Hierarchical Formation of Supramolecular Transient Networks in Water: A Modular Injectable Delivery System

Dankers, Patricia Y. W.; Hermans, Thomas M.; Baughman, Travis W.; Kamikawa, Yuichiro; Kieltyka, Roxanne E.; Bastings, Maartje M. C.; Janssen, Henk M.; Sommerdijk, Nico A. J. M.; Larsen, Antje; Luyn, Marja J. A. van; Bosman, Anton W.; Popa, Eliane R.; Fytas, George; Meijer, E. W.

doi:10.1002/adma.201104072

Cited by 257 publications

(269 citation statements)

References 50 publications

(51 reference statements)

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“…[ 31 ] For solution studies, i.e., using concentrations of 1 wt%, the PEG-20k hydrogel was used since the shorter hydrophilic domain of the PEG-10k materials causes precipitation in time. For the gel and biomedical experiments, the higher stability of the PEG-10k is preferred considering the resulting prolonged lifetime of the gel.…”

Section: Methodsmentioning

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

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263

173

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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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Section: Methodsmentioning

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

Self Cite

263

173

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“…Erosion and release experiments are performed at 37 °C using porous well inserts (Figure 2A and B). By tuning the length of the hydrophobic and hydrophilic block 14 , a gel that erodes over a period of several weeks can be obtained ( Figure 3A). The gel erodes 25% in 2 weeks with an initial erosion of 10% in the first day, presumably due to initial swelling of the hydrogel.…”

Section: Representative Resultsmentioning

confidence: 99%

“…The mild conditions required for switching allow the addition of various biological active components such as often difficult to handle growth factors. 14,16 . Moreover, several bioactive components can be incorporated by simply mixing the supramolecular hydrogelator solution before injection, with drugs or bioactive species, such as growth factors or exosomes, respectively.…”

Section: Introductionmentioning

confidence: 99%

An Injectable and Drug-loaded Supramolecular Hydrogel for Local Catheter Injection into the Pig Heart

Pape

Bakker

Tseng

et al. 2015

JoVE

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Regeneration of lost myocardium is an important goal for future therapies because of the increasing occurrence of chronic ischemic heart failure and the limited access to donor hearts. An example of a treatment to recover the function of the heart consists of the local delivery of drugs and bioactives from a hydrogel. In this paper a method is introduced to formulate and inject a drug-loaded hydrogel non-invasively and side-specific into the pig heart using a long, flexible catheter. The use of 3-D electromechanical mapping and injection via a catheter allows side-specific treatment of the myocardium. To provide a hydrogel compatible with this catheter, a supramolecular hydrogel is used because of the convenient switching from a gel to a solution state using environmental triggers. At basic pH this ureido-pyrimidinone modified poly(ethylene glycol) acts as a Newtonian fluid which can be easily injected, but at physiological pH the solution rapidly switches into a gel. These mild switching conditions allow for the incorporation of bioactive drugs and bioactive species, such as growth factors and exosomes as we present here in both in vitro and in vivo experiments. The in vitro experiments give an on forehand indication of the gel stability and drug release, which allows for tuning of the gel and release properties before the subsequent application in vivo. This combination allows for the optimal tuning of the gel to the used bioactive compounds and species, and the injection system.

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“…10) in hydrophobic hydrogen bonding domains consisting of UPy moieties and the PEG backbone resulted in the formation of solid-like hydrogels. Self-healing of these materials was observed at 50 C when the initial properties switched to those of a viscous liquid [61,62].…”

Section: Hydrogen Bonding Interactions Between Ureidopyrimidone Synthonsmentioning

confidence: 99%

Intrinsic Self-Healing Polymers Based on Supramolecular Interactions: State of the Art and Future Directions

Enke

Döhler

Bode

et al. 2015

Self-Healing Materials

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Supramolecular polymers are an intriguing class of materials with dynamic behavior as a result of the presence of non-covalent bonds. These bonds include hydrogen bonds, metallopolymers, ionomers, host-guest as well as π-π interactions. The strength of these supramolecular bonds can be tuned by varying the binding motifs. Their reversible and dynamic character can be utilized to engineer self-healing polymers. This review briefly presents the preconditions for design of self-healing polymers and summarizes the development of supramolecular self-healing polymers based on various non-covalent interactions. Furthermore, challenges and perspectives for the understanding of self-healing mechanisms and the preparation of novel materials with enhanced properties are discussed.

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Hierarchical Formation of Supramolecular Transient Networks in Water: A Modular Injectable Delivery System

Cited by 257 publications

References 50 publications

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

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

An Injectable and Drug-loaded Supramolecular Hydrogel for Local Catheter Injection into the Pig Heart

Intrinsic Self-Healing Polymers Based on Supramolecular Interactions: State of the Art and Future Directions

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