Rossella Calabrese | Tufts University (original) (raw)

Papers by Rossella Calabrese

Research paper thumbnail of Amphyphilic Derivatives Between Hyaluronic Acid and Polylactic Acid

… ANNUAL MEETING & …, 2006

Research paper thumbnail of Sintesi di nuovi copolimeri graft di acido ialuronico,polietilenglicole ed acido lattico

Research paper thumbnail of PREPARAZIONE E CARATTERIZZAZIONE DI UN NUOVO IDROGEL pH-SENSIBILE E BIODEGRADABILE PER IL RILASCIO COLON-SPECIFICO DI FARMACI

Research paper thumbnail of Tunable Interfacial Properties in Silk Ionomer Microcapsules with Tailored Multilayer Interactions

Macromolecular bioscience, Jan 13, 2018

Microencapsulation techniques represent a critical step in realizing highly controlled transport ... more Microencapsulation techniques represent a critical step in realizing highly controlled transport of functional materials in multiphase systems. The first demonstration of microcapsules prepared from minimally grafted silk ionomers (silk fibroin modified with cationic/anionic charge groups) are presented here. These tailored biomacromolecules have shown significantly increased biocompatibility over traditional polyelectrolytes and heavily grafted silk ionomers, but the low grafting density had previously limited attempts to fabricate stable microcapsules. In addition, the first microcapsules from polyethylene-glycol-grafted silk ionomers are fabricated and the corresponding impact on microcapsule behavior is demonstrated. The materials are shown to exhibit pH-responsive properties, with the microcapsules demonstrating an approx. tenfold decrease in stiffness and an approx. threefold change in diffusion coefficient when moving from acidic to basic buffer. Finally, the effect of assemb...

Research paper thumbnail of Interfacial Shear Strength and Adhesive Behavior of Silk Ionomer Surfaces

Biomacromolecules, 2017

The interfacial shear strength between different layers in multi-layered structures of layerby-la... more The interfacial shear strength between different layers in multi-layered structures of layerby-layer (LbL) microcapsules is a crucial mechanical property to ensure their robustness. In this work, we investigated the interfacial shear strength of modified silk fibroin ionomers utilized in LbL shells, an ionic-cationic pair with complimentary ionic pairing, (SF)-poly-Lglutamic acid (Glu) and SF-poly-L-lysine (Lys) and a complementary pair with partially screened Coulombic interactions due to the presence of poly(ethylene glycol) (PEG) segments, SF-Glu/SF-Lys[PEG] pair. Shearing and adhesive behavior between these silk ionomer surfaces in the swollen state were probed at different spatial scales and pressure ranges by using functionalized atomic force microscopy (AFM) tips as well as functionalized colloidal probes. The results show that both approaches were consistent in analyzing the interfacial shear strength of LbL silk ionomers at different spatial scales from a nanoscale to a fraction of a micron. Surprisingly, the interfacial shear strength between SF-Glu and SF-Lys[PEG] pair with partially screened ionic pairing was greater than the interfacial shear strength of the SF-Glu and SF-Lys pair with a high density of complementary ionic groups. The difference in interfacial shear strength and adhesive strength is suggested to be predominantly facilitated by the interlayer hydrogen bonding of complementary aminoacids and overlap of highly swollen PEG segments.

Research paper thumbnail of Silk Microsheets with Controlled Actuating Behavior: Experimental Analysis and Computer Simulations

ACS applied materials & interfaces, Jan 16, 2016

The micro-scaled self-rolling constructs sheets from silk protein material have been fabricated s... more The micro-scaled self-rolling constructs sheets from silk protein material have been fabricated silk bimorph composed of silk ionomers as an active layer and crosslinked silk β-sheet as the passive layer. The programmable morphology was experimentally explored along with a computational simulation to understand the mechanism of shape reconfiguration. The neutron reflectivity shows that active silk ionomers layer undergoes remarkable swelling (eight times increase in thickness) after deprotonation while the passive silk β-sheet retains constant volume under the same conditions and support the bimorph construct. This selective swelling within the silk-on-silk bimorph microsheets generates strong interfacial stress between layers and out-of-plane forces, which trigger autonomous self-rolling into various 3D constructs with such as tubules, helical tubules. The experimental observations and computational modeling confirmed the role of interfacial stresses and allow programming the morph...

Research paper thumbnail of Silk-ionomer and silk-tropoelastin hydrogels as charged three-dimensional culture platforms for the regulation of hMSC response

Journal of Tissue Engineering and Regenerative Medicine, 2016

The response of human bone marrow-derived mesenchymal stem cells (hMSCs) encapsulated in three-di... more The response of human bone marrow-derived mesenchymal stem cells (hMSCs) encapsulated in three-dimensional (3D) charged protein hydrogels was studied. Combining silk fibroin (S) with recombinant human tropoelastin (E) or silk ionomers (I) provided protein composite alloys with tunable physicochemical and biological features for regulating the bioactivity of encapsulated hMSCs. The effects of the biomaterial charges on hMSC viability, proliferation and chondrogenic or osteogenic differentiation were assessed. The silk-tropoelastin or silk-ionomers hydrogels supported hMSC viability, proliferation and differentiation. Gene expression of markers for chondrogenesis and osteogenesis, as well as biochemical and histological analysis, showed that hydrogels with different S/E and S/I ratios had different effects on cell fate. The negatively charged hydrogels upregulated hMSC chondrogenesis or osteogenesis, with or without specific differentiation media, and hydrogels with higher tropoelastin content inhibited the differentiation potential even in the presence of the differentiation media. The results provide insight on charge-tunable features of protein-based biomaterials to control hMSC differentiation in 3D hydrogels, as well as providing a new set of hydrogels for the compatible encapsulation and utility for cell functions.

Research paper thumbnail of Self-(Un)rolling Biopolymer Microstructures: Rings, Tubules, and Helical Tubules from the Same Material

Angewandte Chemie International Edition, 2015

Figure 4. Reversibles elf-rolling/unrolling behavior of silk-on-silk sheets with various geometri... more Figure 4. Reversibles elf-rolling/unrolling behavior of silk-on-silk sheets with various geometries (rectangular sheets shown in (a) and (d);1 5 8 8 parallelograms shown in (b) and (e). a, b) CLSM images of reversible "opened" sheets at pH 5.5 and d, e) corresponding microtubules under basic conditions.

Research paper thumbnail of Printed Dual Cell Arrays for Multiplexed Sensing

ACS Biomaterials Science & Engineering, 2015

We demonstrated inkjet printing of large-scale dual-type encapsulated bacterial cell arrays for p... more We demonstrated inkjet printing of large-scale dual-type encapsulated bacterial cell arrays for prospective multiplexing sensing. The dual cell arrays were constructed based on two types of bioengineered E. coli cells hosting fluorescent reporters (green-GFPa1 and red-turboRFP) capable to detect different target chemicals. The versatility of inkjet printing allows for the fabrication of uniform multilayered confined structures composed of silk ionomers that served as nests for in-printing different cells. Furthermore, sequential encapsulation of "red" and "green" cells in microscopic silk nest arrays with the preservation of their function allowed for facile confinement of cells into microscopic silk nests, where cells retained dual red-green response to mixed analyte environment. Whole-cell dual arrays immobilized in microscopic biocompatible silk matrices were readily activated after prolonged storage (up to 3 months, ambient conditions), showing red-green pattern and demonstrating an effective prototype of robust and long-living multiplexed biosensors for field applications.

Research paper thumbnail of Titane et soie

Research paper thumbnail of Silk Macromolecules with Amino Acid-Poly(Ethylene Glycol) Grafts for Controlling Layer-by-Layer Encapsulation and Aggregation of Recombinant Bacterial Cells

ACS nano, Jan 24, 2015

This study introduces double-brush designs of functionalized silk polyelectrolytes based upon reg... more This study introduces double-brush designs of functionalized silk polyelectrolytes based upon regenerated silk fibroin (SF), which is modified with poly-l-lysine (SF-PLL), poly-l-glutamic acid (SF-PGA), and poly(ethylene glycol) (PEG) side chains with different grafting architecture and variable amino acid-PEG graft composition for cell encapsulation. The molecular weight of poly amino acids (length of side chains), molecular weight and degree of PEG grafting (D) were varied in order to assess the formation of cytocompatible and robust layer-by-layer (LbL) shells on two types of bacterial cells (Gram-negative and Gram-positive bacteria). We observed that shells assembled with charged polycationic amino acids adversely effected the properties of microbial cells while promoting the formation of large cell aggregates. In contrast, hydrogen-bonded shells with high PEG grafting density were the most cytocompatible, while promoting formation of stable colloidal suspensions of individual c...

Research paper thumbnail of Robust microcapsules with controlled permeability from silk fibroin reinforced with graphene oxide

Small (Weinheim an der Bergstrasse, Germany), Jan 29, 2014

Robust and stable microcapsules are assembled from poly-amino acid-modified silk fibroin reinforc... more Robust and stable microcapsules are assembled from poly-amino acid-modified silk fibroin reinforced with graphene oxide flakes using layer-by-layer (LbL) assembly, based on biocompatible natural protein and carbon nanosheets. The composite microcapsules are extremely stable in acidic (pH 2.0) and basic (pH 11.5) conditions, accompanied with pH-triggered permeability, which facilitates the controllable encapsulation and release of macromolecules. Furthermore, the graphene oxide incorporated into ultrathin LbL shells induces greatly reinforced mechanical properties, with an elastic modulus which is two orders of magnitude higher than the typical values of original silk LbL shells and shows a significant, three-fold reduction in pore size. Such strong nanocomposite microcapsules can provide solid protection of encapsulated cargo under harsh conditions, indicating a promising candidate with controllable loading/unloading for drug delivery, reinforcement, and bioengineering applications.

Research paper thumbnail of Polysaccharide/polyaminoacid composite scaffolds for modified DNA release

International Journal of Pharmaceutics, 2009

In this work composite polymeric films or sponges, based on hyaluronic acid (HA) covalently cross... more In this work composite polymeric films or sponges, based on hyaluronic acid (HA) covalently crosslinked with ␣,␤-poly(N-2-hydroxyethyl)(2-aminoethylcarbamate)-d,l-aspartamide (PE), have been prepared and characterized as local gene delivery systems. In particular, HA/PE scaffolds have been loaded with PE/DNA interpolyelectrolyte complexes, employing PE as a macromolecular crosslinker for HA and as a non-viral vector for DNA. In vitro studies showed that HA/PE films and sponges have high compatibility with human dermal fibroblasts and they give a sustained DNA release, whose trend can be easily tailored by varying the crosslinking ratio between HA and PE. Electrophoresis analysis and transfection studies on B16-F10 cells revealed that DNA is released as a complex with PE and it retains its bioactivity.

Research paper thumbnail of Polysaccharide/polyaminoacid composite scaffolds for modified DNA release

International Journal of Pharmaceutics, 2009

In this work composite polymeric films or sponges, based on hyaluronic acid (HA) covalently cross... more In this work composite polymeric films or sponges, based on hyaluronic acid (HA) covalently crosslinked with ␣,␤-poly(N-2-hydroxyethyl)(2-aminoethylcarbamate)-d,l-aspartamide (PE), have been prepared and characterized as local gene delivery systems. In particular, HA/PE scaffolds have been loaded with PE/DNA interpolyelectrolyte complexes, employing PE as a macromolecular crosslinker for HA and as a non-viral vector for DNA. In vitro studies showed that HA/PE films and sponges have high compatibility with human dermal fibroblasts and they give a sustained DNA release, whose trend can be easily tailored by varying the crosslinking ratio between HA and PE. Electrophoresis analysis and transfection studies on B16-F10 cells revealed that DNA is released as a complex with PE and it retains its bioactivity.

Research paper thumbnail of Hydrogels for Potential Colon Drug Release by Thiol-ene Conjugate Addition of a New Inulin Derivative

Macromolecular Bioscience, 2008

Research paper thumbnail of Fluorinated derivatives of a polyaspartamide bearing polyethylene glycol chains as oxygen carriers

Journal of Fluorine Chemistry, 2008

Research paper thumbnail of Crosslinked hyaluronan with a protein-like polymer: Novel bioresorbable films for biomedical applications

Journal of Biomedical Materials Research Part A, 2007

In this work, novel hydrogel films based on hyaluronan (HA) chemically crosslinked with the a,b-p... more In this work, novel hydrogel films based on hyaluronan (HA) chemically crosslinked with the a,b-poly(N-2-hydroxyethyl) (2-aminoethylcarbamate)-D,L-aspartamide (PHEA-EDA) were produced by solution casting method. The goal was to exploit both the biological key role of HA in tissue repair and regeneration, and the versatility of a synthetic protein-like polymer as the PHEA-EDA, in order to obtain biomaterials with physicochemical and biological properties suitable for a clinical use. By varying the molar ratio between the PHEA-EDA amino groups and HA carboxyl groups, three different films were obtained and characterized. Particularly FTIR, swelling, hydrolysis, and enzymatic degradation studies were performed. In addition, the cytocompatibility of HA/PHEA-EDA hydrogel films was evaluated using human derm fibroblasts, by means of MTT and trypan blue exclusion assays. The high swelling capability, the long-term hydrolysis resistance, and the resistance to hyaluronidase greater than that of only HA, together with the cell compatibility, have suggested the potential application of these novel HA-based hydrogel films in the biomedical field of tissue engineering.

Research paper thumbnail of Characteristics of platelet gels combined with silk

Biomaterials, 2014

Platelet gel, a fibrin network containing activated platelets, is widely used in regenerative med... more Platelet gel, a fibrin network containing activated platelets, is widely used in regenerative medicine due the capacity of platelet-derived growth factors to accelerate and direct healing processes. However, limitations to this approach include poor mechanical properties, relatively rapid degradation, and the lack of control of release of growth factors at the site of injection. These issues compromise the ability of platelet gels for sustained function in regenerative medicine. In the present study, a combination of platelet gels with silk fibroin gel was studied to address the above limitations. Mixing sonicated silk gels with platelet gels extended the release of growth factors without inhibiting gel forming ability. The released growth factors were biologically active and their delivery was modified further by manipulation of the charge of the silk protein. Moreover, the silk gel augmented both the rheological properties and compressive stiffness of the platelet gel, tuned by the silk concentration and/or silk/platelet gel ratio. Silk-platelet gel injections in nude rats supported enhanced cell infiltration and blood vessel formation representing a step towards new platelet gel formulations with enhanced therapeutic impact.

Research paper thumbnail of Inkjet Printing of Silk Nest Arrays for Cell Hosting

Biomacromolecules, 2014

An inkjet printing approach is presented for the facile fabrication of microscopic arrays of bioc... more An inkjet printing approach is presented for the facile fabrication of microscopic arrays of biocompatible silk "nests" capable of hosting live cells for prospective biosensors. The patterning of silk fibroin nests were constructed by the layer-by-layer (LbL) assembly of silk polyelectrolytes chemically modified with poly-(L-lysine) and poly-(L-glutamic acid) side chains. The inkjet-printed silk circular regions with a characteristic "nest" shape had diameters of 70−100 μm and a thickness several hundred nanometers were stabilized by ionic pairing and by the formation of the silk II crystalline secondary structure. These "locked-in" silk nests remained anchored to the substrate during incubation in cell growth media to provide a biotemplated platform for printing-in, immobilization, encapsulation and growth of cells. The process of inkjet-assisted printing is versatile and can be applied on any type of substrate, including rigid and flexible, with scalability and facile formation.

Research paper thumbnail of Biodegradable and pH-Sensitive Hydrogels for Potential Colon-Specific Drug Delivery: Characterization and In Vitro Release Studies

Biomacromolecules, 2008

A novel pH-sensitive and biodegradable composite hydrogel, based on a methacrylated and succinic ... more A novel pH-sensitive and biodegradable composite hydrogel, based on a methacrylated and succinic derivative of dextran, named Dex-MA-SA, and a methacrylated and succinic derivative of R,-poly(N-2-hydroxyethyl)-DLaspartamide (PHEA), named PHM-SA, was produced by photocross-linking. The goal was to obtain a colonspecific drug delivery system, exploiting both the pH-sensitive behavior and the colon-specific degradability. The hydrogel prepared with a suitable ratio between the polysaccharide and the polyaminoacid was characterized regarding its swelling behavior in gastrointestinal simulated conditions, chemical and enzymatic degradability, interaction with mucin, and cell compatibility on CaCo-2 cells. Moreover, 2-methoxyestradiol was chosen as a model of anticancer drug and release studies, were performed in the absence or in the presence of dextranase and esterase. The obtained hydrogel, due to its pH-sensitive swelling and enzymatic degradability, together with mucoadhesion and cell compatibility, could be potentially useful as system for the oral treatment of colonic cancer.

Research paper thumbnail of Amphyphilic Derivatives Between Hyaluronic Acid and Polylactic Acid

… ANNUAL MEETING & …, 2006

Research paper thumbnail of Sintesi di nuovi copolimeri graft di acido ialuronico,polietilenglicole ed acido lattico

Research paper thumbnail of PREPARAZIONE E CARATTERIZZAZIONE DI UN NUOVO IDROGEL pH-SENSIBILE E BIODEGRADABILE PER IL RILASCIO COLON-SPECIFICO DI FARMACI

Research paper thumbnail of Tunable Interfacial Properties in Silk Ionomer Microcapsules with Tailored Multilayer Interactions

Macromolecular bioscience, Jan 13, 2018

Microencapsulation techniques represent a critical step in realizing highly controlled transport ... more Microencapsulation techniques represent a critical step in realizing highly controlled transport of functional materials in multiphase systems. The first demonstration of microcapsules prepared from minimally grafted silk ionomers (silk fibroin modified with cationic/anionic charge groups) are presented here. These tailored biomacromolecules have shown significantly increased biocompatibility over traditional polyelectrolytes and heavily grafted silk ionomers, but the low grafting density had previously limited attempts to fabricate stable microcapsules. In addition, the first microcapsules from polyethylene-glycol-grafted silk ionomers are fabricated and the corresponding impact on microcapsule behavior is demonstrated. The materials are shown to exhibit pH-responsive properties, with the microcapsules demonstrating an approx. tenfold decrease in stiffness and an approx. threefold change in diffusion coefficient when moving from acidic to basic buffer. Finally, the effect of assemb...

Research paper thumbnail of Interfacial Shear Strength and Adhesive Behavior of Silk Ionomer Surfaces

Biomacromolecules, 2017

The interfacial shear strength between different layers in multi-layered structures of layerby-la... more The interfacial shear strength between different layers in multi-layered structures of layerby-layer (LbL) microcapsules is a crucial mechanical property to ensure their robustness. In this work, we investigated the interfacial shear strength of modified silk fibroin ionomers utilized in LbL shells, an ionic-cationic pair with complimentary ionic pairing, (SF)-poly-Lglutamic acid (Glu) and SF-poly-L-lysine (Lys) and a complementary pair with partially screened Coulombic interactions due to the presence of poly(ethylene glycol) (PEG) segments, SF-Glu/SF-Lys[PEG] pair. Shearing and adhesive behavior between these silk ionomer surfaces in the swollen state were probed at different spatial scales and pressure ranges by using functionalized atomic force microscopy (AFM) tips as well as functionalized colloidal probes. The results show that both approaches were consistent in analyzing the interfacial shear strength of LbL silk ionomers at different spatial scales from a nanoscale to a fraction of a micron. Surprisingly, the interfacial shear strength between SF-Glu and SF-Lys[PEG] pair with partially screened ionic pairing was greater than the interfacial shear strength of the SF-Glu and SF-Lys pair with a high density of complementary ionic groups. The difference in interfacial shear strength and adhesive strength is suggested to be predominantly facilitated by the interlayer hydrogen bonding of complementary aminoacids and overlap of highly swollen PEG segments.

Research paper thumbnail of Silk Microsheets with Controlled Actuating Behavior: Experimental Analysis and Computer Simulations

ACS applied materials & interfaces, Jan 16, 2016

The micro-scaled self-rolling constructs sheets from silk protein material have been fabricated s... more The micro-scaled self-rolling constructs sheets from silk protein material have been fabricated silk bimorph composed of silk ionomers as an active layer and crosslinked silk β-sheet as the passive layer. The programmable morphology was experimentally explored along with a computational simulation to understand the mechanism of shape reconfiguration. The neutron reflectivity shows that active silk ionomers layer undergoes remarkable swelling (eight times increase in thickness) after deprotonation while the passive silk β-sheet retains constant volume under the same conditions and support the bimorph construct. This selective swelling within the silk-on-silk bimorph microsheets generates strong interfacial stress between layers and out-of-plane forces, which trigger autonomous self-rolling into various 3D constructs with such as tubules, helical tubules. The experimental observations and computational modeling confirmed the role of interfacial stresses and allow programming the morph...

Research paper thumbnail of Silk-ionomer and silk-tropoelastin hydrogels as charged three-dimensional culture platforms for the regulation of hMSC response

Journal of Tissue Engineering and Regenerative Medicine, 2016

The response of human bone marrow-derived mesenchymal stem cells (hMSCs) encapsulated in three-di... more The response of human bone marrow-derived mesenchymal stem cells (hMSCs) encapsulated in three-dimensional (3D) charged protein hydrogels was studied. Combining silk fibroin (S) with recombinant human tropoelastin (E) or silk ionomers (I) provided protein composite alloys with tunable physicochemical and biological features for regulating the bioactivity of encapsulated hMSCs. The effects of the biomaterial charges on hMSC viability, proliferation and chondrogenic or osteogenic differentiation were assessed. The silk-tropoelastin or silk-ionomers hydrogels supported hMSC viability, proliferation and differentiation. Gene expression of markers for chondrogenesis and osteogenesis, as well as biochemical and histological analysis, showed that hydrogels with different S/E and S/I ratios had different effects on cell fate. The negatively charged hydrogels upregulated hMSC chondrogenesis or osteogenesis, with or without specific differentiation media, and hydrogels with higher tropoelastin content inhibited the differentiation potential even in the presence of the differentiation media. The results provide insight on charge-tunable features of protein-based biomaterials to control hMSC differentiation in 3D hydrogels, as well as providing a new set of hydrogels for the compatible encapsulation and utility for cell functions.

Research paper thumbnail of Self-(Un)rolling Biopolymer Microstructures: Rings, Tubules, and Helical Tubules from the Same Material

Angewandte Chemie International Edition, 2015

Figure 4. Reversibles elf-rolling/unrolling behavior of silk-on-silk sheets with various geometri... more Figure 4. Reversibles elf-rolling/unrolling behavior of silk-on-silk sheets with various geometries (rectangular sheets shown in (a) and (d);1 5 8 8 parallelograms shown in (b) and (e). a, b) CLSM images of reversible "opened" sheets at pH 5.5 and d, e) corresponding microtubules under basic conditions.

Research paper thumbnail of Printed Dual Cell Arrays for Multiplexed Sensing

ACS Biomaterials Science & Engineering, 2015

We demonstrated inkjet printing of large-scale dual-type encapsulated bacterial cell arrays for p... more We demonstrated inkjet printing of large-scale dual-type encapsulated bacterial cell arrays for prospective multiplexing sensing. The dual cell arrays were constructed based on two types of bioengineered E. coli cells hosting fluorescent reporters (green-GFPa1 and red-turboRFP) capable to detect different target chemicals. The versatility of inkjet printing allows for the fabrication of uniform multilayered confined structures composed of silk ionomers that served as nests for in-printing different cells. Furthermore, sequential encapsulation of "red" and "green" cells in microscopic silk nest arrays with the preservation of their function allowed for facile confinement of cells into microscopic silk nests, where cells retained dual red-green response to mixed analyte environment. Whole-cell dual arrays immobilized in microscopic biocompatible silk matrices were readily activated after prolonged storage (up to 3 months, ambient conditions), showing red-green pattern and demonstrating an effective prototype of robust and long-living multiplexed biosensors for field applications.

Research paper thumbnail of Titane et soie

Research paper thumbnail of Silk Macromolecules with Amino Acid-Poly(Ethylene Glycol) Grafts for Controlling Layer-by-Layer Encapsulation and Aggregation of Recombinant Bacterial Cells

ACS nano, Jan 24, 2015

This study introduces double-brush designs of functionalized silk polyelectrolytes based upon reg... more This study introduces double-brush designs of functionalized silk polyelectrolytes based upon regenerated silk fibroin (SF), which is modified with poly-l-lysine (SF-PLL), poly-l-glutamic acid (SF-PGA), and poly(ethylene glycol) (PEG) side chains with different grafting architecture and variable amino acid-PEG graft composition for cell encapsulation. The molecular weight of poly amino acids (length of side chains), molecular weight and degree of PEG grafting (D) were varied in order to assess the formation of cytocompatible and robust layer-by-layer (LbL) shells on two types of bacterial cells (Gram-negative and Gram-positive bacteria). We observed that shells assembled with charged polycationic amino acids adversely effected the properties of microbial cells while promoting the formation of large cell aggregates. In contrast, hydrogen-bonded shells with high PEG grafting density were the most cytocompatible, while promoting formation of stable colloidal suspensions of individual c...

Research paper thumbnail of Robust microcapsules with controlled permeability from silk fibroin reinforced with graphene oxide

Small (Weinheim an der Bergstrasse, Germany), Jan 29, 2014

Robust and stable microcapsules are assembled from poly-amino acid-modified silk fibroin reinforc... more Robust and stable microcapsules are assembled from poly-amino acid-modified silk fibroin reinforced with graphene oxide flakes using layer-by-layer (LbL) assembly, based on biocompatible natural protein and carbon nanosheets. The composite microcapsules are extremely stable in acidic (pH 2.0) and basic (pH 11.5) conditions, accompanied with pH-triggered permeability, which facilitates the controllable encapsulation and release of macromolecules. Furthermore, the graphene oxide incorporated into ultrathin LbL shells induces greatly reinforced mechanical properties, with an elastic modulus which is two orders of magnitude higher than the typical values of original silk LbL shells and shows a significant, three-fold reduction in pore size. Such strong nanocomposite microcapsules can provide solid protection of encapsulated cargo under harsh conditions, indicating a promising candidate with controllable loading/unloading for drug delivery, reinforcement, and bioengineering applications.

Research paper thumbnail of Polysaccharide/polyaminoacid composite scaffolds for modified DNA release

International Journal of Pharmaceutics, 2009

In this work composite polymeric films or sponges, based on hyaluronic acid (HA) covalently cross... more In this work composite polymeric films or sponges, based on hyaluronic acid (HA) covalently crosslinked with ␣,␤-poly(N-2-hydroxyethyl)(2-aminoethylcarbamate)-d,l-aspartamide (PE), have been prepared and characterized as local gene delivery systems. In particular, HA/PE scaffolds have been loaded with PE/DNA interpolyelectrolyte complexes, employing PE as a macromolecular crosslinker for HA and as a non-viral vector for DNA. In vitro studies showed that HA/PE films and sponges have high compatibility with human dermal fibroblasts and they give a sustained DNA release, whose trend can be easily tailored by varying the crosslinking ratio between HA and PE. Electrophoresis analysis and transfection studies on B16-F10 cells revealed that DNA is released as a complex with PE and it retains its bioactivity.

Research paper thumbnail of Polysaccharide/polyaminoacid composite scaffolds for modified DNA release

International Journal of Pharmaceutics, 2009

In this work composite polymeric films or sponges, based on hyaluronic acid (HA) covalently cross... more In this work composite polymeric films or sponges, based on hyaluronic acid (HA) covalently crosslinked with ␣,␤-poly(N-2-hydroxyethyl)(2-aminoethylcarbamate)-d,l-aspartamide (PE), have been prepared and characterized as local gene delivery systems. In particular, HA/PE scaffolds have been loaded with PE/DNA interpolyelectrolyte complexes, employing PE as a macromolecular crosslinker for HA and as a non-viral vector for DNA. In vitro studies showed that HA/PE films and sponges have high compatibility with human dermal fibroblasts and they give a sustained DNA release, whose trend can be easily tailored by varying the crosslinking ratio between HA and PE. Electrophoresis analysis and transfection studies on B16-F10 cells revealed that DNA is released as a complex with PE and it retains its bioactivity.

Research paper thumbnail of Hydrogels for Potential Colon Drug Release by Thiol-ene Conjugate Addition of a New Inulin Derivative

Macromolecular Bioscience, 2008

Research paper thumbnail of Fluorinated derivatives of a polyaspartamide bearing polyethylene glycol chains as oxygen carriers

Journal of Fluorine Chemistry, 2008

Research paper thumbnail of Crosslinked hyaluronan with a protein-like polymer: Novel bioresorbable films for biomedical applications

Journal of Biomedical Materials Research Part A, 2007

In this work, novel hydrogel films based on hyaluronan (HA) chemically crosslinked with the a,b-p... more In this work, novel hydrogel films based on hyaluronan (HA) chemically crosslinked with the a,b-poly(N-2-hydroxyethyl) (2-aminoethylcarbamate)-D,L-aspartamide (PHEA-EDA) were produced by solution casting method. The goal was to exploit both the biological key role of HA in tissue repair and regeneration, and the versatility of a synthetic protein-like polymer as the PHEA-EDA, in order to obtain biomaterials with physicochemical and biological properties suitable for a clinical use. By varying the molar ratio between the PHEA-EDA amino groups and HA carboxyl groups, three different films were obtained and characterized. Particularly FTIR, swelling, hydrolysis, and enzymatic degradation studies were performed. In addition, the cytocompatibility of HA/PHEA-EDA hydrogel films was evaluated using human derm fibroblasts, by means of MTT and trypan blue exclusion assays. The high swelling capability, the long-term hydrolysis resistance, and the resistance to hyaluronidase greater than that of only HA, together with the cell compatibility, have suggested the potential application of these novel HA-based hydrogel films in the biomedical field of tissue engineering.

Research paper thumbnail of Characteristics of platelet gels combined with silk

Biomaterials, 2014

Platelet gel, a fibrin network containing activated platelets, is widely used in regenerative med... more Platelet gel, a fibrin network containing activated platelets, is widely used in regenerative medicine due the capacity of platelet-derived growth factors to accelerate and direct healing processes. However, limitations to this approach include poor mechanical properties, relatively rapid degradation, and the lack of control of release of growth factors at the site of injection. These issues compromise the ability of platelet gels for sustained function in regenerative medicine. In the present study, a combination of platelet gels with silk fibroin gel was studied to address the above limitations. Mixing sonicated silk gels with platelet gels extended the release of growth factors without inhibiting gel forming ability. The released growth factors were biologically active and their delivery was modified further by manipulation of the charge of the silk protein. Moreover, the silk gel augmented both the rheological properties and compressive stiffness of the platelet gel, tuned by the silk concentration and/or silk/platelet gel ratio. Silk-platelet gel injections in nude rats supported enhanced cell infiltration and blood vessel formation representing a step towards new platelet gel formulations with enhanced therapeutic impact.

Research paper thumbnail of Inkjet Printing of Silk Nest Arrays for Cell Hosting

Biomacromolecules, 2014

An inkjet printing approach is presented for the facile fabrication of microscopic arrays of bioc... more An inkjet printing approach is presented for the facile fabrication of microscopic arrays of biocompatible silk "nests" capable of hosting live cells for prospective biosensors. The patterning of silk fibroin nests were constructed by the layer-by-layer (LbL) assembly of silk polyelectrolytes chemically modified with poly-(L-lysine) and poly-(L-glutamic acid) side chains. The inkjet-printed silk circular regions with a characteristic "nest" shape had diameters of 70−100 μm and a thickness several hundred nanometers were stabilized by ionic pairing and by the formation of the silk II crystalline secondary structure. These "locked-in" silk nests remained anchored to the substrate during incubation in cell growth media to provide a biotemplated platform for printing-in, immobilization, encapsulation and growth of cells. The process of inkjet-assisted printing is versatile and can be applied on any type of substrate, including rigid and flexible, with scalability and facile formation.

Research paper thumbnail of Biodegradable and pH-Sensitive Hydrogels for Potential Colon-Specific Drug Delivery: Characterization and In Vitro Release Studies

Biomacromolecules, 2008

A novel pH-sensitive and biodegradable composite hydrogel, based on a methacrylated and succinic ... more A novel pH-sensitive and biodegradable composite hydrogel, based on a methacrylated and succinic derivative of dextran, named Dex-MA-SA, and a methacrylated and succinic derivative of R,-poly(N-2-hydroxyethyl)-DLaspartamide (PHEA), named PHM-SA, was produced by photocross-linking. The goal was to obtain a colonspecific drug delivery system, exploiting both the pH-sensitive behavior and the colon-specific degradability. The hydrogel prepared with a suitable ratio between the polysaccharide and the polyaminoacid was characterized regarding its swelling behavior in gastrointestinal simulated conditions, chemical and enzymatic degradability, interaction with mucin, and cell compatibility on CaCo-2 cells. Moreover, 2-methoxyestradiol was chosen as a model of anticancer drug and release studies, were performed in the absence or in the presence of dextranase and esterase. The obtained hydrogel, due to its pH-sensitive swelling and enzymatic degradability, together with mucoadhesion and cell compatibility, could be potentially useful as system for the oral treatment of colonic cancer.