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Title of the project

Functionalization of ellectrospun polymeric dressings with complexes of collagen type I and antimicrobial peptides for enhanced wound-healing

Envisaged Program for funding / other sources for funding

M-ERA.NET

Domain of interest

Interfaces between materials and biological hosts for health applications

Abstract

(up to 500 words)

Wound dressing is an important segment of the medical and pharmaceutical market worldwide. In the past, traditional dressings were used to simply manage wounds. Nowadays, wound dressings aim faster skin regeneration, oxygen exchange and lower microbial colonization. Acute wound therapies target specific phases of wound-healing, hemostasis, inflammation, proliferation and maturation, but do not consider possible disrupts on the usual conduct of each phase. Due to a number of potential stimuli, ischemia, bioburden, necrotic tissue, trauma, etc., wounds can stall in one phase of healing, typically inflammation, contributing to wound chronicity. Chronic wounds are often characterized by a defective matrix and cell debris impair healing, high bacteria counts, prolonged inflammation and moisture imbalance. Conventional therapies identify and remove these barriers to wound-healing by applying individualized treatments to each barrier.

In the last years, synthetic polymeric matrixes, i.e. polyurethane (PU), polyl-Ɛ-caprolactone (PCL) and poly(methylmethacrylate) (PMMA), with versatile physical and mechanical properties have demonstrated wound-healing abilities and enhanced re-epthelialization. The same capacities have been highlighted in naturally occurring polymers, like cellulose and collagen. Collagen type I (Col I) is uniquely suited for wound dressing therapies because of its involvement in all phases of wound-healing. Platelets aggregate around exposed collagen and secrete factors that stimulate the intrinsic clotting cascade responsible for a stable hemostatic "plug". In addition, collagen dressings have the ability to absorb wound exudates to maintain a moist environment. Recently, the unique diverse function and architecture of antimicrobial peptides (AMPs) has attracted considerable attention as a tool in the design of molecular templates for new anti-infective drugs. AMPs are gene-encoded short amphipathic molecules with broad-spectrum antimicrobial activity. Some AMPs of mammal and amphibian origins have been identified as promoters of wound-healing activities. LL37 (37 a.a.), the only cathelicidin-derived AMP found in humans, plays a central role in the innate immune response and inflammation. Esculentin-1a(1-21)NH₂ (20 a.a.) derived from the frog skin AMP esculentin-1a, and Tiger 17 (11 a.a.) synthesized from tigerinin AMPs, are known to act on different phases of wound-healing. Pexiganan (22 a.a.) synthesized from magaining is known to reduce microbial burden without enhancing bacterial resistance.

In this project, we propose a new dressing design for acute to chronic wounds in which one single strategy will act on all barriers and promote all phases of healing. Synthetic and natural polymers will be combined with collagen type I and the AMPs LL37, Esculentin-1a(1-21)NH₂, Tiger 17 and Pexiganan. PU, PCL, PMMA and cellulose mats of controlled fiber diameter will be produced by electrospinning. Each element of the dressing will be strategically linked to the other. Two strategies will be followed: (i) AMPs will be linked by pegylation to Col I treated dressings or (i) Col I-AMP complexes will be adsorbed onto the dressings. The wound-healing abilities (platelet adhesion, clotting time, fibroblasts migration/proliferation) and antimicrobial properties (bacterial adhesion, biofilm formation) of the engineered dressing will be then tested in vitro. Finally, in vivo testing will be performed to proof our concept.

Keywords (up to 5)

Wound-healing, polymeric dressings, collagen type I, antimicrobial peptides.

Envisaged partners sought

1- Synthesis of antimicrobial peptides

2- In vivo testing

Contact data

(Name/Surname, Organization, email)

Helena P. Felgueiras

2C2T Laboratory, University of Minho

felgueiras.helena@gmail.com