alternative material for clinical hemostatic materials.

Sodium alginate/carboxycellulose/polydopamine composite microspheres for rapid hemostasis of deep irregular wounds.

Hemostasis of deep irregular wounds is a severe problem in clinical practice. The development of rapid-acting hemostatic agents for deep and irregular wound is urgently needed. Here, sodium alginate/carboxycellulose/polydopamine (SA/CNF/PDA) microspheres was prepared by reverse emulsification and crosslinking with Ca2+, and SA/CNF/PDA composite hemostatic microspheres with porous structure were obtained by freeze-drying. SA/CNF/PDA composite hemostatic microspheres exhibited excellent porosity and water absorption which could rapidly absorb blood on the wound surface. Moreover, SA/CNF/PDA composite microspheres demonstrated remarkable hemostatic capabilities both in vitro and in vivo. It exhibited strong hemostatic performance in models of mouse tail-break and liver damage. Especially in liver injury model, it was completely hemostatic in 95 s, and blood loss (19.3 mg). The hemostatic efficacy of the SA/CNF/PDA composite microspheres was amplified through the stimulation of both exogenous and endogenous coagulation pathways. Therefore, SA/CNF/PDA composite hemostatic microspheres are suitable for rapid hemostasis of deep irregular wounds which are potential rapid hemostatic material for surgical application.

Improving osseointegration and antimicrobial properties of titanium implants with black phosphorus nanosheets-hydroxyapatite composite coatings for vascularized bone regeneration.

For decades, titanium implants have shown impressive advantages in bone repair. However, the preparation of implants with excellent antimicrobial properties as well as better osseointegration ability remains difficult for clinical application. In this study, black phosphorus nanosheets (BPNSs) were doped into hydroxyapatite (HA) coatings using electrophoretic deposition. The coatings' surface morphology, roughness, water contact angle, photothermal properties, and antibacterial properties were investigated. The BP/HA coating exhibited a surface roughness of 59.1 nm, providing an ideal substrate for cell attachment and growth. The water contact angle on the BP/HA coating was measured to be approximately 8.55°, indicating its hydrophilic nature. The BPNSs demonstrated efficient photothermal conversion, with a temperature increase of 42.2°C under laser irradiation. The BP/HA composite coating exhibited a significant reduction in bacterial growth, with inhibition rates of 95.6% and 96.1% against Staphylococcus aureus and Escherichia coli. In addition, the cytocompatibility of the composite coating was evaluated by cell adhesion, CCK8 and AM/PI staining; the effect of the composite coating in promoting angiogenesis was assessed by scratch assay, transwell assay, and protein blotting; and the osteoinductivity of the composite coating was evaluated by alkaline phosphatase assay, alizarin red staining, and Western blot. The results showed that the BP/HA composite coating exhibited superior performance in promoting biological functions such as cell proliferation and adhesion, antibacterial activity, osteogenic differentiation, and angiogenesis, and had potential applications in vascularized bone regeneration.

Enhancing osseointegration of titanium implants through MC3T3-E1 protein-gelatin polyelectrolyte multilayers.

Titanium and its alloys have found extensive use in the biomedical field, however, implant loosening due to weak osseointegration remains a concern. Improved surface morphology and chemical composition can enhance the osseointegration of the implant. Bioactive molecules have been utilized to modify the surface of the titanium-based material to achieve rapid and efficient osseointegration between the implant and bone tissues. In this study, the bioactive substance MC3T3-E1 protein-gelatin polyelectrolyte multilayers were constructed on the surface of the titanium implants by means of layer-by-layer self-assembly to enhance the strength of the bond between the bone tissue and the implant. The findings of the study indicate that the layer-by-layer self-assembly technique can enhance surface roughness and hydrophilicity to a considerable extent. Compared to pure titanium, the hydrophilicity of TiOH LBL was significantly increased with a water contact angle of 75.0 ± $$ \pm $$ 2.4°. The modified titanium implant exhibits superior biocompatibility and wound healing ability upon co-culture with cells. MC3T3-E1 cells were co-cultured with TiOH LBL for 1, 3, and 5 days and their viability was higher than 85%. In addition, the wound healing results demonstrate that TiOH LBL exhibited the highest migratory ability (243 ± 10 µm). Furthermore, after 7 days of osteogenic induction, the modified titanium implant significantly promotes osteoblast differentiation.

[Progress in antibacterial coatings of titanium implants surfaces].

In recent years, bone implant materials such as titanium and titanium alloys have been widely used in the biomedical field due to their excellent mechanical properties and good biocompatibility. However, in clinical practice, bacterial adhesion to the material surface and postoperative infection issues may lead to implantation failure. Based on the antibacterial mechanism, this review elaborated on the antibacterial surface design of titanium implants from the aspects of anti-bacterial adhesion, contact sterilization and photocontrol sterilization. Surface modification of titanium or titanium-based alloy implants with different techniques can inhibit bacteria and promote osseointegration. Thus, the application range of multifunctional titanium-based implants in the field of orthopedics will be expanded.

Hydroxyapatite/Polyurethane Scaffolds for Bone Tissue Engineering.

Polyurethane (PU) and PU ceramic scaffolds are the principal materials investigated for developing synthetic bone materials due to their excellent biocompatibility and biodegradability. PU has been combined with calcium phosphate (such as hydroxyapatite [HA] and tricalcium phosphate) to prepare scaffolds with enhanced mechanical properties and biocompatibility. This article reviews the latest progress in the design, synthesis, modification, and biological attributes of HA/PU scaffolds for bone tissue engineering. Diverse HA/PU scaffolds have been proposed and discussed in terms of their osteogenic, antimicrobial, biocompatibility, and bioactivities. The application progress of HA/PU scaffolds in bone tissue engineering is predominantly introduced, including bone repair, bone defect filling, drug delivery, and long-term implants.

Cellulose based composite sponges with oriented porous structure and superabsorptive capacity for quick hemostasis.

Excessive bleeding is the leading cause of death in accidents and operations. Ca2+ crosslinked carboxyl nanocellulose (CN)/montmorillonite (MMT) composite (CaCNMMT) sponges were prepared by uniform mixing and directional freeze-drying methods which was inspired by the coordination mechanism of blood clot formation and coagulation cascade activation in natural hemostasis process. Carboxyl nanocellulose (CaCN) sponge has instantaneous water absorption capacity, and CaCNMMT sponges could further activate clotting factors. Therefore, CaCNMMT sponges achieved quick hemostasis by efficient concentrating blood, inducing hemocyte aggregation and stimulating coagulation cascade activation based on the synergistic effects of CN and MMT. Blood clotting index of CaCNMMT (15.90 ± 0.52 %) was significantly lower than CaCN (59.3 ± 1.43 %), and APTT time (22 ± 2 s) was almost equivalent to MMT (20 ± 2 s). CaCNMMT sponge showed good quick hemostatic effect on massive hemorrhage in both tail-breaking and liver injury model which provided a new strategy for the application of MMT in hemostatic and trauma treatment fields.

Double-crosslinked PNIPAM-based hydrogel dressings with adjustable adhesion and contractility.

Rapid post-wound closure is necessary to avoid wound infection and promote scar-free healing when skin trauma occurs. In this study, new types of hydrogel dressings with adjustable contractility were fabricated based on N-isopropyl acrylamide/sodium alginate/graphene oxide (P/SA/GO). Then, the chitosan (CS) solution was used as a bridging polymer to achieve tissue adhesion to the hydrogel. The results show that the hydrogel based on poly(N-isopropyl acrylamide) (PNIPAM) not only has the ability to self-shrink but also can adjust the rate of shrinkage through near-infrared thermal stimulation. At the same time, high adhesion strength (7.86 ± 1.22 kPa) between the tissue and the dressing is achieved through the introduction of bridging polymers (CS), and the coating area of the bridging polymer can be adjusted to achieve regional adhesion. The mouse total skin defects experiments have shown that sutures-free wound closure in the early stages of wound healing could be obtained by adjusting the material temperature. Besides, the dressings can promote scar-free wound healing by reducing inflammatory cell infiltration and collagen deposition. These results indicate that double-crosslinked PNIPAM-based hydrogel dressings with adjustable adhesion and contractility proposed in this study provide a candidate material for achieving trackless wound healing.

[Progress in preparation and application of sodium alginate microspheres].

Sodium alginate (SA) is a kind of natural polymer material extracted from kelp, which has excellent biocompatibility, non-toxicity, biodegradability and abundant storage capacity. The formation condition of sodium alginate gel is mild, effectively avoiding the inactivation of active substances. After a variety of preparation methods, sodium alginate microspheres are widely used in the fields of biomaterials and tissue engineering. This paper reviewed the common methods of preparing alginate microspheres, including extrusion, emulsification, electrostatic spraying, spray drying and coaxial airflow, and discussed their applications in biomedical fields such as bone repair, hemostasis and drug delivery.

Complexation-Induced Resolution Enhancement Pleiotropic Small Diameter Vascular Constructs with Superior Antibacterial and Angiogenesis Properties.

3D printing has been widely applied for preparing artificial blood vessels, which will bring innovation to cardiovascular disorder intervention. However, the printing resolution and anti-infection properties of small-diameter vessels (Φ < 6 mm) have been challenging in 3D printing. The primary objective of this research is to design a novel coaxial 3D-printing postprocessing method for preparing small-size blood vessels with improved antibacterial and angiogenesis properties. The coaxial printing resolution can be more conveniently improved. Negatively charged polyvinyl alcohol (PVA) and alginate (Alg) interpenetrating networks artificial vessels are immersed in positively charged chitosan (CTS) solution. Rapid dimensional shrinkage takes place on its outer surface through electrostatic interactions. The maximum shrinkage size of wall thickness can reach 61.2%. The vessels demonstrate strong antibacterial properties against Escherichia coli (98.8 ± 0.5%) and Staphylococcus aureus (97.6 ± 1.4%). In rat dorsal skin grafting experiments, Cu2+ can promote angiogenesis by regulating hypoxia-inducible factor-1 pathway. No artificial blood vessel blockage occurs after 5 days of blood circulation in vitro.

Injectable antibacterial Ag-HA/ GelMA hydrogel for bone tissue engineering.

Background: Fracture or bone defect caused by accidental trauma or disease is a growing medical problem that threats to human health.Currently, most orthopedic implant materials must be removed via follow-up surgery, which requires a lengthy recovery period and may result in bacterial infection. Building bone tissue engineering scaffolds with hydrogel as a an efficient therapeutic strategy has outstanding bionic efficiency.By combining some bionic inorganic particles and hydrogels to imitate the organic-inorganic characteristics of natural bone extracellular matrix, developing injectable multifunctional hydrogels with bone tissue repair effects and also displaying excellent antibacterial activity possesses attractive advantages in the field of minimally invasive therapy in clinical. Methods: In the present work, a multifunctional injectable hydrogel formed by photocrosslinking was developed by introducing hydroxyapatite (HA) microspheres to Gelatin Methacryloyl (GelMA) hydrogel. Results: The composite hydrogels exhibited good adhesion and bending resistance properties due to the existence of HA. In addition, when the concentration of GelMA is 10% and the concentration of HA microspheres is 3%, HA/GelMA hydrogel system displayed increased microstructure stability, lower swelling rate, increased viscosity, and improved mechanical properties. Furthermore, the Ag-HA/GelMA demonstrated good antibacterial activity against Staphylococcus aureus and Escherichia coli, which could signifificantly lower the risk of bacterial infection following implantation. According to cell experiment, the Ag-HA/GelMA hydrogel is capable of cytocompatibility and has low toxicity to MC3T3 cell. Conclusion: Therefore, the new photothermal injectable antibacterial hydrogel materials proposed in this study will provide a promising clinical bone repair strategy and is expected to as a minimally invasive treatment biomaterial in bone repair fields.

High biocompatible polyacrylamide hydrogels fabricated by surface mineralization for subchondral bone tissue engineering.

The subchondral bone is an important part of cartilage which contains a large amount of hydroxyapatite. The mineral components of subchondral bone is the key factor which determines the biomechanical strength, and then affects the biological function of articular cartilage. Here, a mineralized polyacrylamide (PAM-Mineralized) hydrogel with good ALP activity, cell adhesion and biocompatibility was fabricated for subchondral bone tissue engineering. The micromorphology, composition and mechanical properties of PAM and PAM-Mineralized hydrogels were studied. The PAM hydrogels showed a porous structure, while the PAM-Mineralized hydrogels had well-distributed layers of hydroxyapatite mineralization on the surface. The XRD results show that the characteristic peak of hydroxyapatite (HA) was measured in PAM-Mineralized, indicating that the main component of the mineralized structure formed on the surface of the hydrogel after mineralization is HA. The formation of HA ectively decreased the rate of equilibrium swelling of the PAM hydrogel, with PAM-M reaching swelling equilibrium at 6 h. Meanwhile, compressive strength of PAM-Mineralized hydrogel (moisture state) reached 290 ± 30 kPa, compressive modulus reached 130 ± 4 kPa. PAM-Mineralized hydrogels did not affect the growth and proliferation of MC3T3-E1 cells. Surface mineralization of PAM hydrogel could significantly improve osteogenic differentiation of MC3T3-E1 cells. These results showed that PAM-Mineralized hydrogel could possess potential application in the field of subchondral bone tissue engineering.

Bifunctional electrospun poly (L-lactic acid) membranes incorporating black phosphorus nanosheets and nano-zinc oxide for enhanced biocompatibility and antibacterial properties in catheter materials.

For several decades, urinary tract infections caused by catheter-associated devices have negatively impacted not only medical device utilization, but also patient health. As such, the creation of catheter materials with both superior biocompatibility and antibacterial properties has become necessary. This study aimed to produce electrospun membranes based on polylactic acid (PLA) with the incorporation of black phosphorus nanosheets (BPNS) and nano-zinc oxide (nZnO) particles, as well as a mixture of both, in order to design bifunctional membranes with enhanced bioactivity and antibacterial features. The optimum spinning process was determined through examination of various PLA mass concentrations, spinning solution propelling speeds, and receiving drum rotating speeds, with emphasis on the mechanical properties of PLA membranes. Additionally, the antibacterial properties and cytocompatibility of the ZnO-BP/PLA antibacterial membranes were explored. Results demonstrated that the ZnO-BP/PLA antibacterial membranes displayed a rich porous structure, with uniform distribution of nZnO particles and BPNS. With the increase of polylactic acid concentration and the decrease of spinning solution advancing and drum rotation speeds, the mechanical properties of the fiber membrane were significantly improved. Furthermore, the composite membranes exhibited remarkable photothermal therapy (PTT) capabilities when aided by the synergistic effect of BP nanosheets and ZnO. This was achieved through near-infrared (NIR) irradiation, which not only dissipated the biofilm but also enhanced the release capability of Zn2+. Consequently, the composite membrane demonstrated an improved inhibitory effect on both Escherichia coli and Staphylococcus aureus. The results of cytotoxicity and adhesion experiments also indicated good cytocompatibility, with cells growing normally on the surface of the ZnO-BP/PLA antibacterial membrane. Overall, these findings validate the utilization of both BPNS and n-ZnO fillers in the creation of novel bifunctional PLA-based membranes, which possess both biocompatibility and antibacterial properties for interventional catheter materials.

Fabrication of gelatin methacryloyl/graphene oxide conductive hydrogel for bone repair.

The ideal bone repair materials possess a series of properties, such as injectability, good mechanical properties and bone inducibility. In the present study, gelatin methacryloyl (GelMA) and graphene oxide (GO) were selected to prepare conductive hydrogel by changing the concentration of GelMA and GO during the cross-link process. The effects of different contents of GelMA and GO to the hydrogel performance were investigated. The results showed that the mechanical properties of the hydrogel kept 16.37 ± 1.89 KPa after adding 0.1% GO, while the conductivity was improved to 1.36 ± 0.09 µS/cm. The porosity of hydrogel before and after mineralization could reach more than 90%. The mechanical properties of mineralized hydrogel was improved significantly, could reach 26.38 ± 2.29 KPa. Cell experiments indicated that the mineralized hydrogel with electrical stimulation obviously improve the alkaline phosphatase activity of the cells. GelMA/GO conductive hydrogel could be a promising candidate for bone repair and bone tissue engineering.

The study of self-regulating α-TCP based composite by micro/nano scaled silk fibroin and α-CSH on physicochemical and biological properties of bone cement.

A novel self-hardening α-tricalcium phosphate (α-TCP) bone cement complexed with different content of α-calcium sulfate hemihydrate (α-CSH) and micrometer hydroxyapatite mineralized silk fibroin (HA-SF) using micro/SF as curing liquid has been investigated in this work, which was capable of tunable setting time, degradation, mechanical property and ability to anti-washout. After addition 0 ∼ 25% α-CSH to the α-TCP cement with SFFs as curing liquid, it shortened the setting time of the modified composite to 10 ∼ 30 min. Furthermore, the addition of SFFs improved the compressive strength of the composite from 5.41 MPa to 9.44 MPa. The composites with both Na2HPO4 and SFFs as curing liquid showed good anti-collapse performance. The weight loss ratio of bone cement was -0.18 ∼ 12.08% in 4 weeks when the content of α-CSH in α-TCP/α-CSH was between 0 ∼ 25 wt%. During the degradation of α-CSH, the amorphous α-TCP were deposited as hydroxyapatite to formed a plate-like products on the surface of composite. Compared to the composite with Na2HPO4 solution as the curing liquid, alkaline phosphatase (ALP) activity of the composites using SFFs as curing liquid were maintained at high levels on the 14th day especially when the Ca/P ratio was 1.7. This study provides a theoretical basis for the regeneration of bone defects guided by bone cement materials.

Multilayer functional bionic fabricated polycaprolactone based fibrous membranes for osteochondral integrated repair.

Osteochondral defect repair is one of the challenging problems in orthopedics. In this study, a multilayer polycaprolactone (PCL) based fibrous membrane for osteochondral defect repair was biomimetically fabricated by combining self-induced crystallization, biomimetic mineralization and layer-by-layer electrospinning techniques. The multilayer functional bionic fibrous membrane consisted of cartilage repair layer, intermediate transition repair layer and subchondral bone repair layer. Glucosamine hydrochloride (GAH) encapsulated in core-shell structured PCL fibrous membrane (MGPCL) was suitable for cartilage repair. Shish-kebab (SK) structured PCL fibrous membrane with calcium phosphate coating (MSKPCL) was designed for subchondral bone repair. SK structured MGPCL fibrous membrane (SKMGPCL) was used as intermediate transition repair. The tensile modulus of MG/SKMG/MSKPCL fibrous membrane was 34.24 ± 2.39 MPa which met the requirements of cartilage and subchondral bone repair scaffolds, and in vitro culture results showed that MG/SKMG/MSKPCL fibrous membrane had good biological activity and osteogenic ability. These results showed that MG/SKMG/MSKPCL fibrous membrane provides a promising material basis for osteochondral integrated repair scaffold.

Abundant tannic acid modified gelatin/sodium alginate biocomposite hydrogels with high toughness, antifreezing, antioxidant and antibacterial properties.

The acidity of high tannic acid (TA) content solution can destroy the structure of protein, such as gelatin (G). This causes a big challenge to introduce abundant TA into the G-based hydrogels. Here, the G-based hydrogel system with abundant TA as hydrogen bonds provider was constructed by a "protective film" strategy. The protective film around the composite hydrogel was first formed by the chelation of sodium alginate (SA) and Ca2+. Subsequently, abundant TA and Ca2+ were successively introduced into the hydrogel system by immersing method. This strategy effectively protected the structure of the designed hydrogel. After treatment with 0.3 w/v TA and 0.06 w/v Ca2+ solutions, the tensile modulus, elongation at break and toughness of G/SA hydrogel increased about 4-, 2-, and 6-fold, respectively. Besides, G/SA-TA/Ca2+ hydrogels exhibited good water retention, anti-freezing, antioxidant, antibacterial properties and low hemolysis ratio. Cell experiments showed that G/SA-TA/Ca2+ hydrogels possessed good biocompatibility and could promote cell migration. Therefore, G/SA-TA/Ca2+ hydrogels are expected to be used in the field of biomedical engineering. The strategy proposed in this work also provides a new idea for improving the properties of other protein-based hydrogels.

In situ titanium phosphate formation on a titanium implant as ultrahigh bonding with nano-hydroxyapatite coating for rapid osseointegration.

Titanium (Ti) has been widely used as a dental implant material due to its excellent mechanical property and good biocompatibility. However, its poor biological activity severely limits its ability to bond with bony tissues. To ameliorate this situation, a preparation method of ultra-high bonding nano-hydroxyapatite (n-HA) coating on the Ti surface is urgently needed. Here, Ti phosphate/n-HA (TiP-Ca) composite coatings with ultra-high bonding were prepared by a two-step hydrothermal treatment. The TiP coating was first formed in situ on the pure Ti substrate and then n-HA crystals further grew on the TiP surface. The formation mechanism of composite coating and reasons for increased bonding strength were systematically investigated. The results show that the TiP-Ca coating remains stable and exhibits an ultra-high bonding strength with the Ti implant (up to 783.30 ± 207.46 N). An effective solution was designed to address the problems of easy peel off. Cell experiments showed that TiP-Ca could promote the adhesion of MC3T3-E1 and expression of OCN, Runx2, and ALP. In vivo evaluation further confirmed that the TiP-Ca composite coating significantly enhanced osseointegration. The designed coating shows great potential in clinical application of implants.

Nanocatalytic Hydrogel with Rapid Photodisinfection and Robust Adhesion for Fortified Cutaneous Regeneration.

Chronic inflammation caused by invasive bacterial infections severely interferes with the normal healing process of skin regeneration. Hypoxia of the infection microenvironment (IME) seriously affects the antibacterial effect of photodynamic therapy in phototherapy. To address this serious issue, a nanocatalytic hydrogel with an enhanced phototherapy effect consisting of a hydrogel polyvinyl alcohol (PVA) scaffold, MXene/CuS bio-heterojunction, and polydopamine (PDA) for photothermal antibacterial effects and promoting skin regeneration is designed. The MXene/CuS bio-heterojunction has a benign photothermal effect. Singlet oxygen (1O2) and hydroxyl radicals (·OH) were generated under near-infrared light, which made the hydrogel system have good antioxidant and antibacterial properties. The addition of PDA further improves the biocompatibility and endows the nanocatalytic hydrogel with adhesion. Additionally, in vivo assays display that the nanocatalytic hydrogel has good skin regeneration ability, including ability to kill bacteria, and promotes capillary angiogenesis and collagen deposition. This work proposes an approach for nanocatalyzed hydrogels with an activated IME response to treat wound infections by enhancing the phototherapeutic effects.