Antibacterial and Osteoinductive Implant Surface Using Layer-by-Layer Assembly.

Osseointegration of dental, craniofacial, and orthopedic implants is critical for their long-term success. Multifunctional surface treatment of implants was found to significantly improve cell adhesion and induce osteogenic differentiation of dental-derived stem cells in vitro. Moreover, local and sustained release of antibiotics via nanolayers from the surface of implants can present unparalleled therapeutic benefits in implant dentistry. Here, we present a layer-by-layer surface treatment of titanium implants capable of incorporating BMP-2-mimicking short peptides and gentamicin to improve their osseointegration and antibacterial features. Additionally, instead of conventional surface treatments, we employed polydopamine coating before layer-by-layer assembly to initiate the formation of the nanolayers on rough titanium surfaces. Cytocompatibility analysis demonstrated that modifying the titanium implant surface with layer-by-layer assembly did not have adverse effects on cellular viability. The implemented nanoscale coating provided sustained release of osteoinductive peptides with an antibacterial drug. The surface-functionalized implants showed successful osteogenic differentiation of periodontal ligament stem cells and antimicrobial activity in vitro and increased osseointegration in a rodent animal model 4 wk postsurgery as compared with untreated implants. Altogether, our in vitro and in vivo studies suggest that this approach can be extended to other dental and orthopedic implants since this surface functionalization showed improved osseointegration and an enhanced success rate.

Exosome-inspired targeting of cancer cells with enhanced affinity.

One of the major challenges in the area of novel drug delivery systems (NDDSs) is finding distinguished ligands for specific receptors represented by many cancer cells in order to enhance their cancer homing efficacy. Exosomes, the so-called natural nanocarriers or "Trojan horses," are secreted by the majority of cancer cells. These carriers exchange biomolecular information (e.g. proteins, siRNA, enzymes) between cancer cells and their stromal compartments in order to adjust a variety of cellular behaviours, including metastasis, apoptosis in T cells and angiogenesis. By exhibiting exosomal smart functions and biomimetic traits, exosome-mimicking nanocarriers will be one step ahead of the conventional targeted DDSs for the efficient delivery of antitumor drugs. In the present study, we tried to describe an engineering route to make some surface-functionalized nanoparticles that can mimic the targeting mechanism recruited by tumor-derived exosomes. The ligand-receptor interactions were investigated by molecular dynamics (MD) simulations. In addition, the selected ligand was experimentally studied to verify its improved targeting efficacy. The present study describes a novel targeting method that forces the mucin-domain-containing molecule-4 (TIM4)-embellished nanoparticles (NPs) to swarm towards the cancerous cells. These NPs can interact with the phosphatidylserine (PS) receptor on the surface of several kinds of cancer cells, such as U-87 MG (glioblastoma cell line). The molecular affinity between TIM4 as a homing device and PS, the target receptor, was investigated using MD simulations and surface plasmon resonance (SPR). According to the calculated free energies and the cellular uptake of TIM4-functionalized NPs, it seems that the TIM4/PS complex releases enough free energy to induce endocytosis. Our results emphasize on the potential of the proposed ligand as a good candidate for many targeted drug delivery applications. In this report, we present our proof-of-concept results in order to spotlight the importance of using computer-based simulating methods at the molecular level for the next-generation nanomedicine.