title: Interleukin-10 conjugated electrospun polycaprolactone (PCL) nanofibre scaffolds for promoting alternatively activated (M2) macrophages around the peripheral nerve in vivo.
abstract: Macrophages play a key role in tissue regeneration following peripheral nerve injury by preparing the surrounding parenchyma for regeneration, however, they can be damaging if the response is excessive. Interleukin 10 (IL-10) is a cytokine that promotes macrophages toward an anti-inflammatory/wound healing state (M2 phenotype). The bioactive half-life of IL-10 is dependent on the cellular microenvironment and ranges from minutes to hours in vivo. Our objective was to extend the in vivo bioavailability and bioactivity of IL-10 by attaching the protein onto nanofibrous scaffolds and demonstrating increased expression levels of M2 macrophages when placed around healthy intact peripheral nerves. IL-10 was adsorbed and covalently bound to electrospun poly(ε-caprolactone) (PCL) nanofibrous scaffolds. In vivo bioavailability and bioactivity of IL-10 was confirmed by wrapping IL-10 conjugated nanofibres around the sciatic nerves of Wistar rats and quantifying M2 macrophages immunohistochemically double labelled with ED1 and either arginase 1 or CD206. IL-10 remained immobilised to PCL scaffolds for more than 120 days when stored in phosphate buffered saline at room temperature and for up to 14d ays when implanted around the sciatic nerve. IL-10 conjugated nanofibres successfully induced macrophage polarisation towards the M2 activated state within the scaffold material as well as the adjacent tissue surrounding the nerve. PCL biofunctionalised nanofibres are useful for manipulating the cellular microenvironment. Materials such as these could potentially lead to new therapeutic strategies for nervous tissue injuries as well as provide novel investigative tools for biological research.
authors.affiliation: Eccles Institute of Neuroscience, John Curtin School of Medical Research, The Australian National University, Acton, ACT 0200, Australia; ANU Medical School, The Australian National University, Acton, ACT 0200, Australia. Electronic address: jason.potas@anu.edu.au.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Potas
authors.affiliation: Eccles Institute of Neuroscience, John Curtin School of Medical Research, The Australian National University, Acton, ACT 0200, Australia.
authors.forename: Farhia
authors.initials: F
authors.lastname: Haque
authors.affiliation: Research School of Engineering, The Australian National University, Acton, ACT 0200, Australia.
authors.forename: Francesca L
authors.initials: FL
authors.lastname: Maclean
authors.affiliation: Research School of Engineering, The Australian National University, Acton, ACT 0200, Australia.
authors.forename: David R
authors.initials: DR
authors.lastname: Nisbet
mesh_terms: D000818:Animals; D055767:Immobilized Proteins / Q000737:chemistry / Q000494:pharmacology; D016753:Interleukin-10 / Q000737:chemistry / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D008297:Male; D057139:Nanofibers / Q000737:chemistry*; D010525:Peripheral Nerves / Q000276:immunology* / Q000473:pathology; D011091:Polyesters / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D054457:Tissue Scaffolds
chemical_list: D055767:Immobilized Proteins; D011091:Polyesters; D016753:Interleukin-10; C016240:polycaprolactone
keywords: Artificial nerve graft; Connective tissue; Electrospinning; Neural tissue engineering; Perineural; Sub-micron scaffolds