Photodynamically Active Electrospun Fibers for Antibiotic-Free Infection Control

Abstract

Antimicrobial biomaterials are critical to aid in the regeneration of oral soft tissue and prevent or treat localised bacterial infections. With the rising trend in antibiotic resistance, there is a pressing clinical need for new antimicrobial chemistries and biomaterial design approaches enabling on-demand activation of antibiotic-free antimicrobial functionality following an infection that are environment-friendly, flexible and commercially-viable. This study explores the feasibility of integrating a bioresorbable electrospun polymer scaffold with localised antimicrobial photodynamic therapy (aPDT) capability. To enable aPDT, we encapsulated a photosensitiser (PS) in polyester fibres in the PS inert state, so that the antibacterial function would be activated on-demand via a visible light source. Fibrous scaffolds were successfully electrospun from FDA-approved polyesters, either poly( -caprolactone (PCL) or poly[(rac-lactide)-co-glycolide] (PLGA) with encapsulated PS (either methylene blue (MB) or erythrosin B (ER)). These were prepared and characterised with regards to their loading efficiency (UV-Vis spectroscopy), microarchitecture (SEM, porometry and BET (Brunauer-Emmett-Teller) analysis), tensile properties, hydrolytic behaviour (contact angle, dye release capability, degradability) and aPDT effect. The electrospun fibres achieved an ~100 wt.% loading efficiency of PS, which significantly increased their tensile modulus and reduced their average fibre diameter and pore size with respect to PS-free controls. In vitro, PS release varied between a burst release profile to limited release within 100 hours depending on the selected scaffold formulation, whilst PLGA scaffolds displayed significant macroscopic shrinkage and fibre merging following incubation in phosphate buffered saline solution. Exposure of

Hydrolytic Degradability, Cell Tolerance and On-Demand Antibacterial Effect of Electrospun Photodynamically Active Fibres

“…Electrospinning has recently been shown to generate PAFs with significant antibacterial photodynamic effect against multiple bacteria [ 16 , 17 , 18 , 22 , 33 , 35 ]. Despite these initial advances, however, the biocompatibility of PAFs in both inert and antimicrobial states has only partially been addressed [ 24 , 33 , 35 ], which is critical to enable applicability in medical devices.…”

“…Despite these initial advances, however, the biocompatibility of PAFs in both inert and antimicrobial states has only partially been addressed [ 24 , 33 , 35 ], which is critical to enable applicability in medical devices. Furthermore, electrospun fibres often suffer from instability and macroscopic shrinking in aqueous environments due to water-induced fibre swelling and merging [ 16 , 27 , 35 ], which can lead to uncontrolled release of PS and fast hydrolytic degradation [ 34 ]. To address these challenges, we aimed to build the structure–function relations of PAFs, whereby the effect of fibre-forming polymers, PS type and dosage on fibre micro- and macroscale was studied.…”

“…Polymers were stirred in HFIP for 48 h in dark, as per our previous protocol [ 16 ]. PLGA and PCL were dissolved in varied weight ratios (PLGA:PCL = 20:80; 50:50; 80:20) with an overall polymer concentration of 6 wt.%.…”

“…These limitations restrict the applicability of PDT in the clinical management of infectious diseases [ 13 ], at a time when the need for new antimicrobial strategies has never been more critical. Although the synthesis and testing of new PSs to address the above-mentioned challenges has been reported [ 10 , 11 , 14 ], encapsulation of PSs already in use in the clinic in polymer carriers represents a promising route to minimise PS aggregation, ensure a prolonged therapeutic window and comply with current regulatory framework [ 15 , 16 , 17 , 18 ]. With this strategy, control of the (i) release profile of PS from the carrier, (ii) PS uptake in both cells and bacteria and (iii) selectivity between the bactericidal effect and sparing effect upon host cells are key to successful performance.…”

Polydopamine-assisted PDGF-BB immobilization on PLGA fibrous substrate enhances wound healing via regulating anti-inflammatory and cytokine secretion

“…The PLGA fibers has outstanding sustained-release ability [8]. Amy Contreras' group encapsulated a photosensitizer (PS) in PCL/PLGA fibers in the PS inert state, so that the antibacterial function would be activated on-demand via a visible light source [9]. This study successfully demonstrates the significant potential of PS-encapsulated electrospun fibers as photodynamically active biomaterial for antibiotic-free infection control.…”