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

Autor(es)

Champeau, Mathilde ^{[1, 2]} ; Povoa, Valeria ^[3] ; Militao, Lucas ^[1] ; Cabrini, Flavia M. ^[1] ; Picheth, Guilherme F. ^[1] ; Meneau, Florian ^[4] ; Jara, Carlos P. ^[3] ; de Araujo, Eliana P. ^[3] ; de Oliveira, Marcelo G. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, UNICAMP, Inst Chem, CP 6154, BR-13083970 Campinas, SP - Brazil

^[2] Univ Fed ABC, Dept Mat Engn CECS, Santo Andre - Brazil

^[3] Univ Estadual Campinas, UNICAMP, Nursing Sch, BR-13084970 Campinas, SP - Brazil

^[4] Brazilian Synchrotron Light Lab LNLS, Beamline SAXS1, BR-13083970 Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Acta Biomaterialia; v. 74, p. 312-325, JUL 1 2018.
• Citações Web of Science: 12

Resumo

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 mu mol/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-beta, 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. Statement of Significance 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-beta, IGF-1, SDF-1, and 1L-10 gene expressions in the cicatricial tissue after topical treatment with a PAA:F127/GSNO hydrogel. (C) 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. (AU)

• Processo FAPESP: 16/02414-5 - Biomateriais absorvíveis e tópicos para a liberação localizada de óxido nítrico
• Beneficiário: Marcelo Ganzarolli de Oliveira
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 17/19253-7 - Hidrogéis termosensíveis de Pluronic F127 funcionalizados com grupos terminais liberadores de óxido nítrico
• Beneficiário: Guilherme Fadel Picheth
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 14/24955-2 - Hidrogéis de rede dupla para a liberação térmica e fotoquímica de óxido nítrico
• Beneficiário: Mathilde Julienne Gisele Champeau
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 15/17515-9 - Hidrogéis de poli(ácido acrílico)/PEO-PPO-PEO doadores de óxido nítrico para o tratamento tópico de lesões
• Beneficiário: Lucas Militão
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 13/07607-8 - CMPO - Centro Multidisciplinar de Pesquisa em Obesidade e Doenças Associadas
• Beneficiário: Licio Augusto Velloso
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs