Experimental study and geometrical method to design bio-inspired robotic kinematic chains of inching-locomotion caterpillars.

Inching-locomotion caterpillars (ILAR) show impressive environmental adaptation, having high dexterity and flexibility. To design robots that mimic these abilities, a novel bioinspired robotic design (BIROD) method is presented. The method is composed by an algorithm for geometrical kinematic analysis (GEKINS) to standardize the proportional dimensions according to the insect's anatomy and obtain the kinematic chains. The approach is experimentally applied to analyze the locomotion and kinematic chain of these specimens:Geometridae-two pair of prolegs (represents 35 000 species) andPlusiinae-three pair of prolegs (represents 400 species). The obtained data indicate that the application of the proposed method permits to locate the attachment mechanisms, joints, links, and to calculate angular displacement, angular average velocity, number of degrees of freedom, and thus the kinematic chain.Geometridaein contrast toPlusiinae, shows a longer walk-stride length, a lower number of single-rotational joints in 2D (3 DOF versus 4 DOF), and a lower number of dual-rotational joints in 3D (6 DOF versus 8 DOF). The application of BIROD and GEKINS provides the forward kinematics for 35 400 ILAR species and are expected to be useful as a preliminary phase for the design of bio-inspired arthropod robots.

Titanium Boston keratoprosthesis with corneal cell adhesive and bactericidal dual coating.

The Boston keratoprosthesis (BKPro) is a medical device used to restore vision in complicated cases of corneal blindness. This device is composed by a front plate of polymethylmethacrylate (PMMA) and a backplate usually made of titanium (Ti). Ti is an excellent biomaterial with numerous applications, although there are not many studies that address its interaction with ocular cells. In this regard, despite the good retention rates of the BKPro, two main complications compromise patients' vision and the viability of the prosthesis: imperfect adhesion of the corneal tissue to the upside of the backplate and infections. Thus, in this work, two topographies (smooth and rough) were generated on Ti samples and tested with or without functionalization with a dual peptide platform. This molecule consists of a branched structure that links two peptide moieties to address the main complications associated with BKPro: the well-known RGD peptide in its cyclic version (cRGD) as cell pro-adherent motif and the first 11 residues of lactoferrin (LF1-11) as antibacterial motif. Samples were physicochemically characterized, and their biological response was evaluated in vitro with human corneal keratocytes (HCKs) and against the gram-negative bacterial strain Pseudomonas aeruginosa. The physicochemical characterization allowed to verify the functionalization in a qualitative and quantitative manner. A higher amount of peptide was anchored to the rough surfaces. The studies performed using HCKs showed increased long-term proliferation on the functionalized samples. Gene expression was affected by topography and peptide functionalization. Roughness promoted α-smooth muscle actin (α-SMA) overexpression, and the coating notably increased the expression of extracellular matrix components (ECM). Such changes may favour the development of unwanted fibrosis, and thus, corneal haze. In contrast, the combination of the coating with a rough topography decreased the expression of α-SMA and ECM components, which would be desirable for the long-term success of the prosthesis. Regarding the antibacterial activity, the functionalized smooth and rough surfaces promoted the death of bacteria, as well as a perturbation in their wall definition and cellular morphology. Bacterial killing values were 58 % for smooth functionalised and 68 % for rough functionalised samples. In summary, this study suggests that the use of the dual peptide platform with cRGD and LF1-11 could be a good strategy to improve the in vitro and in vivo performance of the rough topography used in the commercial BKPro.

Titanium Surface Characteristics Induce the Specific Reprogramming of Toll-like Receptor Signaling in Macrophages.

Most of the research on titanium-based dental implants (Ti-discs) is focused on how they are able to stimulate the formation of new tissue and/or cytotoxic studies, with very scarce data on their effects on functional responses by immunocompetent cells. In particular, the link between the rewiring of innate immune responses and surface biomaterials properties is poorly understood. To address this, we characterize the functional response of macrophage cultures to four different dental titanium surfaces (MA: mechanical abrasion; SB + AE: sandblasting plus etching; SB: sandblasting; AE: acid etching). We use different Toll-like receptor (TLR) ligands towards cell surface receptors (bacterial lipopolysaccharide LPS for TLR4; imiquimod for TLR7; synthetic bacterial triacylated lipoprotein for TLR2/TLR1) and endosomal membrane receptor (poly I:C for TLR3) to simulate bacterial (cell wall bacterial components) or viral infections (dsRNA and ssRNA). The extracellular and total LDH levels indicate that exposure to the different Ti-surfaces is not cytotoxic for macrophages under resting or TLR-stimulated conditions, although there is a tendency towards an impairment in macrophage proliferation, viability or adhesion under TLR4, TLR3 and TLR2/1 stimulations in SB discs cultures. The secreted IL-6 and IL-10 levels are not modified upon resting macrophage exposure to the Ti-surfaces studied as well as steady state levels of iNos or ArgI mRNA. However, macrophage exposure to MA Ti-surface do display an enhanced immune response to TLR4, TLR7 or TLR2/1 compared to other Ti-surfaces in terms of soluble immune mediators secreted and M1/M2 gene expression profiling. This change of characteristics in cellular phenotype might be related to changes in cellular morphology. Remarkably, the gene expression of Tlr3 is the only TLR that is differentially affected by distinct Ti-surface exposure. These results highlight the relevance of patterned substrates in dental implants to achieve a smart manipulation of the immune responses in the context of personalized medicine, cell-based therapies, preferential lineage commitment of precursor cells or control of tissue architecture in oral biology.

Patient General Condition at Diagnosis: A Systematic Evaluation for Adults Diagnosed with Hematologic Malignancies.

Several societies have published recommendations for evaluating older adults with cancer in standard conditions. It is vital to assure a proper systematic patient condition evaluation, not only in the oldest (geriatric assessment) but in all adult patients. We have investigated the feasibility of a systematic evaluation of the general condition of all patients diagnosed with hematologic malignancies, and the degree of acceptance by the clinical team, in a prospective cohort of 182 consecutive adults, by using the ECOG performance status scale (ECOG, age 18 and over, 18+), Lee Index for Older Adults (LEE, 50+), Geriatric Assessment in Hematology (GAH, 65+), and the Comprehensive Geriatric Assessment (CGA, 75+). Clinical team acceptance was analyzed with a visual analogue scale, and the objective feasibility was calculated as the proportion of patients that could be finally evaluated with each tool. Acceptance was high, but the objective feasibility was progressively lower as the complexity of the different tools increased (ECOG 100%, LEE 99.4%, GAH 93.2%, and CGA 67.9%). LEE and GAH categories showed a weak concordance (Cohen's Kappa 0.24) that was slight between LEE and CGA (Kappa 0.18). Unexpectedly, we found no significant association between the GAH and CGA categories (p = 0.16). We confirm that a systematic evaluation of all adult patients diagnosed with hematologic malignancies is feasible in daily practice by using an age-adapted approach. Direct comparisons among the different predictive tools in regard to patients' tolerance to treatments of different intensities must be a priority research subject in the coming years.

A Non-Interventional Study Documenting Use and Success of Tissue Level Implants.

Numerous randomised controlled multicentric studies have investigated various responses to different treatment modalities with dental implants. These studies do not always show the results of daily practice as they are performed under controlled and strict clinical conditions. This multicentric, non-interventionist trial aimed to document the behaviour of implants when used in daily dental practice, without inclusion or exclusion criteria. One hundred and ninety-six screw-shaped, tissue-level implants were placed, and each clinician decided which implant, surgical loading and prosthetic protocol to use. At surgery, data related to the implants were recorded. Additionally, the crestal bone level changes were evaluated for up to two years of follow-up. Two implants were lost before they were loaded. The success rate was 98.31%, and the survival rate was 98.79%. The implant stability quotient (ISQ) at surgery was 68.61 ± 10.35 and at 2 years was 74.39 ± 9.64. The crestal-shoulder distances were 1.25 ± 1.09 mm and 1.68 ± 1.07 mm in the mesial and distal aspects on the day of surgery, respectively, and 2.04 ± 0.91 and 2.16 ± 0.99 mm at 2 years, respectively. At 2 years, 69.3% of the patients were highly satisfied. The use of implants under standard conditions seemed to have success rates similar to their placement in controlled studies.

Porous titanium-hydroxyapatite composite coating obtained on titanium by cold gas spray with high bond strength for biomedical applications.

The lack of bioactivity of titanium (Ti) is one of the main drawbacks for its application in biomedical implants since it can considerable reduce its osseointegration capacities. One strategy to overcome this limitation is the coating of Ti with hydroxyapatite (HA), which presents similar chemical composition than bone. Nonetheless, most of the strategies currently used generate a non-stable coating and may produce the formation of amorphous phases when high temperatures are used. Herein, we proposed to generate a Ti-HA composite coating on Ti surface to improve the stability of the bioactive coating. The coating was produced by cold gas spraying, which uses relatively low temperatures, and compared to a Ti coating. The coating was thoroughly characterized in terms of morphology, roughness, porosity and phase composition. In addition, the coating was mechanically characterized using a tensile loading machine. Finally, biological response was evaluated after seeding SaOS-2 osteoblasts and measuring cell adhesion, proliferation and differentiation. The novel Ti-HA coating presented high porosity and high adhesion and bond strengths. No change in HA phases was observed after coating formation. Moreover, osteoblast-like cells adhered, proliferated and differentiated on Ti-HA coated surfaces suggesting that the novel coating might be a good candidate for biomedical applications.

In vitro cell response on CP-Ti surfaces functionalized with TGF-ß1 inhibitory peptides.

Osseointegration of implants is conversely related to the generation of a fibrous tissue capsule around the implant by the host environment. Although TGF-ß1 plays many roles in regeneration processes, it is the cytokine to be mostly associated to the production of fibrotic tissue and thus, its inhibition has demonstrated to be beneficial to prevent several fibrotic reactions. Surface biofunctionalization enables the immobilization of biologically active molecules on an implant surface to tailor the biological response of the host. Here, we studied in vitro biological effects of biofunctionalized CP-Ti surfaces with a TGF-ß1 inhibitor peptide, P144. A reliable biofunctionalization process that tethers P144 peptides to commercially pure titanium was developed. Differentiation of human mesenchymal stem cells, osteoblasts and fibroblasts on P144-functionalized and control surfaces was assessed at the gene expression and protein production levels. Results showed that P144-functionalized surfaces reduced expression and production of fibrotic differentiation markers and increased osteoblastic differentiation markers. Therefore, biofunctionalization of surfaces with TGF-ß1 inhibitor peptides are an alternative promising strategy for inducing osseointegration around medical devices and implants.

Double acid etching treatment of dental implants for enhanced biological properties.

BACKGROUND: The topographical features on the surface of dental implants have been considered as a critical parameter for enhancing the osseointegration of implants. In this work, we proposed a surface obtained by a combination of shot blasting and double acid etching. The double acid etching was hypothesized to increase the submicron topography and hence further stimulate the biological properties of the titanium implant. METHODS: The topographical features (surface roughness and real surface area), wettability and surface chemical composition were analyzed. RESULTS: The results showed that the proposed method produced a dual roughness, mainly composed of randomly distributed peaks and valleys with a superimposed nanoroughness, and hence with an increased specific surface area. Despite the fact that the proposed method does not introduce significant chemical changes, this treatment combination slightly increased the amount of titanium available on the surface, reducing potential surface contaminants. Furthermore, the surface showed increased contact angle values demonstrating an enhanced hydrophobicity on the surface. The biological behavior of the implants was then assessed by culturing osteoblast-like cells on the surface, showing enhanced osteoblast adhesion, proliferation and differentiation on the novel surface. CONCLUSIONS: Based on these results, the described surface with dual roughness obtained by double acid etching may be a novel route to obtain key features on the surface to enhance the osseointegration of the implant. Our approach is a simple method to obtain a dual roughness that mimics the bone structure modified by osteoclasts and increases surface area, which enhances osseointegration of dental implants.

Modification of titanium surfaces by adding antibiotic-loaded PHB spheres and PEG for biomedical applications.

Novel researches are focused on the prevention and management of post-operative infections. To avoid this common complication of implant surgery, it is preferable to use new biomaterials with antibacterial properties. Therefore, the aim of this work is to develop a method of combining the antibacterial properties of antibiotic-loaded poly(3-hydroxybutyrate) (PHB) nano- and micro-spheres and poly(ethylene glycol) (PEG) as an antifouling agent, with titanium (Ti), as the base material for implants, in order to obtain surfaces with antibacterial activity. The Ti surfaces were linked to both PHB particles and PEG by a covalent bond. This attachment was carried out by firstly activating the surfaces with either Oxygen plasma or Sodium hydroxide. Further functionalization of the activated surfaces with different alkoxysilanes allows the reaction with PHB particles and PEG. The study confirms that the Ti surfaces achieved the antibacterial properties by combining the antibiotic-loaded PHB spheres, and PEG as an antifouling agent.

Oxidized nickel-titanium foams for bone reconstructions: chemical and mechanical characterization.

This work examines NiTi foams that have been treated using a new oxidation treatment for obtaining Ni-free surfaces that could allow the ingrowth of living tissue, thereby increasing the mechanical anchorage of implants. A significant increase in the real surface area of these materials can decrease corrosion resistance and favour the release of Ni. This chemical degradation can induce allergic reactions or toxicity in the surrounding tissues. This study determines the porosity, surface characteristics, phase transformation, mechanical properties, corrosion behaviour and Ni release into the simulated body fluid medium of foams treated by a new surface oxidation treatment that produces Ni-free surfaces. These foams have pores in an appropriate range of sizes and interconnectivity, and thus their morphology is similar to that of bone. Their mechanical properties are biomechanically compatible with bone. The titanium oxide on the surface significantly improves corrosion resistance and decreases nickel ion release, while barely affecting transformation temperatures.

El signo de Babinski: sensibilidad, especificidad y valor predictivo, validez diagnóstica de un signo clásico en medicina / Babinski sign sensibility, specificity and predictive value: diagnosis evaluation of a classical sign in medicine

El signo de Babinski es considerado el más importante de la neurología clínica. Sin embargo a pesar de que ya ha pasado casi un siglo desde su descripción original, desconocemos su verdadero valor diagnóstico. Estudiamos a 49 pacientes con evidencia de lesión de la vía piramidal y a 100 controles sanos. El signo de Babinski estuvo presente en 41/49 pacientes y en ninguno del grupo control; la sensibilidad fue de 84 por ciento y la especialidad del 100 por ciento, con un valor predictivo positivo casi perfecto (99 por ciento, negativo excelente (92 por ciento) y una eficacia global del 94.6 por ciento. La alta sensibilidad y especificidad del signo de Babinski permite al clínico afirmar que la vía piramidal está alterada cuando el signo está presente y confianza, para decir que la vía piramidal está sana, cuando el signo esta ausente. Dificilmente se puede pensar en una prueba clínica, con toda la tecnología moderna, que reúne estas características.