Can Nanotechnology Shine a New Light on Antimicrobial Photodynamic Therapies?

Recent developments in light‐controlled therapies (e.g., photodynamic and photothermal therapies) provide promising strategies to prevent and suppress bacterial infections, which are a leading cause of morbidity and mortality. Antibacterial photodynamic therapy (aPDT) has drawn increasing attention from the scientific society for its potential to kill multidrug‐resistant pathogenic bacteria and for its low tendency to induce drug resistance. In this chapter, we summarize the mechanism of action of aPDT, the photosensitizers, as well the current developments in terms of treating Gram‐positive and Gram‐negative bacteria. The chapter also describes the recent progress relating to photomedicine for preventing bacterial infections and biofilm formation. We focus on the laser device used in aPDT and on the light‐treatment parameters that may have a strong impact on the results of aPDT experiments. In the last part of this chapter, we survey on the various nanoparticles delivering photoactive molecules, and photoactive‐nanoparticles that can potentially enhance the antimicrobial action of aPDT

Nano-biocomposite films with modified cellulose nanocrystals and synthesized silver nanoparticles

Ternary nano-biocomposite films based on poly(lactic acid) (PLA) with modified cellulose nanocrystals (s-CNC) and synthesized silver nanoparticles (Ag) have been prepared and characterized. The functionalization of the CNC surface with an acid phosphate ester of ethoxylated nonylphenol favoured its dispersion in the PLA matrix. The positive effects of the addition of cellulose and silver on the PLA barrier properties were confirmed by reductions in the water permeability (WVP) and oxygen transmission rate (OTR) of the films tested. The migration level of all nano-biocomposites in contact with food simulants were below the permitted limits in both non-polar and polar simulants. PLA nano-biocomposites showed a significant antibacterial activity influenced by the Ag content, while composting tests showed that the materials were visibly disintegrated after 15 days with the ternary systems showing the highest rate of disintegration under composting conditions.L.V. would like to acknowledge the financial support from MIUR, PRIN 2010–11 project entitled “Nanomed” (prot.2010FPTBSH 009). M.P. and A.J. acknowledge the financial support from the Spanish Ministry of Economy and Competitiveness (MAT2011-28648-C02-1)

From micro- to nanostructured implantable device for local anesthetic delivery

Local anesthetics block the transmission of painful stimuli to the brain by acting on ion channels of nociceptor fibers, and find application in the management of acute and chronic pain. Despite the key role they play in modern medicine, their cardio and neurotoxicity (together with their short half-life) stress the need for developing implantable devices for tailored local drug release, with the aim of counterbalancing their side effects and prolonging their pharmacological activity. This review discusses the evolution of the physical forms of local anesthetic delivery systems during the past decades. Depending on the use of different biocompatible materials (degradable polyesters, thermosensitive hydrogels, and liposomes and hydrogels from natural polymers) and manufacturing processes, these systems can be classified as films or micro- or nanostructured devices. We analyze and summarize the production techniques according to this classification, focusing on their relative advantages and disadvantages. The most relevant trend reported in this work highlights the effort of moving from microstructured to nanostructured systems, with the aim of reaching a scale comparable to the biological environment. Improved intracellular penetration compared to microstructured systems, indeed, provides specific drug absorption into the targeted tissue and can lead to an enhancement of its bioavailability and retention time. Nanostructured systems are realized by the modification of existing manufacturing processes (interfacial deposition and nanoprecipitation for degradable polyester particles and high- or low-temperature homogenization for liposomes) or development of novel strategies (electrospun matrices and nanogels). The high surface-to-volume ratio that characterizes nanostructured devices often leads to a burst drug release. This drawback needs to be addressed to fully exploit the advantage of the interaction between the target tissues and the drug: possible strategies could involve specific binding between the drug and the material chosen for the device, and a multiscale approach to reach a tailored, prolonged drug release

Hep3Gel: A Shape-Shifting Extracellular Matrix-Based, Three-Dimensional Liver Model Adaptable to Different Culture Systems

Drug-induced hepatotoxicity is a leading cause of clinical trial withdrawal. Therefore, in vitro modeling the hepatic behavior and functionalities is not only crucial to better understand physiological and pathological processes but also to support drug development with reliable high-throughput platforms. Different physiological and pathological models are currently under development and are commonly implemented both within platforms for standard 2D cultures and within tailor-made chambers. This paper introduces Hep3Gel: a hybrid alginate-extracellular matrix (ECM) hydrogel to produce 3D in vitro models of the liver, aiming to reproduce the hepatic chemomechanical niche, with the possibility of adapting its shape to different manufacturing techniques. The ECM, extracted and powdered from porcine livers by a specifically set-up procedure, preserved its crucial biological macromolecules and was embedded within alginate hydrogels prior to crosslinking. The viscoelastic behavior of Hep3Gel was tuned, reproducing the properties of a physiological organ, according to the available knowledge about hepatic biomechanics. By finely tuning the crosslinking kinetics of Hep3Gel, its dualistic nature can be exploited either by self-spreading or adapting its shape to different culture supports or retaining the imposed fiber shape during an extrusion-based 3D-bioprinting process, thus being a shape-shifter hydrogel. The self-spreading ability of Hep3Gel was characterized by combining empirical and numerical procedures, while its use as a bioink was experimentally characterized through rheological a priori printability evaluations and 3D printing tests. The effect of the addition of the ECM was evident after 4 days, doubling the survival rate of cells embedded within control hydrogels. This study represents a proof of concept of the applicability of Hep3Gel as a tool to develop 3D in vitro models of the liver

Treatment of Biofilm Communities: An Update on New Tools from the Nanosized World

Traditionally regarded as single cell organisms, bacteria naturally and preferentially build multicellular communities that enable them to react efficiently to external stimuli in a coordinated fashion and with extremely effective outcomes. These communities are bacterial biofilms, where single cells or microcolonies are embedded in self-built Extracellular Polymeric Substance (EPS), composed of different macromolecules, e.g., polysaccharides, proteins, lipids, and extracellular DNA (eDNA). Despite being the most common form in nature and having many biotechnologically useful applications, biofilm is often regarded as a life-threatening form of bacterial infection. Since this form of bacterial life is intrinsically more resistant to antibiotic treatment and antimicrobial resistance is reaching alarming levels, we will focus our attention on how nanotechnology made new tools available to the medical community for the prevention and treatment of these infections. After a brief excursus on biofilm formation and its main characteristics, different types of nanomaterials developed to prevent or counteract these multicellular forms of bacterial infection will be described. A comparison of different classifications adopted for nanodrugs and a final discussion of challenges and future perspectives are also presente

Human Bone RIgeneration in MAXillo-facial area using an innovative medical device for Tissue engineering (BRIMAX)

Bone regeneration today is one of the most important challenges for medicine and the need for this is particularly evident in the maxillo-facial area: our clinical trial will be based on a model of bone defect as in alveolar socket preservation and sinus lift augmentation, well described surgical techniques. The RIGENERA® system permits extraction of stem cells from a small sample of connective tissue obtained from the patient’s lingual mucosa or from a post-extraction surgical site (where an endosseous implant may be inserted), dental pulp or dental follicle. Our project is to demonstrate the efficacy in the maxillo-facial area of an innovative clinical protocol of bone tissue engineering based on a new medical device called Rigeneracons (CE certified Class I). Our clinical trial use already acquired technologies in comparation with new technologies (new selection methods, new Bio-compatible materials etc.) produced by us. Besides, we perform an in-vitro test to quantify the proliferative capacity of a cellular suspension obtained after disaggregation of connective tissue originating from the oral cavity using the RIGENERA® system, a biologic tissue disaggregator (Human Brain Wave–Torino, Italy) that recently came on the market. Evaluation of the histologic characteristics of neo-formed osseous tissue will be shown and discussed

Ether-Oxygen Containing Electrospun Microfibrous and Sub-Microfibrous Scaffolds Based on Poly(butylene 1,4-cyclohexanedicarboxylate) for Skeletal Muscle Tissue Engineering

We report the study of novel biodegradable electrospun scaffolds from poly(butylene 1,4-cyclohexandicarboxylate-co-triethylene cyclohexanedicarboxylate) (P(BCE-co-TECE)) as support for in vitro and in vivo muscle tissue regeneration. We demonstrate that chemical composition, i.e., the amount of TECE co-units (constituted of polyethylene glycol-like moieties), and fibre morphology, i.e., aligned microfibrous or sub-microfibrous scaffolds, are crucial in determining the material biocompatibility. Indeed, the presence of ether linkages influences surface wettability, mechanical properties, hydrolytic degradation rate, and density of cell anchoring points of the studied materials. On the other hand, electrospun scaffolds improve cell adhesion, proliferation, and differentiation by favouring cell alignment along fibre direction (fibre morphology), also allowing for better cell infiltration and oxygen and nutrient diffusion (fibre size). Overall, C2C12 myogenic cells highly differentiated into mature myotubes when cultured on microfibres realised with the copolymer richest in TECE co-units (micro-P73 mat). Lastly, when transplanted in the tibialis anterior muscles of healthy, injured, or dystrophic mice, micro-P73 mat appeared highly vascularised, colonised by murine cells and perfectly integrated with host muscles, thus confirming the suitability of P(BCE-co-TECE) scaffolds as substrates for skeletal muscle tissue engineering

Gold Nanoparticles Contact with Cancer Cell: A Brief Update

The fine-tuning of the physicochemical properties of gold nanoparticles has facilitated the rapid development of multifunctional gold-based nanomaterials with diagnostic, therapeutic, and therapeutic applications. Work on gold nanoparticles is increasingly focusing on their cancer application. This review provides a summary of the main biological effects exerted by gold nanoparticles on cancer cells and highlights some critical factors involved in the interaction process (protein corona, tumor microenvironment, surface functionalization). The review also contains a brief discussion of the application of gold nanoparticles in target discovery