Supramolecular poly(acrylic acid)/F127 hydrogel with hydration-controlled nitric oxide release for enhancing wound healing

[Display omitted] Topical nitric oxide (NO) delivery has been shown to accelerate wound healing. However, delivering NO to wounds at appropriate rates and doses requires new biomaterial-based strategies. Here, we describe the development of supramolecular interpolymer complex hydrogels comprising PE...

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Bibliographic Details
Published in:Acta biomaterialia 2018-07, Vol.74, p.312-325
Main Authors: Champeau, Mathilde, Póvoa, Valéria, Militão, Lucas, Cabrini, Flávia M., Picheth, Guilherme F., Meneau, Florian, Jara, Carlos P., de Araujo, Eliana P., de Oliveira, Marcelo G.
Format: Article
Language:English
Subjects:
Absorption
Acids
Acrylic acid
Acrylics
Angiogenesis
Biomaterials
Collagen
Exudation
F127
Hydration
Hydrogels
In vivo methods and tests
Insulin-like growth factor I
Interleukin 10
Long range order
Medical dressings
Micelles
Molecular biology
Morphology
Nitric oxide
Poly(acrylic acid)
S-nitrosoglutathione
SDF-1 protein
Strategy
Water absorption
Wound healing
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Summary:[Display omitted] Topical nitric oxide (NO) delivery has been shown to accelerate wound healing. However, delivering NO to wounds at appropriate rates and doses requires new biomaterial-based strategies. Here, we describe the development of supramolecular interpolymer complex hydrogels comprising PEO-PPO-PEO (F127) micelles embedded in a poly(acrylic acid) (PAA) matrix, with S-nitrosoglutathione (GSNO) molecules dissolved in the hydrophilic domain. We show that PAA:F127/GSNO hydrogels start releasing NO upon hydration at rates controlled by their rates of water absorption. SAXS measurements indicate that the supramolecular structure of the hydrogels retains long-range order domains of F127 micelles. The PAA/F1227 hydrogels displayed dense morphologies and reduced rates of hydration. The NO release rates remain constant over the first 200 min, are directly correlated with the hydration rates of the PAA:F127/GSNO hydrogels, and can be modulated in the range of 40 nmol/g h to 1.5 μmol/g h by changing the PAA:F127 mass ratio. Long-term NO-release profiles over 5 days are governed by the first-order exponential decay of GSNO, with half-lives in the range of 0.5–3.4 days. A preliminary in vivo study on full-thickness excisional wounds in mice showed that topical NO release from the PAA:F127/GSNO hydrogels is triggered by exudate absorption and leads to increased angiogenesis and collagen fiber organization, as well as TGF-β, IGF-1, SDF-1, and IL-10 gene expressions in the cicatricial tissue. In summary, these results suggest that hydration-controlled NO release from topical PAA:F127/GSNO hydrogels is a potential strategy for enhancing wound healing. The topical delivery of nitric oxide (NO) to wounds may provide significant beneficial results and represent a promising strategy to treat chronic wounds. However, wound dressings capable of releasing NO after application and allowing the modulation of NO release rates, demand new platforms. Here, we describe a novel strategy to overcome these challenges, based on the use of supramolecular poly(acrylic acid) (PAA):F127 hydrogels charged with the NO donor S-nitrosoglutathione (GSNO) from whereby the NO release can be triggered by exudate absorption and delivered to the wound at rates controlled by the PAA:F127 mass ratio. Preliminary in vivo results offer a proof of concept for this strategy by demonstrating increased angiogenesis; collagen fibers organization; and TGF-β, IGF-1, SDF-1, and IL-10 gene expressions in th
ISSN:1742-7061
1878-7568
DOI:10.1016/j.actbio.2018.05.025