RESUMO
The continued evolution of biomedical nanotechnology has enabled clinicians to better detect, prevent, manage, and treat human disease. In order to further push the limits of nanoparticle performance and functionality, there has recently been a paradigm shift towards biomimetic design strategies. By taking inspiration from nature, the goal is to create next-generation nanoparticle platforms that can more effectively navigate and interact with the incredibly complex biological systems that exist within the body. Of great interest are cellular membranes, which play essential roles in biointerfacing, self-identification, signal transduction, and compartmentalization. In this review, we explore the major ways in which researchers have directly leveraged cell membrane-derived biomaterials for the fabrication of novel nanotherapeutics and nanodiagnostics. Such emerging technologies have the potential to significantly advance the field of nanomedicine, helping to improve upon traditional modalities while also enabling novel applications.
Assuntos
Tecnologia Biomédica/métodos , Membrana Celular/metabolismo , Nanoestruturas/química , Animais , Técnicas Biossensoriais , Sistemas de Liberação de Medicamentos , Humanos , ImunomodulaçãoRESUMO
Attachment and biofilm formation by bacterial pathogens on surfaces in natural, industrial, and hospital settings lead to infections and illnesses and even death. Minimizing bacterial attachment to surfaces using controlled topography could reduce the spreading of pathogens and, thus, the incidence of illnesses and subsequent human and financial losses. In this context, the attachment of key microorganisms, including Escherichia coli, Listeria innocua, and Pseudomonas fluorescens, to silica and alumina surfaces with micron and nanoscale topography was investigated. The results suggest that orientation of the attached cells occurs preferentially such as to maximize their contact area with the surface. Moreover, the bacterial cells exhibited different morphologies, including different number and size of cellular appendages, depending on the topographical details of the surface to which they attached. This suggests that bacteria may utilize different mechanisms of attachment in response to surface topography. These results are important for the design of novel microbe-repellant materials.
Assuntos
Aderência Bacteriana/fisiologia , Biofilmes , Escherichia coli/fisiologia , Listeria/fisiologia , Pseudomonas fluorescens/fisiologia , Óxido de Alumínio , Materiais Biocompatíveis , Interações Hidrofóbicas e Hidrofílicas , Dióxido de Silício , Propriedades de SuperfícieRESUMO
Spray layer-by-layer assembly is used to create hemostatic films containing thrombin and tannic acid. The spray assembly technique enables coating of porous and absorbent commercial gelatin sponges with these films. Coated sponges are able to promote instantaneous hemostasis in a porcine spleen bleeding model.
Assuntos
Hemostáticos/química , Animais , Gelatina/química , Hemostasia/efeitos dos fármacos , Hemostáticos/farmacologia , Ligação de Hidrogênio , Polifenóis/química , Eletricidade Estática , Suínos , Taninos/química , Trombina/química , Água/químicaRESUMO
Wounds have the potential to become infected during any surgical procedure. Gelatin sponges that are commonly used to absorb blood during invasive surgeries would benefit tremendously if they released antibiotics. In this work, we have examined coating a commercial gelatin sponge with degradable polymer multilayer films containing vancomycin. The effect of the film on sponge absorption capabilities and the effect of the sponge on drug release kinetics were both examined. Application of vancomycin containing layer-by-layer assembled films to this highly porous substrate greatly increased drug loading up to approximately 880% compared to a flat substrate. Vancomycin drug release was extended out to 6 days compared to 2 days for film coated flat substrates. Additionally, the absorbent properties of the gelatin sponge were actually enhanced by up to 170% due to the presence of the vancomycin film coating. A comparison of film coated sponges with sponges soaked directly in vancomycin demonstrated the ability of the multilayer films to control drug release. Film released vancomycin was also found to remain highly therapeutic with unchanged antimicrobial properties compared to the neat drug, demonstrated by quantifying vancomycin activity against Staphylococcus aureus in vitro.
Assuntos
Curativos Hidrocoloides , Esponja de Gelatina Absorvível/administração & dosagem , Gelatina/administração & dosagem , Vancomicina/administração & dosagem , Absorção/efeitos dos fármacos , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/farmacocinética , Sulfato de Dextrana/administração & dosagem , Sulfato de Dextrana/farmacocinética , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/farmacocinética , Gelatina/farmacocinética , Esponja de Gelatina Absorvível/farmacocinética , Vancomicina/farmacocinéticaRESUMO
The integration of orthopedic implants with host bone presents a major challenge in joint arthroplasty, spinal fusion and tumor reconstruction. The cellular microenvironment can be programmed via implant surface functionalization allowing direct modulation of osteoblast adhesion, proliferation, and differentiation at the implant--bone interface. The development of layer-by-layer assembled polyelectrolyte multilayer (PEM) architectures has greatly expanded our ability to fabricate intricate nanometer to micron scale thin film coatings that conform to complex implant geometries. The in vivo therapeutic efficacy of thin PEM implant coatings for numerous biomedical applications has previously been reported. We have fabricated protamine-based PEM thin films that support the long-term proliferation and differentiation of pre-osteoblast cells on non-cross-linked film-coated surfaces. These hydrophilic PEM functionalized surfaces with nanometer-scale roughness facilitated increased deposition of calcified matrix by osteoblasts in vitro, and thus offer the potential to enhance implant integration with host bone. The coatings can make an immediate impact in the osteogenic culture of stem cells and assessment of the osteogenic potential of new therapeutic factors.
Assuntos
Materiais Revestidos Biocompatíveis/química , Osteoblastos/citologia , Protaminas/química , Animais , Adesão Celular , Diferenciação Celular , Linhagem Celular , Proliferação de Células , Materiais Revestidos Biocompatíveis/metabolismo , Eletrólitos/química , Eletrólitos/metabolismo , Camundongos , Protaminas/metabolismo , Propriedades de SuperfícieRESUMO
Local drug delivery methods allow for the opportunity to supply potent multispectrum antibiotics such as vancomycin hydrochloride to sites of infection, while avoiding systemic toxicity. In this work, layer-by-layer assembly of polymer multilayer films is applied to create vancomycin delivery coatings. By taking advantage of the versatile layer-by-layer spray and dip coating techniques, thin films were generated based on electrostatic and other secondary interactions discovered to exist between the film components. The importance of film interdiffusion during growth in promoting interactions between film components is found to be critical in the direct incorporation of the weakly charged vancomycin drug in these multilayer films. The resulting coatings are engineered with unprecedented drug densities ranging from 17-220 µg mm(-3) (approximately 20 wt%) for films that are micron to submicron scale in thickness, delivering vancomycin over timescales of 4 h to 2.5 days. The released drug is highly effective in inhibiting Staphylococcus aureus growth in vitro. Taking advantage of the difference in release characteristics between dip and spray assembled films, a composite film architecture was engineered to have both a bolus vancomycin release followed by a period of linear sustained drug release. The control over drug densities and release profiles displayed in this work is necessary to address the requirements of varying medical conditions, including those where immediate infection elimination is needed or long term infection prevention is required.