Facile synthesis and detailed characterization of photopolymerizable and biocompatible poly(ethyl... more Facile synthesis and detailed characterization of photopolymerizable and biocompatible poly(ethylene glycol) dimethacrylates (PEGDM) and poly(ethylene glycol) urethane-dimethacrylates (PEGUDM) are described. Poly(ethylene glycol)s of various molecular masses (M n) 1000 to 8000 g/mol) were reacted with methacrylic anhydride or with 2-isocyanatoethyl methacrylate to form PEGDMs and PEGUDMs, respectively. PEGDMs were also prepared by a microwave-assisted route to achieve fast reaction conversions under solvent free conditions. Combined analyses of 1 H NMR and MALDI-TOF MS confirmed the formation of prepolymers of high purity and narrow mass distribution (PD < 1.02). Aqueous solutions of the PEGDMs and PEGUDMs (10% and 20% by mass fraction) were photopolymerized to yield hydrogels. Bovine chondrocytes, seeded in the hydrogels, were used to assess the biocompatibility. Preliminary rheology and uniaxial compression measurements showed varied mechanical response, and biocompatibility studies showed that cells are completely viable in both types of hydrogels after two weeks.
Electrically responsive hydrogels hold potential utility in numerous areas including robotic actu... more Electrically responsive hydrogels hold potential utility in numerous areas including robotic actuation, microfl uidic control , sensory technology, optical devices, drug delivery, and tissue engineering. [ 1-4 ] These polyelectrolytic [ 1,2 ] hydrogels are of particular interest in applications that demand the material properties of hydrogels coupled with precisely timed, stimuli-proportioned control. [ 3,4 ] Indeed, their compatibility with electrical circuitry and microprocessor-based control systems provides great potential in coordinating complex actuations while using simple and inexpensive equipment. Despite this promise, electrically responsive hydrogels have been plagued by poor responsivity, precluding their use in many applications. A previous investigation [ 5 ] describes the electro-collapsibility of such polyelectrolytic hydrogels as a two-part process where an electric fi eld exerts i) a force on the charged polymer, which draws the gel towards one electrode and ii) an opposite force that draws mobile counterions towards the opposing electrode and out of the gel. Therefore, rapid hydrogel responsivity requires a design that enhances the movement of both water and ions in and through the hydrogel. The time required for water and ion diffusion can be reduced by simply scaling down the size of the hydrogels, [ 6 ] but this does not directly address the need to facilitate transport. Larger electrically responsive hydrogels have been limited to response times of 30 min, [ 7 ] to hours, [ 8-10 ] or tens of hours. [ 5 ] We hypothesized that gels with interconnected macroporous structures would allow for more effi cient syneresis of water and emergence of ions from the hydrogel, thus providing improved electrical responsivity. Additionally, apparent reductions in gel volume would be directly related to the volumetric collapse of macropores and not large-scale polymer matrix rearrangement per se. This would allow more rapid reductions in gel volume while preserving the structural integrity of the gel. Finally, an interconnected macroporous structure would render the gel much softer, and therefore more electromechanically mutable. A cryopolymerization approach [ 11,12 ] (Figure S1, Supporting Information) was used to fabricate macroporous electrogels. Gels were formed in a semi-frozen state where nascent ice crystals concentrate monomer into the space between them, thus forming a concentrated gel structure interstitially between ice crystals following polymerization. When gels were thawed, ice crystals melted, leaving voids, or pores. Cryogels fabricated from acrylic acid (AAc) and acrylamide (AAm) exhibited large, interconnected pores while gels formed at room temperature had no large pores (Figure 1 a). The composition of the poly-meric network infl uenced the macropore morphology. As total polymeric content increased, pores were generally more aligned and planar, but at the highest polymer concentrations, the walls between pores became thicker. Quantifi cation of gel properties confi rmed that cryogels exhibited much higher degrees of pore interconnectivity (Figure 1 b) and lower modulus (Figure 1 c) than their room-temperature-polymerized, nanoporous counterparts. Note that at low overall polymer content, only cryogels were successfully formed. This is likely due to the increase in polymer concentration between ice crystals during cryotreat-ment. Macroporous cryogels were able to rapidly collapse to small diameters without loss of structural integrity when exposed to 50 V in deionized water, while nanoporous gels of the same makeup fragmented after about 30 s (Figure 1 d). The ability to undergo large and rapid volumetric changes was associated with the transition of the cryogels' macropores from an open (Figure 1 e, top) to a closed state (Figure 1 e, bottom). While macroporosity may compromise potential utility in some applications (e.g., for use as valves), one can imagine straightforward ways to circumnavigate these compromises (e.g., using a macroporous gel as an actuator fi xed to a nanoporous plug). The rapid and extensive collapse observed here was primarily due to exposure to an electric fi eld (estimated to be a radially graded fi eld between 20-80 V cm −1), with electrochemically induced changes in pH and ionic content having secondary roles (Figure S2, Supporting Information). The electro-responsivity of these macroporous gels could be further enhanced by varying the concentration of charged polymer and net hydrogel charge. Gels were formed with different AAc concentrations while holding the bisacrylamide (BA) concentration constant at 0.1 wt%, and gels composed of higher AAc concentrations generally collapsed slower and to a lesser extent (Figure 2 a). However, quantifi cation of the rate (Figure 2 b) and extent (Figure 2 c) of collapse revealed that they did not monotonically vary with AAc concentration. For the 11 wt% AAc gels, in particular, the rate of collapse Adv. Healthcare Mater. 2013,
Millimeter to centimeter-sized injectable neural scaffolds based on macropo-rous cryogels are pre... more Millimeter to centimeter-sized injectable neural scaffolds based on macropo-rous cryogels are presented. The polymer-scaffolds are made from alginate and carboxymethyl-cellulose by a novel simple one-pot cryosynthesis. They allow surgical sterility by means of autoclaving, and present native laminin as an attachment motive for neural adhesion and neurite development. They are designed to protect an extended, living neuronal network during compression to a small fraction of the original volume in order to enable minimally inva-sive delivery. The scaffolds behave as a mechanical meta-material: they are soft at the macroscopic scale, enabling injection through narrow-bore tubing and potentially good cellular scaffold integration in soft target tissues such as the brain. At the same time, the scaffold material has a high local Young modulus, allowing protection of the neuronal network during injection. Based on macroscopic and nanomechanical characterization, the generic geometrical and mechanical design rules are presented, enabling macroporous cellular scaffold injectability.
An investigation of encapsulated plasmid DNA release from degradable poly(ethylene glycol)-co-pol... more An investigation of encapsulated plasmid DNA release from degradable poly(ethylene glycol)-co-poly(gly-colic acid) hydrogels (PEG-co-PGA) is presented. We determined by varying the chemistry of the cross-linker group, significant variations in hydrogel degradation kinetics could be achieved to control the release profiles of plasmid DNA. We prepared three analogues of PEG-co-PGA hydro-gels by a photopolymerization process and measured variation in degradation rates by monitoring mechanical properties and release of plasmid DNA. 1 H 1D DOSY NMR (one-dimensional diffusion ordered nuclear magnetic resonance spectroscopy) was used to measure conversion of vinyl groups after photocross-linking. Nearly full vinyl conversion was reached after 10 min exposure under ultraviolet light. Gel electrophoresis analysis confirmed that plasmid DNA remained structurally intact after photoen-capsulation and release from the gels. This approach provides an additional strategy for controlling the release of biologically active compounds from hydrogels. Ó
We present the preparation and characterization of viscoelastic formulations of hyaluronic acid f... more We present the preparation and characterization of viscoelastic formulations of hyaluronic acid functionalized with polymerizable methacrylate groups. We explored three different processing strategies for controlling microstructure and interchain interactions: lightly cross-linked near-gels, emulsion-cross-linked microspheres, and an elastic microgel formed through centrifuging the microspheres. The component structure and rheological properties of these formulations were compared to those of high molecular weight hyaluronic acid solutions, which displayed classical behavior of high molecular weight polymer solutions reported by other investigators. We demonstrate that these processing strategies allow the tuning of solution properties from strongly viscoelastic behavior, observed in lightly cross-linked near-gels and concentrated microsphere solutions to elastic behavior in elastic microgels, behaving like pseudoplastic liquids having a well-defined yield stress above which viscous behavior was observed. In the centrifuged microspheres, the hyaluronic acid degree of methacrylation was inversely proportional to the gel elasticity, and a mechanism based on failure due to microsphere brittleness is proposed to explain this behavior. These results suggest that processing methacrylated hyaluronic acid can lead to a diversity of solution properties, providing methods for delivering this biologically active polymer in a broad range of applications.
Facile synthesis and detailed characterization of photopolymerizable and biocompatible poly(ethyl... more Facile synthesis and detailed characterization of photopolymerizable and biocompatible poly(ethylene glycol) dimethacrylates (PEGDM) and poly(ethylene glycol) urethane-dimethacrylates (PEGUDM) are described. Poly(ethylene glycol)s of various molecular masses (M n) 1000 to 8000 g/mol) were reacted with methacrylic anhydride or with 2-isocyanatoethyl methacrylate to form PEGDMs and PEGUDMs, respectively. PEGDMs were also prepared by a microwave-assisted route to achieve fast reaction conversions under solvent free conditions. Combined analyses of 1 H NMR and MALDI-TOF MS confirmed the formation of prepolymers of high purity and narrow mass distribution (PD < 1.02). Aqueous solutions of the PEGDMs and PEGUDMs (10% and 20% by mass fraction) were photopolymerized to yield hydrogels. Bovine chondrocytes, seeded in the hydrogels, were used to assess the biocompatibility. Preliminary rheology and uniaxial compression measurements showed varied mechanical response, and biocompatibility studies showed that cells are completely viable in both types of hydrogels after two weeks.
Electrically responsive hydrogels hold potential utility in numerous areas including robotic actu... more Electrically responsive hydrogels hold potential utility in numerous areas including robotic actuation, microfl uidic control , sensory technology, optical devices, drug delivery, and tissue engineering. [ 1-4 ] These polyelectrolytic [ 1,2 ] hydrogels are of particular interest in applications that demand the material properties of hydrogels coupled with precisely timed, stimuli-proportioned control. [ 3,4 ] Indeed, their compatibility with electrical circuitry and microprocessor-based control systems provides great potential in coordinating complex actuations while using simple and inexpensive equipment. Despite this promise, electrically responsive hydrogels have been plagued by poor responsivity, precluding their use in many applications. A previous investigation [ 5 ] describes the electro-collapsibility of such polyelectrolytic hydrogels as a two-part process where an electric fi eld exerts i) a force on the charged polymer, which draws the gel towards one electrode and ii) an opposite force that draws mobile counterions towards the opposing electrode and out of the gel. Therefore, rapid hydrogel responsivity requires a design that enhances the movement of both water and ions in and through the hydrogel. The time required for water and ion diffusion can be reduced by simply scaling down the size of the hydrogels, [ 6 ] but this does not directly address the need to facilitate transport. Larger electrically responsive hydrogels have been limited to response times of 30 min, [ 7 ] to hours, [ 8-10 ] or tens of hours. [ 5 ] We hypothesized that gels with interconnected macroporous structures would allow for more effi cient syneresis of water and emergence of ions from the hydrogel, thus providing improved electrical responsivity. Additionally, apparent reductions in gel volume would be directly related to the volumetric collapse of macropores and not large-scale polymer matrix rearrangement per se. This would allow more rapid reductions in gel volume while preserving the structural integrity of the gel. Finally, an interconnected macroporous structure would render the gel much softer, and therefore more electromechanically mutable. A cryopolymerization approach [ 11,12 ] (Figure S1, Supporting Information) was used to fabricate macroporous electrogels. Gels were formed in a semi-frozen state where nascent ice crystals concentrate monomer into the space between them, thus forming a concentrated gel structure interstitially between ice crystals following polymerization. When gels were thawed, ice crystals melted, leaving voids, or pores. Cryogels fabricated from acrylic acid (AAc) and acrylamide (AAm) exhibited large, interconnected pores while gels formed at room temperature had no large pores (Figure 1 a). The composition of the poly-meric network infl uenced the macropore morphology. As total polymeric content increased, pores were generally more aligned and planar, but at the highest polymer concentrations, the walls between pores became thicker. Quantifi cation of gel properties confi rmed that cryogels exhibited much higher degrees of pore interconnectivity (Figure 1 b) and lower modulus (Figure 1 c) than their room-temperature-polymerized, nanoporous counterparts. Note that at low overall polymer content, only cryogels were successfully formed. This is likely due to the increase in polymer concentration between ice crystals during cryotreat-ment. Macroporous cryogels were able to rapidly collapse to small diameters without loss of structural integrity when exposed to 50 V in deionized water, while nanoporous gels of the same makeup fragmented after about 30 s (Figure 1 d). The ability to undergo large and rapid volumetric changes was associated with the transition of the cryogels' macropores from an open (Figure 1 e, top) to a closed state (Figure 1 e, bottom). While macroporosity may compromise potential utility in some applications (e.g., for use as valves), one can imagine straightforward ways to circumnavigate these compromises (e.g., using a macroporous gel as an actuator fi xed to a nanoporous plug). The rapid and extensive collapse observed here was primarily due to exposure to an electric fi eld (estimated to be a radially graded fi eld between 20-80 V cm −1), with electrochemically induced changes in pH and ionic content having secondary roles (Figure S2, Supporting Information). The electro-responsivity of these macroporous gels could be further enhanced by varying the concentration of charged polymer and net hydrogel charge. Gels were formed with different AAc concentrations while holding the bisacrylamide (BA) concentration constant at 0.1 wt%, and gels composed of higher AAc concentrations generally collapsed slower and to a lesser extent (Figure 2 a). However, quantifi cation of the rate (Figure 2 b) and extent (Figure 2 c) of collapse revealed that they did not monotonically vary with AAc concentration. For the 11 wt% AAc gels, in particular, the rate of collapse Adv. Healthcare Mater. 2013,
Millimeter to centimeter-sized injectable neural scaffolds based on macropo-rous cryogels are pre... more Millimeter to centimeter-sized injectable neural scaffolds based on macropo-rous cryogels are presented. The polymer-scaffolds are made from alginate and carboxymethyl-cellulose by a novel simple one-pot cryosynthesis. They allow surgical sterility by means of autoclaving, and present native laminin as an attachment motive for neural adhesion and neurite development. They are designed to protect an extended, living neuronal network during compression to a small fraction of the original volume in order to enable minimally inva-sive delivery. The scaffolds behave as a mechanical meta-material: they are soft at the macroscopic scale, enabling injection through narrow-bore tubing and potentially good cellular scaffold integration in soft target tissues such as the brain. At the same time, the scaffold material has a high local Young modulus, allowing protection of the neuronal network during injection. Based on macroscopic and nanomechanical characterization, the generic geometrical and mechanical design rules are presented, enabling macroporous cellular scaffold injectability.
An investigation of encapsulated plasmid DNA release from degradable poly(ethylene glycol)-co-pol... more An investigation of encapsulated plasmid DNA release from degradable poly(ethylene glycol)-co-poly(gly-colic acid) hydrogels (PEG-co-PGA) is presented. We determined by varying the chemistry of the cross-linker group, significant variations in hydrogel degradation kinetics could be achieved to control the release profiles of plasmid DNA. We prepared three analogues of PEG-co-PGA hydro-gels by a photopolymerization process and measured variation in degradation rates by monitoring mechanical properties and release of plasmid DNA. 1 H 1D DOSY NMR (one-dimensional diffusion ordered nuclear magnetic resonance spectroscopy) was used to measure conversion of vinyl groups after photocross-linking. Nearly full vinyl conversion was reached after 10 min exposure under ultraviolet light. Gel electrophoresis analysis confirmed that plasmid DNA remained structurally intact after photoen-capsulation and release from the gels. This approach provides an additional strategy for controlling the release of biologically active compounds from hydrogels. Ó
We present the preparation and characterization of viscoelastic formulations of hyaluronic acid f... more We present the preparation and characterization of viscoelastic formulations of hyaluronic acid functionalized with polymerizable methacrylate groups. We explored three different processing strategies for controlling microstructure and interchain interactions: lightly cross-linked near-gels, emulsion-cross-linked microspheres, and an elastic microgel formed through centrifuging the microspheres. The component structure and rheological properties of these formulations were compared to those of high molecular weight hyaluronic acid solutions, which displayed classical behavior of high molecular weight polymer solutions reported by other investigators. We demonstrate that these processing strategies allow the tuning of solution properties from strongly viscoelastic behavior, observed in lightly cross-linked near-gels and concentrated microsphere solutions to elastic behavior in elastic microgels, behaving like pseudoplastic liquids having a well-defined yield stress above which viscous behavior was observed. In the centrifuged microspheres, the hyaluronic acid degree of methacrylation was inversely proportional to the gel elasticity, and a mechanism based on failure due to microsphere brittleness is proposed to explain this behavior. These results suggest that processing methacrylated hyaluronic acid can lead to a diversity of solution properties, providing methods for delivering this biologically active polymer in a broad range of applications.
Facile synthesis and detailed characterization of photopolymerizable and biocompatible poly(ethyl... more Facile synthesis and detailed characterization of photopolymerizable and biocompatible poly(ethylene glycol) dimethacrylates (PEGDM) and poly(ethylene glycol) urethane-dimethacrylates (PEGUDM) are described. Poly(ethylene glycol)s of various molecular masses (M n) 1000 to 8000 g/mol) were reacted with methacrylic anhydride or with 2-isocyanatoethyl methacrylate to form PEGDMs and PEGUDMs, respectively. PEGDMs were also prepared by a microwave-assisted route to achieve fast reaction conversions under solvent free conditions. Combined analyses of 1 H NMR and MALDI-TOF MS confirmed the formation of prepolymers of high purity and narrow mass distribution (PD < 1.02). Aqueous solutions of the PEGDMs and PEGUDMs (10% and 20% by mass fraction) were photopolymerized to yield hydrogels. Bovine chondrocytes, seeded in the hydrogels, were used to assess the biocompatibility. Preliminary rheology and uniaxial compression measurements showed varied mechanical response, and biocompatibility studies showed that cells are completely viable in both types of hydrogels after two weeks.
Electrically responsive hydrogels hold potential utility in numerous areas including robotic actu... more Electrically responsive hydrogels hold potential utility in numerous areas including robotic actuation, microfl uidic control , sensory technology, optical devices, drug delivery, and tissue engineering. [ 1-4 ] These polyelectrolytic [ 1,2 ] hydrogels are of particular interest in applications that demand the material properties of hydrogels coupled with precisely timed, stimuli-proportioned control. [ 3,4 ] Indeed, their compatibility with electrical circuitry and microprocessor-based control systems provides great potential in coordinating complex actuations while using simple and inexpensive equipment. Despite this promise, electrically responsive hydrogels have been plagued by poor responsivity, precluding their use in many applications. A previous investigation [ 5 ] describes the electro-collapsibility of such polyelectrolytic hydrogels as a two-part process where an electric fi eld exerts i) a force on the charged polymer, which draws the gel towards one electrode and ii) an opposite force that draws mobile counterions towards the opposing electrode and out of the gel. Therefore, rapid hydrogel responsivity requires a design that enhances the movement of both water and ions in and through the hydrogel. The time required for water and ion diffusion can be reduced by simply scaling down the size of the hydrogels, [ 6 ] but this does not directly address the need to facilitate transport. Larger electrically responsive hydrogels have been limited to response times of 30 min, [ 7 ] to hours, [ 8-10 ] or tens of hours. [ 5 ] We hypothesized that gels with interconnected macroporous structures would allow for more effi cient syneresis of water and emergence of ions from the hydrogel, thus providing improved electrical responsivity. Additionally, apparent reductions in gel volume would be directly related to the volumetric collapse of macropores and not large-scale polymer matrix rearrangement per se. This would allow more rapid reductions in gel volume while preserving the structural integrity of the gel. Finally, an interconnected macroporous structure would render the gel much softer, and therefore more electromechanically mutable. A cryopolymerization approach [ 11,12 ] (Figure S1, Supporting Information) was used to fabricate macroporous electrogels. Gels were formed in a semi-frozen state where nascent ice crystals concentrate monomer into the space between them, thus forming a concentrated gel structure interstitially between ice crystals following polymerization. When gels were thawed, ice crystals melted, leaving voids, or pores. Cryogels fabricated from acrylic acid (AAc) and acrylamide (AAm) exhibited large, interconnected pores while gels formed at room temperature had no large pores (Figure 1 a). The composition of the poly-meric network infl uenced the macropore morphology. As total polymeric content increased, pores were generally more aligned and planar, but at the highest polymer concentrations, the walls between pores became thicker. Quantifi cation of gel properties confi rmed that cryogels exhibited much higher degrees of pore interconnectivity (Figure 1 b) and lower modulus (Figure 1 c) than their room-temperature-polymerized, nanoporous counterparts. Note that at low overall polymer content, only cryogels were successfully formed. This is likely due to the increase in polymer concentration between ice crystals during cryotreat-ment. Macroporous cryogels were able to rapidly collapse to small diameters without loss of structural integrity when exposed to 50 V in deionized water, while nanoporous gels of the same makeup fragmented after about 30 s (Figure 1 d). The ability to undergo large and rapid volumetric changes was associated with the transition of the cryogels' macropores from an open (Figure 1 e, top) to a closed state (Figure 1 e, bottom). While macroporosity may compromise potential utility in some applications (e.g., for use as valves), one can imagine straightforward ways to circumnavigate these compromises (e.g., using a macroporous gel as an actuator fi xed to a nanoporous plug). The rapid and extensive collapse observed here was primarily due to exposure to an electric fi eld (estimated to be a radially graded fi eld between 20-80 V cm −1), with electrochemically induced changes in pH and ionic content having secondary roles (Figure S2, Supporting Information). The electro-responsivity of these macroporous gels could be further enhanced by varying the concentration of charged polymer and net hydrogel charge. Gels were formed with different AAc concentrations while holding the bisacrylamide (BA) concentration constant at 0.1 wt%, and gels composed of higher AAc concentrations generally collapsed slower and to a lesser extent (Figure 2 a). However, quantifi cation of the rate (Figure 2 b) and extent (Figure 2 c) of collapse revealed that they did not monotonically vary with AAc concentration. For the 11 wt% AAc gels, in particular, the rate of collapse Adv. Healthcare Mater. 2013,
Millimeter to centimeter-sized injectable neural scaffolds based on macropo-rous cryogels are pre... more Millimeter to centimeter-sized injectable neural scaffolds based on macropo-rous cryogels are presented. The polymer-scaffolds are made from alginate and carboxymethyl-cellulose by a novel simple one-pot cryosynthesis. They allow surgical sterility by means of autoclaving, and present native laminin as an attachment motive for neural adhesion and neurite development. They are designed to protect an extended, living neuronal network during compression to a small fraction of the original volume in order to enable minimally inva-sive delivery. The scaffolds behave as a mechanical meta-material: they are soft at the macroscopic scale, enabling injection through narrow-bore tubing and potentially good cellular scaffold integration in soft target tissues such as the brain. At the same time, the scaffold material has a high local Young modulus, allowing protection of the neuronal network during injection. Based on macroscopic and nanomechanical characterization, the generic geometrical and mechanical design rules are presented, enabling macroporous cellular scaffold injectability.
An investigation of encapsulated plasmid DNA release from degradable poly(ethylene glycol)-co-pol... more An investigation of encapsulated plasmid DNA release from degradable poly(ethylene glycol)-co-poly(gly-colic acid) hydrogels (PEG-co-PGA) is presented. We determined by varying the chemistry of the cross-linker group, significant variations in hydrogel degradation kinetics could be achieved to control the release profiles of plasmid DNA. We prepared three analogues of PEG-co-PGA hydro-gels by a photopolymerization process and measured variation in degradation rates by monitoring mechanical properties and release of plasmid DNA. 1 H 1D DOSY NMR (one-dimensional diffusion ordered nuclear magnetic resonance spectroscopy) was used to measure conversion of vinyl groups after photocross-linking. Nearly full vinyl conversion was reached after 10 min exposure under ultraviolet light. Gel electrophoresis analysis confirmed that plasmid DNA remained structurally intact after photoen-capsulation and release from the gels. This approach provides an additional strategy for controlling the release of biologically active compounds from hydrogels. Ó
We present the preparation and characterization of viscoelastic formulations of hyaluronic acid f... more We present the preparation and characterization of viscoelastic formulations of hyaluronic acid functionalized with polymerizable methacrylate groups. We explored three different processing strategies for controlling microstructure and interchain interactions: lightly cross-linked near-gels, emulsion-cross-linked microspheres, and an elastic microgel formed through centrifuging the microspheres. The component structure and rheological properties of these formulations were compared to those of high molecular weight hyaluronic acid solutions, which displayed classical behavior of high molecular weight polymer solutions reported by other investigators. We demonstrate that these processing strategies allow the tuning of solution properties from strongly viscoelastic behavior, observed in lightly cross-linked near-gels and concentrated microsphere solutions to elastic behavior in elastic microgels, behaving like pseudoplastic liquids having a well-defined yield stress above which viscous behavior was observed. In the centrifuged microspheres, the hyaluronic acid degree of methacrylation was inversely proportional to the gel elasticity, and a mechanism based on failure due to microsphere brittleness is proposed to explain this behavior. These results suggest that processing methacrylated hyaluronic acid can lead to a diversity of solution properties, providing methods for delivering this biologically active polymer in a broad range of applications.
Facile synthesis and detailed characterization of photopolymerizable and biocompatible poly(ethyl... more Facile synthesis and detailed characterization of photopolymerizable and biocompatible poly(ethylene glycol) dimethacrylates (PEGDM) and poly(ethylene glycol) urethane-dimethacrylates (PEGUDM) are described. Poly(ethylene glycol)s of various molecular masses (M n) 1000 to 8000 g/mol) were reacted with methacrylic anhydride or with 2-isocyanatoethyl methacrylate to form PEGDMs and PEGUDMs, respectively. PEGDMs were also prepared by a microwave-assisted route to achieve fast reaction conversions under solvent free conditions. Combined analyses of 1 H NMR and MALDI-TOF MS confirmed the formation of prepolymers of high purity and narrow mass distribution (PD < 1.02). Aqueous solutions of the PEGDMs and PEGUDMs (10% and 20% by mass fraction) were photopolymerized to yield hydrogels. Bovine chondrocytes, seeded in the hydrogels, were used to assess the biocompatibility. Preliminary rheology and uniaxial compression measurements showed varied mechanical response, and biocompatibility studies showed that cells are completely viable in both types of hydrogels after two weeks.
Electrically responsive hydrogels hold potential utility in numerous areas including robotic actu... more Electrically responsive hydrogels hold potential utility in numerous areas including robotic actuation, microfl uidic control , sensory technology, optical devices, drug delivery, and tissue engineering. [ 1-4 ] These polyelectrolytic [ 1,2 ] hydrogels are of particular interest in applications that demand the material properties of hydrogels coupled with precisely timed, stimuli-proportioned control. [ 3,4 ] Indeed, their compatibility with electrical circuitry and microprocessor-based control systems provides great potential in coordinating complex actuations while using simple and inexpensive equipment. Despite this promise, electrically responsive hydrogels have been plagued by poor responsivity, precluding their use in many applications. A previous investigation [ 5 ] describes the electro-collapsibility of such polyelectrolytic hydrogels as a two-part process where an electric fi eld exerts i) a force on the charged polymer, which draws the gel towards one electrode and ii) an opposite force that draws mobile counterions towards the opposing electrode and out of the gel. Therefore, rapid hydrogel responsivity requires a design that enhances the movement of both water and ions in and through the hydrogel. The time required for water and ion diffusion can be reduced by simply scaling down the size of the hydrogels, [ 6 ] but this does not directly address the need to facilitate transport. Larger electrically responsive hydrogels have been limited to response times of 30 min, [ 7 ] to hours, [ 8-10 ] or tens of hours. [ 5 ] We hypothesized that gels with interconnected macroporous structures would allow for more effi cient syneresis of water and emergence of ions from the hydrogel, thus providing improved electrical responsivity. Additionally, apparent reductions in gel volume would be directly related to the volumetric collapse of macropores and not large-scale polymer matrix rearrangement per se. This would allow more rapid reductions in gel volume while preserving the structural integrity of the gel. Finally, an interconnected macroporous structure would render the gel much softer, and therefore more electromechanically mutable. A cryopolymerization approach [ 11,12 ] (Figure S1, Supporting Information) was used to fabricate macroporous electrogels. Gels were formed in a semi-frozen state where nascent ice crystals concentrate monomer into the space between them, thus forming a concentrated gel structure interstitially between ice crystals following polymerization. When gels were thawed, ice crystals melted, leaving voids, or pores. Cryogels fabricated from acrylic acid (AAc) and acrylamide (AAm) exhibited large, interconnected pores while gels formed at room temperature had no large pores (Figure 1 a). The composition of the poly-meric network infl uenced the macropore morphology. As total polymeric content increased, pores were generally more aligned and planar, but at the highest polymer concentrations, the walls between pores became thicker. Quantifi cation of gel properties confi rmed that cryogels exhibited much higher degrees of pore interconnectivity (Figure 1 b) and lower modulus (Figure 1 c) than their room-temperature-polymerized, nanoporous counterparts. Note that at low overall polymer content, only cryogels were successfully formed. This is likely due to the increase in polymer concentration between ice crystals during cryotreat-ment. Macroporous cryogels were able to rapidly collapse to small diameters without loss of structural integrity when exposed to 50 V in deionized water, while nanoporous gels of the same makeup fragmented after about 30 s (Figure 1 d). The ability to undergo large and rapid volumetric changes was associated with the transition of the cryogels' macropores from an open (Figure 1 e, top) to a closed state (Figure 1 e, bottom). While macroporosity may compromise potential utility in some applications (e.g., for use as valves), one can imagine straightforward ways to circumnavigate these compromises (e.g., using a macroporous gel as an actuator fi xed to a nanoporous plug). The rapid and extensive collapse observed here was primarily due to exposure to an electric fi eld (estimated to be a radially graded fi eld between 20-80 V cm −1), with electrochemically induced changes in pH and ionic content having secondary roles (Figure S2, Supporting Information). The electro-responsivity of these macroporous gels could be further enhanced by varying the concentration of charged polymer and net hydrogel charge. Gels were formed with different AAc concentrations while holding the bisacrylamide (BA) concentration constant at 0.1 wt%, and gels composed of higher AAc concentrations generally collapsed slower and to a lesser extent (Figure 2 a). However, quantifi cation of the rate (Figure 2 b) and extent (Figure 2 c) of collapse revealed that they did not monotonically vary with AAc concentration. For the 11 wt% AAc gels, in particular, the rate of collapse Adv. Healthcare Mater. 2013,
Facile synthesis and detailed characterization of photopolymerizable and biocompatible poly(ethyl... more Facile synthesis and detailed characterization of photopolymerizable and biocompatible poly(ethylene glycol) dimethacrylates (PEGDM) and poly(ethylene glycol) urethane-dimethacrylates (PEGUDM) are described. Poly(ethylene glycol)s of various molecular masses (M n) 1000 to 8000 g/mol) were reacted with methacrylic anhydride or with 2-isocyanatoethyl methacrylate to form PEGDMs and PEGUDMs, respectively. PEGDMs were also prepared by a microwave-assisted route to achieve fast reaction conversions under solvent free conditions. Combined analyses of 1 H NMR and MALDI-TOF MS confirmed the formation of prepolymers of high purity and narrow mass distribution (PD < 1.02). Aqueous solutions of the PEGDMs and PEGUDMs (10% and 20% by mass fraction) were photopolymerized to yield hydrogels. Bovine chondrocytes, seeded in the hydrogels, were used to assess the biocompatibility. Preliminary rheology and uniaxial compression measurements showed varied mechanical response, and biocompatibility studies showed that cells are completely viable in both types of hydrogels after two weeks.
Electrically responsive hydrogels hold potential utility in numerous areas including robotic actu... more Electrically responsive hydrogels hold potential utility in numerous areas including robotic actuation, microfl uidic control , sensory technology, optical devices, drug delivery, and tissue engineering. [ 1-4 ] These polyelectrolytic [ 1,2 ] hydrogels are of particular interest in applications that demand the material properties of hydrogels coupled with precisely timed, stimuli-proportioned control. [ 3,4 ] Indeed, their compatibility with electrical circuitry and microprocessor-based control systems provides great potential in coordinating complex actuations while using simple and inexpensive equipment. Despite this promise, electrically responsive hydrogels have been plagued by poor responsivity, precluding their use in many applications. A previous investigation [ 5 ] describes the electro-collapsibility of such polyelectrolytic hydrogels as a two-part process where an electric fi eld exerts i) a force on the charged polymer, which draws the gel towards one electrode and ii) an opposite force that draws mobile counterions towards the opposing electrode and out of the gel. Therefore, rapid hydrogel responsivity requires a design that enhances the movement of both water and ions in and through the hydrogel. The time required for water and ion diffusion can be reduced by simply scaling down the size of the hydrogels, [ 6 ] but this does not directly address the need to facilitate transport. Larger electrically responsive hydrogels have been limited to response times of 30 min, [ 7 ] to hours, [ 8-10 ] or tens of hours. [ 5 ] We hypothesized that gels with interconnected macroporous structures would allow for more effi cient syneresis of water and emergence of ions from the hydrogel, thus providing improved electrical responsivity. Additionally, apparent reductions in gel volume would be directly related to the volumetric collapse of macropores and not large-scale polymer matrix rearrangement per se. This would allow more rapid reductions in gel volume while preserving the structural integrity of the gel. Finally, an interconnected macroporous structure would render the gel much softer, and therefore more electromechanically mutable. A cryopolymerization approach [ 11,12 ] (Figure S1, Supporting Information) was used to fabricate macroporous electrogels. Gels were formed in a semi-frozen state where nascent ice crystals concentrate monomer into the space between them, thus forming a concentrated gel structure interstitially between ice crystals following polymerization. When gels were thawed, ice crystals melted, leaving voids, or pores. Cryogels fabricated from acrylic acid (AAc) and acrylamide (AAm) exhibited large, interconnected pores while gels formed at room temperature had no large pores (Figure 1 a). The composition of the poly-meric network infl uenced the macropore morphology. As total polymeric content increased, pores were generally more aligned and planar, but at the highest polymer concentrations, the walls between pores became thicker. Quantifi cation of gel properties confi rmed that cryogels exhibited much higher degrees of pore interconnectivity (Figure 1 b) and lower modulus (Figure 1 c) than their room-temperature-polymerized, nanoporous counterparts. Note that at low overall polymer content, only cryogels were successfully formed. This is likely due to the increase in polymer concentration between ice crystals during cryotreat-ment. Macroporous cryogels were able to rapidly collapse to small diameters without loss of structural integrity when exposed to 50 V in deionized water, while nanoporous gels of the same makeup fragmented after about 30 s (Figure 1 d). The ability to undergo large and rapid volumetric changes was associated with the transition of the cryogels' macropores from an open (Figure 1 e, top) to a closed state (Figure 1 e, bottom). While macroporosity may compromise potential utility in some applications (e.g., for use as valves), one can imagine straightforward ways to circumnavigate these compromises (e.g., using a macroporous gel as an actuator fi xed to a nanoporous plug). The rapid and extensive collapse observed here was primarily due to exposure to an electric fi eld (estimated to be a radially graded fi eld between 20-80 V cm −1), with electrochemically induced changes in pH and ionic content having secondary roles (Figure S2, Supporting Information). The electro-responsivity of these macroporous gels could be further enhanced by varying the concentration of charged polymer and net hydrogel charge. Gels were formed with different AAc concentrations while holding the bisacrylamide (BA) concentration constant at 0.1 wt%, and gels composed of higher AAc concentrations generally collapsed slower and to a lesser extent (Figure 2 a). However, quantifi cation of the rate (Figure 2 b) and extent (Figure 2 c) of collapse revealed that they did not monotonically vary with AAc concentration. For the 11 wt% AAc gels, in particular, the rate of collapse Adv. Healthcare Mater. 2013,
Millimeter to centimeter-sized injectable neural scaffolds based on macropo-rous cryogels are pre... more Millimeter to centimeter-sized injectable neural scaffolds based on macropo-rous cryogels are presented. The polymer-scaffolds are made from alginate and carboxymethyl-cellulose by a novel simple one-pot cryosynthesis. They allow surgical sterility by means of autoclaving, and present native laminin as an attachment motive for neural adhesion and neurite development. They are designed to protect an extended, living neuronal network during compression to a small fraction of the original volume in order to enable minimally inva-sive delivery. The scaffolds behave as a mechanical meta-material: they are soft at the macroscopic scale, enabling injection through narrow-bore tubing and potentially good cellular scaffold integration in soft target tissues such as the brain. At the same time, the scaffold material has a high local Young modulus, allowing protection of the neuronal network during injection. Based on macroscopic and nanomechanical characterization, the generic geometrical and mechanical design rules are presented, enabling macroporous cellular scaffold injectability.
An investigation of encapsulated plasmid DNA release from degradable poly(ethylene glycol)-co-pol... more An investigation of encapsulated plasmid DNA release from degradable poly(ethylene glycol)-co-poly(gly-colic acid) hydrogels (PEG-co-PGA) is presented. We determined by varying the chemistry of the cross-linker group, significant variations in hydrogel degradation kinetics could be achieved to control the release profiles of plasmid DNA. We prepared three analogues of PEG-co-PGA hydro-gels by a photopolymerization process and measured variation in degradation rates by monitoring mechanical properties and release of plasmid DNA. 1 H 1D DOSY NMR (one-dimensional diffusion ordered nuclear magnetic resonance spectroscopy) was used to measure conversion of vinyl groups after photocross-linking. Nearly full vinyl conversion was reached after 10 min exposure under ultraviolet light. Gel electrophoresis analysis confirmed that plasmid DNA remained structurally intact after photoen-capsulation and release from the gels. This approach provides an additional strategy for controlling the release of biologically active compounds from hydrogels. Ó
We present the preparation and characterization of viscoelastic formulations of hyaluronic acid f... more We present the preparation and characterization of viscoelastic formulations of hyaluronic acid functionalized with polymerizable methacrylate groups. We explored three different processing strategies for controlling microstructure and interchain interactions: lightly cross-linked near-gels, emulsion-cross-linked microspheres, and an elastic microgel formed through centrifuging the microspheres. The component structure and rheological properties of these formulations were compared to those of high molecular weight hyaluronic acid solutions, which displayed classical behavior of high molecular weight polymer solutions reported by other investigators. We demonstrate that these processing strategies allow the tuning of solution properties from strongly viscoelastic behavior, observed in lightly cross-linked near-gels and concentrated microsphere solutions to elastic behavior in elastic microgels, behaving like pseudoplastic liquids having a well-defined yield stress above which viscous behavior was observed. In the centrifuged microspheres, the hyaluronic acid degree of methacrylation was inversely proportional to the gel elasticity, and a mechanism based on failure due to microsphere brittleness is proposed to explain this behavior. These results suggest that processing methacrylated hyaluronic acid can lead to a diversity of solution properties, providing methods for delivering this biologically active polymer in a broad range of applications.
Facile synthesis and detailed characterization of photopolymerizable and biocompatible poly(ethyl... more Facile synthesis and detailed characterization of photopolymerizable and biocompatible poly(ethylene glycol) dimethacrylates (PEGDM) and poly(ethylene glycol) urethane-dimethacrylates (PEGUDM) are described. Poly(ethylene glycol)s of various molecular masses (M n) 1000 to 8000 g/mol) were reacted with methacrylic anhydride or with 2-isocyanatoethyl methacrylate to form PEGDMs and PEGUDMs, respectively. PEGDMs were also prepared by a microwave-assisted route to achieve fast reaction conversions under solvent free conditions. Combined analyses of 1 H NMR and MALDI-TOF MS confirmed the formation of prepolymers of high purity and narrow mass distribution (PD < 1.02). Aqueous solutions of the PEGDMs and PEGUDMs (10% and 20% by mass fraction) were photopolymerized to yield hydrogels. Bovine chondrocytes, seeded in the hydrogels, were used to assess the biocompatibility. Preliminary rheology and uniaxial compression measurements showed varied mechanical response, and biocompatibility studies showed that cells are completely viable in both types of hydrogels after two weeks.
Electrically responsive hydrogels hold potential utility in numerous areas including robotic actu... more Electrically responsive hydrogels hold potential utility in numerous areas including robotic actuation, microfl uidic control , sensory technology, optical devices, drug delivery, and tissue engineering. [ 1-4 ] These polyelectrolytic [ 1,2 ] hydrogels are of particular interest in applications that demand the material properties of hydrogels coupled with precisely timed, stimuli-proportioned control. [ 3,4 ] Indeed, their compatibility with electrical circuitry and microprocessor-based control systems provides great potential in coordinating complex actuations while using simple and inexpensive equipment. Despite this promise, electrically responsive hydrogels have been plagued by poor responsivity, precluding their use in many applications. A previous investigation [ 5 ] describes the electro-collapsibility of such polyelectrolytic hydrogels as a two-part process where an electric fi eld exerts i) a force on the charged polymer, which draws the gel towards one electrode and ii) an opposite force that draws mobile counterions towards the opposing electrode and out of the gel. Therefore, rapid hydrogel responsivity requires a design that enhances the movement of both water and ions in and through the hydrogel. The time required for water and ion diffusion can be reduced by simply scaling down the size of the hydrogels, [ 6 ] but this does not directly address the need to facilitate transport. Larger electrically responsive hydrogels have been limited to response times of 30 min, [ 7 ] to hours, [ 8-10 ] or tens of hours. [ 5 ] We hypothesized that gels with interconnected macroporous structures would allow for more effi cient syneresis of water and emergence of ions from the hydrogel, thus providing improved electrical responsivity. Additionally, apparent reductions in gel volume would be directly related to the volumetric collapse of macropores and not large-scale polymer matrix rearrangement per se. This would allow more rapid reductions in gel volume while preserving the structural integrity of the gel. Finally, an interconnected macroporous structure would render the gel much softer, and therefore more electromechanically mutable. A cryopolymerization approach [ 11,12 ] (Figure S1, Supporting Information) was used to fabricate macroporous electrogels. Gels were formed in a semi-frozen state where nascent ice crystals concentrate monomer into the space between them, thus forming a concentrated gel structure interstitially between ice crystals following polymerization. When gels were thawed, ice crystals melted, leaving voids, or pores. Cryogels fabricated from acrylic acid (AAc) and acrylamide (AAm) exhibited large, interconnected pores while gels formed at room temperature had no large pores (Figure 1 a). The composition of the poly-meric network infl uenced the macropore morphology. As total polymeric content increased, pores were generally more aligned and planar, but at the highest polymer concentrations, the walls between pores became thicker. Quantifi cation of gel properties confi rmed that cryogels exhibited much higher degrees of pore interconnectivity (Figure 1 b) and lower modulus (Figure 1 c) than their room-temperature-polymerized, nanoporous counterparts. Note that at low overall polymer content, only cryogels were successfully formed. This is likely due to the increase in polymer concentration between ice crystals during cryotreat-ment. Macroporous cryogels were able to rapidly collapse to small diameters without loss of structural integrity when exposed to 50 V in deionized water, while nanoporous gels of the same makeup fragmented after about 30 s (Figure 1 d). The ability to undergo large and rapid volumetric changes was associated with the transition of the cryogels' macropores from an open (Figure 1 e, top) to a closed state (Figure 1 e, bottom). While macroporosity may compromise potential utility in some applications (e.g., for use as valves), one can imagine straightforward ways to circumnavigate these compromises (e.g., using a macroporous gel as an actuator fi xed to a nanoporous plug). The rapid and extensive collapse observed here was primarily due to exposure to an electric fi eld (estimated to be a radially graded fi eld between 20-80 V cm −1), with electrochemically induced changes in pH and ionic content having secondary roles (Figure S2, Supporting Information). The electro-responsivity of these macroporous gels could be further enhanced by varying the concentration of charged polymer and net hydrogel charge. Gels were formed with different AAc concentrations while holding the bisacrylamide (BA) concentration constant at 0.1 wt%, and gels composed of higher AAc concentrations generally collapsed slower and to a lesser extent (Figure 2 a). However, quantifi cation of the rate (Figure 2 b) and extent (Figure 2 c) of collapse revealed that they did not monotonically vary with AAc concentration. For the 11 wt% AAc gels, in particular, the rate of collapse Adv. Healthcare Mater. 2013,
Millimeter to centimeter-sized injectable neural scaffolds based on macropo-rous cryogels are pre... more Millimeter to centimeter-sized injectable neural scaffolds based on macropo-rous cryogels are presented. The polymer-scaffolds are made from alginate and carboxymethyl-cellulose by a novel simple one-pot cryosynthesis. They allow surgical sterility by means of autoclaving, and present native laminin as an attachment motive for neural adhesion and neurite development. They are designed to protect an extended, living neuronal network during compression to a small fraction of the original volume in order to enable minimally inva-sive delivery. The scaffolds behave as a mechanical meta-material: they are soft at the macroscopic scale, enabling injection through narrow-bore tubing and potentially good cellular scaffold integration in soft target tissues such as the brain. At the same time, the scaffold material has a high local Young modulus, allowing protection of the neuronal network during injection. Based on macroscopic and nanomechanical characterization, the generic geometrical and mechanical design rules are presented, enabling macroporous cellular scaffold injectability.
An investigation of encapsulated plasmid DNA release from degradable poly(ethylene glycol)-co-pol... more An investigation of encapsulated plasmid DNA release from degradable poly(ethylene glycol)-co-poly(gly-colic acid) hydrogels (PEG-co-PGA) is presented. We determined by varying the chemistry of the cross-linker group, significant variations in hydrogel degradation kinetics could be achieved to control the release profiles of plasmid DNA. We prepared three analogues of PEG-co-PGA hydro-gels by a photopolymerization process and measured variation in degradation rates by monitoring mechanical properties and release of plasmid DNA. 1 H 1D DOSY NMR (one-dimensional diffusion ordered nuclear magnetic resonance spectroscopy) was used to measure conversion of vinyl groups after photocross-linking. Nearly full vinyl conversion was reached after 10 min exposure under ultraviolet light. Gel electrophoresis analysis confirmed that plasmid DNA remained structurally intact after photoen-capsulation and release from the gels. This approach provides an additional strategy for controlling the release of biologically active compounds from hydrogels. Ó
We present the preparation and characterization of viscoelastic formulations of hyaluronic acid f... more We present the preparation and characterization of viscoelastic formulations of hyaluronic acid functionalized with polymerizable methacrylate groups. We explored three different processing strategies for controlling microstructure and interchain interactions: lightly cross-linked near-gels, emulsion-cross-linked microspheres, and an elastic microgel formed through centrifuging the microspheres. The component structure and rheological properties of these formulations were compared to those of high molecular weight hyaluronic acid solutions, which displayed classical behavior of high molecular weight polymer solutions reported by other investigators. We demonstrate that these processing strategies allow the tuning of solution properties from strongly viscoelastic behavior, observed in lightly cross-linked near-gels and concentrated microsphere solutions to elastic behavior in elastic microgels, behaving like pseudoplastic liquids having a well-defined yield stress above which viscous behavior was observed. In the centrifuged microspheres, the hyaluronic acid degree of methacrylation was inversely proportional to the gel elasticity, and a mechanism based on failure due to microsphere brittleness is proposed to explain this behavior. These results suggest that processing methacrylated hyaluronic acid can lead to a diversity of solution properties, providing methods for delivering this biologically active polymer in a broad range of applications.
Facile synthesis and detailed characterization of photopolymerizable and biocompatible poly(ethyl... more Facile synthesis and detailed characterization of photopolymerizable and biocompatible poly(ethylene glycol) dimethacrylates (PEGDM) and poly(ethylene glycol) urethane-dimethacrylates (PEGUDM) are described. Poly(ethylene glycol)s of various molecular masses (M n) 1000 to 8000 g/mol) were reacted with methacrylic anhydride or with 2-isocyanatoethyl methacrylate to form PEGDMs and PEGUDMs, respectively. PEGDMs were also prepared by a microwave-assisted route to achieve fast reaction conversions under solvent free conditions. Combined analyses of 1 H NMR and MALDI-TOF MS confirmed the formation of prepolymers of high purity and narrow mass distribution (PD < 1.02). Aqueous solutions of the PEGDMs and PEGUDMs (10% and 20% by mass fraction) were photopolymerized to yield hydrogels. Bovine chondrocytes, seeded in the hydrogels, were used to assess the biocompatibility. Preliminary rheology and uniaxial compression measurements showed varied mechanical response, and biocompatibility studies showed that cells are completely viable in both types of hydrogels after two weeks.
Electrically responsive hydrogels hold potential utility in numerous areas including robotic actu... more Electrically responsive hydrogels hold potential utility in numerous areas including robotic actuation, microfl uidic control , sensory technology, optical devices, drug delivery, and tissue engineering. [ 1-4 ] These polyelectrolytic [ 1,2 ] hydrogels are of particular interest in applications that demand the material properties of hydrogels coupled with precisely timed, stimuli-proportioned control. [ 3,4 ] Indeed, their compatibility with electrical circuitry and microprocessor-based control systems provides great potential in coordinating complex actuations while using simple and inexpensive equipment. Despite this promise, electrically responsive hydrogels have been plagued by poor responsivity, precluding their use in many applications. A previous investigation [ 5 ] describes the electro-collapsibility of such polyelectrolytic hydrogels as a two-part process where an electric fi eld exerts i) a force on the charged polymer, which draws the gel towards one electrode and ii) an opposite force that draws mobile counterions towards the opposing electrode and out of the gel. Therefore, rapid hydrogel responsivity requires a design that enhances the movement of both water and ions in and through the hydrogel. The time required for water and ion diffusion can be reduced by simply scaling down the size of the hydrogels, [ 6 ] but this does not directly address the need to facilitate transport. Larger electrically responsive hydrogels have been limited to response times of 30 min, [ 7 ] to hours, [ 8-10 ] or tens of hours. [ 5 ] We hypothesized that gels with interconnected macroporous structures would allow for more effi cient syneresis of water and emergence of ions from the hydrogel, thus providing improved electrical responsivity. Additionally, apparent reductions in gel volume would be directly related to the volumetric collapse of macropores and not large-scale polymer matrix rearrangement per se. This would allow more rapid reductions in gel volume while preserving the structural integrity of the gel. Finally, an interconnected macroporous structure would render the gel much softer, and therefore more electromechanically mutable. A cryopolymerization approach [ 11,12 ] (Figure S1, Supporting Information) was used to fabricate macroporous electrogels. Gels were formed in a semi-frozen state where nascent ice crystals concentrate monomer into the space between them, thus forming a concentrated gel structure interstitially between ice crystals following polymerization. When gels were thawed, ice crystals melted, leaving voids, or pores. Cryogels fabricated from acrylic acid (AAc) and acrylamide (AAm) exhibited large, interconnected pores while gels formed at room temperature had no large pores (Figure 1 a). The composition of the poly-meric network infl uenced the macropore morphology. As total polymeric content increased, pores were generally more aligned and planar, but at the highest polymer concentrations, the walls between pores became thicker. Quantifi cation of gel properties confi rmed that cryogels exhibited much higher degrees of pore interconnectivity (Figure 1 b) and lower modulus (Figure 1 c) than their room-temperature-polymerized, nanoporous counterparts. Note that at low overall polymer content, only cryogels were successfully formed. This is likely due to the increase in polymer concentration between ice crystals during cryotreat-ment. Macroporous cryogels were able to rapidly collapse to small diameters without loss of structural integrity when exposed to 50 V in deionized water, while nanoporous gels of the same makeup fragmented after about 30 s (Figure 1 d). The ability to undergo large and rapid volumetric changes was associated with the transition of the cryogels' macropores from an open (Figure 1 e, top) to a closed state (Figure 1 e, bottom). While macroporosity may compromise potential utility in some applications (e.g., for use as valves), one can imagine straightforward ways to circumnavigate these compromises (e.g., using a macroporous gel as an actuator fi xed to a nanoporous plug). The rapid and extensive collapse observed here was primarily due to exposure to an electric fi eld (estimated to be a radially graded fi eld between 20-80 V cm −1), with electrochemically induced changes in pH and ionic content having secondary roles (Figure S2, Supporting Information). The electro-responsivity of these macroporous gels could be further enhanced by varying the concentration of charged polymer and net hydrogel charge. Gels were formed with different AAc concentrations while holding the bisacrylamide (BA) concentration constant at 0.1 wt%, and gels composed of higher AAc concentrations generally collapsed slower and to a lesser extent (Figure 2 a). However, quantifi cation of the rate (Figure 2 b) and extent (Figure 2 c) of collapse revealed that they did not monotonically vary with AAc concentration. For the 11 wt% AAc gels, in particular, the rate of collapse Adv. Healthcare Mater. 2013,
Millimeter to centimeter-sized injectable neural scaffolds based on macropo-rous cryogels are pre... more Millimeter to centimeter-sized injectable neural scaffolds based on macropo-rous cryogels are presented. The polymer-scaffolds are made from alginate and carboxymethyl-cellulose by a novel simple one-pot cryosynthesis. They allow surgical sterility by means of autoclaving, and present native laminin as an attachment motive for neural adhesion and neurite development. They are designed to protect an extended, living neuronal network during compression to a small fraction of the original volume in order to enable minimally inva-sive delivery. The scaffolds behave as a mechanical meta-material: they are soft at the macroscopic scale, enabling injection through narrow-bore tubing and potentially good cellular scaffold integration in soft target tissues such as the brain. At the same time, the scaffold material has a high local Young modulus, allowing protection of the neuronal network during injection. Based on macroscopic and nanomechanical characterization, the generic geometrical and mechanical design rules are presented, enabling macroporous cellular scaffold injectability.
An investigation of encapsulated plasmid DNA release from degradable poly(ethylene glycol)-co-pol... more An investigation of encapsulated plasmid DNA release from degradable poly(ethylene glycol)-co-poly(gly-colic acid) hydrogels (PEG-co-PGA) is presented. We determined by varying the chemistry of the cross-linker group, significant variations in hydrogel degradation kinetics could be achieved to control the release profiles of plasmid DNA. We prepared three analogues of PEG-co-PGA hydro-gels by a photopolymerization process and measured variation in degradation rates by monitoring mechanical properties and release of plasmid DNA. 1 H 1D DOSY NMR (one-dimensional diffusion ordered nuclear magnetic resonance spectroscopy) was used to measure conversion of vinyl groups after photocross-linking. Nearly full vinyl conversion was reached after 10 min exposure under ultraviolet light. Gel electrophoresis analysis confirmed that plasmid DNA remained structurally intact after photoen-capsulation and release from the gels. This approach provides an additional strategy for controlling the release of biologically active compounds from hydrogels. Ó
We present the preparation and characterization of viscoelastic formulations of hyaluronic acid f... more We present the preparation and characterization of viscoelastic formulations of hyaluronic acid functionalized with polymerizable methacrylate groups. We explored three different processing strategies for controlling microstructure and interchain interactions: lightly cross-linked near-gels, emulsion-cross-linked microspheres, and an elastic microgel formed through centrifuging the microspheres. The component structure and rheological properties of these formulations were compared to those of high molecular weight hyaluronic acid solutions, which displayed classical behavior of high molecular weight polymer solutions reported by other investigators. We demonstrate that these processing strategies allow the tuning of solution properties from strongly viscoelastic behavior, observed in lightly cross-linked near-gels and concentrated microsphere solutions to elastic behavior in elastic microgels, behaving like pseudoplastic liquids having a well-defined yield stress above which viscous behavior was observed. In the centrifuged microspheres, the hyaluronic acid degree of methacrylation was inversely proportional to the gel elasticity, and a mechanism based on failure due to microsphere brittleness is proposed to explain this behavior. These results suggest that processing methacrylated hyaluronic acid can lead to a diversity of solution properties, providing methods for delivering this biologically active polymer in a broad range of applications.
Facile synthesis and detailed characterization of photopolymerizable and biocompatible poly(ethyl... more Facile synthesis and detailed characterization of photopolymerizable and biocompatible poly(ethylene glycol) dimethacrylates (PEGDM) and poly(ethylene glycol) urethane-dimethacrylates (PEGUDM) are described. Poly(ethylene glycol)s of various molecular masses (M n) 1000 to 8000 g/mol) were reacted with methacrylic anhydride or with 2-isocyanatoethyl methacrylate to form PEGDMs and PEGUDMs, respectively. PEGDMs were also prepared by a microwave-assisted route to achieve fast reaction conversions under solvent free conditions. Combined analyses of 1 H NMR and MALDI-TOF MS confirmed the formation of prepolymers of high purity and narrow mass distribution (PD < 1.02). Aqueous solutions of the PEGDMs and PEGUDMs (10% and 20% by mass fraction) were photopolymerized to yield hydrogels. Bovine chondrocytes, seeded in the hydrogels, were used to assess the biocompatibility. Preliminary rheology and uniaxial compression measurements showed varied mechanical response, and biocompatibility studies showed that cells are completely viable in both types of hydrogels after two weeks.
Electrically responsive hydrogels hold potential utility in numerous areas including robotic actu... more Electrically responsive hydrogels hold potential utility in numerous areas including robotic actuation, microfl uidic control , sensory technology, optical devices, drug delivery, and tissue engineering. [ 1-4 ] These polyelectrolytic [ 1,2 ] hydrogels are of particular interest in applications that demand the material properties of hydrogels coupled with precisely timed, stimuli-proportioned control. [ 3,4 ] Indeed, their compatibility with electrical circuitry and microprocessor-based control systems provides great potential in coordinating complex actuations while using simple and inexpensive equipment. Despite this promise, electrically responsive hydrogels have been plagued by poor responsivity, precluding their use in many applications. A previous investigation [ 5 ] describes the electro-collapsibility of such polyelectrolytic hydrogels as a two-part process where an electric fi eld exerts i) a force on the charged polymer, which draws the gel towards one electrode and ii) an opposite force that draws mobile counterions towards the opposing electrode and out of the gel. Therefore, rapid hydrogel responsivity requires a design that enhances the movement of both water and ions in and through the hydrogel. The time required for water and ion diffusion can be reduced by simply scaling down the size of the hydrogels, [ 6 ] but this does not directly address the need to facilitate transport. Larger electrically responsive hydrogels have been limited to response times of 30 min, [ 7 ] to hours, [ 8-10 ] or tens of hours. [ 5 ] We hypothesized that gels with interconnected macroporous structures would allow for more effi cient syneresis of water and emergence of ions from the hydrogel, thus providing improved electrical responsivity. Additionally, apparent reductions in gel volume would be directly related to the volumetric collapse of macropores and not large-scale polymer matrix rearrangement per se. This would allow more rapid reductions in gel volume while preserving the structural integrity of the gel. Finally, an interconnected macroporous structure would render the gel much softer, and therefore more electromechanically mutable. A cryopolymerization approach [ 11,12 ] (Figure S1, Supporting Information) was used to fabricate macroporous electrogels. Gels were formed in a semi-frozen state where nascent ice crystals concentrate monomer into the space between them, thus forming a concentrated gel structure interstitially between ice crystals following polymerization. When gels were thawed, ice crystals melted, leaving voids, or pores. Cryogels fabricated from acrylic acid (AAc) and acrylamide (AAm) exhibited large, interconnected pores while gels formed at room temperature had no large pores (Figure 1 a). The composition of the poly-meric network infl uenced the macropore morphology. As total polymeric content increased, pores were generally more aligned and planar, but at the highest polymer concentrations, the walls between pores became thicker. Quantifi cation of gel properties confi rmed that cryogels exhibited much higher degrees of pore interconnectivity (Figure 1 b) and lower modulus (Figure 1 c) than their room-temperature-polymerized, nanoporous counterparts. Note that at low overall polymer content, only cryogels were successfully formed. This is likely due to the increase in polymer concentration between ice crystals during cryotreat-ment. Macroporous cryogels were able to rapidly collapse to small diameters without loss of structural integrity when exposed to 50 V in deionized water, while nanoporous gels of the same makeup fragmented after about 30 s (Figure 1 d). The ability to undergo large and rapid volumetric changes was associated with the transition of the cryogels' macropores from an open (Figure 1 e, top) to a closed state (Figure 1 e, bottom). While macroporosity may compromise potential utility in some applications (e.g., for use as valves), one can imagine straightforward ways to circumnavigate these compromises (e.g., using a macroporous gel as an actuator fi xed to a nanoporous plug). The rapid and extensive collapse observed here was primarily due to exposure to an electric fi eld (estimated to be a radially graded fi eld between 20-80 V cm −1), with electrochemically induced changes in pH and ionic content having secondary roles (Figure S2, Supporting Information). The electro-responsivity of these macroporous gels could be further enhanced by varying the concentration of charged polymer and net hydrogel charge. Gels were formed with different AAc concentrations while holding the bisacrylamide (BA) concentration constant at 0.1 wt%, and gels composed of higher AAc concentrations generally collapsed slower and to a lesser extent (Figure 2 a). However, quantifi cation of the rate (Figure 2 b) and extent (Figure 2 c) of collapse revealed that they did not monotonically vary with AAc concentration. For the 11 wt% AAc gels, in particular, the rate of collapse Adv. Healthcare Mater. 2013,
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