Scientific Program

Day 1 :

  • Biomaterials

Session Introduction

Iolanda Francolini

Editorial board member for International Journal of Molecular Science.

Title: Polymeric and inorganic nanomaterials as promising tools for the battle against microbial biofilms
Speaker
Biography:

Iolanda Francolini has obtained a degree in Industrial Chemistry in 2000 from the Sapienza University of Rome. In 2003, she was a visiting scientist at the Center for Biofilm Engineering, Montana, USA. In 2005, she obtained a Ph.D. degree in Chemical and Industrial Processes at the Sapienza University of Rome. She currently serves as a Lecturer in the Science and Technologies of Polymers at the Sapienza University of Rome and performs research on antimicrobial polymers. She has published more than 55 papers in reputed journals and has been serving as an editorial board member for International Journal of Molecular Science.

 

 

Abstract:

The application of nanotechnology in medicine has opened new perspectives for the management of different kinds of pathological conditions, including cancer and neurodegenerative diseases.

Indeed, thanks to their unique size-dependent properties (e.g. large surface to volume ratios) and tailor-made physicochemical properties, nanomaterials may improve the precision and accuracy of diagnosis as well as can significantly improve the therapy by drug targeting and reduction of drug side effects. Nanoparticles (NPs) are therefore definitely promising for the care of diseases recalcitrant to therapy, including microbial biofilm-based infections.

Biofilms are sessile microbial communities often multispecies growing on both tissues and abiotic surfaces, like the surfaces of medical devices. Biofilms are recognized to cause difficult to treat infections that persist despite antibiotic therapy. Indeed, cells in biofilm are known to express phenotypic traits that are distinct from those expressed during planktonic growth. As a consequence, biofilm-growing cells show increased tolerance to antibiotics and host immune response.

In this regards, nanotechnology may provide promising advancements in the prevention and treatment of biofilm-based infections. Indeed, NPs can be properly surface-engineered in order to  have a prolonged retention time at the specific target site and, of most relevance, they can act towards cells in a non-growing state, such as persister cells. Finally, nanotechnology may permit to combine intrinsically antimicrobial nanomaterials with drugs. A pletora of different kind of antimicrobial NPs is nowadays available and under investigation.

In this talk, an overview of the main nanotechnology approaches facing with biofilm-based-related infections will be provided with particular reference to polymer nanoparticles, metal/metal oxide nanomaterials and graphene-based materials.

 

Cinzia Ferrario

Department of Environmental Science and Policy, University of Milan, Italy

Title: The potential of innovative marine-derived Biomaterials
Speaker
Biography:

Abstract:

Nowadays, the use of marine-derived biomaterials is one of the most promising in the tissue engineering and biotechnology field. Among these, marine collagens are particularly useful in regenerative medicine. Sea urchins have been recently proposed as innovative and sustainable source of collagen for this purpose. Indeed, by using by-products of the edible sea urchin Paracentrotus lividus we could obtain valuable GAGdecorated fibrillar collagen which was used to produce very thin but resistant two-dimensional (2D) membranes. In this work, we optimized a new protocol to produce three-dimensional (3D) scaffolds for novel tissue engineering applications, such as skin regeneration. The obtained 3D scaffolds were characterized in terms of ultrastructure, stability and behaviour in wet conditions. At SEM analyses, the scaffolds presented a highly porous structure whose features could be tuned at need. Scaffolds of 1-2 mm in thickness were prepared to perform experiments of cell seeding with mammalian fibroblasts. Results indicated that the scaffold was easily infiltrated and progressively colonised by the cells which remained vital and proliferated over prolonged period. In parallel, to evaluate the biocompatibility of the biomaterial, preliminary in vivo tests were performed by sub-cutaneous implantation of thin membranes in rat models. First results indicated that the animals did not show clinical signs of sufferance nor marked inflammatory reactions (i.e. rejection, abscess formation) compared to commercial bovine collagen devices used as controls, suggesting a general promising biocompatibility. Overall, our data showed that sea urchin connective tissues might be considered a valuable eco-friendly alternative source of marine collagen to produce different types of devices for regenerative medicine applications, including complex 3D scaffolds. Further tests are necessary to validate the biocompatibility in vivo and to test the actual efficacy in promoting tissue (i.e. skin) regeneration

Speaker
Biography:

Abstract:

Pesticides / Insecticides have been used by mankind since times immemorial to control pests and mosquitoes [1]. They are also used by industries as solvents, plasticizers, flame retardants and are present as major ingredient of commercially available insecticides. This means that every person gets exposed to these chemicals in some form, during his/her lifetime. Due to their high penetration via oral, inhalation and/or dermal route and long biological half-life, these toxic chemicals can cause severe health effects over chronic exposure [2]. Their toxicity is well noticed as chemical warfare agents and their mechanism of toxicity is due to the irreversible binding to serine residue of enzyme Acetylcholine Esterase (AChE) lending it incapable of Acetylcholine (Ach) recycling at neuronal synapse Herein, we are using oxime based chemistry to synthesize para and ortho amphi oxime catalysts that show high hydrolytic activity against the different classes of pesticides in micellar medium. The rate constant values of amphiphillic catalysts show that the positioning of oxime group in the structure contributes to their activity in the micellar condition. Amongst all the catalysts, ortho-amphi oxime proves to be the most potent catalyst which shows 10 fold higher activities than para-amphi oxime. The conjugation of aliphatic chain to ortho and para-oximes enhance their interaction with the cationic surfactant helping in decreasing their pKa value and make it more reactive around physiological pH. In future, these amphiphiles can be commercially formulated into spray/cleansing solution to decontaminate insecticides/ pesticides present on the surfaces. 

Sarah Shafaat

Department of Material Science & Engineering, Kroto Research Institute, University of Sheffield, UK.

Title: Developing 17-β-estradiol releasing electrospun polyurethane scaffolds for pelvic floor repair
Speaker
Biography:

Abstract:

Statement of the Problem: Pelvic organ prolapse (POP) and stress urinary incontinence (SUI) are two urogynecological diseases that affect 40-50% of postmenopausal women worldwide. Surgical interventions for these disorders require polypropylene (PPL) mesh placement to support the pelvic floor that can lead to severe complications in some patients. The need for synthetic materials more suited for use in pelvic floor repair is widely accepted. This study aims at developing an electrospun 17-β-estradiol releasing polyurethane scaffold that not only mimics the structural design of native human fascia but can also stimulate new extracellular matrix production and angiogenesis.

Methodology: Polyurethane (PU) scaffolds with and/or without 17-β-estradiol (25mg/g and 50mg/g) were prepared by blend electrospinning and mechanical properties of constructed scaffolds were assessed by uniaxial cyclic and non-cyclic testing. Water contact angle (WCA) measurements showed the hydrophilicity of the scaffolds. The viability and extracellular matrix production of cultured human adipose derived mesenchymal stem cells (hADMSCs) cultured on 17-β-estradiol releasing PU scaffolds was evaluated. The angiogenic potential of estradiol releasing scaffolds was evaluated using an ex ovo chick chorioallantoic membrane (CAM) assay.

Findings: The inclusion of 17-β-estradiol in PU scaffolds did not change the ultrastructure rather it significantly increased the UTS of scaffolds. Estradiol was released gradually from the scaffolds over a period of 3 months and hADMSCs on estradiol-releasing PU scaffolds showed more ECM production. The CAM assay showed a significantly higher angiogenic potential of estradiol-releasing PU scaffolds and histological examination showed appropriate cellular infiltration and improved tissue integration for all electrospun scaffolds compared to PPL.

Conclusion and Significance: We demonstrate the angiogenic potential of estradiol-releasing PU scaffolds with appropriate strength and elasticity desirable to support the pelvic floor.

 

  • 3D printing of Biomaterials
Speaker
Biography:

Edwin-Joffrey Courtial has completed his PhD from IMP (Ingénierie des Matériaux Polymères) lab, Université Claude Bernard Lyon 1. He is a researcher specialized in materials science and rheological behaviors. These main activities are focus on correlation beetween (bio)materials formulations and rheological behaviors to define 3D (bio)printable conditions.

Abstract:

3D Bioprinting, i.e. biomaterials 3D printing including living cells, is one of the most advance technology in tissue engineering and regenerative medicine [1]. The technique presents the capacity to produce efficiently and in a cost-effective way, tissues with cell density and shape recapitulating human tissue behaviours [1]. Nevertheless, the use of extrusion based technology presents limitations such as low resolution and cells mortality, due to a high shear stress value inside the nozzle [2,3]. We are herein proposing the development and validation of a new routine enabling the monitoring of cells viability during 3D bioprinting. The method is based on the relation between bioink rheological properties, shear stress induced by the bioprinting process and cells viability. Rotational rheometer was used to define the bioink rheological behaviour. To access the shear stress map inside the bioprinting nozzle, a specific algorithm was developed based on Poiseuille tube flow of a pseudoplastic power law fluid [4]. Fibroblast primary cells, already applied inhouse for skin tissue bioprinting, were chosen as a model cell line for our study. Living and labelled necrotic cells were counted before and post-printing process to evaluated cell viability and total cell recovery in various conditions. In view of preliminary results, the shear stress gradient can be controlled through bioink rheological behaviour and nozzle geometry. Moreover, memory effect of the flow, controlled by the nozzle shape, seems to have an impact on cell viability. In any case, it was shown that using adequate bioink rheological properties, cells viability can be optimal whatever the nozzle geometry and the applied flow value; protecting cells during the 3D bioprinting process.

  • Tissue Engineering
Speaker
Biography:

ahdi Hadi has been involved in stem cell and tissue engineering in research and industrial centers of Iran for 12 years. At first, he has done a lot of research at Royan Institute of Tehran and in the following, because of interest in production of a commercial product in the medical field and also eagerness on assisting in people’s treatment, has joined the modern Biopharmaceutical industry. At first, he was the project manager of cell therapy medicines production and tissue engineering, and currently he is working as Biological Medicines Director at Tofigh Daru Research and Engineering Company in Tehran and is engaged in developing advanced bio-based pharmaceuticals complying with GMP requirements. His commercial products that are under production include human cartilage tissue in the field of tissue engineering, human autologous fibroblast cell and autologous human chondrocyte product in the field of cell therapy.

 

Abstract:

Statement of the Problem: One of the most important problems in humans is damage to the cartilage of the joints. Of the common case which affects most people of different ages is osteoarthritis that is due to the loss of the articular cartilage of the knee that in most cases, the subchondral bones in the cartilage subcutaneous are also damaged. These lesions are not thoroughly curable due to the limited repair power in the normal cartilage because of absence of lymph, vascular and nerve tissue. One of the newest remedies for cartilage treatment is making autologous cartilage in vitro and linking it to the patient's joint. By using tissue engineering methods, one can design a biocompatible scaffold, using natural protein and seed it to the patient's autologous chondrocyte cells and produce living human tissue. The purpose of this study is comparison of different methods in the freeze drying process of designing and constructing an appropriate
bio-scaffold with effective porosity size and shape, so that the highest efficiency required for the implantation and proliferation in the scaffold is created. Methodology: During a study, identical collagen hydro gels and different scaffolds were prepared by different conditions of freeze drying. Then, the patient's cartilage was biopsied in accordance with ethical principles and chondrocyte cells were extracted and multiplied from the tissue. The cells were then placed adjacent to the scaffolds and cartilage tissues of different qualities were prepared in a month. Findings: After performing specialized tests related to cartilage tissue, the scaffold which had a freeze drying that reached -40° C over a 90-minute ambient temperature, manifested the best cartilage tissue formation compared to the other groups. Conclusion: Human cells can, in the form of three-dimensional tissues in the scaffolds, be prepared with physical and chemical conditions in vitro, and lead to fabrication of living human cartilage tissues, and be used in treatment of diseases associated with cartilage damage.

 

Speaker
Biography:

Ali Taghibakhshi is a bachelor student in the mechanical engineering department of Sharif University Technology. Under supervision of Professor M.S.Saidi and with guidance of Mrs. Barisam, he has done some research in the field of biomechanics and has presented a well-modified model for tumor growth which is applicable to 3D spheroidal tumor growth in microfluidic devices. This is a responsive approach and the results can be used for further researches in this field of study.

 

Abstract:

Nowadays, cancer is one of the most fatal diseases in the world and number of deaths associated with it is escalating in an uncontrolled way. Thus, determining the characteristics of tumor cells and how they grow is of a great importance. Furthermore, rapid advancement in biomechanics and biomechanical devices has led to the promotion of examining biological phenomena. Monitoring multicellular aggregates and tumor spheroids in a microfluidic system is an elaborate way to determine the characteristics of cancerous tumors. In this paper, such system is numerically investigated to study tumor growth. A modified model for tumor growth procedure based on diffusion of crucial nutrients as well as the formation of quiescent and necrotic zones and their retarding impact on the growth is presented. Assuming spherical symmetry for the spheroidal tumor growth, when it is exposed to unlimited stationary culture medium, the effects of two essential nutrients, i.e., glucose and oxygen, on the tumor growth has been studied and compared to one another. Moreover, the growth of 3D spheroidal tumor, which is exposed to the culture medium fluid flow in a microfluidic system containing an array of microwell traps is studied. Further, for the first time, the formation of necrotic and quiescent zones and their inhibitory influences on the in-microwell-trapped cellular aggregates have been demonstrated. The simulation was done under a specific culture medium flow rate for several days in order to observe the effect of nutrient concentration deficiency on the tumor growth. The results indicate that the glucose concentration is the key item to predict the onset of the quiescent zone in comparison with the oxygen concentration. However, the oxygen concentration determines the formation of the necrotic core. Subsequently, the results state that the tumor growth rate in the microfluidic device is lower than the static culture medium.      

  • Tissue Engineering in Tissue Repair
Speaker
Biography:

Abstract:

Injury and diseases that affect articular cartilage present a daunting challenge in orthopedic medicine. During the onset of injury or disease, low oxygen environments decrease healthy cartilage cell growth and regeneration. Ultimately, this environment reduces the efficacy of traditional biomaterial scaffolds to provide a regenerative interface. Our research group has developed a therapeutic injectable hydrogel that provides a regenerative interface for cartilage tissue engineering via a cell-protective mechanism. Using Poly(Nvinylcaprolactam)[PVCL] a smart biomaterial that changes its molecular orientation upon temperature change along with its mechanical properties in conjunction with other natural products. This hydrogel composite, containing PVCL-hyaluronic acid-therapeutic (PVC-HA-TH) affords a robust hydrogel with tunable (lower critical solution temperature) [LCST] parameters near physiological temperature. Hydrogels were synthesized and used in vitro static cell culture studies and in vivo studies. Using 3D printing, hydrogels were also fabricated to compare the effect of material properties on cell proliferation and metabolism on extra cellular matrix (ECM) proteins. Fetal bovine chondrocytes were harvested and seeded [or 3D bioprinted] into various formulations of PVCLHA-TH under normoxia (21%) and hypoxia (1%) low oxygen conditions. Chondrocyte cell viability at 1% O2 levels remained higher than that of 20% O2 levels in PVCL-HA for each time point. PVCL-HA hydrogels reached a maximum of 89% on the third day of observance. Higher cell viability was also noted on meHA samples at 1% O2 levels than at 20% O2 levels, with the peak value at 74% on the first day of observance. Animal studies were performed for 30 days after injection of therapeutic hydrogels into the defective knee joint confirm higher amounts of chondrocyte cloning within the murine joint. This work shows promise in providing a cyto-protective biomaterial construct that will begin to regenerate diseased articular cartilage.