Scalable Fabrication of Polymeric Composite Microspheres to Inhibit Oral Pathogens and Promote Osteogenic Differentiation of Periodontal Membrane Stem Cells.

Periodontitis is a worldwide bacterial infectious disease, resulting in the resorption of tooth-supporting structures. Biodegradable polymeric microspheres are emerging as an appealing local therapy candidate for periodontal defect regeneration but suffer from tedious procedures and low yields. Herein, we developed a facile yet scalable approach to prepare polylactide composite microspheres with outstanding drug-loading capability. It was realized by blending equimolar polylactide enantiomers at the temperature between the melting point of homocrystallites and stereocomplex (sc) crystallites, enabling the precipitation of sc crystallites in the form of microspheres. Meanwhile, epigallocatechin gallate (EGCG) and nano-hydroxyapatite were encapsulated in the microspheres in the designated amount. Such an assembly allowed the fast and sustained release of EGCG and Ca2+ ions. The resultant hybrid composite microspheres not only exhibited strong antimicrobial activity against typical oral pathogens (Porphyromonas gingivalis and Enterococcus faecalis), but also directly promoted osteogenic differentiation of periodontal ligament stem cells with good cytocompatibility. These dual-functional composite microspheres offer a desired drug delivery platform to address the practical needs for periodontitis treatment.

Polycaprolactone Electrospun Nanofiber Membrane with Sustained Chlorohexidine Release Capability against Oral Pathogens.

Multiple-pathogen periodontal disease necessitates a local release and concentration of antibacterial medication to control inflammation in a particular location of the mouth cavity. Therefore, it is necessary to effectively load and deliver medicine/antibiotics to treat numerous complex bacterial infections. This study developed chlorhexidine (CHX)/polycaprolactone (PCL) nanofiber membranes with controlled release properties as periodontal dressings to prevent or treat oral disorders. Electrostatic spinning was adopted to endow the nanofiber membranes with a high porosity, hydrophilicity, and CHX loading capability. The release of CHX occurred in a concentration-dependent manner. The CHX/PCL nanofiber membranes exhibited good biocompatibility with human periodontal ligament stem cells, with cell viability over 85% in each group via CCK-8 assay and LIVE/DEAD staining; moreover, the good attachment of the membrane was illustrated by scanning electron microscopy imaging. Through the agar diffusion assay, the nanofiber membranes with only 0.075 wt% CHX exhibited high antibacterial activity against three typical oral infection-causing bacteria: Porphyromonas gingivalis, Enterococcus faecalis, and Prevotella intermedia. The results indicated that the CHX/PCL nanofiber holds great potential as a periodontal dressing for the prevention and treatment periodontal disorders associated with bacteria.

Polyphenol-Assisted Chemical Crosslinking: A New Strategy to Achieve Highly Crosslinked, Antioxidative, and Antibacterial Ultrahigh-Molecular-Weight Polyethylene for Total Joint Replacement.

Highly crosslinked ultrahigh-molecular-weight polyethylene (UHMWPE) bearings are wear-resistant to reduce aseptic loosening but are susceptible to oxidize in vivo/in vitro, as reported in clinical studies. Despite widespread acceptance of antioxidants in preventing oxidation, the crosslinking efficiency of UHMWPE is severely impacted by antioxidants, the use of which was trapped in a trace amount. Herein, we proposed a new strategy of polyphenol-assisted chemical crosslinking to facilitate the formation of a crosslinking network in high-loaded tea polyphenol/UHMWPE blends. Epigallocatechin gallate (EGCG), a representative of tea polyphenol, was mixed with UHMWPE and peroxide. Multiple reactive phenolic hydroxyl groups of tea polyphenol coupled with the nearby free radicals to form extra crosslinking sites. The crosslinking efficiency was remarkably enhanced with increasing tea polyphenol content, even at a concentration of 8 wt %. Given by the hydrogen donation principle, the high-loaded tea polyphenol also enhanced the oxidation stability of the crosslinked UHMWPE. The antioxidative performance was preserved even after tea polyphenol elution. Moreover, superior antibacterial performance was achieved by the in situ tea polyphenol release from the interconnected pathways in the present design. The strategy of polyphenol-assisted chemical crosslinking is applicable for producing highly crosslinked, antioxidative, and antibacterial UHMWPE, which has promising prospects in clinical applications.

Controlled bacteriostasis of tea polyphenol loaded ultrahigh molecular weight polyethylene with high crosslink density and oxidation resistance for total joint replacement.

To avoid catastrophic bacterial infection in prosthesis failure, ultrahigh molecular weight polyethylene (UHMWPE), a common bearing material of artificial joints, has been formulated with antibiotics to eliminate bacteria locally at the implant site. However, the pressing issues regarding cytotoxic effects and evolution of drug resistant bacteria necessitates the development of bio-friendly bacteriostat with long bacteriostatic efficacy. Herein, tea polyphenol extracted from nature source was introduced in UHMWPE as a biogenic antimicrobial. Controlled antimicrobial activity was achieved by chemical crosslinking to regulate the release of the tea polyphenol. In addition, the crosslinking efficiency of UHMWPE blends with high loaded tea polyphenol was significantly improved in comparison to radiation crosslinking. The immobilized tea polyphenols also enhanced the oxidation stability of the UHMWPE, which is essential to prolong the service life in vivo and the storage time in vitro. The blends presented good biocompatibility, despite cell repellent on the highly crosslinked surface. Chemically crosslinked tea polyphenol/UHMWPE exhibited feasible properties for total joint implants, which is promising for clinical application.

Antibacterial and anti-inflammatory ultrahigh molecular weight polyethylene/tea polyphenol blends for artificial joint applications.

Periprosthetic joint infection (PJI) is one of the main causes for the failure of joint arthroplasty. In view of the limited clinical effect of oral/injectable antibiotics and the drug resistance problem, there is a pressing need to develop antibacterial implants with therapeutic antimicrobial properties. In this work, we prepared a highly antibacterial ultrahigh molecular weight polyethylene (UHMWPE) implant by incorporating tea polyphenols. The presence of tea polyphenols not only improved the oxidation stability of irradiated UHMWPE, but also gave it the desirable antibacterial property. The potent antibacterial activity was attributed to the tea polyphenols that produced excess intracellular reactive oxygen species and destroyed the bacterial membrane structure. The tea polyphenol-blended UHMWPE had no biological toxicity to human adipose-derived stem cells and effectively reduced bacteria-induced inflammation in vivo. These results indicate that tea polyphenol-blended UHMWPE is promising for joint replacement prostheses with multifunctionality to meet patient satisfaction.