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Robotic technology and functional electrical stimulation (FES) have emerged as highly effective rehabilitative techniques for individuals with neuromuscular diseases, showcasting their ability to restore motor functions. Within the proposed study, we developed and tested a new hybrid controller combining an upper-limb exoskeleton with FES to enhance haptic feedback when performing task-oriented and bimanual movement, like pick-and-place, in a virtual environment. We investigated the performance of the proposed approach on eight unimpaired participants providing haptic feedback either only by the exoskeleton or by the hybrid system. The hybrid control presents two different modalities, assistive and resistive, to modulate the perception of the load. FES intensity is calibrated to the subjects’ biomechanical properties and it is adjusted in real-time according to the real-time motion of the upper limbs. Experimental results highlighted the ability of the hybrid control to improve kinematic performance: in both hybrid modalities subjects reduced the target matching error(values between 0.048±0.007 m and 0.06±0.006 m) without affecting the normal motion smoothness (SPARC values in the hybrid conditions range from −2.58±0.12 to −3.30±0.13). Moreover, the resistive approach resulted in greater metabolic consumption (1.04±0.03 W/kg), indicating a more realistic experience of lifting a virtual object through FES that increased the perceived weight. The innovation in our hybrid control relies on the modulation of muscular activation during manipulation tasks, which could be a promising approach in the clinical treatment of neuromuscular diseases.

The objective of this work was to develop a versatile strategy for preparing multifunctional composite films with tunable properties. Novel conductive composites based on the combination of single walled carbon nanotubes (SWCNTs) and biodegradable poly(butylene cyclohexanedicarboxylate/diglycolate) random copolymers (P(BCEmBDGn)) are here presented. In particular, synthesized PBCE homopolymer and two copolymers containing different amounts of ether–oxygen containing co-units, P(BCE90BDG10) and P(BCE70BDG30), have been considered as matrices of SWCNTs based composites. The effect of incorporation of different amounts of SWCNTs (0.1–0.5–0.75–1 wt%) on morphological, thermal, mechanical and electrical properties was deeply investigated. The morphology of the fracture surfaces is affected by the SWCNT presence, while the increase in the SWCNT content does not provide significant microstructure modifications. The thermal properties underlined that nanotubes can act as nucleating agents, favouring the polymer crystallization process. The mechanical behavior demonstrated that the introduction of carbon nanotubes both in the case of PBCE homopolymer and in random copolymers based formulations exerted a reinforcing effect. All composites exhibit high electrical conductivity in comparison to the neat polymers. This work demonstrates that this combinatorial approach can be used to develop materials with tunable and advanced functional properties.

A series of novel random copolymers of poly(propylene 1,4-cyclohexanedicarboxylate) (PPCE) containing neo -pentyl glycol sub-unit (P(PCExNCEy)) were synthesized and characterized in terms of molecular and solid-state properties. In addition, biodegradability studies in compost have been conducted. The copolymers displayed a high and similar thermal stability with respect to PPCE. At room temperature, all the copolymers appeared as semicrystalline materials: the main effect of copolymerization was a lowering of crystallinity degree (χc) and a decrease of the melting temperature compared to the parent homopolymer. In particular, Wide Angle X-Ray diffraction (WAXD) measurements indicated that P(PCExNCEy) copolymers are characterized by cocrystallization, PNCE counits cocrystallizing in PPCE crystalline phase. Final properties and biodegradation rate of the materials under study were strictly dependent on copolymer composition and χc. As a matter of fact, the elastic modulus and the elongation at break decreased and increased, respectively, as neopentyl glycol cyclohexanedicarboxylate (NCE) unit content was increased. The presence of a rigid-amorphous phase was evidenced by means of Dynamic Mechanical Thermal Analysis (DMTA) analysis in all the samples under investigation. Lastly, the biodegradation rate of P(PCExNCEy) copolymers was found to slightly increase with the increasing of NCE molar content.

Gene editing following designer nuclease cleavage in the presence of a DNA donor template can revert mutations in disease-causing genes. For optimal benefit, reversion of the point mutation in HBB leading to sickle cell disease (SCD) would permit precise homology-directed repair (HDR) while concurrently limiting on-target non-homologous end joining (NHEJ)-based HBB disruption. In this study, we directly compared the relative efficiency of co-delivery of a novel CRISPR/Cas9 ribonucleoprotein targeting HBB in association with recombinant adeno-associated virus 6 (rAAV6) versus single-stranded oligodeoxynucleotides (ssODNs) to introduce the sickle mutation (GTC or GTG; encoding E6V) or a silent change (GAA; encoding E6optE) in human CD34+ mobilized peripheral blood stem cells (mPBSCs) derived from healthy donors. In vitro, rAAV6 outperformed ssODN donor template delivery and mediated greater HDR correction, leading to both higher HDR rates and a higher HDR:NHEJ ratio. In contrast, at 12–14 weeks post-transplant into recipient, immunodeficient, NOD, B6, SCID Il2rγ−/− Kit(W41/W41) (NBSGW) mice, a ∼6-fold higher proportion of ssODN-modified cells persisted in vivo compared to recipients of rAAV6-modified mPBSCs. Together, our findings highlight that methodology for donor template delivery markedly impacts long-term persistence of HBB gene-modified mPBSCs, and they suggest that the ssODN platform is likely to be most amenable to direct clinical translation. Keywords: sickle cell disease, gene editing, rAAV6, ssODN, homology-directed repair, Crispr/Cas9, hemoglobin disorders, NHEJ versus HDR, in vivo engraftment, NBSGW41 mice, CD34, hematopoietic stem cells, stem cell cures

Controlling the cooling rate experienced by a material during a manufacturing process is a challenge and a major issue. Industrial processing techniques are very diverse and may involve a whole range of cooling rates, which are sometimes extremely high for small and/or thin manufactured parts. For polymers, the cooling rate has consequences on both the microstructure and the time-dependent properties. The common cooling rates associated with conventional calorimetric measurements are generally limited to a few tens of degrees per minute. This work combines several calorimetric techniques (DSC, modulated-temperature DSC, stochastically-modulated DSC and Fast Scanning Calorimetry) to estimate the critical cooling rate required to melt-quench fast-crystallizing polyesters to their fully amorphous state, based on the example of a series of poly(alkylene trans -1,4-cyclohexanedicarboxylate) (PCHs) with a number of methylene groups in the main structure of the repeating unit nCH2 varying from 3 to 6. The even-numbered ones require faster cooling rates (about 3000 K s -1 for nCH2 = 4, between 500 and 1000 K s -1 for nCH2 = 6) compared to the odd-numbered ones (between 50 K min -1 and 100 K s -1 for nCH2 = 3, between 10 and 30 K min -1 for nCH2 = 5).

In the present study, bio-based polymeric blends have been prepared for applications in the field of sustainable food packaging, starting from two furan-based homopolymers, poly(hexamethylene 2,5-furanoate) (PHF) and poly(pentamethylene 2,5-furanoate) (PPeF). PHF and PPeF were synthesized by two-step melt polycondensation-a solvent-free synthetic strategy-and then binary physical mixtures, PHF/PPeF, with different weight compositions were prepared by dissolution in a common solvent. The blends were processed into compression-moulded films, and molecular, morphological, structural, thermal, and mechanical characterizations were subsequently carried out. Blending did not negatively affect the thermal stability of the parent homopolymers, and good compatibility between them was observed. This strategy also allowed for the modulation of the chain rigidity as well as of the crystallinity, simply by acting on the relative weight amount of the homopolymers. From a mechanical point of view, the presence of PPeF led to a reduction in stiffness and an increase in the elongation at break, obtaining materials with an elastomeric behaviour. Evaluation of the gas barrier properties confirmed that the good barrier properties of PHF were preserved by blending. Finally, lab-scale composting tests confirmed a greater weight loss of the mixtures with respect to the PHF homopolymer.

Cardiovascular disease (CVD), the leading cause of death globally, affects the heart and arteries with a variety of clinical manifestations, the most dramatic of which are myocardial infarction (MI), abdominal aortic aneurysm (AAA), and intracranial aneurysm (IA) rupture. In MI, necrosis of the myocardium, scar formation, and loss of cardiomyocytes result from insufficient blood supply due to coronary artery occlusion. Beyond stenosis, the arteries that are structurally and functionally connected to the cardiac tissue can undergo pathological dilation, i.e., aneurysmal dilation, with high risk of rupture. Aneurysms of the intracranial arteries (IAs) are more commonly seen in young adults, whereas those of the abdominal aorta (AAA) are predominantly seen in the elderly. IAs, unpredictably, can undergo rupture and cause life-threatening hemorrhage, while AAAs can result in rupture, internal bleeding and high mortality rate. In this clinical context, hydrogels, three-dimensional networks of water-seizing polymers, have emerged as promising biomaterials for cardiovascular tissue repair or protection due to their biocompatibility, tunable properties, and ability to encapsulate and release bioactive molecules. This review provides an overview of the current state of research on the use of hydrogels as an innovative platform to promote cardiovascular-specific tissue repair in MI and functional recovery or protection in aneurysmal dilation.

Here, we present novel biocompatible poly(butylene trans -1,4-cyclohexanedicarboxylate) (PBCE)-based random copolymer nanostructured scaffolds with tailored stiffness and hydrophilicity. The introduction of a butylene diglycolate (BDG) co-unit, containing ether oxygen atoms, along the PBCE chain remarkably improved the hydrophilicity and chain flexibility. The copolymer containing 50 mol% BDG co-units (BDG50) and the parent homopolymer (PBCE) were synthesized and processed as electrospun scaffolds and compression-molded films, added for the sake of comparison. We performed thermal, wettability, and stress-strain measures on the PBCE-derived scaffolds and films. We also conducted biocompatibility studies by evaluating the adhesion and proliferation of multipotent mesenchymal/stromal cells (hBM-MSCs) on each polymeric film and scaffold. We demonstrated that solid-state properties can be tailored by altering sample morphology besides chemical structure. Thus, scaffolds were characterized by a higher hydrophobicity and a lower elastic modulus than the corresponding films. The three-dimensional nanostructure conferred a higher adsorption protein capability to the scaffolds compared to their film counterparts. Finally, the PBCE and BDG50 scaffolds were suitable for the long-term culture of hBM-MSCs. Collectively, the PBCE homopolymer and copolymer are good candidates for tissue engineering applications.

Mechanotransduction is a molecular process by which cells translate physical stimuli exerted by the external environment into biochemical pathways to orchestrate the cellular shape and function. Even with the advancements in the field, the molecular events leading to the signal cascade are still unclear. The current biotechnology of tissue engineering offers the opportunity to study in vitro the effect of the physical stimuli exerted by biomaterial on stem cells and the mechanotransduction pathway involved in the process. Here, we cultured multipotent human mesenchymal/stromal cells (hMSCs) isolated from bone marrow (hBM-MSCs) and adipose tissue (hASCs) on films of poly(butylene 1,4-cyclohexane dicarboxylate) (PBCE) and a PBCE-based copolymer containing 50 mol% of butylene diglycolate co-units (BDG50), to intentionally tune the surface hydrophilicity and the stiffness (PBCE = 560 Mpa; BDG50 = 94 MPa). We demonstrated the activated distinctive mechanotransduction pathways, resulting in the acquisition of an elongated shape in hBM-MSCs on the BDG50 film and in maintaining the canonical morphology on the PBCE film. Notably, hASCs acquired a new, elongated morphology on both the PBCE and BDG50 films. We found that these events were mainly due to the differences in the expression of Cofilin1, Vimentin, Filamin A, and Talin, which established highly sensitive machinery by which, rather than hASCs, hBM-MSCs distinguished PBCE from BDG50 films.

High molecular weight, fully biobased random copolymers of 2,5-furandicarboxylic acid (2,5-FDCA) containing different amounts of (1R, 3S)-(+)-Camphoric Acid (CA) have been successfully synthesized by two-stage melt polycondensation and compression molding in the form of films. The synthesized copolyesters have been first subjected to molecular characterization by nuclear magnetic resonance spectroscopy and gel-permeation chromatography. Afterward, the samples have been characterized from a thermal and structural point of view by means of differential scanning calorimetry, thermogravimetric analysis, and wide-angle X-ray scattering, respectively. Mechanical and barrier properties to oxygen and carbon dioxide were also tested. The results obtained revealed that chemical modification permitted a modulation of the abovementioned properties depending on the amount of camphoric co-units present in the copolymers. The outstanding functional properties promoted by camphor moieties addition could be associated with improved interchain interactions (π-π ring stacking and hydrogen bonds).

Estimation of the force exerted by muscles from their electromyographic (EMG) activity may be useful to control robotic devices. Approximating end-point forces as a linear combination of the activities of multiple muscles acting on a limb may lead to an inaccurate estimation because of the dependency between the EMG signals, i.e., multi-collinearity. This study compared the EMG-to-force mapping estimation performed with standard multiple linear regression and with three other algorithms designed to reduce different sources of the detrimental effects of multi-collinearity: Ridge Regression, which performs an L2 regularization through a penalty term; linear regression with constraints from foreknown anatomical boundaries, derived from a musculoskeletal model; linear regression of a reduced number of muscular degrees of freedom through the identification of muscle synergies. Two datasets, both collected during the exertion of submaximal isometric forces along multiple directions with the upper limb, were exploited. One included data collected across five sessions and the other during the simultaneous exertion of force and generation of different levels of co-contraction. The accuracy and consistency of the EMG-to-force mappings were assessed to determine the strengths and drawbacks of each algorithm. When applied to multiple sessions, Ridge Regression achieved higher accuracy (R 2 = 0.70) but estimations based on muscle synergies were more consistent (differences between the pulling vectors of mappings extracted from different sessions: 67%). In contrast, the implementation of anatomical constraints was the best solution, both in terms of consistency (R 2 = 0.64) and accuracy (74%), in the case of different co-contraction conditions. These results may be used for the selection of the mapping between EMG and force to be implemented in myoelectrically controlled robotic devices.

Robotic technology and functional electrical stimulation (FES) have emerged as highly effective rehabilitative techniques for individuals with neuromuscular diseases, showcasting their ability to restore motor functions. Within the proposed study, we developed and tested a new hybrid controller combining an upper-limb exoskeleton with FES to enhance haptic feedback when performing task-oriented and bimanual movement, like pick-and-place, in a virtual environment. We investigated the performance of the proposed approach on eight unimpaired participants providing haptic feedback either only by the exoskeleton or by the hybrid system. The hybrid control presents two different modalities, assistive and resistive, to modulate the perception of the load. FES intensity is calibrated to the subjects' biomechanical properties and it is adjusted in real-time according to the real-time motion of the upper limbs. Experimental results highlighted the ability of the hybrid control to improve kinematic performance: in both hybrid modalities subjects reduced the target matching error(values between 0.048±0.007 m and 0.06±0.006 m) without affecting the normal motion smoothness (SPARC values in the hybrid conditions range from -2.58±0.12 to -3.30±0.13). Moreover, the resistive approach resulted in greater metabolic consumption (1.04±0.03 W/kg), indicating a more realistic experience of lifting a virtual object through FES that increased the perceived weight. The innovation in our hybrid control relies on the modulation of muscular activation during manipulation tasks, which could be a promising approach in the clinical treatment of neuromuscular diseases.

Fully bio-based poly(lactic acid) (PLA) and poly(3-hydroxybutyrate) (PHB) blends plasticized with tributyrin (TB), and their nanocomposite based on chitin nanoparticles (ChNPs) was developed using melt mixing followed by a compression molding process. The combination of PHB and ChNPs had an impact on the crystallinity of the plasticized PLA matrix, thus improving its oxygen and carbon dioxide barrier properties as well as displaying a UV light-blocking effect. The addition of 2 wt% of ChNP induced an improvement on the initial thermal degradation temperature and the overall migration behavior of blends, which had been compromised by the presence of TB. All processed materials were fully disintegrated under composting conditions, suggesting their potential application as fully biodegradable packaging materials.

Haptic feedback is the sensory modality to enhance the so-called "immersion", meant as the extent to which senses are engaged by the mediated environment during virtual reality applications. However, it can be challenging to meet this requirement using conventional robotic design approaches that rely on rigid mechanical systems with limited workspace and bandwidth. An alternative solution can be seen in the adoption of lightweight wearable systems equipped with Neuromuscular Electrical Stimulation (NMES): in fact, NMES offers a wide range of different forces and qualities of haptic feedback. In this study, we present an experimental setup able to enrich the virtual reality experience by employing NMES to create in the antagonists' muscles the haptic sensation of being loaded. We developed a subject-specific biomechanical model that estimated elbow torque during object lifting to deliver suitable electrical muscle stimulations. We experimentally tested our system by exploring the differences between the implemented NMES-based haptic feedback ( NMES condition), a physical lifted object ( Physical condition), and a condition without haptic feedback ( Visual condition) in terms of kinematic response, metabolic effort, and participants' perception of fatigue. Our results showed that both in terms of metabolic consumption and user fatigue perception, the condition with electrical stimulation and the condition with the real weight differed significantly from the condition without any load: the implemented feedback was able to faithfully reproduce interactions with objects, suggesting its possible application in different areas such as gaming, work risk assessment simulation, and education.

In the present work, the effect of ether oxygen atom introduction in a furan ring-containing polymer has been evaluated. Solvent-free polycondensation process permitted the preparation of high molecular weight poly(diethylene 2,5-furandicarboxylate) (PDEF), by reacting the dimethyl ester of 2,5-furandicarboxylic acid with diethylene glycol. After molecular and thermal characterization, PDEF mechanical response and gas barrier properties to O 2 and CO 2 , measured at different temperatures and humidity, were studied and compared with those of poly(butylene 2,5-furandicarboxylate) (PBF) and poly(pentamethylene 2,5-furanoate) (PPeF) previously determined. Both PDEF and PPeF films were amorphous, differently from PBF one. Glass transition temperature of PDEF (24 °C) is between those of PBF (39 °C) and PPeF (13 °C). As concerns mechanical response, PDEF is more flexible (elastic modulus [E] = 673 MPa) than PBF (E = 1290 MPa) but stiffer than PPeF (E = 9 MPa). Moreover, PDEF is the most thermally stable (temperature of maximum degradation rate being 418 for PDEF, 407 for PBF and 414 °C for PPeF) and hydrophilic (water contact angle being 74° for PDEF, 90° for PBF and 93° for PPeF), with gas barrier performances very similar to those of PPeF (O 2 and CO 2 transmission rate being 0.0022 and 0.0018 for PDEF and, 0.0016 and 0.0014 cm 3  cm/m 2 d atm for PPeF). Lab scale composting experiments indicated that PDEF and PPeF were compostable, the former degrading faster, in just one day. The results obtained are explained on the basis of the high electronegativity of ether oxygen atom with respect to the carbon one, and the consequent increase of dipoles along the macromolecule., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Using a computer vision approach we have extracted the Haralick's texture features of randomly oriented electrospun nanomaterials in order to predict the proliferative behavior of cells which were subsequently seeded onto the nanosurfaces., Competing Interests: The authors declare that there are not conflicting interests., (This journal is © The Royal Society of Chemistry.)

In the past 20 years, scientific research focused on the identification of valid alternatives to materials of fossil origin, in particular, related to biobased polymers. Recently, the efforts led to the synthesis of thiophene-based polymers (TBPs), a new class of polyesters based on 2,5-thiophenedicarboxylic acid (TPCA) that can be industrially produced using biomass-derived molecules. In this study, TBPs were synthesized using diols with different chain length (from C4 to C6) leading to poly(butylene 2,5-thiophenedicarboxylate) (PBTF), poly(pentamethylene 2,5-thiophenedicarboxylate) (PPeTF), and poly(hexamethylene 2,5-thiophenedicarboxylate) (PHTF), respectively, that were processed to thin films. To investigate enzymatic hydrolysis of these polymer films, cutinase 1 (Thc_cut1) and cutinase 2 (Thc_cut2) from Thermobifida cellulosilytica were recombinantly expressed in the host E. coli and purified. After 72 h of incubation at 65°C with 5 µM Thc_cut1, weight loss and HPLC analysis indicated 9, 100, and 80% degradation of PBTF, PPeTF, and PHTG with a concomitant release of 0.12, 2.70, and 0.67 mM of TPCA. The SEM analysis showed that tiny holes were formed on the surface of the films and after 72 h PPeTF was completely degraded. The LC-TOF/MS analysis indicated that Thc_cut2 in particular released various oligomers from the polymer during the reaction. In addition, the FTIR analysis showed the formation of novel acid and hydroxyl groups on the polymer surfaces. The results showed that the two used thermostable cutinases are promising biocatalysts for the environmentally friendly degradation of TPCA-based polyesters, in view of a possible sustainable recycling of plastic waste through resynthesis processes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bertolini, Soccio, Weinberger, Guidotti, Gazzano, Guebitz, Lotti and Pellis.)

The overall migration behavior and the disintegration under composting conditions of films based on plasticized poly(lactic acid)/poly(3-hydroxybutyrate) (PLA-PHB) blends were studied, with the main aim of determining the feasibility of their application as biodegradable food packaging materials. The role of composition in the disintegration process was evaluated by monitoring the changes in physical and thermal properties that originated during the degradation process. PLA and PHB were blended in two weight ratios with 15 wt% of tributyrin, using a Haake mixer and then compression molded into ~150 μm films. We found that the migration level of all of the studied blends was below check intended meaning retained in non-polar simulants, while only plasticized blends could withstand the contact with polar solvents. The disintegration of all of the materials in compost at 58 °C was completed within 42 days; the plasticized PHB underwent the fastest degradation, taking only 14 days. The presence of the TB plasticizer speeded up the degradation process. Different degradation mechanisms were identified for PLA and PHB. To evaluate the annealing effect separately from bacteria degradation, the influence of temperature on materials in the absence of a compost environment was also studied. With the increasing time of degradation in compost, both melting temperature and maximum degradation temperature progressively decreased, while the crystallinity degree increased, indicating that the samples were definitely degrading and that the amorphous regions were preferentially eroded by bacteria.

Among the several actions contributing to the development of a sustainable society, there is the eco-design of new plastic materials with zero environmental impact but that are possibly characterized by properties comparable to those of the traditional fossil-based plastics. This action is particularly urgent for food packaging sector, which involves large volumes of plastic products that quickly become waste. This work aims to contribute to the achievement of this important goal, proposing new bio-based cycloaliphatic polymers based on trans -1,4-cyclohexanedicarboxylic acid and containing different amount of camphoric acid (from 0 to 15 mol %), a cheap and bio-based building block. Such chemical modification was conducted in the melt by avoiding the use of solvents. The so-obtained polymers were processed in the form of films by compression molding. Afterwards, the new and successfully synthesized random copolymers were characterized by molecular (NMR spectroscopy and GPC analysis), thermal (DSC and TGA analyses), diffractometric (wide angle X-ray scattering), mechanical (through tensile tests), and O 2 and CO 2 barrier point of view together with the parent homopolymer. The article aims to relate the results obtained with the amount of camphoric moiety introduced and to present, the different microstructure in the copolymers in more detail; indeed, in these samples, a different crystalline form developed (the so-called β-PBCE). This latter form was the kinetically favored and less packed one, as proven by the lower equilibrium melting temperature determined for the first time by Baur's equation.