Mariacristina Gagliardi - Academia.edu (original) (raw)

Uploads

Papers by Mariacristina Gagliardi

Research paper thumbnail of Polymeric PEGylated nanoparticles as drug carriers: How preparation and loading procedures influence functional properties

Journal of Applied Polymer Science, 2014

ABSTRACT The application of emerging nanotechnologies in medicine showed in the last years a sign... more ABSTRACT The application of emerging nanotechnologies in medicine showed in the last years a significant potential in the improvement of therapies. In particular, polymeric nanocarriers are currently tested to evaluate their capability to reduce side effects, to increase the residence time in the body and also to obtain a controlled release over time. In the present work a novel polymeric nanocarrier was developed and optimized to obtain, with the same chemical formulation, three different typologies of nanocarriers: dense nanospheres loaded with an active molecule (1) during nanoparticle formation and (2) after the preparation and (3) hollow nanocapsules to increase the starting drug payload. Synthetic materials considered were PEGylated acrylic copolymers, folic acid was used as model of a hydrophobic drug. The main aim is to develop an optimized nanocarrier for the transport and the enhanced release of poorly water-soluble drugs. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 41310.

Research paper thumbnail of Relevance of Mesh Dimension Optimization, Geometry Simplification and Discretization Accuracy in the Study of Mechanical Behaviour of Bare Metal Stents

International Journal of Computational Models and Algorithms in Medicine, 2010

In this paper, the authors propose a set of analyses on the deployment of coronary stents by usin... more In this paper, the authors propose a set of analyses on the deployment of coronary stents by using a nonlinear finite element method. The goal is to propose a convergence test able to select the appropriate mesh dimension and a methodology to perform the simplification of structures composed of cyclically repeated units to reduce the number of degrees of freedom and the analysis run time. A systematic study, based on the analysis of seven meshes for each model, was performed, gradually reducing the element dimension. In addition, geometric models were simplified considering symmetries; adequate boundary conditions were applied and verified based on the results obtained from the analysis of the whole model.

Research paper thumbnail of Computational models for the in silico analysis of drug delivery from drug-eluting stents

Therapeutic delivery, 2011

Research paper thumbnail of On the effect of macromolecular composition and drug loading on thermal and tensile mechanical properties of methyl methacrylate and butyl methacrylate copolymers

Polymer Bulletin, 2014

The application of emerging nanotechnologies in medicine showed in the last years a significant p... more The application of emerging nanotechnologies in medicine showed in the last years a significant potential in the improvement of therapies. In particular, polymeric nanocarriers are currently tested to evaluate their capability to reduce side effects, to increase the residence time in the body and also to obtain a controlled release over time. In the present work a novel polymeric nanocarrier was developed and optimized to obtain, with the same chemical formulation, three different typologies of nanocarriers: dense nanospheres loaded with an active molecule (1) during nanoparticle formation and (2) after the preparation and (3) hollow nanocapsules to increase the starting drug payload. Synthetic materials considered were PEGylated acrylic copolymers, folic acid was used as model of a hydrophobic drug. The main aim is to develop an optimized nanocarrier for the transport and the enhanced release of poorly water-soluble drugs.

Research paper thumbnail of In vitro haematic proteins adsorption and cytocompatibility study on acrylic copolymer to realise coatings for drug-eluting stents

Materials Science and Engineering: C, 2012

ABSTRACT In the present paper, a preliminary in vitro analysis of biocompatibility of newly-synth... more ABSTRACT In the present paper, a preliminary in vitro analysis of biocompatibility of newly-synthesised acrylic copolymers is reported. In particular, with the aim to obtain coatings for drug-eluting stents, blood protein absorption and cytocompatibility were studied. For protein absorption tests, bovine serum albumin and bovine plasma fibrinogen were considered. Cytocompatibility was tested using C2C12 cell line as model, analysing the behaviour of polymeric matrices and of drug-eluting systems, obtained loading polymeric matrices with paclitaxel, an anti-mitotic drug, in order to evaluate the efficacy of a pharmacological treatment locally administered from these materials. Results showed that the amount of albumin absorbed was greater than the amount of fibrinogen (comprised in the range of 70%–85% and 10%–22% respectively) and it is a good behaviour in terms of haemocompatibility. Cell culture tests showed good adhesion properties and a relative poor proliferation. In addition, a strong effect related to drug elution and a correlation with the macromolecular composition were detected. In this preliminary analysis, tested materials showed good characteristics and can be considered possible candidates to obtain coatings for drug-eluting stents.

Research paper thumbnail of Composites between collagen and hydroxyapatite

Research paper thumbnail of Surface functionalization regulates PAMAM dendrimer toxicity on Blood Brain Barrier cells and the modulation of key inflammatory receptors on microglia

Nanotoxicology

Abstract Dendrimers are branched polymers with spherical morphology. Their tunable chemistry and ... more Abstract Dendrimers are branched polymers with spherical morphology. Their tunable chemistry and surface modification make them valuable nanomaterials for biomedical applications. In view of possible dendrimer uses as brain-aimed nanocarriers we studied amine- and lipid-functionalized (G4) polyamidoamine (PAMAM) biocompatibility with cell population forming the Blood Brain Barrier (BBB). Both PAMAM dendrimers were able to enter endothelial and primary neural cells. However, only amine- PAMAM damaged cell membranes in a dose dependent manner. Transmission electron microscopy (TEM) evidenced the ability of dendrimers to precipitate salts and serum components present in culture medium that slightly increased toxicity of the amine-PAMAM. Amine- and lipid-PAMAM were both able to cross the BBB and differently induced CD11b and CCR2 over-expression on primary CX3CR1-GFP murine microglia in vitro. These data emphasize the role of dendrimer surface functionalization in toxicity and neural im...

Research paper thumbnail of Biomedical Nanoparticles: Overview of Their Surface Immune-Compatibility

Diagnostic-and therapeutic release-aimed nanoparticles require the highest degree of biocompatibi... more Diagnostic-and therapeutic release-aimed nanoparticles require the highest degree of biocompatibility. Some physical and chemical characteristics of such nanomaterials are often at odds with this requirement. For instance, metals with specific features used as contrast agents in magnetic resonance imaging need particular coatings to improve their blood solubility and increase their biocompatibility. Other examples come from the development of nanocarriers exploiting the different characteristics of two or more materials, i.e., the ability to encapsulate a certain drug by one core-material and the targeting capability of a different coating surface. Furthermore, all these "human-non-self" modifications necessitate proofs of compatibility with the immune system to avoid inflammatory reactions and resultant adverse effects for the patient. In the present review we discuss the molecular interactions and responses of the immune system to the principal nanoparticle surface modif...

Research paper thumbnail of Chemical synthesis of a biodegradable PEGylated copolymer from ε-caprolactone and γ-valerolactone: evaluation of reaction and functional properties

Journal of Polymer Research, 2015

This paper reports the chemical synthesis of methoxy poly(ethyleneglycol)-block-poly(ε-caprolacto... more This paper reports the chemical synthesis of methoxy poly(ethyleneglycol)-block-poly(ε-caprolactone-co-4-hydroxyvalerate) from ε-caprolactone and γ-valerolactone, a five-membered ring rarely used in chemical synthesis due to its low reactivity. This procedure enabled production of copolymers with controlled ratios of repeating units and molecular weights, as demonstrated by GPC, FT-IR and NMR characterization. Copolymer degradation rate was found to depend on macromolecular composition, and finely tuneable in a wide range of values. Similarly, hydrophilicity was dependent on γvalerolactone content, and could be accurately controlled by varying the composition of the reaction feed. Importantly, this copolymer showed lower levels of acidic degradation products than other biodegradable polymers, thus resulting in improved biocompatibility. These encouraging results demonstrate the feasibility of the chemical synthesis of a novel and versatile material with interesting properties that fill a gap in the range of commercially available biodegradable polymers.

Research paper thumbnail of Our thanks to all those who have helped with this issue of Therapeutic Delivery. Listed below are authors, referees and others who have kindly given their time, effort and expertise; their generosity has helped establish this publication

Atchison J Aurilio C Baastrup C Barbarisi M Baron R Brett B Canavero S Coates B Cohrs R Connolly ... more Atchison J Aurilio C Baastrup C Barbarisi M Baron R Brett B Canavero S Coates B Cohrs R Connolly M Cope D Coyne P Davis K Dworkin R Erdek M Finnerup N ... Furlan A Gálvez R Gatchel R Ghiasi H Goodchild C Habib A Hans G Hayes K Higa K Hulsebosch C Job C Johnson R ...

Research paper thumbnail of Drug elution of hydrophilic and hydrophobic drugs from biostable acrylic matrices

Research paper thumbnail of Poly (methylmethacrylate-co-butylmethacrylate) copolymer from monomer-starved seeded semi-batch reaction for biomedical use

Research paper thumbnail of Study of drug release mechanisms from PLGA/PHBHV bi-layered biodegradable polymeric matrices

Research paper thumbnail of Molecularly Imprinted Scaffolds For Tissue Growth Technology

Research paper thumbnail of NON CONVENTIONAL SURFACE FUNCTIONALIZATION OF POROUS POLY-ε-CAPROLACTONE SCAFFOLDS USING BIOACTIVE MOLECULARLY IMPRINTED NANOSPHERES

Research paper thumbnail of Targeted drug delivery across biological barriers using polymer nanoparticles

Research paper thumbnail of Chitosan-Based Macromolecular Biomaterials for the Regeneration of Chondroskeletal and Nerve Tissue

Research paper thumbnail of Polymeric nanocarriers for controlled and enhanced delivery of therapeutic agents to the CNS

The development of drug-loaded nanocarriers to vehiculate active principles to a target site is a... more The development of drug-loaded nanocarriers to vehiculate active principles to a target site is an emerging topic in the field of nanoscience. Recently, several systems have been developed for the treatment of various neurological disorders. The main advantages of using nanocarriers are: protection of the active principle from the biological environment; enhanced transport through biological barriers; and targeted transport to specific cells or tissues, with the final goal to improve efficacy and safety of the pharmacological treatment. All these characteristics are related to the extreme versatility of nanocarriers, which can be functionalized and designed to be responsive to external stimuli [1, 2] . Nanocarriers provide a promising approach for the delivery of various agents, including drugs [3], proteins Polymeric nanocarriers for controlled and enhanced delivery of therapeutic agents to the CNS Polymeric nanocarriers are versatile structures that can be engineered to obtain high drug loading, good delivery yields and tunable release kinetics. Moreover, the particle surface can be modiied for selective targeting of organs or tissues. In particular, polymeric nanocarriers can be conjugated with functional groups promoting translocation through the blood-brain barrier, thus providing a promising system to deliver therapeutic agents and/or diagnostic probes to the brain. Here we review recent literature on the preparation and characterization of polymeric nanoparticles as potential agents for drug delivery to the CNS, with an emphasis on materials chemistry and functionalization strategies for improved selectivity and delivery. Finally, we underline the immunotoxicological aspects of this class of nanostructured materials in view of potential clinical applications.

Research paper thumbnail of Biomedical Nanoparticles: Overview of Their Surface Immune-Compatibility

Coatings, 2014

Diagnostic-and therapeutic release-aimed nanoparticles require the highest degree of biocompatibi... more Diagnostic-and therapeutic release-aimed nanoparticles require the highest degree of biocompatibility. Some physical and chemical characteristics of such nanomaterials are often at odds with this requirement. For instance, metals with specific features used as contrast agents in magnetic resonance imaging need particular coatings to improve their blood solubility and increase their biocompatibility. Other examples come from the development of nanocarriers exploiting the different characteristics of two or more materials, i.e., the ability to encapsulate a certain drug by one core-material and the targeting capability of a different coating surface. Furthermore, all these "human-non-self" modifications necessitate proofs of compatibility with the immune system to avoid inflammatory reactions and resultant adverse effects for the patient. In the present review we discuss the molecular interactions and responses of the immune system to the principal nanoparticle surface modifications used in nanomedicine.

Research paper thumbnail of Controlled Release of the Anti-cancer Drug Paclitaxel from Bioresorbable Poly (ester-ether-ester) Microspheres

wseas.us

... UOS of Pisa; 2Department of Chemical Engineering 1Italian National Research Council (CNR), 2U... more ... UOS of Pisa; 2Department of Chemical Engineering 1Italian National Research Council (CNR), 2University of Pisa 1,2Largo Lucio Lazzarino, I ... 13. P. Cerrai, GD Guerra, M. Tricoli, A. Krajewski, S. Guicciardi, A. Ravaglioli, S. Maltinti, G. Masetti, New Composites of Hydroxyapatite ...

Research paper thumbnail of Polymeric PEGylated nanoparticles as drug carriers: How preparation and loading procedures influence functional properties

Journal of Applied Polymer Science, 2014

ABSTRACT The application of emerging nanotechnologies in medicine showed in the last years a sign... more ABSTRACT The application of emerging nanotechnologies in medicine showed in the last years a significant potential in the improvement of therapies. In particular, polymeric nanocarriers are currently tested to evaluate their capability to reduce side effects, to increase the residence time in the body and also to obtain a controlled release over time. In the present work a novel polymeric nanocarrier was developed and optimized to obtain, with the same chemical formulation, three different typologies of nanocarriers: dense nanospheres loaded with an active molecule (1) during nanoparticle formation and (2) after the preparation and (3) hollow nanocapsules to increase the starting drug payload. Synthetic materials considered were PEGylated acrylic copolymers, folic acid was used as model of a hydrophobic drug. The main aim is to develop an optimized nanocarrier for the transport and the enhanced release of poorly water-soluble drugs. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 41310.

Research paper thumbnail of Relevance of Mesh Dimension Optimization, Geometry Simplification and Discretization Accuracy in the Study of Mechanical Behaviour of Bare Metal Stents

International Journal of Computational Models and Algorithms in Medicine, 2010

In this paper, the authors propose a set of analyses on the deployment of coronary stents by usin... more In this paper, the authors propose a set of analyses on the deployment of coronary stents by using a nonlinear finite element method. The goal is to propose a convergence test able to select the appropriate mesh dimension and a methodology to perform the simplification of structures composed of cyclically repeated units to reduce the number of degrees of freedom and the analysis run time. A systematic study, based on the analysis of seven meshes for each model, was performed, gradually reducing the element dimension. In addition, geometric models were simplified considering symmetries; adequate boundary conditions were applied and verified based on the results obtained from the analysis of the whole model.

Research paper thumbnail of Computational models for the in silico analysis of drug delivery from drug-eluting stents

Therapeutic delivery, 2011

Research paper thumbnail of On the effect of macromolecular composition and drug loading on thermal and tensile mechanical properties of methyl methacrylate and butyl methacrylate copolymers

Polymer Bulletin, 2014

The application of emerging nanotechnologies in medicine showed in the last years a significant p... more The application of emerging nanotechnologies in medicine showed in the last years a significant potential in the improvement of therapies. In particular, polymeric nanocarriers are currently tested to evaluate their capability to reduce side effects, to increase the residence time in the body and also to obtain a controlled release over time. In the present work a novel polymeric nanocarrier was developed and optimized to obtain, with the same chemical formulation, three different typologies of nanocarriers: dense nanospheres loaded with an active molecule (1) during nanoparticle formation and (2) after the preparation and (3) hollow nanocapsules to increase the starting drug payload. Synthetic materials considered were PEGylated acrylic copolymers, folic acid was used as model of a hydrophobic drug. The main aim is to develop an optimized nanocarrier for the transport and the enhanced release of poorly water-soluble drugs.

Research paper thumbnail of In vitro haematic proteins adsorption and cytocompatibility study on acrylic copolymer to realise coatings for drug-eluting stents

Materials Science and Engineering: C, 2012

ABSTRACT In the present paper, a preliminary in vitro analysis of biocompatibility of newly-synth... more ABSTRACT In the present paper, a preliminary in vitro analysis of biocompatibility of newly-synthesised acrylic copolymers is reported. In particular, with the aim to obtain coatings for drug-eluting stents, blood protein absorption and cytocompatibility were studied. For protein absorption tests, bovine serum albumin and bovine plasma fibrinogen were considered. Cytocompatibility was tested using C2C12 cell line as model, analysing the behaviour of polymeric matrices and of drug-eluting systems, obtained loading polymeric matrices with paclitaxel, an anti-mitotic drug, in order to evaluate the efficacy of a pharmacological treatment locally administered from these materials. Results showed that the amount of albumin absorbed was greater than the amount of fibrinogen (comprised in the range of 70%–85% and 10%–22% respectively) and it is a good behaviour in terms of haemocompatibility. Cell culture tests showed good adhesion properties and a relative poor proliferation. In addition, a strong effect related to drug elution and a correlation with the macromolecular composition were detected. In this preliminary analysis, tested materials showed good characteristics and can be considered possible candidates to obtain coatings for drug-eluting stents.

Research paper thumbnail of Composites between collagen and hydroxyapatite

Research paper thumbnail of Surface functionalization regulates PAMAM dendrimer toxicity on Blood Brain Barrier cells and the modulation of key inflammatory receptors on microglia

Nanotoxicology

Abstract Dendrimers are branched polymers with spherical morphology. Their tunable chemistry and ... more Abstract Dendrimers are branched polymers with spherical morphology. Their tunable chemistry and surface modification make them valuable nanomaterials for biomedical applications. In view of possible dendrimer uses as brain-aimed nanocarriers we studied amine- and lipid-functionalized (G4) polyamidoamine (PAMAM) biocompatibility with cell population forming the Blood Brain Barrier (BBB). Both PAMAM dendrimers were able to enter endothelial and primary neural cells. However, only amine- PAMAM damaged cell membranes in a dose dependent manner. Transmission electron microscopy (TEM) evidenced the ability of dendrimers to precipitate salts and serum components present in culture medium that slightly increased toxicity of the amine-PAMAM. Amine- and lipid-PAMAM were both able to cross the BBB and differently induced CD11b and CCR2 over-expression on primary CX3CR1-GFP murine microglia in vitro. These data emphasize the role of dendrimer surface functionalization in toxicity and neural im...

Research paper thumbnail of Biomedical Nanoparticles: Overview of Their Surface Immune-Compatibility

Diagnostic-and therapeutic release-aimed nanoparticles require the highest degree of biocompatibi... more Diagnostic-and therapeutic release-aimed nanoparticles require the highest degree of biocompatibility. Some physical and chemical characteristics of such nanomaterials are often at odds with this requirement. For instance, metals with specific features used as contrast agents in magnetic resonance imaging need particular coatings to improve their blood solubility and increase their biocompatibility. Other examples come from the development of nanocarriers exploiting the different characteristics of two or more materials, i.e., the ability to encapsulate a certain drug by one core-material and the targeting capability of a different coating surface. Furthermore, all these "human-non-self" modifications necessitate proofs of compatibility with the immune system to avoid inflammatory reactions and resultant adverse effects for the patient. In the present review we discuss the molecular interactions and responses of the immune system to the principal nanoparticle surface modif...

Research paper thumbnail of Chemical synthesis of a biodegradable PEGylated copolymer from ε-caprolactone and γ-valerolactone: evaluation of reaction and functional properties

Journal of Polymer Research, 2015

This paper reports the chemical synthesis of methoxy poly(ethyleneglycol)-block-poly(ε-caprolacto... more This paper reports the chemical synthesis of methoxy poly(ethyleneglycol)-block-poly(ε-caprolactone-co-4-hydroxyvalerate) from ε-caprolactone and γ-valerolactone, a five-membered ring rarely used in chemical synthesis due to its low reactivity. This procedure enabled production of copolymers with controlled ratios of repeating units and molecular weights, as demonstrated by GPC, FT-IR and NMR characterization. Copolymer degradation rate was found to depend on macromolecular composition, and finely tuneable in a wide range of values. Similarly, hydrophilicity was dependent on γvalerolactone content, and could be accurately controlled by varying the composition of the reaction feed. Importantly, this copolymer showed lower levels of acidic degradation products than other biodegradable polymers, thus resulting in improved biocompatibility. These encouraging results demonstrate the feasibility of the chemical synthesis of a novel and versatile material with interesting properties that fill a gap in the range of commercially available biodegradable polymers.

Research paper thumbnail of Our thanks to all those who have helped with this issue of Therapeutic Delivery. Listed below are authors, referees and others who have kindly given their time, effort and expertise; their generosity has helped establish this publication

Atchison J Aurilio C Baastrup C Barbarisi M Baron R Brett B Canavero S Coates B Cohrs R Connolly ... more Atchison J Aurilio C Baastrup C Barbarisi M Baron R Brett B Canavero S Coates B Cohrs R Connolly M Cope D Coyne P Davis K Dworkin R Erdek M Finnerup N ... Furlan A Gálvez R Gatchel R Ghiasi H Goodchild C Habib A Hans G Hayes K Higa K Hulsebosch C Job C Johnson R ...

Research paper thumbnail of Drug elution of hydrophilic and hydrophobic drugs from biostable acrylic matrices

Research paper thumbnail of Poly (methylmethacrylate-co-butylmethacrylate) copolymer from monomer-starved seeded semi-batch reaction for biomedical use

Research paper thumbnail of Study of drug release mechanisms from PLGA/PHBHV bi-layered biodegradable polymeric matrices

Research paper thumbnail of Molecularly Imprinted Scaffolds For Tissue Growth Technology

Research paper thumbnail of NON CONVENTIONAL SURFACE FUNCTIONALIZATION OF POROUS POLY-ε-CAPROLACTONE SCAFFOLDS USING BIOACTIVE MOLECULARLY IMPRINTED NANOSPHERES

Research paper thumbnail of Targeted drug delivery across biological barriers using polymer nanoparticles

Research paper thumbnail of Chitosan-Based Macromolecular Biomaterials for the Regeneration of Chondroskeletal and Nerve Tissue

Research paper thumbnail of Polymeric nanocarriers for controlled and enhanced delivery of therapeutic agents to the CNS

The development of drug-loaded nanocarriers to vehiculate active principles to a target site is a... more The development of drug-loaded nanocarriers to vehiculate active principles to a target site is an emerging topic in the field of nanoscience. Recently, several systems have been developed for the treatment of various neurological disorders. The main advantages of using nanocarriers are: protection of the active principle from the biological environment; enhanced transport through biological barriers; and targeted transport to specific cells or tissues, with the final goal to improve efficacy and safety of the pharmacological treatment. All these characteristics are related to the extreme versatility of nanocarriers, which can be functionalized and designed to be responsive to external stimuli [1, 2] . Nanocarriers provide a promising approach for the delivery of various agents, including drugs [3], proteins Polymeric nanocarriers for controlled and enhanced delivery of therapeutic agents to the CNS Polymeric nanocarriers are versatile structures that can be engineered to obtain high drug loading, good delivery yields and tunable release kinetics. Moreover, the particle surface can be modiied for selective targeting of organs or tissues. In particular, polymeric nanocarriers can be conjugated with functional groups promoting translocation through the blood-brain barrier, thus providing a promising system to deliver therapeutic agents and/or diagnostic probes to the brain. Here we review recent literature on the preparation and characterization of polymeric nanoparticles as potential agents for drug delivery to the CNS, with an emphasis on materials chemistry and functionalization strategies for improved selectivity and delivery. Finally, we underline the immunotoxicological aspects of this class of nanostructured materials in view of potential clinical applications.

Research paper thumbnail of Biomedical Nanoparticles: Overview of Their Surface Immune-Compatibility

Coatings, 2014

Diagnostic-and therapeutic release-aimed nanoparticles require the highest degree of biocompatibi... more Diagnostic-and therapeutic release-aimed nanoparticles require the highest degree of biocompatibility. Some physical and chemical characteristics of such nanomaterials are often at odds with this requirement. For instance, metals with specific features used as contrast agents in magnetic resonance imaging need particular coatings to improve their blood solubility and increase their biocompatibility. Other examples come from the development of nanocarriers exploiting the different characteristics of two or more materials, i.e., the ability to encapsulate a certain drug by one core-material and the targeting capability of a different coating surface. Furthermore, all these "human-non-self" modifications necessitate proofs of compatibility with the immune system to avoid inflammatory reactions and resultant adverse effects for the patient. In the present review we discuss the molecular interactions and responses of the immune system to the principal nanoparticle surface modifications used in nanomedicine.

Research paper thumbnail of Controlled Release of the Anti-cancer Drug Paclitaxel from Bioresorbable Poly (ester-ether-ester) Microspheres

wseas.us

... UOS of Pisa; 2Department of Chemical Engineering 1Italian National Research Council (CNR), 2U... more ... UOS of Pisa; 2Department of Chemical Engineering 1Italian National Research Council (CNR), 2University of Pisa 1,2Largo Lucio Lazzarino, I ... 13. P. Cerrai, GD Guerra, M. Tricoli, A. Krajewski, S. Guicciardi, A. Ravaglioli, S. Maltinti, G. Masetti, New Composites of Hydroxyapatite ...