Multifunctional Coating to Simultaneously Encapsulate Drug and Prevent Infection of Radiopaque Agent.

Poly(methyl methacrylate) (PMMA) bone cements have been widely used in clinical practices. In order to enhance PMMA's imaging performance to facilitate surgical procedures, a supplementation of radiopaque agent is needed. However, PMMA bone cements are still facing problems of loosening and bacterial infection. In this study, a multifunctional coating to simultaneously encapsulate drug and prevent the infection of radiopaque agent has been developed. Barium sulfate (BaSO4), a common radiopaque agent, is used as a substrate material. We successfully fabricated porous BaSO4 microparticles, then modified with hexakis-(6-iodo-6-deoxy)-alpha-cyclodextrin (I-CD) and silver (Ag) to obtain porous BaSO4@PDA/I-CD/Ag microparticles. The porous nature and presence of PDA coating and I-CD on the surface of microparticles result in efficient loading and release of drugs such as protein. Meanwhile, the radiopacity of BaSO4@PDA/I-CD/Ag microparticles is enhanced by this multifunctional coating containing Ba, I and Ag. PMMA bone cements containing BaSO4@PDA/I-CD/Ag microparticles show 99% antibacterial rate against both Staphylococcus aureus (S. aureus) and Escherichia Coli (E. coli), yet without apparently affecting its biocompatibility. Together, this multifunctional coating possessing enhanced radiopacity, controlled drug delivery capability and exceptional antibacterial performance, may be a new way to modify radiopaque agents for bone cements.

Construction of multifunctional coating with cationic amino acid-coupled peptides for osseointegration of implants.

Osseointegration is an important indicator of implant success. This process can be improved by coating modified bioactive molecules with multiple functions on the surface of implants. Herein, a simple multifunctional coating that could effectively improve osseointegration was prepared through layer-by-layer self-assembly of cationic amino acids and tannic acid (TA), a negatively charged molecule. Osteogenic growth peptide (OGP) and the arginine-glycine-aspartic acid (RGD) functional polypeptides were coupled with Lys6 (K6), the two polypeptides then self-assembled with TA layer by layer to form a composite film, (TA-OGP@RGD)n. The surface morphology and biomechanical properties of the coating were analyzed in gas and liquid phases, and the deposition process and kinetics of the two peptides onto TA were monitored using a quartz crystal microbalance. In addition, the feeding consistency and adsorption ratios of the two peptides were explored by using fluorescence visualization and quantification. The (TA-OGP@RGD)n composite membrane mediated the early migration and adhesion of cells and significantly promoted osteogenic differentiation and mineralization of the extracellular matrix in vitro. Additionally, the bifunctional peptide exhibited excellent osteogenesis and osseointegration owing to the synergistic effect of the OGP and RGD peptides in vivo. Simultaneously, the (TA-OGP@RGD)n membrane regulated the balance of reactive oxygen species in the cell growth environment, thereby influencing the complex biological process of osseointegration. Thus, the results of this study provide a novel perspective for constructing multifunctional coatings for implants and has considerable application potential in orthopedics and dentistry.

Bioactive Silk Coatings Reduce the Adhesion of Staphylococcus aureus while Supporting Growth of Osteoblast-like Cells.

Orthopedic and dental implants are associated with a substantial risk of failure due to biomaterial-associated infections and poor osseointegration. To prevent such outcomes, a coating can be applied on the implant to ideally both reduce the risk of bacterial adhesion and support establishment of osteoblasts. We present a strategy to construct dual-functional silk coatings with such properties. Silk coatings were made from a recombinant partial spider silk protein either alone (silkwt) or fused with a cell-binding motif derived from fibronectin (FN-silk). The biofilm-dispersal enzyme Dispersin B (DspB) and two peptidoglycan degrading endolysins, PlySs2 and SAL-1, were produced recombinantly. A sortase recognition tag (SrtTag) was included to allow site-specific conjugation of each enzyme onto silkwt and FN-silk coatings using an engineered variant of the transpeptidase Sortase A (SrtA*). To evaluate bacterial adhesion on the samples, Staphylococcus aureus was incubated on the coatings and subsequently subjected to live/dead staining. Fluorescence microscopy revealed a reduced number of bacteria on all silk coatings containing enzymes. Moreover, the bacteria were mobile to a higher degree, indicating a negative influence on the bacterial adhesion. The capability to support mammalian cell interactions was assessed by cultivation of the osteosarcoma cell line U-2 OS on dual-functional surfaces, prepared by conjugating the enzymes onto FN-silk coatings. U-2 OS cells could adhere to silk coatings with enzymes and showed high spreading and viability, demonstrating good cell compatibility.

Osteogenic and antiseptic nanocoating by in situ chitosan regulated electrochemical deposition for promoting osseointegration.

Ti and titanium alloy have been extensively utilized in the areas of orthopedics and other related fields, however, limited abilities in antibiosis, ossification and vascularization restrict the application of these materials in clinical. In this research, pulse electrochemical deposition was used as a method to make chitosan regulate Ag+ and Ca2+ in situ, achieving ions' dual regulations and coprecipitation of HA nanoparticles (HA-NPs) and Ag nanoparticles (Ag-NPs) on the surface of Ti. The spherical nanoparticles with even distribution were fabricated by optimizing deposition potential and the concentration of Ag+. The physical stabilities of coatings were significantly improved by the chelation among CS, Ag+ and Ca2+ reducing the release rate of Ag+, Ca2+. The coatings also exhibited noticeable abilities in anti-bacteria. Bone marrow mesenchymal stem cells (BMSCs) displayed adhesion, proliferation and differentiation abilities on the surface of coatings, at the same time the composite coatings revealed promising capability in inducing BMSCs differentiation to osteoblast, which is proved by the results of fluorescent dye. Similar results also can be found in investigations about vascular endothelial cells, desirable adhesion between cells and materials and proliferation are able to prove that this kind of materials has outstanding biocompatibility with VECs cells. The animal experiments indicated that the composite coatings were biocompatible with smooth muscle, myocardium and lung with slightly negative impacts on liver and kidney. According to the results of alizarin red staining, the calcified nodules were dyed red, which reveal that this material can promote bone formation. Electrochemical method was utilized in this research to successfully construct multifunctional composite coatings, such as antibiosis, osteogenesis and angiogenesis, on the surface of Ti.

Effects of Programmed Local Delivery from a Micro/Nano-Hierarchical Surface on Titanium Implant on Infection Clearance and Osteogenic Induction in an Infected Bone Defect.

The two major causes for implant failure are postoperative infection and poor osteogenesis. Initial period of osteointegration is regulated by immunocytes and osteogenic-related cells resulting in inflammatory response and tissue healing. The healing phase can be influenced by various environmental factors and biological cascade effect. To synthetically orchestrate bone-promoting factors on biomaterial surface, built is a dual delivery system coated on a titanium surface (abbreviated as AH-Sr-AgNPs). The results show that this programmed delivery system can release Ag+ and Sr2+ in a temporal-spatial manner to clear pathogens and activate preosteoblast differentiation partially through manipulating the polarization of macrophages. Both in vitro and in vivo assays show that AH-Sr-AgNPs-modified surface renders a microenvironment adverse for bacterial survival and favorable for macrophage polarization (M2), which further promotes the differentiation of preosteoblasts. Infected New Zealand rabbit femoral metaphysis defect model is used to confirm the osteogenic property of AH-Sr-AgNPs implants through micro-CT, histological, and histomorphometric analyses. These findings demonstrate that the programmed surface with dual delivery of Sr2+ and Ag+ has the potential of achieving an enhanced osteogenic outcome through favorable immunoregulation.

Controlling Molecular Weight of Hyaluronic Acid Conjugated on Amine-rich Surface: Toward Better Multifunctional Biomaterials for Cardiovascular Implants.

The molecular weights (MWs) of hyaluronic acid (HA) in extracellular matrix secreted from both vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs) play crucial roles in the cardiovascular physiology, as HA with appropriate MW influences important pathways of cardiovascular homeostasis, inhibits VSMC synthetic phenotype change and proliferation, inhibits platelet activation and aggregation, promotes endothelial monolayer repair and functionalization, and prevents inflammation and atherosclerosis. In this study, HA samples with gradients of MW (4 × 103, 1 × 105, and 5 × 105 Da) were prepared by covalent conjugation to a copolymerized film of polydopamine and hexamethylendiamine (PDA/HD) as multifunctional coatings (PDA/HD-HA) with potential to improve the biocompatibility of cardiovascular biomaterials. The coatings immobilized with high-MW-HA (PDA/HD-HA-2: 1 × 105 Da; PDA/HD-HA-3: 5 × 105 Da) exhibited a remarkable suppression of platelet activation/aggregation and thrombosis under 15 dyn/cm2 blood flow and simultaneously suppressed the adhesion and proliferation of VSMC and the adhesion, activation, and inflammatory cytokine release of macrophages. In particular, PDA/HD-HA-2 significantly enhanced VEC adhesion, proliferation, migration, and functional factors release, as well as the captured number of endothelial progenitor cells under dynamic condition. The in vivo results indicated that the multifunctional surface (PDA/HD-HA-2) created a favorable microenvironment of endothelial monolayer formation and functionalization for promoting reendothelialization and reducing restenosis of cardiovascular biomaterials.

Multifunctional copolymer coating of polyethylene glycol, glycidyl methacrylate, and REDV to enhance the selectivity of endothelial cells.

Multifunctional polymer coatings have potential applications in biomaterials. These coatings possess reactive functional groups for the immobilization of specific biological factors that can influence cellular behavior. These coatings also display low nonspecific protein adsorption. In this study, we prepared a multifunctional polymer coating through the deposition of random copolymers of poly(ethylene glycol) methacrylate (PEGMA) and glycidyl methacrylate (GMA) to prevent nonspecific attachment and enable the covalence of Arg-Glu-Asp-Val (REDV) peptide with endothelial cells (ECs) selectivity. Coatings were characterized by X-ray photoelectron spectroscopy (XPS). The adhesion and proliferation of ECs and smooth muscle cells (SMCs) onto the REDV-modified surface were investigated to understand the synergistic action of antifouling PEG and EC selective REDV peptide conjugated GMA. The copolymers containing GMA and PEG groups are very useful as a multifunctional coating material with anti-fouling and ECs specific adhesion for implant materials surface modification.