Indirect microfabrication of biomimetic materials for locomotor tissues regeneration

Tissue Engineering is a new field of the scientific research with a final aim to develop techniques for regeneration, repair, maintenance and growth of tissues or organs to overcome the limitations intrinsic to current therapeutic strategies. A fundamental element of this approach is the scaffold. The scaffold is a 2D and 3D structure, made with natural or synthetic material, that emulates the extracellular matrix, that is it offers mechanical, topological, biochemical and chemical stimuli to promote cellular organization, growth and differentiation to create a tissue with adequate functional and morphological characteristic. Scaffolds are therefore characterized by peculiar features (e.g. porosity, mechanical properties) determined by the material and by the manufacture process. Nowadays, the additive Rapid Prototyping (RP) techniques are the best approach to realize complex structures, because overcome all the problem of conventional (subtractive) techniques. Despite the high potential, RP techniques are not always compatible with all materials. In particular, hydrogels, an elective class of biomaterial for scaffolds realization because the lot of features in common with the extracellular matrix, results very difficult to be processed. To overcome these limitations and take advantage of all benefits of rapid prototyping, indirect rapid prototyping (iRP) was developed, that is the realization of scaffold or other structures starting from sacrificial molds realized by RP. The iRP offers the benefits to fabricate composite scaffold realized with different materials, with less waste and high fidelity in the realization of the designed structure. One of the critical aspect of this class of realization process is the extraction of the final object from the mold. A possible solution, proposed in this research, is to realize the mold with low melting point materials, dissolving the mold at the end of the process without damaging the scaffold. Moving in this direction, the attention of this research is focused on two classes of materials, low melting point waxes and agarose. Two alternative RP techniques have been evaluated: new modules of the PAM^2, a continuous flow system, and a inkjet-based device have been designed and realized to test the feasibility of this approach. In addiction, an alternative approach to fabricate agarose microstructure, by exploiting the different agarose gelling ability in DMSO and water, has been proposed. In a future perspective, casting of the desired material, which may include also cells, should be performed directly in the surgery room using an anatomical shaped mold designed on the patient needs. Following this approach, two plugins for bioimages de-noising and segmentation, based on the ITK library, have been implemented for the OsiriX software. To further test the versatility of the two microfabrication devices, other applications have been explored, such as the realization of microfluidic circuits using PAM^2 or printing carbon nanotubes suspension for polymeric actuators

Touch sensor for social robots and interactive objects affective interaction

The recognised importance of physical experience in empathic exchanges has led to the development of touch sensors for human–robot affective interaction. Most of these sensors, implemented as matrix of pressure sensors, are rigid, cannot be fabricated in complex shapes, cannot be subjected to large deformations, and usually allow to capture only the contact event, without any information about the interaction context. This paper presents a tactile flux sensor able to capture the entire context of the interaction including gestures and patterns. The sensor is made of alternate layers of sensitive and insulating silicone: the soft nature of the sensor makes it adaptable to complex and deformable bodies. The main features from electrical signals are extracted with the principal component analysis, and a self-organising neural network is in charge for the classification and spatial identification of the events to acknowledge and measure the gesture. The results open to interesting applications, which span from toy manufacturing, to human-robot interaction, and even to sport and biomedical equipment and applications

Molecular Imprinting Strategies for Tissue Engineering Applications: A Review

Tissue Engineering (TE) represents a promising solution to fabricate engineered constructs able to restore tissue damage after implantation. In the classic TE approach, biomaterials are used alongside growth factors to create a scaffolding structure that supports cells during the construct maturation. A current challenge in TE is the creation of engineered constructs able to mimic the complex microenvironment found in the natural tissue, so as to promote and guide cell migration, proliferation, and differentiation. In this context, the introduction inside the scaffold of molecularly imprinted polymers (MIPs)-synthetic receptors able to reversibly bind to biomolecules-holds great promise to enhance the scaffold-cell interaction. In this review, we analyze the main strategies that have been used for MIP design and fabrication with a particular focus on biomedical research. Furthermore, to highlight the potential of MIPs for scaffold-based TE, we present recent examples on how MIPs have been used in TE to introduce biophysical cues as well as for drug delivery and sequestering

Open-source automated external defibrillator

The Automated External Defibrillator (AED) is a medical device that analyzes a patient's electrocardiogram in order to establish whether he/she is suffering from the fatal condition of Sudden Cardiac Arrest (SCA), and subsequently allows the release of a therapeutic dose of electrical energy (i.e. defibrillation). SCA is responsible for over 300,000 deaths per year both in Europe and in USA, and immediate clinical assistance through defibrillation is fundamental for recovery. In this context, an open-source approach can easily lead in improvements to the distribution and efficiency of AEDs. The proposed Open-Source AED (OAED) is composed of two separate electric boards: a high voltage board (HV-B), which contains the circuitry required to perform defibrillation and a control board (C-B), which detects SCA in the patient and controls the HV-B. Computer simulations and preliminary tests show that the OAED can release a 200 J biphasic defibrillation in about 12 s and detects SCA with sensitivity higher than 90% and specificity of about 99%. The OAED was also conceived as a template and teaching tool in the framework of UBORA, a platform for design and sharing medical devices compliant to international standards

Improving African healthcare through open source biomedical engineering

The lack of accessible quality healthcare is one of the biggest problems in Africa and other developing countries. This is not only due to the unavailability of resources, but also to the absence of a structured formative process for the design and management of healthcare facilities. Crucial to the effective and efficient exploitation of healthcare facilities and biomedical technology is the support of Biomedical engineers, who form the link between technology and medical practice. Indeed Biomedical engineers, together with nurses and doctors, form the pillars of healthcare systems in the developed world. In this paper, the Open Source for BioMedical Engineering (OS4BME) project and its kick off summer school are presented. The OS4BME project aims at developing a new generation of biomedical engineers, able to exploit emerging technologies generated by the recent "Makers" revolution. During the one week summer school, students from various sub-Saharan countries were introduced to these new design, development and sharing paradigms. Students worked together to identify new simple biomedical devices, which could help in daily clinical practice in their countries. A cheap and easy-to-use neonatal monitoring device was chosen as a Crowd design project. The OS4BME Baby Monitor was designed and assembled by the students during the one week summer school, demonstrating the creative potential of the new generation of biomedical engineers empowered with the paradigms of crowdsourcing and rapid prototyping

The Kahawa Declaration: a manifesto for the democratization of medical technology

Most medical technology is employed and accepted passively by patients and doctors who have little or no influence in its design or usability. Patients are not involved in the development of medical technology, which is undertaken behind closed doors and whose global impact is hindered by proprietary know-how and by costs. This has so far impeded equitable healthcare as most of the world does not have access to the technology or healthcare coverage. Understanding the relevance of international partnerships for achieving the Sustainable Development Goals, feeling specially committed to the promotion of the Goal on “Good Health and Well-Being”, and convinced about the role that open-source biomedical engineering approaches may play in the future of medical technology, we commit ourselves, through the Kahawa Declaration, to enlighten the transformation of the biomedical engineering field, towards the democratization of medical technology as a key for achieving universal equitable health care. This paper presents the content of the Kahawa Declaration, which was signed in Nairobi in December 2017

A combined electrospinning and microestrusion apparatus

Combined electrospinning and microextrusion apparatus, comprising a robotic manipulator (10) provided with a plurality of degrees of freedom, an end effector (20) supported and movable by the robotic manipulator (10), a plurality of extruders (30) housed on the end effector (20), each of the extruders being provided with an interchangeable nozzle (3 1) for the extrusion of at least one material, a working plane (40) configured for the deposition of the extruded material, a pneumatic circuit (120) configured to supply a fluid flow to the extruders (30) for controlling the extrusion of the material, and an electric generator (50) selectively activatable to apply a potential difference between the nozzles (3 1) of the extruders (30) and the working plane (40), whereby the extruders (30) are capable of operating selectively in microextrusion mode with inactive electric generator or in electrospinning mode with active electric generator, in an independent manner from each other

Building Efficiency Adopting Ecological Materials and Bio Architecture Techniques

Objective. There are many measures that individual consumers, families, companies, contractors, real estate developers, household owners and governments can take to promote post-carbon cities. Thermal insulation is definitely one of the most important investment to make in order to achieve these future goals. Method and solutions   Insulation can be carried out by using ecological cork panels. Cork is a natural and renewable material, which in itself, is the result of a CO2 sequestration, and it can also store C. Therefore it can effectively contribute to the design of the Post-Carbon City by reducing energy waste, improving the quality and the insulation of buildings.The expansion of the area occupied by the cork oak forests would permanently increase the absorption and sequestration of carbon. Forest policy guidelines must aim at the restoration of the existing cork oak forests, as well as the rehabilitation of cork oak forests destroyed by man. This will increase and strengthen the contribution made by forest resources to the construction of the Post Carbon City.Outcomes and benefits   Some benefits of such policy are as follows: the sequestration of CO2 eliminated from the atmosphere (creating carbon credits), because it is used for the growth of trees and the creation of cork bark; the availability of cork planks which are the raw material for bio-building; the positive consequences of using cork panels and granules in Bio Green Buildings, such as energy saving for heating and cooling and the consequent reduction of CO2  emissions. Risparmio energetico negli edifici mediante adozione di eco materiali e tecniche di Bio EdiliziaObiettivo. L’obiettivo di ridurre i sovra consumi energetici negli edifici e promuovere le città post-carbone può essere raggiunto adottando diverse misure ad opera di individui, famiglie, imprese, costruttori, promotori immobiliari, governi. L’isolamento termico degli edifici, o “passivazione” risulta essere uno dei più importanti investimenti per raggiungere questi risultati.Metodi e soluzioni.L’isolamento termico (o “passivazione”) può essere realizzato con pannelli di sughero. Il sughero è un materiale naturale e rinnovabile. Esso stesso è il risultato della eliminazione (sequestration) della CO2 . Non solo, è un depositi di C. Può quindi efficacemente contribuire a realizzare concretamente la Post Carbon City migliorando l’ isolamento e la qualità degli edifici ed eliminando lo spreco di energia. Ampliare le aree occupate da sugherete aumenta in modo permanente l’assorbimento e la eliminazione definitivo ovvero il sequestro della CO2 . Per questa ragione la policy urbana può essere integrata con la policy ambientale e forestale, propugnando il restauro delle sugherete esistenti e il re impianto di quelle compromesse dall’azione antropica. In tal modo si rafforza il contributo natura-based alla costruzione della Post Carbon City. Risultati e beneficiSolo alcuni dei primi benefici derivanti dalla policy integrata natura-based sopra sintetizzata: la  CO2  non solo si sequestra e si elimina dall’atmosfera ma addirittura viene utilizzata dalle sughere per crescere e per produrre il sughero;si rendono disponibili nuovi quantitativi di sughero grezzo, come materia prima versatile; utilizzando i lavorati per la passivazione dei Bio Edifici Verdi, non solo si risparmia significativamente energia, ma anche si abbattono le conseguenti emissioni di  CO2.Objective. There are many measures that individual consumers, families, companies, contractors, real estate developers, household owners and governments can take to promote post-carbon cities. Thermal insulation is definitely one of the most important investment to make in order to achieve these future goals. Method and solutions   Insulation can be carried out by using ecological cork panels. Cork is a natural and renewable material, which in itself, is the result of a CO2 sequestration, and it can also store C. Therefore it can effectively contribute to the design of the Post-Carbon City by reducing energy waste, improving the quality and the insulation of buildings.The expansion of the area occupied by the cork oak forests would permanently increase the absorption and sequestration of carbon. Forest policy guidelines must aim at the restoration of the existing cork oak forests, as well as the rehabilitation of cork oak forests destroyed by man. This will increase and strengthen the contribution made by forest resources to the construction of the Post Carbon City.Outcomes and benefits   Some benefits of such policy are as follows: the sequestration of CO2 eliminated from the atmosphere (creating carbon credits), because it is used for the growth of trees and the creation of cork bark; the availability of cork planks which are the raw material for bio-building; the positive consequences of using cork panels and granules in Bio Green Buildings, such as energy saving for heating and cooling and the consequent reduction of CO2  emissions. Risparmio energetico negli edifici mediante adozione di eco materiali e tecniche di Bio EdiliziaObiettivo. L’obiettivo di ridurre i sovra consumi energetici negli edifici e promuovere le città post-carbone può essere raggiunto adottando diverse misure ad opera di individui, famiglie, imprese, costruttori, promotori immobiliari, governi. L’isolamento termico degli edifici, o “passivazione” risulta essere uno dei più importanti investimenti per raggiungere questi risultati.Metodi e soluzioni.L’isolamento termico (o “passivazione”) può essere realizzato con pannelli di sughero. Il sughero è un materiale naturale e rinnovabile. Esso stesso è il risultato della eliminazione (sequestration) della CO2 . Non solo, è un depositi di C. Può quindi efficacemente contribuire a realizzare concretamente la Post Carbon City migliorando l’ isolamento e la qualità degli edifici ed eliminando lo spreco di energia. Ampliare le aree occupate da sugherete aumenta in modo permanente l’assorbimento e la eliminazione definitivo ovvero il sequestro della CO2 . Per questa ragione la policy urbana può essere integrata con la policy ambientale e forestale, propugnando il restauro delle sugherete esistenti e il re impianto di quelle compromesse dall’azione antropica. In tal modo si rafforza il contributo natura-based alla costruzione della Post Carbon City. Risultati e beneficiSolo alcuni dei primi benefici derivanti dalla policy integrata natura-based sopra sintetizzata: la CO2  non solo si sequestra e si elimina dall’atmosfera ma addirittura viene utilizzata dalle sughere per crescere e per produrre il sughero;si rendono disponibili nuovi quantitativi di sughero grezzo, come materia prima versatile; utilizzando i lavorati per la passivazione dei Bio Edifici Verdi, non solo si risparmia significativamente energia, ma anche si abbattono le conseguenti emissioni di CO2

Genipin diffusion and reaction into a gelatin matrix for tissue engineering applications

Genipin is a natural low-toxic cross-linker for molecules with primary amino groups, and its use with collagen and gelatin has shown a great potential in tissue engineering applications. The fabrication of scaffolds with a well-organized micro and macro topology using additive manufacturing systems requires an accurate control of working parameters, such as reaction rate, gelling time, and diffusion constant. A polymeric system of 5% w/v gelatin in PBS with 2 mg/mL collagen solutions in a 1:1 weight ratio was used as template to perform measurements varying genipin concentration in a range of 0.1-1.5% w/w with respect to gelatin. In the first part of this work, the reaction rate of the polymeric system was estimated using a new colorimetric analysis of the reaction. Then its workability time, closely related to the gelling time, was evaluated thanks to rheological analysis: finally, the quantification of static and dynamic diffusion constants of genipin across nonreacting and reacting membranes, made respectively by agarose and gelatin, was performed. It was shown that the colorimetric analysis is a good indicator of the reaction progress. The gelling time depends on the genipin concentration, but a workability window of 40 min guaranteed up to 0.5% w/w genipin. The dynamic diffusion constant of genipin in the proposed polymeric system is in the order of magnitude of 10(-7) . The obtained results indicated the possibility to use the genipin, gelatin, and collagen, in the proposed concentrations, to build well-defined hydrogel scaffolds with both extrusion-based and 3D ink-jet system. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2015

A new 3D concentration gradient maker and its application in building hydrogels with a 3D stiffness gradient

For a deeper knowledge of phenomena at cell and tissue level, for understanding the role on bimolecular signalling and for the development of new drugs it is important to recreate in vitro environments that mimic the physiological one. Spatial gradients of soluble species guide the cells' morphogenesis, and they range in a three-dimensional (3D) environment. Gradients of mechanical properties, which have a 3D pattern, could lead cell migration and differentiation. In this work, a new 3D Concentration Gradient Maker able to generate 3D concentration gradients of soluble species was developed, which could be used for differential perfusion of scaffolds. The same device can be applied to build hydrogel matrixes with a 3D gradient of mechanical properties. Computational dynamic fluid analysis was used to develop the gradient generator; the validation of the 3D gradient of stiffness was carried out using finite elements analysis and experimental studies. The device and its application could bring improvements in studying phenomena related to cell chemotaxis and mechanotaxis, but also to differentiation in the simultaneous presence of gradients in both soluble chemical species and substrate stiffnes