[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.

[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.

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.

Develop a novel and multifunctional soy protein adhesive constructed by rosin acid emulsion and TiO2 organic-inorganic hybrid structure.

Soy protein adhesives (SPI) exhibit broad prospects in substituting aldehyde-based resin due to the economic and environmental-friendly characteristics, but still face a challenge because of the dissatisfied bonding strength and terrible water resistance. Herein, prompted by organic-inorganic hierarchy, a multifunctional and novel soy protein adhesive (SPI-RAE-TiO2) consisting of rosin acid emulsion (RAE) and TiO2 nanoparticles (TiO2) were proposed. In comparison with original SPI, the dry and wet shear strengths of modified adhesive reached 2.01 and 1.21 MPa, respectively, which were increased by 130 % and 200 %. Furthermore, SPI-6RAE-0.5TiO2 was selected as the best proportion via the method of response surface methodology (RSM). What's more, SPI-6RAE-0.5TiO2 adhesive demonstrated prominent coating performance in both dry and wet surface conditions. Meanwhile, SPI-6RAE-0.5TiO2 adhesive possessed excellent mildew resistance and antibacterial ability with Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), reflecting the antibacterial rates 97.71 % and 98.16 %, respectively. In addition, SPI-6RAE-0.5TiO2 adhesive also exhibited the outstanding green features such as the reduction of formaldehyde pollution and greenhouse effect through Life Cycle Assessment (LCA). Thus, this work provided a novel and functional approach to design multifunctional, superior-property and low-carbon footprint soy protein adhesive.

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.

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.

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.

Gelatin­sodium alginate composite hydrogel doped with black phosphorus@ZnO heterojunction for cutaneous wound healing with antibacterial, immunomodulatory, and angiogenic properties.

Hydrogels with novel antimicrobial properties and accelerated wound healing are of great interest in the field of wound dressings because they not only prevent bacterial infections but also fulfill the essential needs of wound healing. In this study, multifunctional hydrogel dressings consisting of black phosphorus nanosheets(BPNS) surface-modified Zinc oxide (BP@ZnO heterojunction) based on gelatin (Gel), sodium alginate (SA), glutamine transferase (mTG), and calcium ions with a three-dimensional crosslinked network were prepared. The BP@ZnO-Gel/SA hydrogel has excellent mechanical properties, hemocompatibility (hemolysis rate: 3.29 %), swelling rate(832.8 ± 19.2 %), cytocompatibility, photothermal and photodynamic antibacterial properties(Sterilization rate: 96.4 ± 3.3 %). In addition, the hydrogel accelerates wound healing by promoting cell migration, immune regulation and angiogenesis. Thus, this hydrogel achieves the triple effect of antimicrobial, immunomodulation and angiogenesis, and is a tissue engineering strategy with great potential.

Electrohydrodynamic Direct-Writing Micro/Nanofibrous Architectures: Principle, Materials, and Biomedical Applications.

Electrohydrodynamic (EHD) direct-writing has recently gained attention as a highly promising additive manufacturing strategy for fabricating intricate micro/nanoscale architectures. This technique is particularly well-suited for mimicking the extracellular matrix (ECM) present in biological tissue, which serves a vital function in facilitating cell colonization, migration, and growth. The integration of EHD direct-writing with other techniques has been employed to enhance the biological performance of scaffolds, and significant advancements have been made in the development of tailored scaffold architectures and constituents to meet the specific requirements of various biomedical applications. Here, a comprehensive overview of EHD direct-writing is provided, including its underlying principles, demonstrated materials systems, and biomedical applications. A brief chronology of EHD direct-writing is provided, along with an examination of the observed phenomena that occur during the printing process. The impact of biomaterial selection and architectural topographic cues on biological performance is also highlighted. Finally, the major limitations associated with EHD direct-writing are discussed.

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.

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.

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.

Calcium Phosphate Bone Cements Incorporated with Black Phosphorus Nanosheets Enhanced Osteogenesis.

For decades, calcium phosphate bone cements (CPCs) showed impressive advantages for their good biocompatibility, injectability, and osteoconductivity in the bone repair field. However, it is still difficult to prepare CPCs with outstanding antibacterial and self-curing properties, sufficient phosphorus release, and osteoinductivity for clinical application. Herein, we used partially crystallized calcium phosphate and dicalcium phosphate anhydrate particles incorporated with black phosphorous nanosheets to prepare calcium phosphate bone cements (CPCs). The curing time, compressive strength, photothermal properties, and degradation performance of BP/CPC were investigated. In addition, the cytocompatibility and osteoinductivity of BP/CPC were evaluated by cell adhesion, cytotoxicity, alkaline phosphatase detection, alizarin red staining, and western blot assay. The results indicated that BP/CPC showed adjustable curing time, good cytocompatibility, outstanding photothermal properties, and osteoinductivity, suggesting their potential application for bone regeneration.

Hyaluronic acid mediated Fe3O4 nanocubes reversing the EMT through targeted cancer stem cell.

Hepatocellular carcinoma (HCC) is one of the deadliest tumors in the world with a high rate of recurrence and metastasis. Therefore, the most pressing issue today is the development of new drugs, diagnostic and therapeutic approaches for effective cancer treatment. Cancer stem cells (CSCs) play a pivotal role in tumor recurrence, tumor resistance, and tumor metastasis, which provides a new perspective on the development of liver cancer. In the study, a high-temperature thermal breakdown approach was used to create composite magnetic nanocubes modified by polyethyleneimine (PEI) and hyaluronic acid (HA). The Fe3O4 nanocubes can recognize HCC stem cells via receptor-ligand binding of HA and CD44 (HA receptor). While loading a small molecule LDN193189 inhibited the expression of stemness-related genes OCT4 and Nanog. More crucially, the Fe3O4 nanocubes significantly suppressed HCC cell proliferation and migration by regulating the expression of epithelial-mesenchymal transition (EMT) process markers E-cadherin, Vimentin, and N-cadherin. Dual targeting using magnetic and receptor-mediated targeting improved the uptake of the drug delivery system. Our findings imply that the medication delivery method might be a potential therapeutic strategy for HCC.

A facile method to fabricate high performance PVA/PAA-AS hydrogel via the synergy of multiple hydrogen bonding and Hofmeister effect.

Hydrogels are widely used in biomedical engineering, which often require matched mechanical properties to meet specific demands. Recently, numerous research studies have contributed to tissue engineering hydrogels by soaking strategies to obtain designed properties. Herein, a strategy to fabricate poly(vinyl alcohol)/poly(acrylic acid)-ammonium sulfate (PVA/PAA-AS) hydrogel by successively soaking an aqueous PAA solution and (NH4)2SO4 solution based on the synergy of multiple hydrogen bonding and Hofmeister effect is reported, which exhibits remarkable comprehensive mechanical properties: rigidity (elastic modulus: 0.7-3.6 MPa), strength at break (tensile stress: 3.2-12.0 MPa; strain 320-650%), and toughness (fracture energy: 4.5-30.0 MJ m-3). Besides, PVA/PAA-AS hydrogel with unique spring-like microstructure exhibited super-resilience in 30% strain range by energy-transforming mechanism. Compared with pure PVA hydrogel, PVA/PAA-AS hydrogel has the equal excellent cytocompatibility. Therefore, PVA/PAA-AS hydrogel with high strength, modulus, toughness, super-resilience and excellent biocompatibility has potential applications in the soft tissue engineering field such as muscles, tendons, and ligaments.

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.

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.

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.