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1.
Biomaterials ; 313: 122769, 2025 Feb.
Article in English | MEDLINE | ID: mdl-39208698

ABSTRACT

Minimally invasive transcatheter interventional therapy utilizing cardiac occluders represents the primary approach for addressing congenital heart defects and left atrial appendage (LAA) thrombosis. However, incomplete endothelialization and delayed tissue healing after occluder implantation collectively compromise clinical efficacy. In this study, we have customized a recombinant humanized collagen type I (rhCol I) and developed an rhCol I-based extracellular matrix (ECM)-mimetic coating. The innovative coating integrates metal-phenolic networks with anticoagulation and anti-inflammatory functions as a weak cross-linker, combining them with specifically engineered rhCol I that exhibits high cell adhesion activity and elicits a low inflammatory response. The amalgamation, driven by multiple forces, effectively serves to functionalize implantable materials, thereby responding positively to the microenvironment following occluder implantation. Experimental findings substantiate the coating's ability to sustain a prolonged anticoagulant effect, enhance the functionality of endothelial cells and cardiomyocyte, and modulate inflammatory responses by polarizing inflammatory cells into an anti-inflammatory phenotype. Notably, occluder implantation in a canine model confirms that the coating expedites reendothelialization process and promotes tissue healing. Collectively, this tailored ECM-mimetic coating presents a promising surface modification strategy for improving the clinical efficacy of cardiac occluders.


Subject(s)
Coated Materials, Biocompatible , Extracellular Matrix , Wound Healing , Animals , Extracellular Matrix/metabolism , Dogs , Humans , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Wound Healing/drug effects , Collagen Type I/metabolism , Biomimetic Materials/chemistry , Biomimetic Materials/pharmacology , Human Umbilical Vein Endothelial Cells , Re-Epithelialization/drug effects , Cell Adhesion/drug effects
2.
Biomaterials ; 313: 122800, 2025 Feb.
Article in English | MEDLINE | ID: mdl-39241551

ABSTRACT

The (002) crystallographic plane-oriented hydroxyapatite (HA) and anatase TiO2 enable favorable hydrophilicity, osteogenesis, and biocorrosion resistance. Thus, the crystallographic plane control in HA coating and crystalline phase control in TiO2 is vital to affect the surface and interface bioactivity and biocorrosion resistance of titanium (Ti) implants. However, a corresponding facile and efficient fabrication method is absent to realize the HA(002) mineralization and anatase TiO2 formation on Ti. Herein, we utilized the predominant Ti(0002) plane of the fibrous-grained titanium (FG Ti) to naturally form anatase TiO2 and further achieve a (002) basal plane oriented nanoHA (nHA) film through an in situ mild hydrothermal growth strategy. The formed FG Ti-nHA(002) remarkably improved hydrophilicity, mineralization, and biocorrosion resistance. Moreover, the nHA(002) film reserved the microgroove-like topological structure on FG Ti. It could enhance osteogenic differentiation through promoted contact guidance, showing one order of magnitude higher expression of osteogenic-related genes. On the other hand, the nHA(002) film restrained the osteoclast activity by blocking actin ring formation. Based on these capacities, FG Ti-nHA(002) improved new bone growth and binding strength in rabbit femur implantation, achieving satisfactory osseointegration within 2 weeks.


Subject(s)
Durapatite , Osseointegration , Titanium , Titanium/chemistry , Durapatite/chemistry , Animals , Osseointegration/drug effects , Rabbits , Osteogenesis/drug effects , Corrosion , Mice , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Cell Differentiation/drug effects
3.
Sci Rep ; 14(1): 21749, 2024 09 18.
Article in English | MEDLINE | ID: mdl-39294268

ABSTRACT

Implant-related infections pose significant challenges to orthopedic surgeries due to the high risk of severe complications. The widespread use of bioactive prostheses in joint replacements, featuring roughened surfaces and tight integration with the bone marrow cavity, has facilitated bacterial proliferation and complicated treatment. Developing antibacterial coatings for orthopedic implants has been a key research focus in recent years to address this critical issue. Researchers have designed coatings using various materials and antibacterial strategies. In this study, we fabricated 3D-printed porous titanium rods, incorporated vancomycin-loaded mPEG750-b-PCL2500 gel, and coated them with a PCL layer. We then evaluated the antibacterial efficacy through both in vitro and in vivo experiments. Our coating passively inhibits bacterial biofilm formation and actively controls antibiotic release in response to bacterial growth, providing a practical solution for proactive and sustained infection control. This study utilized 3D printing technology to produce porous titanium rod implants simulating bioactive joint prostheses. The porous structure of the titanium rods was used to load a thermoresponsive gel, mPEG750-b-PCL2500 (PEG: polyethylene glycol; PCL: polycaprolactone), serving as a novel drug delivery system carrying vancomycin for controlled antibiotic release. The assembly was then covered with a PCL membrane that inhibits bacterial biofilm formation early in infection and degrades when exposed to lipase solutions, mimicking enzymatic activity during bacterial infections. This setup provides infection-responsive protection and promotes drug release. We investigated the coating's controlled release, antibacterial capability, and biocompatibility through in vitro experiments. We established a Staphylococcus aureus infection model in rabbits, implanting titanium rods in the femoral medullary cavity. We evaluated the efficacy and safety of the composite coating in preventing implant-related infections using imaging, hematology, and pathology. In vitro experiments demonstrated that the PCL membrane stably protects encapsulated vancomycin during PBS immersion. The PCL membrane rapidly degraded at a lipase concentration of 0.2 mg/mL. The mPEG750-b-PCL2500 gel ensured stable and sustained vancomycin release, inhibiting bacterial growth. We investigated the antibacterial effect of the 3D-printed titanium material, coated with PCL and loaded with mPEG750-b-PCL2500 hydrogel, using a rabbit Staphylococcus aureus infection model. Imaging, hematology, and histopathology confirmed that our composite antibacterial coating exhibited excellent antibacterial effects and infection prevention, with good safety in trials. Our results indicate that the composite antibacterial coating effectively protects vancomycin in the hydrogel from premature release in the absence of bacterial infection. The outer PCL membrane inhibits bacterial growth and prevents biofilm formation. Upon contact with bacterial lipase, the PCL membrane rapidly degrades, releasing vancomycin for antibacterial action. The mPEG750-b-PCL2500 gel provides stable and sustained vancomycin release, prolonging its antibacterial effects. Our composite antibacterial coating demonstrates promising potential for clinical application.


Subject(s)
Anti-Bacterial Agents , Hydrogels , Polyesters , Printing, Three-Dimensional , Titanium , Vancomycin , Titanium/chemistry , Vancomycin/pharmacology , Vancomycin/administration & dosage , Vancomycin/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/chemistry , Polyesters/chemistry , Animals , Hydrogels/chemistry , Rabbits , Staphylococcus aureus/drug effects , Drug Liberation , Porosity , Biofilms/drug effects , Polyethylene Glycols/chemistry , Staphylococcal Infections/drug therapy , Staphylococcal Infections/prevention & control , Drug Delivery Systems/methods , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology
4.
ACS Appl Mater Interfaces ; 16(38): 50507-50523, 2024 Sep 25.
Article in English | MEDLINE | ID: mdl-39263871

ABSTRACT

Immunoglobulin G (IgG) comprises a significant portion of the protein corona that forms on biomaterial surfaces and holds a pivotal role in modulating host immune responses. To shed light on the important relationship between biomaterial surface functionality, IgG adsorption, and innate immune responses, we prepared, using plasma deposition, four surface coatings with specific chemistries, wettability, and charge. We found that nitrogen-containing coatings such as these deposited from allylamine (AM) and 2-methyl-2-oxazoline (POX) cause the greatest IgG unfolding, while hydrophilic acrylic acid (AC) surfaces allowed for the retention of the protein structure. Structural changes in IgG significantly modulated macrophage attachment, migration, polarization, and the expression of pro- and anti-inflammatory cytokines. Unfolded IgG on the POX and AM surfaces enhanced macrophage attachment, migration, extracellular trap release, and pro-inflammatory factors production such as IL-6 and TNF-α. Retention of IgG structure on the AC surface downregulated inflammatory responses. The findings of this study demonstrate that the retention of protein structure is an essential factor that must be taken into consideration when designing biomaterial surfaces. Our study indicates that using hydrophilic surface coatings could be a promising strategy for designing immune-modulatory biomaterials for clinical applications.


Subject(s)
Immunoglobulin G , Surface Properties , Immunoglobulin G/chemistry , Immunoglobulin G/immunology , Mice , Animals , Protein Unfolding , Macrophages/immunology , Macrophages/drug effects , Macrophages/metabolism , Humans , RAW 264.7 Cells , Hydrophobic and Hydrophilic Interactions , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Adsorption , Cytokines/metabolism , Cytokines/immunology
5.
ACS Appl Mater Interfaces ; 16(38): 51411-51420, 2024 Sep 25.
Article in English | MEDLINE | ID: mdl-39269915

ABSTRACT

Maintaining the differentiated phenotype and function of primary hepatocytes in vitro and in vivo represents a distinct challenge. Our paper describes microcapsules comprised of a bioactive polymer and overcoated with an ultrathin film as a means of maintaining the function of entrapped hepatocytes for at least two weeks. We previously demonstrated that heparin (Hep)-based microcapsules improved the function of entrapped primary hepatocytes by capturing and releasing cell-secreted inductive signals, including hepatocyte growth factor (HGF). Further enhancement of hepatic function could be gained by loading exogenous HGF into microcapsules. In this study, we demonstrate that an ultrathin coating of tannic acid (TA) further enhances endogenous HGF signaling for entrapped hepatocytes and increases by 2-fold the rate of uptake of exogenous HGF by Hep microcapsules. Hepatocytes in overcoated microcapsules exhibited better function and hepatic gene expression than in capsules without a TA coating. Our study showcases the potential application of ultrathin coatings to modulate the bioactivity of microcapsules and may enable the use of encapsulated hepatocytes for modeling drug toxicity or treating liver diseases.


Subject(s)
Capsules , Heparin , Hepatocytes , Hepatocytes/metabolism , Hepatocytes/cytology , Hepatocytes/drug effects , Capsules/chemistry , Animals , Heparin/chemistry , Heparin/pharmacology , Tannins/chemistry , Tannins/pharmacology , Hepatocyte Growth Factor/metabolism , Hepatocyte Growth Factor/chemistry , Hepatocyte Growth Factor/pharmacology , Spheroids, Cellular/drug effects , Spheroids, Cellular/metabolism , Humans , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Mice
6.
Acta Bioeng Biomech ; 26(1): 37-46, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-39219076

ABSTRACT

Purpose: The paper shows a preliminary study of the basic strength parameters of printed parts made of biocompatible polymers with ceramic layers applied to increase the strength of the tool cutting surface. Methods: The specimens were made from different materials and using different 3D printing technologies and the working surfaces that will eventually form the cutting element of the tool were coated with Al2O3. Gloss tests were conducted, properties of the coating, a scratch test of the coated surface, also evaluated surface to-pography. Results: Based on the conducted research, it was found that polymeric materials are characterized by sufficient strength and can be used for disposable tools, however, the use of thin layers of Al2O3 significantly increases the surface strength parameters, which may have a significant impact on the reliability and durability of the tools. The polymer surface covered with an Al2O3 layer is characterised by increased scratch resistance ranging from 24% to 75% depending on the core material and printing technology. The gloss of the surfaces is disproportionately low compared to currently used metal tools, which indicates that they can be used in endoscopic procedures. Conclusions: Based on the conducted research, it was found that the use of thin layers of Al2O3 covering polymer 3D prints is an excellent way to increase strength parameters such as scratch resistance, tribological parameters and light reflections arising on the surface as a result of endoscopic lighting are disproportionately small compared to metallic biomaterials. This gives great hope for using polymer 3D prints for personalised neurosurgical tools.


Subject(s)
Ceramics , Materials Testing , Printing, Three-Dimensional , Ceramics/chemistry , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Surface Properties , Aluminum Oxide/chemistry
7.
Carbohydr Polym ; 344: 122496, 2024 Nov 15.
Article in English | MEDLINE | ID: mdl-39218539

ABSTRACT

Chitosan is a promising natural polymer for coatings, it combines intrinsic antibacterial and pro-osteoblastic properties, but the literature still has a gap from the development to behavior of these coatings, so this systematic review aimed to answer, "What is the relationship between the physical and chemical properties of polymeric chitosan coatings on titanium implants on antibacterial activity and osteoblast viability?". PRISMA guidelines was followed, the search was applied into 4 databases and grey literature, without the restriction of time and language. The selection process occurred in 2 blinded steps by the authors. The criteria of eligibility were in vitro studies that evaluated the physical, chemical, microbiological, and biological properties of chitosan coatings on titanium surfaces. The risk of bias was analyzed by the specific tool. Of 734 potential articles 10 were included; all had low risk of bias. The coating was assessed according to the technique of fabrication, FT-IR, thickness, adhesion, roughness, wettability, antibacterial activity, and osteoblast viability. The analyzed coatings showed efficacy on antibacterial activity and cytocompatibility dependent on the class of material incorporated. Thus, this review motivates the development of time-dependent studies to optimize manufacturing and allow for an increase in patents and availability on the market.


Subject(s)
Anti-Bacterial Agents , Chitosan , Coated Materials, Biocompatible , Osteoblasts , Titanium , Chitosan/chemistry , Chitosan/pharmacology , Titanium/chemistry , Titanium/pharmacology , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Osteoblasts/drug effects , Osteoblasts/cytology , Surface Properties , Prostheses and Implants , Animals , Cell Survival/drug effects
8.
Int J Mol Sci ; 25(17)2024 Aug 23.
Article in English | MEDLINE | ID: mdl-39273096

ABSTRACT

In recent years, with the advent of a super-aged society, lifelong dental care has gained increasing emphasis, and implant therapy for patients with an edentulous jaw has become a significant option. However, for implant therapy to be suitable for elderly patients with reduced regenerative and immunological capabilities, higher osteoconductive and antimicrobial properties are required on the implant surfaces. Silicon nitride, a non-oxide ceramic known for its excellent mechanical properties and biocompatibility, has demonstrated high potential for inducing hard tissue differentiation and exhibiting antibacterial properties. In this study, silicon nitride was deposited on pure titanium metal surfaces and evaluated for its biocompatibility and antibacterial properties. The findings indicate that silicon nitride improves the hydrophilicity of the material surface, enhancing the initial adhesion of rat bone marrow cells and promoting hard tissue differentiation. Additionally, the antibacterial properties were assessed using Staphylococcus aureus, revealing that the silicon nitride-coated surfaces exhibited significant antibacterial activity. Importantly, no cytotoxicity was observed, suggesting that silicon nitride-coated titanium could serve as a novel implant material.


Subject(s)
Anti-Bacterial Agents , Coated Materials, Biocompatible , Silicon Compounds , Staphylococcus aureus , Surface Properties , Titanium , Titanium/chemistry , Titanium/pharmacology , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Rats , Staphylococcus aureus/drug effects , Silicon Compounds/chemistry , Silicon Compounds/pharmacology , Materials Testing , Cell Adhesion/drug effects , Bone Marrow Cells/drug effects , Cell Differentiation/drug effects
9.
Molecules ; 29(17)2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39275040

ABSTRACT

Graphitic carbon nitride (g-C3N4, CN) has emerged as a promising photocatalytic material due to its inherent stability, antibacterial properties, and eco-friendliness. However, its tendency to aggregate and limited dispersion hinder its efficacy in practical antibacterial applications. To address these limitations, this study focuses on developing a composite hydrogel coating, in which sodium alginate (SA) molecules interact electrostatically and through hydrogen bonding to anchor CN, thereby significantly improving its dispersion. The optimal CN loading of 35% results in a hydrogel with a tensile strength of 120 MPa and an antibacterial rate of 99.87% within 6 h. The enhanced mechanical properties are attributed to hydrogen bonding between the -NH2 groups of CN and the -OH groups of SA, while the -OH groups of SA facilitate the attraction of photogenerated holes from CN, promoting carrier transfer and separation, thereby strengthening the antibacterial action. Moreover, the hydrogel coating exhibits excellent antibacterial and corrosion resistance capabilities against Pseudomonas aeruginosa on 316L stainless steel (316L SS), laying the foundation for advanced antimicrobial and anticorrosion hydrogel systems.


Subject(s)
Alginates , Anti-Bacterial Agents , Graphite , Hydrogels , Pseudomonas aeruginosa , Alginates/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Pseudomonas aeruginosa/drug effects , Hydrogels/chemistry , Hydrogels/pharmacology , Graphite/chemistry , Graphite/pharmacology , Nitrogen Compounds/chemistry , Nitrogen Compounds/pharmacology , Corrosion , Microbial Sensitivity Tests , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Hydrogen Bonding , Stainless Steel/chemistry
10.
Acta Biomater ; 186: 201-214, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-39089350

ABSTRACT

The current techniques for antithrombotic coating on blood-contacting biomedical materials and devices are usually complex and lack practical feasibility with weak coating stability and low heparin immobilization. Here, a heparinized self-healing polymer coating with inflammation modulation is introduced through thermal-initiated radical copolymerization of methacrylate esterified heparin (MA-heparin) with methyl methacrylate (MMA) and n-butyl acrylate (nBA), followed by the anchoring of reactive oxygen species (ROS)-responsive polyoxalate containing vanillyl alcohol (PVAX) onto the coating through esterification. The aspirin, which is readily dissolved in the solution of MMA and nBA, is encapsulated within the coating after copolymerization. The copolymerization of MA-heparin with MMA and nBA significantly increases the heparin content of the coating, effectively inhibiting thrombosis and rendering the coating self-healing to help maintain long-term stability. ROS-responsive PVAX and aspirin released in a temperature-dependent manner resist acute and chronic inflammation, respectively. The heparinized self-healing and inflammation-modulated polymer coating exhibits the ability to confer long-term stability and hemocompatibility to blood-contacting biomedical materials and devices. STATEMENT OF SIGNIFICANCE: Surface engineering for blood-contacting biomedical devices paves a successful way to reduce thrombotic and inflammatory complications. However, lack of effectiveness, long-term stability and practical feasibility hinders the development and clinical application of existing strategies. Here we design a heparinized self-healing and inflammation-modulated polymer coating, which possesses high heparin level and self-healing capability to maintain long-term stability. The polymer coating is practically feasible to varied substrates and demonstrated to manipulate inflammation and prevent thrombosis both in vitro and in vivo. Our work provides a new method to develop coatings for blood-contacting biomedical materials and devices with long-term stability and hemocompatibility.


Subject(s)
Coated Materials, Biocompatible , Heparin , Inflammation , Polymers , Heparin/chemistry , Heparin/pharmacology , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Inflammation/pathology , Inflammation/drug therapy , Animals , Polymers/chemistry , Polymers/pharmacology , Humans , Mice , Reactive Oxygen Species/metabolism , Thrombosis
11.
Acta Biomater ; 186: 185-200, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-39103136

ABSTRACT

Thrombosis and plasma leakage are two of the most frequent dysfunctions of polypropylene (PP) hollow fiber membrane (PPM) used in extracorporeal membrane oxygenation (ECMO) therapy. In this study, a superhydrophilic endothelial membrane mimetic coating (SEMMC) was constructed on polydopamine-polyethyleneimine pre-coated surfaces of the PPM oxygenator and its ECMO circuit to explore safer and more sustainable ECMO strategy. The SEMMC is fabricated by multi-point anchoring of a phosphorylcholine and carboxyl side chained copolymer (PMPCC) and grafting of heparin (Hep) to form PMPCC-Hep interface, which endows the membrane superior hemocompatibility and anticoagulation performances. Furthermore, the modified PPM reduces protein adsorption amount to less than 30 ng/cm2. More significantly, the PMPCC-Hep coated ECMO system extends the anti-leakage and non-clotting oxygenation period to more than 15 h in anticoagulant-free animal extracorporeal circulation, much better than the bare and conventional Hep coated ECMO systems with severe clots and plasma leakage in 4 h and 8 h, respectively. This SEMMC strategy of grafting bioactive heparin onto bioinert zwitterionic copolymer interface has great potential in developing safer and longer anticoagulant-free ECMO systems. STATEMENT OF SIGNIFICANCE: A superhydrophilic endothelial membrane mimetic coating was constructed on surfaces of polypropylene hollow fiber membrane (PPM) oxygenator and its ECMO circuit by multi-point anchoring of a phosphorylcholine and carboxyl side chain copolymer (PMPCC) and grafting of heparin (Hep). The strong antifouling nature of the PMPCC-Hep coating resists the adsorption of plasma bio-molecules, resulting in enhanced hemocompatibility and anti-leakage ability. The grafted heparin on the zwitterionic PMPCC interface exhibits superior anticoagulation property. More significantly, the PMPCC-Hep coating achieves an extracorporeal circulation in a pig model for at least 15 h without any systemic anticoagulant. This endothelial membrane mimetic anticoagulation strategy shows great potential for the development of safer and longer anticoagulant-free ECMO systems.


Subject(s)
Coated Materials, Biocompatible , Extracorporeal Membrane Oxygenation , Animals , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Heparin/chemistry , Heparin/pharmacology , Humans , Polypropylenes/chemistry , Biomimetic Materials/chemistry , Biomimetic Materials/pharmacology , Fibrinolytic Agents/pharmacology , Fibrinolytic Agents/chemistry , Membranes, Artificial , Adsorption , Thrombosis/prevention & control , Phosphorylcholine/chemistry , Phosphorylcholine/analogs & derivatives , Polymers/chemistry
12.
Acta Biomater ; 186: 215-228, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-39111681

ABSTRACT

Catheter-related infections are one of the most common nosocomial infections with increasing morbidity and mortality, and robust antibacterial or antifouling catheter coatings remain great challenges for long-term implantation. Herein, multifunctional hydrogel coatings were developed to provide persistent and self-adaptive antifouling and antibacterial effects with self-healing and lubricant capabilities. Polyvinyl alcohol (PVA) with ß-cyclodextrin (ß-CD) grafts (PVA-Cd) and 4-arm polyethylene glycol (PEG) with adamantane and quaternary ammonium compound (QAC) terminals (QA-PEG-Ad) were crosslinked through host-guest recognitions between adamantane and ß-CD moieties to acquire PVEQ coatings. In response to bacterial infections, QACs exhibit reversible transformation between zwitterions (pH 7.4) and cationic lactones (pH 5.5) to generate on-demand bactericidal effect. Highly hydrophilic PEG/PVA backbones and zwitterionic QACs build a lubricate surface and decrease the friction coefficient 10 times compared with that of bare catheters. The antifouling hydrated layer significantly inhibits blood protein adsorption and platelet activation and reveals negligible hemolysis and cytotoxicity. The dynamic host-guest crosslinking achieves full self-healing of cracks in PVEQ hydrogels, and the mechanical profiles were recovered to over 90 % after rejuvenating the broken hydrogels, exhibiting a long-term stability after mechanical stretching, twisting, knotting and compression. After subcutaneous implantation and local bacterial infection, the retrieved PVEQ-coated catheters display no tissue adhesion and 3 log folds lower bacterial number than that of bare catheters. PVEQ coatings effectively prevent the repeated bacterial infections and there are few inflammatory reactions in the surrounding tissue, while substantial lymphoid infiltration and inflammatory cell aggregation occur in muscle tissues around the bare catheter. Thus, this study demonstrates a catheter coating strategy by on-demand bactericidal, self-adaptive antifouling, self-healing and lubricant hydrogels to address medical devices-related infections. STATEMENT OF SIGNIFICANCE: It is estimated over two billion peripheral intravenous catheters are annually used in hospitals around the world, and catheter-associated infection has become a great clinical challenge with rapidly rising morbidity and mortality. Surface coating is considered a promising approach, but substantial challenges remain in the development of coatings that simultaneously satisfy both anti-fouling and antibacterial attributes. Even more, few attempts have been made to design mechanically robust coatings and reversible antibacterial or antifouling capabilities, which are critical for long-term medical implants. To address these challenges, we propose a concise strategy to develop hydrogel coatings from commercially available poly(ethylene glycol) and polyvinyl alcohol. In addition to self-healing and lubricant capabilities, the reversible conversion between zwitterionic and cationic lactones of quaternary ammonium compounds enables on-demand bactericidal and self-adaptive antifouling effects.


Subject(s)
Anti-Bacterial Agents , Catheters , Coated Materials, Biocompatible , Hydrogels , Lubricants , Hydrogels/chemistry , Hydrogels/pharmacology , Coated Materials, Biocompatible/pharmacology , Coated Materials, Biocompatible/chemistry , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Lubricants/pharmacology , Lubricants/chemistry , Polyvinyl Alcohol/chemistry , Polyvinyl Alcohol/pharmacology , Biofouling/prevention & control , Polyethylene Glycols/chemistry , Polyethylene Glycols/pharmacology , Mice , beta-Cyclodextrins/chemistry , Humans
13.
ACS Appl Mater Interfaces ; 16(34): 44451-44466, 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39141574

ABSTRACT

Bone and tooth defects can considerably affect the quality of life and health of patients, and orthopedic implants remain the primary method of addressing such defects. However, implant materials cannot coordinate with the immune microenvironment because of their biological inertness, which may lead to implant loosening or failure. Motivated by the microstructure of nacre, we engineered a biomimetic micro/nanoscale topography on a tantalum surface using a straightforward method. This comprised an organized array of tantalum nanotubes arranged in a brick wall structure, with epigallocatechin gallate acting as "mortar." The coating improved the corrosion resistance, biocompatibility, and antioxidant properties. In vitro and in vivo evaluations further confirmed that coatings can create a favorable bone immune microenvironment through the synergistic effects of mechanochemistry and enhance bone integration. This research offers a new viewpoint on the creation of sophisticated functional implants, possessing vast potential for use in the regeneration and repair of bone tissue.


Subject(s)
Osseointegration , Tantalum , Tantalum/chemistry , Osseointegration/drug effects , Animals , Mice , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Catechin/chemistry , Catechin/analogs & derivatives , Catechin/pharmacology , Nanotubes/chemistry , Immunomodulation/drug effects , Surface Properties , Antioxidants/chemistry , Antioxidants/pharmacology , Humans
14.
Int J Biol Macromol ; 277(Pt 3): 134509, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39111508

ABSTRACT

Aiming to improve the retrieval rate of retrievable vena cava filters (RVCF) and extend its dwelling time in vivo, a novel hydrogel coating loaded with 10 mg/mL heparin and 30 mg/mL cyclodextrin/paclitaxel (PTX) inclusion complex (IC) was prepared. The drug-release behavior in the phosphate buffer solution demonstrated both heparin and PTX could be sustainably released over approximately two weeks. Furthermore, it was shown that the hydrogel-coated RVCF (HRVCF) with 10 mg/mL heparin and 30 mg/mL PTX IC effectively extended the blood clotting time to above the detection limit and inhibited EA.hy926 and CCC-SMC-1 cells' proliferation in vitro compared to the commercially available bare RVCF. Both the HRVCF and the bare RVCF were implanted into the vena cava of sheep and retrieved at at 2nd and 4th week after implantation, revealing that the HRVCF had a significantly higher retrieval rate of 67 % than the bare RVCF (0 %) at 4th week. Comprehensive analyses, including histological, immunohistological, and immunofluorescent assessments of the explanted veins demonstrated the HRVCF exhibited anti-hyperplasia and anticoagulation properties in vivo, attributable to the hydrogel coating, thereby improving the retrieval rate in sheep. Consequently, the as-prepared HRVCF shows promising potential for clinical application to enhance the retrieval rates of RVCFs.


Subject(s)
Cyclodextrins , Heparin , Hydrogels , Paclitaxel , Vena Cava Filters , Cyclodextrins/chemistry , Cyclodextrins/pharmacology , Paclitaxel/pharmacology , Paclitaxel/chemistry , Heparin/chemistry , Heparin/pharmacology , Animals , Hydrogels/chemistry , Hydrogels/pharmacology , Humans , Sheep , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Blood Coagulation/drug effects , Cell Proliferation/drug effects , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Drug Liberation
15.
J Mater Chem B ; 12(37): 9238-9248, 2024 Sep 25.
Article in English | MEDLINE | ID: mdl-39171692

ABSTRACT

Surface modification of biomedical materials and devices using versatile nanocomposite coatings holds great promise for improving functionalities to defend against life-threatening bacterial infections. In this study, a one-step surface modification strategy was developed to deposit gold nanorods (AuNRs)- and curcumin (CUR)-encapsulated zeolitic imidazolate framework-8 (ZIF-8) nanoparticles (AuNRs-ZIF-CUR NPs or AZC) onto phytic acid (PA)-ε-polylysine (Ply) network coatings. In the solution mixture of PA, Ply and AZC, PA interacted with Ply via electrostatic interactions, and can also bind to AZC via metal chelation. The as-formed AZC-PA-Ply aggregates could be deposited onto various substrates via surface adhesion of PA and gravitational effects. The physicochemical and antibacterial properties of the AZC-PA-Ply network coatings on polydimethylsiloxane (PDMS) substrates were evaluated. The sustained release of zinc ions and CUR, as well as the contact-killing ability of Ply, endowed the AZC-PA-Ply network coatings with good antibacterial chemotherapeutic effects. In addition, the embedded AuNRs in the AZC-PA-Ply network coatings exhibited excellent photothermal conversion efficiency for the ablation of bacteria. Upon near-infrared (NIR) laser irradiation, the AZC-PA-Ply-coated PDMS surfaces exhibited strong antibacterial effects by disrupting the membrane integrity and cellular functions of the adhered bacteria. Thus, the AZC-PA-Ply network coatings displayed combined antibacterial chemotherapeutic and photothermal therapeutic effects. Furthermore, the AZC-PA-Ply-coated PDMS substrates exhibited effective bacterial infection prevention and good biocompatibility in an in vivo implant model. Hence, the versatile AZC-PA-Ply network coatings are potentially useful as a multi-modal antibacterial platform to eliminate infectious bacterial pathogens in biomedical applications.


Subject(s)
Anti-Bacterial Agents , Curcumin , Gold , Metal-Organic Frameworks , Metal-Organic Frameworks/chemistry , Metal-Organic Frameworks/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemical synthesis , Gold/chemistry , Gold/pharmacology , Curcumin/chemistry , Curcumin/pharmacology , Staphylococcus aureus/drug effects , Photothermal Therapy , Surface Properties , Microbial Sensitivity Tests , Animals , Polylysine/chemistry , Polylysine/pharmacology , Particle Size , Mice , Polymers/chemistry , Polymers/pharmacology , Nanotubes/chemistry , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Escherichia coli/drug effects , Bacterial Infections/drug therapy
16.
Int J Biol Macromol ; 278(Pt 3): 134940, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39173806

ABSTRACT

The patterns of formation of chitosan nanoparticles doped with vancomycin and coatings based on them in carbonate solutions have been investigated for the first time in this study. Using a technique of radioactive indicators, it was found that at a CO2 pressure of 30 MPa, the yield of the nanoparticles was ∼85 %, and a maximum antibiotic encapsulation efficiency of ∼30 % was achieved. By spectrophotometric and high-resolution microscopy, it was found that the coating of stabilized xenopericardial tissue of bioprosthetic heart valve, based on chitosan nanoparticles doped with vancomycin with a zeta potential |ζ| ∼20 mV completely covers collagen fibers by depositing about 60 nm nanoparticles onto them under direct deposition from carbonic acid at a pressure of 30 MPa CO2. The coating preserves the mechanical strength characteristics of collagen tissue and completely suppresses the growth of S. aureus pathogenic biofilm. This is consistent with the observed increase in antibiotic release of 15 % when the medium was acidified. Histological study demonstrated that the structure of pericardial tissues was not significantly altered by the deposition nanoparticles from carbonic acid. It was found that the rate of biodegradation of polymers and vancomycin in the coating differs by half (16 weeks for the rat model). A significantly lower degradation rate of antibiotics (∼50 % of vancomycin total remaining mass and ∼25 % of chitosan) was associated with its reliable encapsulation into nanoparticles.


Subject(s)
Carbon Dioxide , Chitosan , Nanoparticles , Vancomycin , Chitosan/chemistry , Vancomycin/chemistry , Vancomycin/pharmacology , Nanoparticles/chemistry , Animals , Carbon Dioxide/chemistry , Rats , Water/chemistry , Staphylococcus aureus/drug effects , Staphylococcus aureus/growth & development , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Biofilms/drug effects , Biofilms/growth & development
17.
Int J Biol Macromol ; 278(Pt 4): 134960, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39179080

ABSTRACT

Multilayer conformal coatings have been shown to provide a nanoscale barrier between cells and their environment with adequate stability, while regulating the diffusion of nutrition and waste across the cell membrane. The coating method aims to minimize capsule thickness and implant volume while reducing the need for immunosuppressive drugs, making it a promising approach for islet cell encapsulation in clinical islet transplantation for the treatment of Type 1 diabetes. This study introduces an immunoprotective nanocoating obtained through electrostatic interaction between quaternized phosphocholine-chitosan (PC-QCH) and tetrahydropyran triazole phenyl-alginate (TZ-AL) onto mouse ß-cell spheroids. First, successful synthesis of the proposed polyelectrolytes was confirmed with physico-chemical characterization. A coating with an average thickness of 540 nm was obtained with self-assembly of 4-bilayers of PC-QCH/TZ-AL onto MIN6 ß-cell spheroids. Surface coating of spheroids did not affect cell viability, metabolic activity, or insulin secretion, when compared to non-coated spheroids. The exposure of the polyelectrolytes to THP-1 monocyte-derived macrophages lead to a reduced level of TNF-α secretion and exposure of coated spheroids to RAW264.7 macrophages showed a decreasing trend in the secretion of TNF-α and IL-6. In addition, coated spheroids were able to establish normoglycemia when implanted into diabetic NOD-SCID mice, demonstrating in vivo biocompatibility and cellular function. These results demonstrate the ability of the PC-QCH/TZ-AL conformal coating to mitigate pro-inflammatory responses from macrophages, and thus can be a promising candidate towards nanoencapsulation for cell-based therapy, particularly in type 1 diabetes, where the insulin secreting ß-cells are subjected to inflammation and immune cell attack.


Subject(s)
Alginates , Chitosan , Insulin-Secreting Cells , Islets of Langerhans Transplantation , Spheroids, Cellular , Animals , Mice , Alginates/chemistry , Alginates/pharmacology , Insulin-Secreting Cells/cytology , Insulin-Secreting Cells/drug effects , Insulin-Secreting Cells/metabolism , Chitosan/chemistry , Chitosan/pharmacology , Islets of Langerhans Transplantation/methods , Spheroids, Cellular/drug effects , Spheroids, Cellular/cytology , RAW 264.7 Cells , Humans , Cell Survival/drug effects , Insulin/metabolism , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology
18.
Biomed Mater ; 19(5)2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39094612

ABSTRACT

The therapy of large defects in peripheral nerve injury (PNI) suffers from several drawbacks, especially the lack of autologous nerve donors. Nerve conduits are considered as a solution for nerve injury treatment, but biocompatibility improvements is still required for conduits prepared with synthetic materials. Cell-derived extracellular matrix (ECM) has drawn attention due to its lower risk of immunogenic response and independence from donor availability. The goal of this study is to coat bone mesenchymal stem cell-derived ECMs on poly(lactic-co-glycolic) acid (PLGA) conduits to enhance their ability to support neural growth and neurite extensions. The ECM-coated conduits have better hydrophilic properties than the pure PLGA conduits. A marked increase on PC12 and RSC96 cells' viability, proliferation and dorsal root ganglion neurite extension was observed. Quantitative PCR analysis exhibited a significant increase in markers for cell proliferation (GAP43), neurite extension (NF-H, MAP2, andßIII-tubulin) and neural function (TREK-1). These results show the potential of ECM-coated PLGA conduits in PNI therapy.


Subject(s)
Cell Proliferation , Cell Survival , Extracellular Matrix , Mesenchymal Stem Cells , Nerve Regeneration , Neurites , Polylactic Acid-Polyglycolic Acid Copolymer , Animals , Rats , Neurites/metabolism , PC12 Cells , Extracellular Matrix/metabolism , Mesenchymal Stem Cells/cytology , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Nerve Regeneration/drug effects , Tissue Scaffolds/chemistry , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Ganglia, Spinal , Peripheral Nerve Injuries/therapy , Tissue Engineering/methods , Polymers/chemistry , Materials Testing
19.
Int J Nanomedicine ; 19: 8015-8027, 2024.
Article in English | MEDLINE | ID: mdl-39130690

ABSTRACT

Purpose: This study aimed to confirm the synergy effect of these two materials by evaluating osteoblast and antibacterial activity by applying a double-layered hydroxyapatite(HA) zirconium oxide(ZrO2) coating to titanium. Methods: The specimens used in this study were divided into four groups: a control group (polished titanium; group T) and three experimental groups: Group TH (RF magnetron sputtered HA deposited titanium), Group Z (ZrO2 ALD deposited titanium), and Group ZH (RF magnetron sputtered HA and ZrO2 ALD deposited titanium). The adhesion of Streptococcus mutans (S.mutans) to the surface was assessed using a crystal violet assay. The adhesion, proliferation, and differentiation of MC3T3-E1 cells, a mouse osteoblastic cell line, were assessed through a WST-8 assay and ALP assay. Results: Group Z showed a decrease in the adhesion of S. mutans (p < 0.05) and an improvement in osteoblastic viability (p < 0.0083). Group TH and ZH showed a decrease in adhesion of S. mutans (p < 0.05) and an increase in osteoblastic cell proliferation and cell differentiation (p < 0.0083). Group ZH exhibited the highest antibacterial and osteoblastic differentiation. Conclusion: In conclusion double-layered HA and ZrO2 deposited on titanium were shown to be more effective in inhibiting the adhesion of S. mutans, which induced biofilm formation, and increasing osteoblastic differentiation involved in osseointegration by the synergistic effect of the two materials.


Subject(s)
Bacterial Adhesion , Cell Differentiation , Cell Proliferation , Coated Materials, Biocompatible , Durapatite , Osteoblasts , Streptococcus mutans , Surface Properties , Titanium , Zirconium , Zirconium/chemistry , Zirconium/pharmacology , Titanium/chemistry , Titanium/pharmacology , Streptococcus mutans/drug effects , Animals , Mice , Durapatite/chemistry , Durapatite/pharmacology , Osteoblasts/drug effects , Osteoblasts/cytology , Cell Proliferation/drug effects , Cell Differentiation/drug effects , Bacterial Adhesion/drug effects , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Cell Line , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Cell Adhesion/drug effects , Cell Survival/drug effects
20.
Biomed Mater ; 19(5)2024 Aug 21.
Article in English | MEDLINE | ID: mdl-39121890

ABSTRACT

This study delves into the potential of amorphous titanium oxide (aTiO2) nano-coating to enhance various critical aspects of non-Ti-based metallic orthopedic implants. These implants, such as medical-grade stainless steel (SS), are widely used for orthopedic devices that demand high strength and durability. The aTiO2nano-coating, deposited via magnetron sputtering, is a unique attempt to improve the osteogenesis, the inflammatory response, and to reduce bacterial colonization on SS substrates. The study characterized the nanocoated surfaces (SS-a TiO2) in topography, roughness, wettability, and chemical composition. Comparative samples included uncoated SS and sandblasted/acid-etched Ti substrates (Ti). The biological effects were assessed using human mesenchymal stem cells (MSCs) and primary murine macrophages. Bacterial tests were carried out with two aerobic pathogens (S. aureusandS. epidermidis) and an anaerobic bacterial consortium representing an oral dental biofilm. Results from this study provide strong evidence of the positive effects of the aTiO2nano-coating on SS surfaces. The coating enhanced MSC osteoblastic differentiation and exhibited a response similar to that observed on Ti surfaces. Macrophages cultured on aTiO2nano-coating and Ti surfaces showed comparable anti-inflammatory phenotypes. Most significantly, a reduction in bacterial colonization across tested species was observed compared to uncoated SS substrates, further supporting the potential of aTiO2nano-coating in biomedical applications. The findings underscore the potential of magnetron-sputtering deposition of aTiO2nano-coating on non-Ti metallic surfaces such as medical-grade SS as a viable strategy to enhance osteoinductive factors and decrease pathogenic bacterial adhesion. This could significantly improve the performance of metallic-based biomedical devices beyond titanium.


Subject(s)
Coated Materials, Biocompatible , Macrophages , Materials Testing , Mesenchymal Stem Cells , Osteogenesis , Stainless Steel , Surface Properties , Titanium , Titanium/chemistry , Stainless Steel/chemistry , Animals , Humans , Mesenchymal Stem Cells/cytology , Mice , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Macrophages/metabolism , Osteogenesis/drug effects , Cell Differentiation , Prostheses and Implants , Osteoblasts/cytology , Staphylococcus aureus/drug effects , Biofilms , Staphylococcus epidermidis/drug effects , Bacterial Adhesion , Wettability
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