Monica Boffito | Politecnico di Torino (original) (raw)

Papers by Monica Boffito

Journal of Biomedical Materials Research Part A

Biomaterials should be mechanically tested at both the nano- and macro-scale under conditions sim... more Biomaterials should be mechanically tested at both the nano- and macro-scale under conditions simulating their working state, either in vitro or in vivo, in order to confirm their applicability in tissue engineering applications. In this paper, polyester-urethane-based films and porous scaffolds produced by hot pressing and thermally induced phase separation respectively, were mechanically characterised at both the macro- and nano-scale by tensile tests and indentation-type atomic force microscopy (IT-AFM). All tests were conducted in wet state with the final aim of simulating scaffold real operating conditions. The films showed two distinct Young Moduli populations which can be ascribed to polyurethane hard and soft segments. In the scaffold, the application of a thermal cooling gradient during phase separation was responsible for a nanoscale polymer chain organisation in a preferred direction. At the macroscale, the porous matrices showed a Young Modulus of about 1.5 MPa in dry co...

Journal of Nanoparticle Research, 2012

A novel biodegradable material belonging to the class of polyester-urethanes (PURs), based on pol... more A novel biodegradable material belonging to the class of polyester-urethanes (PURs), based on poly(e-caprolactone) (PCL) blocks, was proposed as matrix-forming material for the preparation of nanoparticles by the solvent displacement method. This method has been widely applied to prepare nanoparticles with reproducible, small size with commercially available polyesters or polyester-polyether copolymers. These carriers often displayed fast and poorly controllable release rates. In response to these problems we proposed the insertion of polyesters into a more complex microstructure, such as that of polyurethanes, characterized by the alternation of hard and soft segments, in order to modulate and control the degradation rate and release profiles. PCL-based PUR (C-BC2000) was synthesized according to a two step synthesis procedure. Commercial PCL and poly(D, L lactide) (PLA) were used as controls; and paclitaxel, a potent anti-neoplastic drug, was encapsulated inside all carriers. Carriers prepared with the new material showed no intrinsic cytotoxicity (A-431 cells), with similar size in the range 211-226 nm and surface charge as the commercial controls. Moreover, C-BC2000 nanoparticles exhibited a slightly faster degradation rate, a much higher encapsulation efficiency (89 % against 24 % and 18 % for PLA and PCL, respectively) and a longer and more controlled release profile. This study highlighted the possibility to successfully employ biodegradable polyurethanes to prepare particles for controlled drug delivery, suggesting further and extensive investigation on the introduction of different PUR formulations in this field.

Polymer International, 2016

Journal of Biomedical Materials Research Part B Applied Biomaterials

The production of efficient heart patches for myocardium repair requires the use of biomaterials ... more The production of efficient heart patches for myocardium repair requires the use of biomaterials with high elastomeric properties and controllable biodegradability. To fulfil these design criteria we propose biodegradable poly(ester urethanes) and poly(ether ester urethanes) from poly(ɛ-caprolactone) (PCL) and poly(ethylene glycol) (PEG) as macrodiols, 1,4-diisocyanatobutane as diisocyanate, l-Lysine Ethyl Ester and Alanine-Alanine-Lysine (AAK) as chain extenders. This peptide was used to tune biodegradability properties, since the Alanine-Alanine sequence is a target for the elastase enzyme. Enzymatic degradation tests demonstrated the feasibility of tuning biodegradability properties due to the introduction of AAK peptide in polyurethane backbone. Two formulations have been processed into porous scaffolds by Thermally-Induced Phase Separation (TIPS). Scanning Electron Microscopy micrographs revealed promising microstructures, which were characterized by stretched and unidirectiona...

Macromolecular Bioscience

One of the main challenges in tissue engineering/regenerative medicine (TERM) is the repair of da... more One of the main challenges in tissue engineering/regenerative medicine (TERM) is the repair of damaged heart tissue, avoiding or minimizing ventricular remodeling which leads to ventricular dilatation and hypertrophy, sphericity increase, and functionality loss. Several approaches have been described to restore or enhance the contractility of the failing heart. One of them is based on the fabrication of 3D substrates that can be implanted in the infarcted area to provide an efficient support to the regenerative process. This review focuses on the strategies adopted to design and realize polymeric scaffolds for heart TERM. The implementation of different polymers and the design of scaffold architecture are described.

Journal of Biomedical Materials Research Part A, 2014

This review focuses on the challenges associated with the design and development of injectable hy... more This review focuses on the challenges associated with the design and development of injectable hydrogels of synthetic origin based on FDA approved blocks, such as polyethylene glycol (PEG) and poly(ɛ-caprolactone) (PCL). An overview of recent studies on inverse thermosensitive PEG/PCL hydrogels is provided. These systems have been proposed to overcome the limitations of previously introduced degradable thermosensitive hydrogels [e.g., PEG/poly(lactide-co-glycolic acid) hydrogels]. PEG/PCL hydrogels are advantageous due to their higher gel strength, slower degradation rate and availability in powder form. Particularly, triblock PEG/PCL copolymers have been widely investigated, with PCL-PEG-PCL (PCEC) hydrogels showing superior gel strength and slower degradation kinetics than PEG-PCL-PEG (PECE) hydrogels. Compared to triblock PEG/PCL copolymers, concentrated solutions of multiblock PEG/PCL copolymers were stable due to their slower crystallization rate. However, the resulting hydrogel gel strength was low. Inverse thermosensitive triblock PEG/PCL hydrogels have been mainly applied in tissue engineering, to decrease tissue adherence or, in combination with bioactive molecules, to promote tissue regeneration. They have also found application as in situ drug delivery carriers. On the other hand, the wide potentialities of multiblock PEG/PCL hydrogels, associated with the stability of their water-based solutions under storage, their higher degradation time compared to triblock copolymer hydrogels and the possibility to insert bioactive building blocks along the copolymer chains, have not been fully exploited yet. A critical discussion is provided to highlight advantages and limitations of currently developed themosensitive PEG/PCL hydrogels, suggesting future strategies for the realization of PEG/PCL-based copolymers with improved performance in the different application fields.

ABSTRACT In this work, novel strategies for the design and characterization of complex nanosized ... more ABSTRACT In this work, novel strategies for the design and characterization of complex nanosized drug delivery systems for the release of different formulations were proposed and investigated. Natural or synthetic polymers, such as chitosan, poly (D,L lactide) (PLA) and proprietary polyesterurethanes, were used to prepare carriers for different applications in nanomedicine.

Reactive and Functional Polymers, 2013

Polymer International, 2014

Cardiac tissue engineering (TE) is an emerging field, whose main goal is the development of innov... more Cardiac tissue engineering (TE) is an emerging field, whose main goal is the development of innovative strategies for the treatment of heart diseases, with the aim of overcoming the drawbacks of traditional therapies. One of these strategies involves the implantation of three-dimensional matrices (scaffolds) capable of supporting tissue formation. Scaffolds designed and fabricated for such application should meet several requirements, concerning both the scaffold-forming materials and the properties of the scaffold itself. A scaffold for cardiac TE should be biocompatible and biodegradable, mimic the properties of the native cardiac tissue, provide a mechanical support to the regenerating heart and possess an interconnected porous structure to favour cell migration, nutrient and oxygen diffusion, and waste removal. Moreover, the mimesis of myocardium characteristic anisotropy is attracting increasing interest to provide engineered constructs with the possibility to be structurally and mechanically integrated in native tissue. Several conventional and non-conventional fabrication techniques have been explored in the literature to produce polymeric scaffolds meeting all these requirements. This review describes these techniques, with a focus on their advantages and disadvantages, and their flexibility, with the final goal of providing the reader with the primal knowledge necessary to develop an effective strategy in cardiac TE.

Macromolecular Bioscience, 2013

One of the main challenges in tissue engineering/regenerative medicine (TERM) is the repair of da... more One of the main challenges in tissue engineering/regenerative medicine (TERM) is the repair of damaged heart tissue, avoiding or minimizing ventricular remodeling which leads to ventricular dilatation and hypertrophy, sphericity increase, and functionality loss. Several approaches have been described to restore or enhance the contractility of the failing heart. One of them is based on the fabrication of 3D substrates that can be implanted in the infarcted area to provide an efficient support to the regenerative process. This review focuses on the strategies adopted to design and realize polymeric scaffolds for heart TERM. The implementation of different polymers and the design of scaffold architecture are described.

Journal of Nanoparticle Research, 2012

A novel biodegradable material belonging to the class of polyester-urethanes (PURs), based on pol... more A novel biodegradable material belonging to the class of polyester-urethanes (PURs), based on poly(e-caprolactone) (PCL) blocks, was proposed as matrix-forming material for the preparation of nanoparticles by the solvent displacement method. This method has been widely applied to prepare nanoparticles with reproducible, small size with commercially available polyesters or polyester-polyether copolymers. These carriers often displayed fast and poorly controllable release rates. In response to these problems we proposed the insertion of polyesters into a more complex microstructure, such as that of polyurethanes, characterized by the alternation of hard and soft segments, in order to modulate and control the degradation rate and release profiles. PCL-based PUR (C-BC2000) was synthesized according to a two step synthesis procedure. Commercial PCL and poly(D, L lactide) (PLA) were used as controls; and paclitaxel, a potent anti-neoplastic drug, was encapsulated inside all carriers. Carriers prepared with the new material showed no intrinsic cytotoxicity (A-431 cells), with similar size in the range 211-226 nm and surface charge as the commercial controls. Moreover, C-BC2000 nanoparticles exhibited a slightly faster degradation rate, a much higher encapsulation efficiency (89 % against 24 % and 18 % for PLA and PCL, respectively) and a longer and more controlled release profile. This study highlighted the possibility to successfully employ biodegradable polyurethanes to prepare particles for controlled drug delivery, suggesting further and extensive investigation on the introduction of different PUR formulations in this field.

Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2013

Journal of Biomedical Materials Research Part A

Biomaterials should be mechanically tested at both the nano- and macro-scale under conditions sim... more Biomaterials should be mechanically tested at both the nano- and macro-scale under conditions simulating their working state, either in vitro or in vivo, in order to confirm their applicability in tissue engineering applications. In this paper, polyester-urethane-based films and porous scaffolds produced by hot pressing and thermally induced phase separation respectively, were mechanically characterised at both the macro- and nano-scale by tensile tests and indentation-type atomic force microscopy (IT-AFM). All tests were conducted in wet state with the final aim of simulating scaffold real operating conditions. The films showed two distinct Young Moduli populations which can be ascribed to polyurethane hard and soft segments. In the scaffold, the application of a thermal cooling gradient during phase separation was responsible for a nanoscale polymer chain organisation in a preferred direction. At the macroscale, the porous matrices showed a Young Modulus of about 1.5 MPa in dry co...

Journal of Nanoparticle Research, 2012

A novel biodegradable material belonging to the class of polyester-urethanes (PURs), based on pol... more A novel biodegradable material belonging to the class of polyester-urethanes (PURs), based on poly(e-caprolactone) (PCL) blocks, was proposed as matrix-forming material for the preparation of nanoparticles by the solvent displacement method. This method has been widely applied to prepare nanoparticles with reproducible, small size with commercially available polyesters or polyester-polyether copolymers. These carriers often displayed fast and poorly controllable release rates. In response to these problems we proposed the insertion of polyesters into a more complex microstructure, such as that of polyurethanes, characterized by the alternation of hard and soft segments, in order to modulate and control the degradation rate and release profiles. PCL-based PUR (C-BC2000) was synthesized according to a two step synthesis procedure. Commercial PCL and poly(D, L lactide) (PLA) were used as controls; and paclitaxel, a potent anti-neoplastic drug, was encapsulated inside all carriers. Carriers prepared with the new material showed no intrinsic cytotoxicity (A-431 cells), with similar size in the range 211-226 nm and surface charge as the commercial controls. Moreover, C-BC2000 nanoparticles exhibited a slightly faster degradation rate, a much higher encapsulation efficiency (89 % against 24 % and 18 % for PLA and PCL, respectively) and a longer and more controlled release profile. This study highlighted the possibility to successfully employ biodegradable polyurethanes to prepare particles for controlled drug delivery, suggesting further and extensive investigation on the introduction of different PUR formulations in this field.

Polymer International, 2016

Journal of Biomedical Materials Research Part B Applied Biomaterials

The production of efficient heart patches for myocardium repair requires the use of biomaterials ... more The production of efficient heart patches for myocardium repair requires the use of biomaterials with high elastomeric properties and controllable biodegradability. To fulfil these design criteria we propose biodegradable poly(ester urethanes) and poly(ether ester urethanes) from poly(ɛ-caprolactone) (PCL) and poly(ethylene glycol) (PEG) as macrodiols, 1,4-diisocyanatobutane as diisocyanate, l-Lysine Ethyl Ester and Alanine-Alanine-Lysine (AAK) as chain extenders. This peptide was used to tune biodegradability properties, since the Alanine-Alanine sequence is a target for the elastase enzyme. Enzymatic degradation tests demonstrated the feasibility of tuning biodegradability properties due to the introduction of AAK peptide in polyurethane backbone. Two formulations have been processed into porous scaffolds by Thermally-Induced Phase Separation (TIPS). Scanning Electron Microscopy micrographs revealed promising microstructures, which were characterized by stretched and unidirectiona...

Macromolecular Bioscience

One of the main challenges in tissue engineering/regenerative medicine (TERM) is the repair of da... more One of the main challenges in tissue engineering/regenerative medicine (TERM) is the repair of damaged heart tissue, avoiding or minimizing ventricular remodeling which leads to ventricular dilatation and hypertrophy, sphericity increase, and functionality loss. Several approaches have been described to restore or enhance the contractility of the failing heart. One of them is based on the fabrication of 3D substrates that can be implanted in the infarcted area to provide an efficient support to the regenerative process. This review focuses on the strategies adopted to design and realize polymeric scaffolds for heart TERM. The implementation of different polymers and the design of scaffold architecture are described.

Journal of Biomedical Materials Research Part A, 2014

This review focuses on the challenges associated with the design and development of injectable hy... more This review focuses on the challenges associated with the design and development of injectable hydrogels of synthetic origin based on FDA approved blocks, such as polyethylene glycol (PEG) and poly(ɛ-caprolactone) (PCL). An overview of recent studies on inverse thermosensitive PEG/PCL hydrogels is provided. These systems have been proposed to overcome the limitations of previously introduced degradable thermosensitive hydrogels [e.g., PEG/poly(lactide-co-glycolic acid) hydrogels]. PEG/PCL hydrogels are advantageous due to their higher gel strength, slower degradation rate and availability in powder form. Particularly, triblock PEG/PCL copolymers have been widely investigated, with PCL-PEG-PCL (PCEC) hydrogels showing superior gel strength and slower degradation kinetics than PEG-PCL-PEG (PECE) hydrogels. Compared to triblock PEG/PCL copolymers, concentrated solutions of multiblock PEG/PCL copolymers were stable due to their slower crystallization rate. However, the resulting hydrogel gel strength was low. Inverse thermosensitive triblock PEG/PCL hydrogels have been mainly applied in tissue engineering, to decrease tissue adherence or, in combination with bioactive molecules, to promote tissue regeneration. They have also found application as in situ drug delivery carriers. On the other hand, the wide potentialities of multiblock PEG/PCL hydrogels, associated with the stability of their water-based solutions under storage, their higher degradation time compared to triblock copolymer hydrogels and the possibility to insert bioactive building blocks along the copolymer chains, have not been fully exploited yet. A critical discussion is provided to highlight advantages and limitations of currently developed themosensitive PEG/PCL hydrogels, suggesting future strategies for the realization of PEG/PCL-based copolymers with improved performance in the different application fields.

ABSTRACT In this work, novel strategies for the design and characterization of complex nanosized ... more ABSTRACT In this work, novel strategies for the design and characterization of complex nanosized drug delivery systems for the release of different formulations were proposed and investigated. Natural or synthetic polymers, such as chitosan, poly (D,L lactide) (PLA) and proprietary polyesterurethanes, were used to prepare carriers for different applications in nanomedicine.

Reactive and Functional Polymers, 2013

Polymer International, 2014

Cardiac tissue engineering (TE) is an emerging field, whose main goal is the development of innov... more Cardiac tissue engineering (TE) is an emerging field, whose main goal is the development of innovative strategies for the treatment of heart diseases, with the aim of overcoming the drawbacks of traditional therapies. One of these strategies involves the implantation of three-dimensional matrices (scaffolds) capable of supporting tissue formation. Scaffolds designed and fabricated for such application should meet several requirements, concerning both the scaffold-forming materials and the properties of the scaffold itself. A scaffold for cardiac TE should be biocompatible and biodegradable, mimic the properties of the native cardiac tissue, provide a mechanical support to the regenerating heart and possess an interconnected porous structure to favour cell migration, nutrient and oxygen diffusion, and waste removal. Moreover, the mimesis of myocardium characteristic anisotropy is attracting increasing interest to provide engineered constructs with the possibility to be structurally and mechanically integrated in native tissue. Several conventional and non-conventional fabrication techniques have been explored in the literature to produce polymeric scaffolds meeting all these requirements. This review describes these techniques, with a focus on their advantages and disadvantages, and their flexibility, with the final goal of providing the reader with the primal knowledge necessary to develop an effective strategy in cardiac TE.

Macromolecular Bioscience, 2013

One of the main challenges in tissue engineering/regenerative medicine (TERM) is the repair of da... more One of the main challenges in tissue engineering/regenerative medicine (TERM) is the repair of damaged heart tissue, avoiding or minimizing ventricular remodeling which leads to ventricular dilatation and hypertrophy, sphericity increase, and functionality loss. Several approaches have been described to restore or enhance the contractility of the failing heart. One of them is based on the fabrication of 3D substrates that can be implanted in the infarcted area to provide an efficient support to the regenerative process. This review focuses on the strategies adopted to design and realize polymeric scaffolds for heart TERM. The implementation of different polymers and the design of scaffold architecture are described.

Journal of Nanoparticle Research, 2012

A novel biodegradable material belonging to the class of polyester-urethanes (PURs), based on pol... more A novel biodegradable material belonging to the class of polyester-urethanes (PURs), based on poly(e-caprolactone) (PCL) blocks, was proposed as matrix-forming material for the preparation of nanoparticles by the solvent displacement method. This method has been widely applied to prepare nanoparticles with reproducible, small size with commercially available polyesters or polyester-polyether copolymers. These carriers often displayed fast and poorly controllable release rates. In response to these problems we proposed the insertion of polyesters into a more complex microstructure, such as that of polyurethanes, characterized by the alternation of hard and soft segments, in order to modulate and control the degradation rate and release profiles. PCL-based PUR (C-BC2000) was synthesized according to a two step synthesis procedure. Commercial PCL and poly(D, L lactide) (PLA) were used as controls; and paclitaxel, a potent anti-neoplastic drug, was encapsulated inside all carriers. Carriers prepared with the new material showed no intrinsic cytotoxicity (A-431 cells), with similar size in the range 211-226 nm and surface charge as the commercial controls. Moreover, C-BC2000 nanoparticles exhibited a slightly faster degradation rate, a much higher encapsulation efficiency (89 % against 24 % and 18 % for PLA and PCL, respectively) and a longer and more controlled release profile. This study highlighted the possibility to successfully employ biodegradable polyurethanes to prepare particles for controlled drug delivery, suggesting further and extensive investigation on the introduction of different PUR formulations in this field.

Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2013