Delivery of Therapeutic miRNA via Plasma-Polymerised Nanoparticles Rescues Diabetes-Impaired Endothelial Function.

MicroRNAs (miRNAs) are increasingly recognised as key regulators of the development and progression of many diseases due to their ability to modulate gene expression post-translationally. While this makes them an attractive therapeutic target, clinical application of miRNA therapy remains at an early stage and in part is limited by the lack of effective delivery modalities. Here, we determined the feasibility of delivering miRNA using a new class of plasma-polymerised nanoparticles (PPNs), which we have recently isolated and characterised.

Evaluation of the Immune Response to Chitosan--poly(caprolactone) Biopolymer Scaffolds.

Biomimetic scaffolds recreating key elements of the architecture and biological activity of the extracellular matrix have enormous potential for soft tissue engineering applications. Combining appropriate mechanical properties with select biological cues presents a challenge for bioengineering, as natural materials are most bioactive but can lack mechanical integrity, while synthetic polymers have strength but are often biologically inert. Blends of synthetic and natural materials, aiming to combine the benefits of each, have shown promise but inherently require a compromise, diluting down favorable properties in each polymer to accommodate the other.

Comprehensive Evaluation of the Toxicity and Biosafety of Plasma Polymerized Nanoparticles.

The rapid growth of nanoparticle-based therapeutics has underpinned significant developments in nanomedicine, which aim to overcome the limitations imposed by conventional therapies. Establishing the safety of new nanoparticle formulations is the first important step on the pathway to clinical translation. We have recently shown that plasma-polymerized nanoparticles (PPNs) are highly efficient nanocarriers and a viable, cost-effective alternative to conventional chemically synthesized nanoparticles.

Immobilized Macrophage Colony-Stimulating Factor (M-CSF) Regulates the Foreign Body Response to Implanted Materials.

The functionality and durability of implanted biomaterials are often compromised by an exaggerated foreign body reaction (FBR). M1/M2 polarization of macrophages is a critical regulator of scaffold-induced FBR. Macrophage colony-stimulating factor (M-CSF), a hematopoietic growth factor, induces macrophages into an M2-like polarized state, leading to immunoregulation and promoting tissue repair.

Plasma polymerized nanoparticles effectively deliver dual siRNA and drug therapy in vivo.

Multifunctional nanocarriers (MNCs) promise to improve therapeutic outcomes by combining multiple classes of molecules into a single nanostructure, enhancing active targeting of therapeutic agents and facilitating new combination therapies. However, nanocarrier platforms currently approved for clinical use can still only carry a single therapeutic agent. The complexity and escalating costs associated with the synthesis of more complex MNCs have been major technological roadblocks in the pathway for clinical translation.

Altered processing enhances the efficacy of small-diameter silk fibroin vascular grafts.

Current synthetic vascular grafts are not suitable for use in low-diameter applications. Silk fibroin is a promising natural graft material which may be an effective alternative. In this study, we compared two electrospun silk grafts with different manufacturing processes, using either water or hexafluoroisopropanol (HFIP) as solvent.

Multifunctional Protein-Immobilized Plasma Polymer Films for Orthopedic Applications.

Osseointegration is essential for ensuring optimal functioning and longevity of orthopedic implants. In a significant number of patients, the body does not fully integrate with the orthopedic implant, which opens the potential for the formation of bacterial biofilms and adverse foreign body reactions. Protein-functionalization of the implant surfaces can reduce this potential by stimulating rapid cell attachment or bone formation.

β-Tripeptides Coassemble into Fluorescent Hydrogels for Serial Monitoring in Vivo.

β-peptides uniquely form shear thinning hydrogels which are proteolytically stable and biocompatible. Herein we describe the synthesis, material and optical characterization of a new class of fluorescently labeled hydrogelators based on a helical -acetylated β-peptide backbone. The resulting hydrogels were analyzed using fluorescence microscopy to confirm successful incorporation of the fluorophore within the fiber matrix without compromising the β-peptide self-assembly.

Rapid Endothelialization of Off-the-Shelf Small Diameter Silk Vascular Grafts.

Synthetic vascular grafts for small diameter revascularization are lacking. Clinically available conduits expanded polytetrafluorethylene and Dacron fail acutely due to thrombosis and in the longer term from neointimal hyperplasia. We report the bioengineering of a cell-free, silk-based vascular graft.

Non-invasive tracking of injected bone marrow mononuclear cells to injury and implanted biomaterials.

Unlabelled: Biomaterial scaffolds enhancing the engraftment of transplanted bone-marrow mononuclear cells (BM-MNC) have enormous potential for tissue regeneration applications. However, development of appropriate materials is challenging given the precise microenvironments required to support BM-MNC engraftment and function. In this study, we have developed a non-invasive, real-time tracking model of injected BM-MNC engraftment to wounds and implanted biomaterial scaffolds.

Mechanically Robust Plasma-Activated Interfaces Optimized for Vascular Stent Applications.

The long-term performance of many medical implants is limited by the use of inherently incompatible and bioinert materials. Metallic alloys, ceramics, and polymers commonly used in cardiovascular devices encourage clot formation and fail to promote the appropriate molecular signaling required for complete implant integration. Surface coating strategies have been proposed for these materials, but coronary stents are particularly problematic as the large surface deformations they experience in deployment require a mechanically robust coating interface.

Immobilization of bioactive plasmin reduces the thrombogenicity of metal surfaces.

Components of many vascular prostheses including endovascular stents, heart valves and ventricular assist devices are made using metal alloys. In these blood contacting applications, metallic devices promote blood clotting, which is managed clinically by profound platelet suppression and/or anticoagulation. Here it is proposed that the localized immobilization of bioactive plasmin, a critical mediator of blood clot stability, may attenuate metallic prosthesis-induced thrombus formation.