Two-Step Self-Assembly of Liposome-Multidomain Peptide Nanofiber Hydrogel for Time-Controlled Release

Wickremasinghe, Navindee C.; Kumar, Vivek; Hartgerink, Jeffrey D.

doi:10.1021/bm500856c

Cited by 73 publications

(112 citation statements)

References 54 publications

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“…Having established these key chemical and biomechanical facets, future studies in sophisticated in vivo cancer models can now be envisioned. These syringe-deliverable constructs may help a variety of strategies that allow localized drug delivery, 34 complemented by functional peptide signaling, 33 that ultimately offer another tool for targeted therapeutics.…”

Section: Measuring In Vivo Activitymentioning

confidence: 99%

Drug-Triggered and Cross-Linked Self-Assembling Nanofibrous Hydrogels

et al. 2015

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Self-assembly of multidomain peptides (MDP) can be tailored to carry payloads that modulate the extracellular environment. Controlled release of growth factors, cytokines, and small-molecule drugs allows for unique control of in vitro and in vivo responses. In this study, we demonstrate this process of ionic cross-linking of peptides using multivalent drugs to create hydrogels for sustained long-term delivery of drugs. Using phosphate, heparin, clodronate, trypan, and suramin, we demonstrate the utility of this strategy. Although all multivalent anions result in good hydrogel formation, demonstrating the generality of this approach, suramin led to the formation of the best hydrogels per unit concentration and was studied in greater detail. Suramin ionically cross-linked MDP into a fibrous meshwork as determined by scanning and transmission electron microscopy. We measured material storage and loss modulus using rheometry and showed a distinct increase in G′ and G″ as a function of suramin concentration. Release of suramin from scaffolds was determined using UV spectroscopy and showed prolonged release over a 30 day period. Suramin bioavailability and function were demonstrated by attenuated M1 polarization of THP-1 cells compared to positive control. Overall, this design strategy has allowed for the development of a novel class of polymeric delivery vehicles with generally long-term release and, in the case of suramin, cross-linked hydrogels that can modulate cellular phenotype.

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Section: Measuring In Vivo Activitymentioning

confidence: 99%

Drug-Triggered and Cross-Linked Self-Assembling Nanofibrous Hydrogels

et al. 2015

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“…3 Here, we used negatively charged liposomes to catalyze the formation of a gelator molecule, attempting to control the location of self-assembly to the vicinity of membranes. This would allow for the formation of multicomponent hydrogels, 16 containing well defined, enclosed areas which may be used to control the bulk material properties, 17 or to serve as a platform for the controlled release of therapeutic compounds. 18 Furthermore, it opens up the opportunity of forming fiber networks at cellular interfaces, which can be used to selectively kill malignant cells.…”

Section: Supporting Information Placeholdermentioning

confidence: 99%

Negatively Charged Lipid Membranes Catalyze Supramolecular Hydrogel Formation

et al. 2016

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In this contribution we show that biological membranes can catalyze the formation of supramolecular hydrogel networks. Negatively charged lipid membranes can generate a local proton gradient, accelerating the acid-catalyzed formation of hydrazone-based supramolecular gelators near the membrane. Synthetic lipid membranes can be used to tune the physical properties of the resulting multicomponent gels as a function of lipid concentration. Moreover, the catalytic activity of lipid membranes and the formation of gel networks around these supramolecular structures are controlled by the charge and phase behavior of the lipid molecules. Finally, we show that the insights obtained from synthetic membranes can be translated to biological membranes, enabling the formation of gel fibers on living HeLa cells.

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“…The ex vivo model system provides a critical framework for more translational in vivo pulp-capping experiments by validating the compatibility of the MDP scaffold in intact pulp tissue. This system can also be employed to test the effectiveness of the MDP scaffold as a delivery vehicle for regenerative bioactive materials into specific target tissues (Wickremasinghe et al 2014). …”

Section: Discussionmentioning

confidence: 99%

Ex Vivo Modeling of Multidomain Peptide Hydrogels with Intact Dental Pulp

et al. 2015

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Preservation of a vital dental pulp is a central goal of restorative dentistry. Currently, there is significant interest in the development of tissue engineering scaffolds that can serve as biocompatible and bioactive pulp-capping materials, driving dentin bridge formation without causing cytotoxic effects. Our earlier in vitro studies described the biocompatibility of multidomain peptide (MDP) hydrogel scaffolds with dental pulp-derived cells but were limited in their ability to model contact with intact 3-dimensional pulp tissues. Here, we utilize an established ex vivo mandible organ culture model to model these complex interactions. MDP hydrogel scaffolds were injected either at the interface of the odontoblasts and the dentin or into the pulp core of mandible slices and subsequently cultured for up to 10 d. Histology reveals minimal disruption of tissue architecture adjacent to MDP scaffolds injected into the pulp core or odontoblast space. Additionally, the odontoblast layer is structurally preserved in apposition to the MDP scaffold, despite being separated from the dentin. Alizarin red staining suggests mineralization at the periphery of MDP scaffolds injected into the odontoblast space. Immunohistochemistry reveals deposition of dentin sialophosphoprotein by odontoblasts into the adjacent MDP hydrogel, indicating continued functionality. In contrast, no mineralization or dentin sialophosphoprotein deposition is evident around MDP scaffolds injected into the pulp core. Collagen III expression is seen in apposition to gels at all experimental time points. Matrix metalloproteinase 2 expression is observed associated with centrally injected MDP scaffolds at early time points, indicating proteolytic digestion of scaffolds. Thus, MDP scaffolds delivered centrally and peripherally within whole dental pulp tissue are shown to be biocompatible, preserving local tissue architecture. Additionally, odontoblast function and pulp vitality are sustained when MDP scaffolds are intercalated between dentin and the odontoblast region, a finding that has significant implications when considering these materials as pulp-capping agents.

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Two-Step Self-Assembly of Liposome-Multidomain Peptide Nanofiber Hydrogel for Time-Controlled Release

Cited by 73 publications

References 54 publications

Drug-Triggered and Cross-Linked Self-Assembling Nanofibrous Hydrogels

Drug-Triggered and Cross-Linked Self-Assembling Nanofibrous Hydrogels

Negatively Charged Lipid Membranes Catalyze Supramolecular Hydrogel Formation

Ex Vivo Modeling of Multidomain Peptide Hydrogels with Intact Dental Pulp

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