Background: Agrifood waste products are often considered rich sources of bioactive compounds that... more Background: Agrifood waste products are often considered rich sources of bioactive compounds that can be conveniently recovered. Due to these peculiar characteristics, the study of these waste products is attracting great interest in nutraceutical research. Olive mill wastewaters (OMWWs) are generated by extra virgin olive oil (EVOO) production, and they pose environmental challenges due to their disposal. This study aimed to characterize the polyphenolic profile and to evaluate the nutraceutical properties of OMWW extracts from two Tuscan olive cultivars, Leccino (CL) and Frantoio (CF), collected during different time points in EVOO production. Method: After a liquid–liquid extraction, the HPLC and LC–MS/MS analysis of OMWW extracts confirmed the presence of 18 polyphenolic compounds. Results: The polyphenol composition varied between the cultivars and during maturation stages. Notably, oleacein was detected at remarkably high levels in CL1 and CF1 extracts (314.628 ± 19.535 and 22...
The delivery of drugs through the skin barrier at a predetermined rate is the aim of transdermal ... more The delivery of drugs through the skin barrier at a predetermined rate is the aim of transdermal drug delivery systems (TDDSs). However, so far, TDDS has not fully attained its potential as an alternative to hypodermic injections and oral delivery. In this study, we presented a proof of concept of a dual drug-loaded patch made of nanoparticles (NPs) and ultrafine fibers fabricated by using one equipment, i.e., the electrospinning apparatus. Such NP/fiber systems can be useful to release drugs locally through the skin and the tympanic membrane. Briefly, dexamethasone (DEX)-loaded poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBHV) fiber meshes were decorated with rhodamine (RHO)-loaded poly(lactic-co-glycolic acid) (PLGA) NPs, with RHO representing as a second drug model. By properly tuning the working parameters of electrospinning, DEX-loaded PHBHV fibers (i.e., by electrospinning mode) and RHO-loaded PLGA NPs (i.e., by electrospray mode) were successfully prepared and straightforw...
The aim of this study was to investigate the effect of different types of nanocellulose, i.e., ce... more The aim of this study was to investigate the effect of different types of nanocellulose, i.e., cellulose nanocrystal (CNC), cellulose nanofiber (CNF) and bacterial nanocellulose (BNC), and also different drying methods (oven-drying and freeze-drying) on the properties of acrylic acid (AA)/sodium alginate (SA) super absorbent polymers (SAPs). In addition, the presence of ammonium per sulfate as an initiator and N-N methylene-bis-acrylamide as a cross-linker were considered. Synthesized SAPs were characterized by Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). The absorption and rheological properties (i.e., storage modulus and loss modulus) were also investigated. The results of FTIR spectroscopy demonstrated several types of interactions, such as hydrogen and esterification, between SA, AA and nanocellulose. SEM analysis revealed a microporous structure in the SAPs. All SAPs had a centrifuge retention capacity (CRC)/free swelling capacity (FSC)...
Three-dimensional scaffold-based culture has been increasingly gaining influence in oncology as a... more Three-dimensional scaffold-based culture has been increasingly gaining influence in oncology as a therapeutic strategy for tumors with a high relapse percentage. This study aims to evaluate electrospun poly(ε-caprolactone) (PCL) and poly(lactic acid) (PLA) scaffolds to create a 3D model of colorectal adenocarcinoma. Specifically, the physico-mechanical and morphological properties of PCL and PLA electrospun fiber meshes collected at different drum velocities, i.e., 500 rpm, 1000 rpm and 2500 rpm, were assessed. Fiber size, mesh porosity, pore size distribution, water contact angle and tensile mechanical properties were investigated. Caco-2 cells were cultured on the produced PCL and PLA scaffolds for 7 days, demonstrating good cell viability and metabolic activity in all the scaffolds. A cross-analysis of the cell–scaffold interactions with morphological, mechanical and surface characterizations of the different electrospun fiber meshes was carried out, showing an opposite trend of ...
Frontiers in Bioengineering and Biotechnology, 2021
Perforation is the most common illness of the tympanic membrane (TM), which is commonly treated w... more Perforation is the most common illness of the tympanic membrane (TM), which is commonly treated with surgical procedures. The success rate of the treatment could be improved by novel bioengineering approaches. In fact, a successful restoration of a damaged TM needs a supporting biomaterial or scaffold able to meet mechano-acoustic properties similar to those of the native TM, along with optimal biocompatibility. Traditionally, a large number of biological-based materials, including paper, silk, Gelfoam®, hyaluronic acid, collagen, and chitosan, have been used for TM repair. A novel biopolymer with promising features for tissue engineering applications is cellulose. It is a highly biocompatible, mechanically and chemically strong polysaccharide, abundant in the environment, with the ability to promote cellular growth and differentiation. Bacterial cellulose (BC), in particular, is produced by microorganisms as a nanofibrous three-dimensional structure of highly pure cellulose, which ...
Engineering Technologies and Clinical Translation, 2022
Abstract Immunotherapy is a relatively newer and promising strategy to combat cancer compared wit... more Abstract Immunotherapy is a relatively newer and promising strategy to combat cancer compared with traditional chemotherapy and radiotherapy strategies. The immune responses are often suppressed in the tumor microenvironment and immunotherapy can be applied to activate or enhance the host immune system response to attack and destroy tumor cells. However, immunotherapy applications by themselves are often associated with low response rates; thus, combination therapies are needed to result in effective anticancer treatments. In this chapter, we discuss the nanoscale biomaterial-based strategies, namely, nanoparticles, to deliver combined immunotherapy and chemotherapy, which enable synergistic effect on anticancer therapy. Moreover, we focus the attention on microrobots/nanorobots (MNRs) that have been employed for drug delivery as potential innovative carriers for immunotherapy and chemotherapy. MNRs are promising solutions for drug delivery applications as they can more precisely access parts of the body that are hard to reach without affecting healthy tissues.
Journal of biomedical materials research. Part B, Applied biomaterials, Jan 23, 2016
This study shows the fabrication of innovative ossicular replacement prostheses (ORPs) based on b... more This study shows the fabrication of innovative ossicular replacement prostheses (ORPs) based on banked cortical bone using computer numerically controlled ultraprecision micromilling, as a substantial improvement of "second generation" ORPs. Our aim is to combine optimal middle ear compatibility and surgical manageability in a single device, by releasing off-the-shelf homograft ORPs provided with the appealing features of synthetic ORPs, such as lightness, safety, measurement accuracy, surface decoration, and geometric plasticity. The new total ORP prototype was 13.1 ± 0.1 mg, leading to 81% weight reduction with respect to the previous model. Surface motifs of the head plate were applied to prevent slipping and migration after surgery, as shown by finite element modeling analysis. In addition, bone ORPs were provided with holed head plates to facilitate their surgical positioning while reducing their mass. A comparative measurement of acoustic responses of bone against sy...
As a recent product of nanotechnology, nanoscale transducers have been invoked as revolutionary t... more As a recent product of nanotechnology, nanoscale transducers have been invoked as revolutionary tools of interaction between the macroscopic and the microscopic worlds, which can most probably offer their best intriguing opportunities in sensing and acting on the living matter at the level of its basilar subunits. This chapter briefly revises the main concepts related to the function and applications of transducers, going from macro-to-microscale, in order to promote the full comprehension of the spill over deriving from the future exploitation of boron nitride nanotubes (BNNTs) as bionanotransducers. BNNTs are piezoelectric nanomaterials. As such, they are entitled to reversibly transform mechanical into electrical energy in the micro domain. This chapter is mainly focused on the application of these nanotubes as bionanoactuators; in particular, the findings of a novel method that exploits ultrasounds as a mechanical energy for BNNT triggering at intracellular level is reviewed and discussed. BNNT nanotransducers are capable of stimulating electrically sensitive cells, such as neural, muscular, and bony cells, thus paving the way to the development of novel therapies for functional impairments and degenerative diseases.
The Annals of otology, rhinology, and laryngology, 2011
The aim of this study was the fabrication of ossicular replacement prostheses (ORPs) from decellu... more The aim of this study was the fabrication of ossicular replacement prostheses (ORPs) from decellularized banked cortical bone via computer numerically controlled (CNC) ultraprecision micromilling, in order to obtain preformed clinical-grade tissue products, reproducing shape, size, and details perfectly comparable to those of synthetic devices. Banked femoral compact bone was used to fabricate partial and total ORPs via CNC micromilling according to Good Manufacturing Practices procedures. Drawings of ORPs with different shapes and sizes were uploaded to the computer interface, and different surface-finish parameters were tested. The obtained products underwent dimensional, weight, and surface characterizations. A histologic analysis was pursued to compare the bone matrix compactness of the produced ORPs to that of the ear ossicles. Banked-bone ORPs were produced with high dimensional accuracy. Partial ORP weights averaged (+/- SD) 31.2 +/- 0.6 mg, and total ORP weights averaged 69....
10th IEEE International Conference on Nanotechnology, 2010
... A. Nanoparticle dispersion and characterization Gianni Ciofani, Leonardo Ricotti, Arianna Men... more ... A. Nanoparticle dispersion and characterization Gianni Ciofani, Leonardo Ricotti, Arianna Menciassi and Virgilio Mattoli are with the Italian Institute of Technology c/o Scuola Superiore SantГAnna, Viale Rinaldo Piaggio, 34, 56025 Pontedera (Pisa), Italy. ...
Journal of Biomedical Materials Research Part A, 2006
Tissue regeneration with autologous cell transplantation is one of the most important goals in cl... more Tissue regeneration with autologous cell transplantation is one of the most important goals in clinical research. In this field, the development of bioactive materials that provide microenvironments for cell–matrix interactions mimicking biological conditions is required. In recent years, many synthetic materials have been developed as scaffolds and many procedures for the surface modification of these materials have been applied using biological molecules. In this study, we analyzed the morphology and the molecule production by ovine embryonic lung fibroblasts cultured on three different sponge‐like matrices based on poly(L‐lactic acid) (PLLA): agarose/PLLA, crosslinked and uncrosslinked gelatin/PLLA. The matrices were produced by using an emulsion freeze‐drying method leading to the formation of sponge‐like materials with high porosity and with interconnection between the pores. In vitro MTT test demonstrated that transplanted cells were viable and metabolically active. Morphologi...
Background: Agrifood waste products are often considered rich sources of bioactive compounds that... more Background: Agrifood waste products are often considered rich sources of bioactive compounds that can be conveniently recovered. Due to these peculiar characteristics, the study of these waste products is attracting great interest in nutraceutical research. Olive mill wastewaters (OMWWs) are generated by extra virgin olive oil (EVOO) production, and they pose environmental challenges due to their disposal. This study aimed to characterize the polyphenolic profile and to evaluate the nutraceutical properties of OMWW extracts from two Tuscan olive cultivars, Leccino (CL) and Frantoio (CF), collected during different time points in EVOO production. Method: After a liquid–liquid extraction, the HPLC and LC–MS/MS analysis of OMWW extracts confirmed the presence of 18 polyphenolic compounds. Results: The polyphenol composition varied between the cultivars and during maturation stages. Notably, oleacein was detected at remarkably high levels in CL1 and CF1 extracts (314.628 ± 19.535 and 22...
The delivery of drugs through the skin barrier at a predetermined rate is the aim of transdermal ... more The delivery of drugs through the skin barrier at a predetermined rate is the aim of transdermal drug delivery systems (TDDSs). However, so far, TDDS has not fully attained its potential as an alternative to hypodermic injections and oral delivery. In this study, we presented a proof of concept of a dual drug-loaded patch made of nanoparticles (NPs) and ultrafine fibers fabricated by using one equipment, i.e., the electrospinning apparatus. Such NP/fiber systems can be useful to release drugs locally through the skin and the tympanic membrane. Briefly, dexamethasone (DEX)-loaded poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBHV) fiber meshes were decorated with rhodamine (RHO)-loaded poly(lactic-co-glycolic acid) (PLGA) NPs, with RHO representing as a second drug model. By properly tuning the working parameters of electrospinning, DEX-loaded PHBHV fibers (i.e., by electrospinning mode) and RHO-loaded PLGA NPs (i.e., by electrospray mode) were successfully prepared and straightforw...
The aim of this study was to investigate the effect of different types of nanocellulose, i.e., ce... more The aim of this study was to investigate the effect of different types of nanocellulose, i.e., cellulose nanocrystal (CNC), cellulose nanofiber (CNF) and bacterial nanocellulose (BNC), and also different drying methods (oven-drying and freeze-drying) on the properties of acrylic acid (AA)/sodium alginate (SA) super absorbent polymers (SAPs). In addition, the presence of ammonium per sulfate as an initiator and N-N methylene-bis-acrylamide as a cross-linker were considered. Synthesized SAPs were characterized by Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). The absorption and rheological properties (i.e., storage modulus and loss modulus) were also investigated. The results of FTIR spectroscopy demonstrated several types of interactions, such as hydrogen and esterification, between SA, AA and nanocellulose. SEM analysis revealed a microporous structure in the SAPs. All SAPs had a centrifuge retention capacity (CRC)/free swelling capacity (FSC)...
Three-dimensional scaffold-based culture has been increasingly gaining influence in oncology as a... more Three-dimensional scaffold-based culture has been increasingly gaining influence in oncology as a therapeutic strategy for tumors with a high relapse percentage. This study aims to evaluate electrospun poly(ε-caprolactone) (PCL) and poly(lactic acid) (PLA) scaffolds to create a 3D model of colorectal adenocarcinoma. Specifically, the physico-mechanical and morphological properties of PCL and PLA electrospun fiber meshes collected at different drum velocities, i.e., 500 rpm, 1000 rpm and 2500 rpm, were assessed. Fiber size, mesh porosity, pore size distribution, water contact angle and tensile mechanical properties were investigated. Caco-2 cells were cultured on the produced PCL and PLA scaffolds for 7 days, demonstrating good cell viability and metabolic activity in all the scaffolds. A cross-analysis of the cell–scaffold interactions with morphological, mechanical and surface characterizations of the different electrospun fiber meshes was carried out, showing an opposite trend of ...
Frontiers in Bioengineering and Biotechnology, 2021
Perforation is the most common illness of the tympanic membrane (TM), which is commonly treated w... more Perforation is the most common illness of the tympanic membrane (TM), which is commonly treated with surgical procedures. The success rate of the treatment could be improved by novel bioengineering approaches. In fact, a successful restoration of a damaged TM needs a supporting biomaterial or scaffold able to meet mechano-acoustic properties similar to those of the native TM, along with optimal biocompatibility. Traditionally, a large number of biological-based materials, including paper, silk, Gelfoam®, hyaluronic acid, collagen, and chitosan, have been used for TM repair. A novel biopolymer with promising features for tissue engineering applications is cellulose. It is a highly biocompatible, mechanically and chemically strong polysaccharide, abundant in the environment, with the ability to promote cellular growth and differentiation. Bacterial cellulose (BC), in particular, is produced by microorganisms as a nanofibrous three-dimensional structure of highly pure cellulose, which ...
Engineering Technologies and Clinical Translation, 2022
Abstract Immunotherapy is a relatively newer and promising strategy to combat cancer compared wit... more Abstract Immunotherapy is a relatively newer and promising strategy to combat cancer compared with traditional chemotherapy and radiotherapy strategies. The immune responses are often suppressed in the tumor microenvironment and immunotherapy can be applied to activate or enhance the host immune system response to attack and destroy tumor cells. However, immunotherapy applications by themselves are often associated with low response rates; thus, combination therapies are needed to result in effective anticancer treatments. In this chapter, we discuss the nanoscale biomaterial-based strategies, namely, nanoparticles, to deliver combined immunotherapy and chemotherapy, which enable synergistic effect on anticancer therapy. Moreover, we focus the attention on microrobots/nanorobots (MNRs) that have been employed for drug delivery as potential innovative carriers for immunotherapy and chemotherapy. MNRs are promising solutions for drug delivery applications as they can more precisely access parts of the body that are hard to reach without affecting healthy tissues.
Journal of biomedical materials research. Part B, Applied biomaterials, Jan 23, 2016
This study shows the fabrication of innovative ossicular replacement prostheses (ORPs) based on b... more This study shows the fabrication of innovative ossicular replacement prostheses (ORPs) based on banked cortical bone using computer numerically controlled ultraprecision micromilling, as a substantial improvement of "second generation" ORPs. Our aim is to combine optimal middle ear compatibility and surgical manageability in a single device, by releasing off-the-shelf homograft ORPs provided with the appealing features of synthetic ORPs, such as lightness, safety, measurement accuracy, surface decoration, and geometric plasticity. The new total ORP prototype was 13.1 ± 0.1 mg, leading to 81% weight reduction with respect to the previous model. Surface motifs of the head plate were applied to prevent slipping and migration after surgery, as shown by finite element modeling analysis. In addition, bone ORPs were provided with holed head plates to facilitate their surgical positioning while reducing their mass. A comparative measurement of acoustic responses of bone against sy...
As a recent product of nanotechnology, nanoscale transducers have been invoked as revolutionary t... more As a recent product of nanotechnology, nanoscale transducers have been invoked as revolutionary tools of interaction between the macroscopic and the microscopic worlds, which can most probably offer their best intriguing opportunities in sensing and acting on the living matter at the level of its basilar subunits. This chapter briefly revises the main concepts related to the function and applications of transducers, going from macro-to-microscale, in order to promote the full comprehension of the spill over deriving from the future exploitation of boron nitride nanotubes (BNNTs) as bionanotransducers. BNNTs are piezoelectric nanomaterials. As such, they are entitled to reversibly transform mechanical into electrical energy in the micro domain. This chapter is mainly focused on the application of these nanotubes as bionanoactuators; in particular, the findings of a novel method that exploits ultrasounds as a mechanical energy for BNNT triggering at intracellular level is reviewed and discussed. BNNT nanotransducers are capable of stimulating electrically sensitive cells, such as neural, muscular, and bony cells, thus paving the way to the development of novel therapies for functional impairments and degenerative diseases.
The Annals of otology, rhinology, and laryngology, 2011
The aim of this study was the fabrication of ossicular replacement prostheses (ORPs) from decellu... more The aim of this study was the fabrication of ossicular replacement prostheses (ORPs) from decellularized banked cortical bone via computer numerically controlled (CNC) ultraprecision micromilling, in order to obtain preformed clinical-grade tissue products, reproducing shape, size, and details perfectly comparable to those of synthetic devices. Banked femoral compact bone was used to fabricate partial and total ORPs via CNC micromilling according to Good Manufacturing Practices procedures. Drawings of ORPs with different shapes and sizes were uploaded to the computer interface, and different surface-finish parameters were tested. The obtained products underwent dimensional, weight, and surface characterizations. A histologic analysis was pursued to compare the bone matrix compactness of the produced ORPs to that of the ear ossicles. Banked-bone ORPs were produced with high dimensional accuracy. Partial ORP weights averaged (+/- SD) 31.2 +/- 0.6 mg, and total ORP weights averaged 69....
10th IEEE International Conference on Nanotechnology, 2010
... A. Nanoparticle dispersion and characterization Gianni Ciofani, Leonardo Ricotti, Arianna Men... more ... A. Nanoparticle dispersion and characterization Gianni Ciofani, Leonardo Ricotti, Arianna Menciassi and Virgilio Mattoli are with the Italian Institute of Technology c/o Scuola Superiore SantГAnna, Viale Rinaldo Piaggio, 34, 56025 Pontedera (Pisa), Italy. ...
Journal of Biomedical Materials Research Part A, 2006
Tissue regeneration with autologous cell transplantation is one of the most important goals in cl... more Tissue regeneration with autologous cell transplantation is one of the most important goals in clinical research. In this field, the development of bioactive materials that provide microenvironments for cell–matrix interactions mimicking biological conditions is required. In recent years, many synthetic materials have been developed as scaffolds and many procedures for the surface modification of these materials have been applied using biological molecules. In this study, we analyzed the morphology and the molecule production by ovine embryonic lung fibroblasts cultured on three different sponge‐like matrices based on poly(L‐lactic acid) (PLLA): agarose/PLLA, crosslinked and uncrosslinked gelatin/PLLA. The matrices were produced by using an emulsion freeze‐drying method leading to the formation of sponge‐like materials with high porosity and with interconnection between the pores. In vitro MTT test demonstrated that transplanted cells were viable and metabolically active. Morphologi...
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