4.5 Article

A bioinspired multifunctional hydrogel patch targeting inflammation and regeneration in chronic intestinal wounds

Journal

BIOMATERIALS SCIENCE
Volume 9, Issue 19, Pages 6510-6527

Publisher

ROYAL SOC CHEMISTRY
DOI: 10.1039/d1bm00118c

Keywords

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Funding

  1. FEDER - Fundo Europeu de Desenvolvimento Regional funds through COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020
  2. FCT - FundacAo para a Ciencia e a Tecnologia/Ministerio da Ciencia, Tecnologia e Ensino Superior
  3. Agencia para o Desenvolvimento e CoesAo
  4. Ministerio de Hacienda, Direccion General de Fondos Europeos for Interreg V-A Spain-Portugal (POCTEP) 2014-2020
  5. FEDER [0245_IBEROS_1_E]
  6. project Institute for Research and innovation in Health Sciences [UID/BIM/04293/2013/POCI-01-0145-FEDER-007274]
  7. FCT [IF/00296/2015]
  8. FCT
  9. Programa Operacional Potencial Humano (POCH), BiotechHealth Programme (Doctoral Programme on Cellular and Molecular Biotechnology Applied to Health Sciences) [PD/BI/128355/2017, PD/BD/135489/2018]
  10. Bioimaging i3S Scientific Platform (Portuguese Platform of Bioimaging (PPBI)) [PPBI-POCI-01-0145-FEDER-022122]
  11. Fundação para a Ciência e a Tecnologia [PD/BD/135489/2018, PD/BI/128355/2017] Funding Source: FCT

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The study introduced an innovative concept of a bioinspired alginate-melanin hybrid 3D scaffold for healing chronic intestinal wounds, addressing inflammation modulation and tissue regeneration. The scaffold demonstrated potential for reuse, remarkable cell colonization ability, and ECM-inspired design features, making it a promising candidate for clinical applications in chronic wound treatment.
Healing of intestinal chronic wounds remains a major challenge as current therapies are ineffective in promoting proper regeneration of the damaged intestinal wall. An innovative concept, based on a bioinspired multifunctional alginate-melanin hybrid 3D scaffold, to target both inflammatory and regenerative processes, is proposed herein. Hydrogel-entrapped melanin nanoparticles demonstrated free-radical scavenging activity, supported by the neutralization of free-radicals in solution (90%), and the in vitro capture of reactive oxygen species (ROS) produced by stimulated macrophages in an inflammatory-mimicking environment. Notably, scaffolds could be reused (at least 3 times), while maintaining these properties. The extracellular matrix (ECM)-inspired biomaterial, containing protease-sensitive and integrin-binding domains, exhibited remarkable ability for cell colonisation. Human intestinal fibroblasts and epithelial cells (Caco-2) co-seeded on lyophilized scaffolds were able to invade/colonize the construct and produce endogenous ECM, key for neo-tissue formation and re-epithelialization. Scaffolds presented tuneable mechanical properties and could be used both in hydrated and freeze-dried states, maintaining their performance upon rehydration, which are attractive features for clinical application. Collectively, our results highlight the potential of biofunctionalized alginate-melanin hybrid 3D scaffolds as multi-therapeutic patches for modulating inflammation and tissue regeneration in chronic intestinal wounds, which address a major but still unmet clinical need. The proposed multi-therapeutic strategy may potentially be extended to the treatment of other chronic wounds.

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