Enhanced Antibacterial Ability and Bioactivity of Polyetherketoneketone Modified with LL-37.

Polyetherketoneketone (PEKK) is considered to be a potential substitute material for metal bone implants because of its advantageous biocompatibility, chemical stability, and mechanical properties, but clinical application has been severely restricted due to PEKK's lack of antibacterial ability and biological activity. In this study, LL-37, a natural human antimicrobial peptide, was successfully modified on the PEKK surface with polydopamine as the intermediate layer and released continuously for more than 6 days. The results of the MTT assay, colony counts, and Live/Dead staining demonstrated that compared to unmodified PEKK, the LL-37-modified PEKK significantly inhibited the adhesion, vitality, and bacterial biofilm growth of Staphylococcus aureus and Escherichia coli in a concentration-dependent way. Furthermore, the LL-37-modified PEKK enhanced biocompatibility (cell adhesion and viability) and promoted osteogenic differentiation of human umbilical cord Wharton's jelly-derived mesenchymal stem cells. Our data suggested that LL-37-modified PEKK might be a promising material for use in orthopedic implants.

Mechanical properties, corrosion resistance, and anti-adherence characterization of pure titanium fabricated by casting, milling, and selective laser melting.

Milling and selective laser melting (SLM) technology have become new options for removable partial denture (RPD) processing. However, whether milling and SLM technology has an impact on the properties of RPD remains unclear, which is also the aim of our study. To investigate the effects of milling and SLM technology on pure titanium, mechanical property, corrosion resistance, and anti-adherence of specimens were evaluated, and specimens processed by lost-wax casting were used as control. Compared with casting and milling groups, the SLM group showed enhanced Vickers hardness (402.1 ± 13.0 HV), tensile stress (694.4 ± 4.5 MPa), and larger electrochemical capacitance arc radius compared with casting and milling groups. A series of adhesion-related genes (Als1, Als3, and HWP1) of Candida albicans cultured on SLM specimens were upregulated for more than two times that of casting and milling groups. However, images from scanning electron microscopy and confocal laser scanning microscopy exhibited similar biofilm morphology and biomass of C. albicans on a titanium disk processed by casting, milling, and SLM. Dwindled water contact angle (64.7 ± 0.6°) and higher TiO2 constituents (40.82%) in the SLM group might lead to the incompatibility of genetic expression and biofilm generation. Our findings indicated that SLM is an ideal process to produce titanium dentures, providing a reference on the selection of processing technology for dentists.

A preliminary study on surface bioactivation of polyaryletherketone by UV-grafting with PolyNaSS: influence on osteogenic and antibacterial activities.

Polyaryletherketone (PAEK) has good biocompatibility and mechanical properties and thus may have great potential in the fields of reparative medicine and bone intervention. In this study, the key representative PAEKs, polyetheretherketone (PEEK) and polyetherketoneketone (PEKK), were modified by UV grafting with sodium polystyrene sulfonate (polyNaSS) to improve their biocompatibility. Toluidine blue staining and Fourier transform infrared spectroscopic analyses showed that sulfonic acid groups were successfully introduced into PAEK, and the hydrophilicity and protein adsorption capacity of the materials were enhanced in a concentration-dependent manner. The effects of the grafted polyNaSS on osteoinduction and antibacterial properties of PAEK were analyzed in detail. We found that polyNaSS enhanced the viability, alkaline phosphatase activity, calcium mineral deposition, and levels of expression of osteoblast-related genes and proteins of adherent human umbilical cord Wharton's jelly-derived mesenchymal stem cells. In addition, when Escherichia coli, Staphylococcus aureus and Porphyromonas gingivalis were incubated with the materials, bacterial colony counting revealed that grafting of polyNaSS onto PAEK led to more potent inhibition of bacterial adhesion, and polyNaSS-grafted PEKK had stronger antibacterial performance than did polyNaSS-grafted PEEK fabricated under the same grafting conditions. These data show that polyNaSS-grafted PAEK, and particularly polyNaSS-grafted PEKK, may be useful as orthopedic and dental implant materials.

Potential Osteoinductive Effects of Hydroxyapatite Nanoparticles on Mesenchymal Stem Cells by Endothelial Cell Interaction.

Nano-hydroxyapatite (nano-HA) has attracted substantial attention in the field of regenerative medicine. Endothelial cell (EC)-mesenchymal stem cell (MSC) interactions are necessary for bone reconstruction, but the manner in which nano-HA interacts in this process remains unknown. Herein, we investigated the cytotoxicity and osteoinductive effects of HA nanoparticles (HANPs) on MSCs using an indirect co-culture model mediated by ECs and highlighted the underlying mechanisms. It was found that at a subcytotoxic dose, HANPs increased the viability and expression of osteoblast genes, as well as mineralized nodules and alkaline phosphatase production of MSCs. These phenomena relied on HIF-1α secreted by ECs, which triggered the ERK1/2 signaling cascade. In addition, a two-stage cell-lineage mathematical model was established to quantitatively analyze the impact of HIF-1α on the osteogenic differentiation of MSCs. It demonstrated that HIF-1α exerted a dose-dependent stimulatory effect on the osteogenic differentiation rate of MSCs up to 1500 pg/mL, which was in agreement with the above results. Our data implied that cooperative interactions between HANPs, ECs, and MSCs likely serve to stimulate bone regeneration. Furthermore, the two-stage cell-lineage model is helpful in vitro system for assessing the potential influence of effector molecules in bone tissue engineering.

Heme Competition Triggers an Increase in the Pathogenic Potential of Porphyromonas gingivalis in Porphyromonas gingivalis-Candida albicans Mixed Biofilm.

As one of the main pathogens of periodontitis, Porphyromonas gingivalis often forms mixed biofilms with other bacteria or fungi under the gingiva, such as Candida albicans. Heme is an important iron source for P. gingivalis and C. albicans that supports their growth in the host. From the perspective of heme competition, this study aims to clarify that the competition for heme enhances the pathogenic potential of P. gingivalis during the interaction between P. gingivalis and C. albicans. Porphyromonas gingivalis single-species biofilm and P. gingivalis-C. albicans dual-species biofilm were established in a low- and high-heme environment. The results showed that the vitality of P. gingivalis was increased in the dual-species biofilm under the condition of low heme, and the same trend was observed under a laser confocal microscope. Furthermore, the morphological changes in P. gingivalis were observed by electron microscope, and the resistance of P. gingivalis in dual-species biofilm was stronger against the killing effect of healthy human serum and antibiotics. The ability of P. gingivalis to agglutinate erythrocyte was also enhanced in dual-species biofilm. These changes disappeared when heme was sufficient, which confirmed that heme competition was the cause of thepathogenicy change in P. gingivalis. Gene level analysis showed that P. gingivalis was in a superior position in the competition relationship by increasing the expression of heme utilization-related genes, such as HmuY, HmuR, HusA, and Tlr. In addition, the expression of genes encoding gingipains (Kgp, RgpA/B) was also significantly increased. They not only participate in the process of utilizing heme, but also are important components of the virulence factors of P. gingivalis. In conclusion, our results indicated that the pathogenic potential of P. gingivalis was enhanced by C. albicans through heme competition, which ultimately promoted the occurrence and development of periodontitis and, therefore, C. albicans subgingival colonization should be considered as a factor in assessing the risk of periodontitis.