Piezoelectric polymers as biomaterials for tissue engineering applications

Tissue engineering often rely on scaffolds for supporting cell differentiation and growth. Novel paradigms for tissue engineering include the need of active or smart scaffolds in order to properly regenerate specific tissues. In particular, as electrical and electromechanical clues are among the most relevant ones in determining tissue functionality in tissues such as muscle and bone, among others, electroactive materials and, in particular, piezoelectric ones, show strong potential for novel tissue engineering strategies, in particular taking also into account the existence of these phenomena within some specific tissues, indicating their requirement also during tissue regeneration. This referee reports on piezoelectric materials used for tissue engineering applications. The most used materials for tissue engineering strategies are reported together with the main achievements, challenges and future needs for research and actual therapies. This review provides thus a compilation of the most relevant results and strategies and a start point for novel research pathways in the most relevant and challenging open questions.

Novel anisotropic magnetoelectric effect on δ-FeO(OH)/P(VDF-TrFE) multiferroic composites

The last decade has witnessed an increased research effort on multi-phase magnetoelectric (ME) composites. In this scope, this paper presents the application of novel materials for the development of anisotropic magnetoelectric (ME) sensors based on δ-FeO(OH)/P(VDF-TrFE) composites. The composite is able to precisely determine the amplitude and direction of the magnetic field. A new ME effect is reported in this study, as it emerges from the magnetic rotation of the δ-FeO(OH) nanosheets inside the piezoelectric P(VDF-TrFE) polymer matrix. δ-FeO(OH)/P(VDF-TrFE) composites with 1, 5, 10 and 20 δ-FeO(OH) filler weigh percentage in three δ-FeO(OH) alignment states (random, transversal and longitudinal) have been developed. Results shown that the modulus of the piezoelectric response (10-24 pC.N-1) is stable at least up to three months, the shape and magnetization maximum value (3 emu.g-1) is dependent on δ-FeO(OH) content and the obtained ME voltage coefficient, with a maximum of ≈0.4 mV.cm-1.Oe-1, is dependent on the incident magnetic field direction and intensity. In this way, the produced materials are suitable for innovative anisotropic sensor and actuator applications.

Thermal–mechanical behaviour of chitosan–cellulose derivative thermoreversible hydrogel films

CH, Chitosan; HPMC, (Hydroxypropyl)methyl cellulose; FT, Freeze-thaw; SC, Solvent casting; CH:HPMC (X:Y), pH Z, FT/SC, Chitosan and (hydroxypropyl)methyl cellulose hydrogel, at X and Y proportion (0-100), at Z pH (3.0-4.0) and prepared by freeze-thaw or solvent casting techniques; DSC, Differential scanning calorimetry; MDSC, Temperature modulated Differential scanning calorimetry; Tg, glass transition temperature; ΔH, enthalpy change; TGA, Thermogravimetric Analysis; TG, Thermogravimetry; DTG, Derivative or Differential thermogravimetry; σ, Tensile strength; ε, elongation at break; DMA, Dynamic mechanical analysis; X-Ray, X-radiation, FTIR-ATR, Attenuated total reflectance Fourier transform infrared spectroscopy; SEM, Scanning electron microscopy.

Erratum to: Thermal–mechanical behaviour of chitosan–cellulose derivative thermoreversible hydrogel films

CH, Chitosan; HPMC, (Hydroxypropyl)methyl cellulose; FT, Freeze-thaw; SC, Solvent casting; CH:HPMC (X:Y), pH Z, FT/SC, Chitosan and (hydroxypropyl)methyl cellulose hydrogel, at X and Y proportion (0-100), at Z pH (3.0-4.0) and prepared by freeze-thaw or solvent casting techniques; DSC, Differential scanning calorimetry; MDSC, Temperature modulated Differential scanning calorimetry; Tg, glass transition temperature; ΔH, enthalpy change; TGA, Thermogravimetric Analysis; TG, Thermogravimetry; DTG, Derivative or Differential thermogravimetry; σ, Tensile strength; ε, elongation at break; DMA, Dynamic mechanical analysis; X-Ray, X-radiation, FTIR-ATR, Attenuated total reflectance Fourier transform infrared spectroscopy; SEM, Scanning electron microscopy.

Enhancement of adhesion and promotion of osteogenic differentiation of human adipose stem cells by poled electroactive poly(vinylidene fluoride)

Poly(vinylidene fluoride) (PVDF) is a biocompatible material with excellent electroactive properties. Non-electroactive α-PVDF and electroactive β-PVDF were used to investigate the substrate polarization and polarity influence on the focal adhesion size and number as well as on human adipose stem cells (hASCs) differentiation. hASCs were cultured on different PVDF surfaces adsorbed with fibronectin and focal adhesion size and number, total adhesion area, cell size, cell aspect ratio and focal adhesion density were estimated using cells expressing EGFP-vinculin. Osteogenic differentiation was also determined using a quantitative alkaline phosphatase assay. The surface charge of the poled PVDF films (positive or negative) influenced the hydrophobicity of the samples, leading to variations in the conformation of adsorbed extracellular matrix (ECM) proteins, which ultimately modulated the stem cell adhesion on the films and induced their osteogenic differentiation.

Piezoelectric poly(vinylidene fluoride) microstructure and poling state in active tissue engineering

Tissue engineering often rely on scaffolds for supporting cell differentiation and growth. Novel paradigms for tissue engineering include the need of active or smart scaffolds in order to properly regenerate specific tissues. In particular, as electrical and electromechanical clues are among the most relevant ones in determining tissue functionality in tissues such as muscle and bone, among others, electroactive materials and, in particular, piezoelectric ones, show strong potential for novel tissue engineering strategies, in particular taking also into account the existence of these phenomena within some specific tissues, indicating their requirement also during tissue regeneration. This referee reports on piezoelectric materials used for tissue engineering applications. The most used materials for tissue engineering strategies are reported together with the main achievements, challenges and future needs for research and actual therapies. This review provides thus a compilation of the most relevant results and strategies and a start point for novel research pathways in the most relevant and challenging open questions.

Mechanical fatigue performance of PCL-chondroprogenitor constructs after cell culture under bioreactor mechanical stimulus

In tissue engineering of cartilage, polymeric scaffolds are implanted in the damaged tissue and subjected to repeated compression loading cycles. The possibility of failure due to mechanical fatigue has not been properly addressed in these scaffolds. Nevertheless, the macroporous scaffold is susceptible to failure after repeated loading-unloading cycles. This is related to inherent discontinuities in the material due to the micropore structure of the macro-pore walls that act as stress concentration points. In this work, chondrogenic precursor cells have been seeded in Poly-ε-caprolactone (PCL) scaffolds with fibrin and some were submitted to free swelling culture and others to cyclic loading in a bioreactor. After cell culture, all the samples were analyzed for fatigue behavior under repeated loading-unloading cycles. Moreover, some components of the extracellular matrix (ECM) were identified. No differences were observed between samples undergoing free swelling or bioreactor loading conditions, neither respect to matrix components nor to mechanical performance to fatigue. The ECM did not achieve the desired preponderance of collagen type II over collagen type I which is considered the main characteristic of hyaline cartilage ECM. However, prediction in PCL with ECM constructs was possible up to 600 cycles, an enhanced performance when compared to previous works. PCL after cell culture presents an improved fatigue resistance, despite the fact that the measured elastic modulus at the first cycle was similar to PCL with poly(vinyl alcohol) samples. This finding suggests that fatigue analysis in tissue engineering constructs can provide additional information missed with traditional mechanical measurements.

In vitro mechanical fatigue behavior of poly-ε-caprolactone macroporous scaffolds for cartilage tissue engineering: Influence of pore filling by a poly(vinyl alcohol) gel

Polymeric scaffolds used in regenerative therapies are implanted in the damaged tissue and subjected to repeated loading cycles. In the case of articular cartilage engineering, an implanted scaffold is typically subjected to long term dynamic compression. The evolution of the mechanical properties of the scaffold during bioresorption has been deeply studied in the past, but the possibility of failure due to mechanical fatigue has not been properly addressed. Nevertheless, the macroporous scaffold is susceptible to failure after repeated loading-unloading cycles. In this work fatigue studies of polycaprolactone scaffolds were carried by subjecting the scaffold to repeated compression cycles in conditions simulating the scaffold implanted in the articular cartilage. The behaviour of the polycaprolactone sponge with the pores filled with a poly(vinyl alcohol) gel simulating the new formed tissue within the pores was compared with that of the material immersed in water. Results were analyzed with Morrow’s criteria for failure and accurate fittings are obtained just up to 200 loading cycles. It is also shown that the presence of poly(vinyl alcohol) increases the elastic modulus of the scaffolds, the effect being more pronounced with increasing the number of freeze/thawing cycles.

Dynamic piezoelectric stimulation enhances osteogenic differentiation of human adipose stem cells

This work reports on the influence of the substrate polarization of electroactive β-PVDF on human adipose stem cells (hASCs) differentiation under static and dynamic conditions. hASCs were cultured on different β-PVDF surfaces (non-poled and “poled -”) adsorbed with fibronectin and osteogenic differentiation was determined using a quantitative alkaline phosphatase assay. “Poled -” β-PVDF samples promote higher osteogenic differentiation, which is even higher under dynamic conditions. It is thus demonstrated that electroactive membranes can provide the necessary electromechanical stimuli for the differentiation of specific cells and therefore will support the design of suitable tissue engineering strategies, such as bone tissue engineering.

Off-line simulation inspires insight: a neurodynamics approach to efficient robot task learning

There is currently an increasing demand for robots able to acquire the sequential organization of tasks from social learning interactions with ordinary people. Interactive learning-by-demonstration and communication is a promising research topic in current robotics research. However, the efficient acquisition of generalized task representations that allow the robot to adapt to different users and contexts is a major challenge. In this paper, we present a dynamic neural field (DNF) model that is inspired by the hypothesis that the nervous system uses the off-line re-activation of initial memory traces to incrementally incorporate new information into structured knowledge. To achieve this, the model combines fast activation-based learning to robustly represent sequential information from single task demonstrations with slower, weight-based learning during internal simulations to establish longer-term associations between neural populations representing individual subtasks. The efficiency of the learning process is tested in an assembly paradigm in which the humanoid robot ARoS learns to construct a toy vehicle from its parts. User demonstrations with different serial orders together with the correction of initial prediction errors allow the robot to acquire generalized task knowledge about possible serial orders and the longer term dependencies between subgoals in very few social learning interactions. This success is shown in a joint action scenario in which ARoS uses the newly acquired assembly plan to construct the toy together with a human partner.

Financiamento público e produtividade das empresas portuguesas

Dissertação de mestrado em Economia Industrial e da Empresa

Influence of climate on clinical diagnostic dry eye tests: pilot study

Purpose. To analyze dry eye disease (DED) tests and their consistency in similar nonsymptomatic population samples living in two geographic locations with different climates (Continental vs. Atlantic). Methods. This is a pilot study including 14 nonsymptomatic residents from Valladolid (Continental climate, Spain) and 14 sex-matched and similarly aged residents from Braga (Atlantic climate, Portugal); they were assessed during the same season (spring) of two consecutive years. Phenol red thread test, conjunctival hyperemia, fluorescein tear breakup time, corneal and conjunctival staining, and Schirmer test were evaluated on three different consecutive visits. Reliability was assessed using the intraclass correlation coefficient and weighted kappa (J) coefficient for quantitative and ordinal variables, respectively. Results. Fourteen subjects were recruited in each city with a mean (TSD) age of 63.0 (T1.7) and 59.1 (T0.9) years (p = 0.08) in Valladolid and Braga, respectively. Intraclass correlation coefficient and J values of the tests performed were below 0.69 and 0.61, respectively, for both samples, thus showing moderate to poor reliability. Subsequently, comparisons were made between the results corresponding to the middle and higher outdoor relative humidity (RH) visit in each location as there were no differences in mean temperature (p Q 0.75) despite RH values significantly differing (p e 0.005). Significant (p e 0.05) differences were observed between Valladolid and Braga samples on tear breakup time (middle RH visit, 2.76 T 0.60 vs. 5.26 T 0.64 seconds; higher RH visit, 2.61 T 0.32 vs. 5.78 T 0.88 seconds) and corneal (middle RH, 0.64 T 0.17 vs. 0.14 T 0.10; higher RH, 0.60 T 0.22 vs. 0.0 T 0.0) and conjunctival staining (middle RH, 0.61 T 0.17 vs. 0.14 T 0.08; higher RH, 0.57 T 0.15 vs. 0.18 T 0.09). Conclusions. This pilot study provides initial evidence to support that DED test outcomes assessing the ocular surface integrity and tear stability are climate dependent. Future large-sample studies should support these outcomes also in DED patients. This knowledge is fundamental for multicenter clinical trials. Lack of consistency in diagnostic clinical tests for DED was also corroborated. (Optom Vis Sci 2015;92:e284Ye289)

Cognitive stimulation for portuguese older adults with cognitive impairment: a randomized controlled trial of efficacy, comparative duration, feasibility and experiential relevance

Although some studies point to cognitive stimulation as a beneficial therapy for older adults with cognitive impairments, this area of research and practice is still lacking dissemination and is underrepresented in many countries. Moreover, the comparative effects of different intervention durations remain to be established and, besides cognitive effects, pragmatic parameters, such as cost-effectiveness and experiential relevance to participants, are seldom explored. In this work, we present a randomized con- trolled wait-list trial evaluating 2 different intervention durations (standard 1⁄4 17 vs brief 1⁄4 11 sessions) of a cognitive stimulation program developed for older adults with cognitive impairments with or without dementia. 20 participants were randomly assigned to the standard duration intervention program (17 sessions, 1.5 months) or to a wait-list group. At postintervention of the standard intervention group, the wait-list group crossed over to receive the brief intervention program (11 sessions, 1 month). Changes in neuropsychological, functionality, quality of life, and caregiver outcomes were evaluated. Experience during intervention and costs and feasibility were also evaluated. The current cognitive stimulation programs (ie, standard and brief) showed high values of experiential relevance for both intervention durations. High adherence, completion rates, and reasonable costs were found for both formats. Further studies are needed to definitively establish the potential efficacy, optimal duration, cost-effectiveness, and experiential relevance for participants of cognitive intervention approaches.

Are cognitive interventions for multiple sclerosis effective and feasible?

Purpose: Fifty percent of patients with Multiple Sclerosis (MS) are estimated to have cognitive impairments leading to considerable decline in productivity and quality of life. Cognitive intervention has been considered to complement pharmacological treatments. However, a lack of agreement concerning the efficacy of cognitive interventions in MS still exists. A systematic review and meta-analysis was conducted to assess the effects of cognitive interventions in MS. Methods: To overcome limitations of previous meta-analyses, several databases were searched only for Randomized Clinical Trials (RCTs) with low risk of bias. Results: Five studies (total of 139 participants) met our eligibility criteria. Although good completion and adherence rates were evident, we found no evidence of intervention effects on cognition or mood in post-intervention or follow-up assessments. Conclusions: This is the first meta-analysis assessing the effects of cognitive intervention in MS including only RCTs with comparable conditions. Research regarding efficacy, cost-effectiveness and feasibility is still in its infancy. Caution is advised when interpreting these results due to the small number of RCTs meeting the inclusion criteria. Considering the costs of disease, good completion and adherence rates of this approach, further research is warranted. Recommendations concerning improved research practices in the field are presented as well.