In Situ‐Gelling, Erodible <i>N</i>‐Isopropylacrylamide Copolymers

Lee, Bae Hoon; Vernon, Brent L.

doi:10.1002/mabi.200500029

Cited by 38 publications

(45 citation statements)

References 22 publications

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“…However, hydrogels based on NIPAAm, HEMAPLA, and AAc alone showed very quick degradation and solubilization rates, with most solubilizing within three days. 12 Tensile mechanical properties were not reported for these materials. Structurally, the major difference between the current work and these previous reports is the incorporation of bioconjugation abilities through the introduction of NAS into the copolymer and the subsequent investigation of this new family of copolymers with and without collagen conjugation.…”

Section: Earlier Reports and Study Limitationsmentioning

confidence: 99%

“…The labile hydrophobic groups temporarily decrease the LCST and the hydrophilic groups increase the LCST above body temperature after hydrolysis. 11,12 Our objective in this work was to synthesize a thermoresponsive hydrogels having robust mechanical properties that would be appropriate for a variety of soft tissue cell therapy applications such as myocardium, muscle, and blood vessel. Specifically, we desired a material that would be readily injectable (soluble) at low temperatures, would form a gel with relatively high tensile strength and distensibility at 37 °C, would hydrolyze to form soluble, nontoxic degradation products, and would be capable of reacting with biomolecules such as collagen to impart bioactivity.…”

Section: Introductionmentioning

confidence: 99%

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Protein-Reactive, Thermoresponsive Copolymers with High Flexibility and Biodegradability

Guan

Hong

et al. 2008

Biomacromolecules

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A family of injectable, biodegradable, and thermosensitive copolymers based on Nisopropylacrylamide, acrylic acid, N-acryloxysuccinimide, and a macromer polylactidehydroxyethyl methacrylate were synthesized by free radical polymerization. Copolymers were injectable at or below room temperature and formed robust hydrogels at 37 °C. The effects of monomer ratio, polylactide length, and AAc content on the chemical and physical properties of the hydrogel were investigated. Copolymers exhibited lower critical solution temperatures (LCSTs) from 18 to 26 °C. After complete hydrolysis, hydrogels were soluble in phosphate buffered saline at 37 °C with LCSTs above 40.8 °C. Incorporation of type I collagen at varying mass fractions by covalent reaction with the copolymer backbone slightly increased LCSTs. Water content was 32-80% without collagen and increased to 230% with collagen at 37 °C. Hydrogels were highly flexible and relatively strong at 37 °C, with tensile strengths from 0.3 to 1.1 MPa and elongations at break from 344 to 1841% depending on NIPAAm/HEMAPLA ratio, AAc content, and polylactide length. Increasing the collagen content decreased both elongation at break and tensile strength. Hydrogel weight loss at 37 °C was 85-96% over 21 days and varied with polylactide content. Hydrogel weight loss at 37 °C was 85-96% over 21 days and varied with polylactide content. Degradation products were shown to be noncytotoxic. Cell adhesion on the hydrogels was 30% of that for tissue culture polystyrene but increased to statistically approximate this control surface after collagen incorporation. These newly described thermoresponsive copolymers demonstrated attractive properties to serve as cell or pharmaceutical delivery vehicles for a variety of tissue engineering applications.

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Section: Earlier Reports and Study Limitationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Protein-Reactive, Thermoresponsive Copolymers with High Flexibility and Biodegradability

Guan

Hong

et al. 2008

Biomacromolecules

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“…[ 16 ] Several synthetic systems have been explored for cardiac injection today, including self-assembling peptides [ 17 ] and synthetic hydrogels that are formed after injection via in situ chemical or physical cross-linking, [ 18 ] photo-induced polymerization, [ 19 ] self-assembly, [ 20 ] or thermal switching. [ 21 ] Again, although easy syringe injection can be obtained with these systems, catheter compatibility remains diffi cult and has not been shown.…”

Section: Introductionmentioning

confidence: 99%

A Fast pH‐Switchable and Self‐Healing Supramolecular Hydrogel Carrier for Guided, Local Catheter Injection in the Infarcted Myocardium

Bastings

Koudstaal

Kieltyka

et al. 2013

Adv Healthcare Materials

272

175

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Minimally invasive intervention strategies after myocardial infarction use state-of-the-art catheter systems that are able to combine mapping of the infarcted area with precise, local injection of drugs. To this end, catheter delivery of drugs that are not immediately pumped out of the heart is still challenging, and requires a carrier matrix that in the solution state can be injected through a long catheter, and instantaneously gelates at the site of injection. To address this unmet need, a pH-switchable supramolecular hydrogel is developed. The supramolecular hydrogel is switched into a liquid at pH > 8.5, with a viscosity low enough to enable passage through a 1-m long catheter while rapidly forming a hydrogel in contact with tissue. The hydrogel has self-healing properties taking care of adjustment to the injection site. Growth factors are delivered from the hydrogel thereby clearly showing a reduction of infarct scar in a pig myocardial infarction model. yield a further rise in mortality and morbidity. [ 1 ] New strategies are aiming at the prevention of the progression of postmyocardial infarction toward heart failure. Catheter-based drug delivery injection approaches [ 2 , 3 ] are substantially less invasive than for example surgical implantation of in vitro engineered tissues, [ 4 ] patches, [ 5 , 6 ] or drug delivery carriers. [ 7 ] Therefore, catheter-injection strategies are the method of choice with regard to clinical applicability. State-of-the-art is the NOGA catheter that enables precise control over the injection location via a special mapping system. [ 8 ] A 3D electromechanical image of the myocardium can be obtained using an ultralow magnetic-fi eld energy source and a sensor-tipped catheter to locate the catheter position. This mapping allows for the accurate identifi cation of normal and infarcted myocardium, and in this way, enables excellent spatial control over the injection of drugs. Generally, the injected drugs are substantially fast removed from the pulsatile heart when not delivered via a solid or gelated carrier material. Therefore, the

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“…The copolymer in a physiological environment will result in the hydrolysis of dimethyl-γ-butyrolactone and this is expected to lead to an increase in the LCST with time. When the LCST increases above body temperature, the polymer becomes soluble again and will diffuse away 21 . The proposed polymer is expected to have no low molecular weight by-product after degradation for the time frame of application which is desired for such a controlled drug delivery system to reduce cytotoxicity.…”

Section: Introductionmentioning

confidence: 99%

New Hydrolysis-Dependent Thermosensitive Polymer for an Injectable Degradable System

2007

Self Cite

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Novel, bioerodible, thermosensitive poly(NIPAAm-co-dimethyl-γ-butyrolactone), with hydrolysisdependent thermosensitivity, were synthesized by radical polymerization with varying dimethyl-γ-butyrolactone content and the properties of the copolymers were characterized using Differential Scanning Calorimetry (DSC), High Performance Liquid Chromatography (HPLC) in conjunction with Static Light Scattering, Fourier Transformed Infrared Spectroscopy (FTIR), Nuclear Magnetic Resonance (NMR) and acid titration. The lower critical solution temperature (LCST) of the copolymers decreased with increasing dimethyl-γ-butyrolactone content, but then increased after ring-opening hydrolysis of the dimethyl-γ-butyrolactone side group. FTIR and NMR spectra showed the copolymerization of these two monomers and the hydrolysis-dependent ring-opening of the dimethyl-γ-butyrolactone side group. It was also found that there are no low-molecular-weight byproducts but rather dissolution of the polymer chains at 37°C during the time frame of application. Models of the kinetics suggest that the hydrolysis reaction is self-catalytic due to an increase in hydrophilicity, and thus accessible water concentration, caused by ring-opening of the dimethyl-γ-butyrolactone.

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In Situ‐Gelling, Erodible N‐Isopropylacrylamide Copolymers

Cited by 38 publications

References 22 publications

Protein-Reactive, Thermoresponsive Copolymers with High Flexibility and Biodegradability

Protein-Reactive, Thermoresponsive Copolymers with High Flexibility and Biodegradability

A Fast pH‐Switchable and Self‐Healing Supramolecular Hydrogel Carrier for Guided, Local Catheter Injection in the Infarcted Myocardium

New Hydrolysis-Dependent Thermosensitive Polymer for an Injectable Degradable System

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