New perspectives for piezoelectric material-based cochlear implants: getting to nano

Sensorineural hearing loss (SNHL) occurs when the sound transduction mechanism in the inner ear is compromised, because of impairments affecting the sensory hair cells—the actual biological transducers (90% of cases)—or the neurons. SNHL results in a broad spectrum of developmental, cognitive and psycho-social damages. To date, only cochlear implants (CIs) can offer a therapeutic solution to patients. They are multi-component electronic devices, surgically implanted, which capture, elaborate and convert the sound into electric stimuli delivered to the cochlea. Due to inherent limitations of the current electronic-based CIs, a new class of devices has been envisioned, which is based on piezoelectric materials. However, using piezoelectric membranes, the obtained sensitivity was not enough. The new frontiers for piezoelectric material-based CI aim at synergizing micro/nanofabrication aided by multiscale materials modeling with an in vivo tissue engineering approach to provide an implantable biomaterial-based system for SNHL, acting as a next-generation CI. Specifically, the envisioned device will move forward the primitive concept of bulk-structured piezoelectric CIs by designing a nanostructured material (e.g., based on nanofibers) to be precisely delivered and be intimately and efficiently integrated with the cochlear microenvironment. Piezoelectric material-based CIs are indeed hypothesized to have a much higher resolution of electrical stimulation with more than hundreds of channels, compared to maximum 22 stimulating elements present in electronic-based CIs. Moreover, the stimulation site will be closest to peripheral nerve fiber endings for maximal resolution. This would be the first sensory implant with a feedback mechanism on a micrometer scale

Nanoparticle drug delivery systems for inner ear therapy: An overview

open7noembargoed_20180701Valente, Filippo; Astolfi, Laura; Simoni, Edi; Danti, Serena; Franceschini, Valeria; Chicca, Milvia; Martini, AlessandroValente, Filippo; Astolfi, Laura; Simoni, Edi; Danti, Serena; Franceschini, Valeria; Chicca, Milvia; Martini, Alessandr

Raman spectroscopy of osteosarcoma cells

Osteosarcoma is the most common primary malignant bone tumor. In the last years, several studies have demonstrated that the increase of Hydroxyapatite (HA) and Interleukin-6 (IL-6) syntheses compared to those expressed by normal osteoblasts could be used to detect the degree of malignancy of osteosarcoma cells. Conventional biochemical methods widely employed to evaluate bone cell differentiation, including normal and cancerous phenotypes, are time consuming and may require a large amount of cells. HA is a mineral form of calcium phosphate whose presence increases with maturation of osteosarcoma cells. Analogously, IL-6 is a fundamental cytokine whose production is highly increased in osteosarcoma cells. In this study, we employ Raman spectroscopy to the identification and discrimination of osteosarcoma cells from osteo-differentiated mesenchymal stromal cells (MSCs) by detecting the presence of HA and IL-6. However, while the identification of HA is facilitated by the characteristic peak at 960 cm-1, corresponding to symmetric stretching (P-O) mode, the quantification of IL-6 it is much more elusive, being its Raman signal characterized by cysteine, but also by phenylalanine, amide I II and III whose signals are common to other proteins. Supported by an accurate multivariate analysis, the results show that Raman spectroscopy is a high sensitivity technique dealing out a direct and quantitative measurement of specific mineralization levels of osteosarcoma cells. In turn, by exploiting the Surface-Enhanced Raman Scattering stimulated by internalized Gold Nanoshells (AuNSs) and combined with scanning probe microscopies, we were able to employ Raman spectroscopy to study subcellular components locally

Mechanics of mineralized collagen fibrils upon transient loads

Collagen is a key structural protein in the human body, which undergoes mineralization during the formation of hard tissues. Earlier studies have described the mechanical behavior of bone at different scales highlighting material features across hierarchical structures. Here we present a study that aims to understand the mechanical properties of mineralized collagen fibrils upon tensile/compressive transient loads, investigating how the kinetic energy propagates and it is dissipated at the molecular scale, thus filling a gap of knowledge in this area. These specific features are the mechanisms that Nature has developed to passively dissipate stress and prevent structural failures. In addition to the mechanical properties of the mineralized fibrils, we observe distinct nanomechanical behaviors for the two regions (i.e., overlap and gap) of the D-period to highlight the effect of the mineralization. We notice decreasing trends for both wave speeds and Young s moduli over input velocity with a marked strengthening effect in the gap region due to the accumulation of the hydroxyapatite. In contrast, the dissipative behavior is not affected by either loading conditions or the mineral percentage, showing a stronger dampening effect upon faster inputs compatible to the bone behavior at the macroscale. Our results improve the understanding of mineralized collagen composites unveiling the energy dissipative behavior of such materials. This impacts, besides the physiology, the design and characterization of new bioinspired composites for replacement devices (e.g., prostheses for sound transmission or conduction) and for optimized structures able to bear transient loads, e.g., impact, fatigue, in structural applications

Liver Cancer: Current and Future Trends Using Biomaterials

Hepatocellular carcinoma (HCC) is the fifth most common type of cancer diagnosed and the second leading cause of death worldwide. Despite advancement in current treatments for HCC, the prognosis for this cancer is still unfavorable. This comprehensive review article focuses on all the current technology that applies biomaterials to treat and study liver cancer, thus showing the versatility of biomaterials to be used as smart tools in this complex pathologic scenario. Specifically, after introducing the liver anatomy and pathology by focusing on the available treatments for HCC, this review summarizes the current biomaterial-based approaches for systemic delivery and implantable tools for locally administrating bioactive factors and provides a comprehensive discussion of the specific therapies and targeting agents to effciently deliver those factors. This review also highlights the novel application of biomaterials to study HCC, which includes hydrogels and scaffolds to tissue engineer 3D in vitro models representative of the tumor environment. Such models will serve to better understand the tumor biology and investigate new therapies for HCC. Special focus is given to innovative approaches, e.g., combined delivery therapies, and to alternative approaches—e.g., cell capture—as promising future trends in the application of biomaterials to treat HCC

Pullulan for advanced sustainable body- and skin-contact applications

The present review had the aim of describing the methodologies of synthesis and properties of biobased pullulan, a microbial polysaccharide investigated in the last decade because of its interesting potentialities in several applications. After describing the implications of pullulan in nano-technology, biodegradation, compatibility with body and skin, and sustainability, the current applications of pullulan are described, with the aim of assessing the potentialities of this biopolymer in the biomedical, personal care, and cosmetic sector, especially in applications in contact with skin

Molecular origin of viscoelasticity in mineralized collagen fibrils

Bone is mineralized tissue constituting the skeletal system, supporting and protecting body organs and tissues. At the molecular level, mineralized collagen fibril is the basic building block of bone tissue, and hence, understanding bone properties down to fundamental tissue structures enables to better identify the mechanisms of structural failures and damages. While efforts have focused on the study of the micro- and macro-scale viscoelasticity related to bone damage and healing based on creep, mineralized collagen has not been explored on a molecular level. We report a study that aims at systematically exploring the viscoelasticity of collagenous fibrils with different mineralization levels. We investigate the dynamic mechanical response upon cyclic and impulsive loads to observe the viscoelastic phenomena from either shear or extensional strains via molecular dynamics. We perform a sensitivity analysis with several key benchmarks: intrafibrillar mineralization percentage, hydration state, and external load amplitude. Our results show a growth of the dynamic moduli with an increase of mineral percentage, pronounced at low strains. When intrafibrillar water is present, the material softens the elastic component but considerably increases its viscosity, especially at high frequencies. This behaviour is confirmed from the material response upon impulsive loads, in which water drastically reduces the relaxation times throughout the input velocity range by one order of magnitude, with respect to the dehydrated counterparts. We find that upon transient loads, water has a major impact on the mechanics of mineralized fibrillar collagen, being able to improve the capability of the tissue to passively and effectively dissipate energy, especially after fast and high-amplitude external loads

Growing bone tissue-engineered niches with graded osteogenicity: an in vitro method for biomimetic construct assembly

The traditional bone tissue-engineering approach exploits mesenchymal stem cells ( MSCs) to be seeded once only on three-dimensional (3D) scaffolds, hence, differentiated for a certain period of time and resulting in a homogeneous osteoblast population at the endpoint. However, after achieving terminal osteodifferentiation, cell viability is usually markedly compromised. On the other hand, naturally occurring osteogenesis results from the coexistence of MSC progenies at distinct differentiative stages in the same microenvironment. This diversification also enables long-term viability of the mature tissue. We report an easy and tunable in vitro method to engineer simple osteogenic cell niches in a biomimetic fashion. The niches were grown via periodic reseeding of undifferentiated MSCs on MSC/scaffold constructs, the latter undergoing osteogenic commitment. Timefractioning of the seeded cell number during differentiation time of the constructs allowed graded osteogenic cell populations to be grown together on the same scaffolds (i.e., not only terminally differentiated osteoblasts). In such cell-dynamic systems, the overall differentiative stage of the constructs could also be tuned by varying the cell density seeded at each inoculation. In this way, we generated two different biomimetic niche models able to host good reservoirs of preosteoblasts and other osteoprogenitors after 21 culture days. At that time, the niche type resulting in 40.8% of immature osteogenic progenies and only 59.2% of mature osteoblasts showed a calcium content comparable to the constructs obtained with the traditional culture method (i.e., 100.03 – 29.30 vs. 78.51 – 28.50 pg/cell, respectively; p = not significant), the latter colonized only by fully differentiated osteoblasts showing exhausted viability. This assembly method for tissue-engineered constructs enabled a set of important parameters, such as viability, colonization, and osteogenic yield of the MSCs to be balanced on 3D scaffolds, thus achieving biomimetic in vitro models with graded osteogenicity, which are more complex and reliable than those currently used by tissue engineers