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Bioactive insulin-loaded electrospun wound dressings for localized drug delivery and stimulation of protein expression associated with wound healing

ABSTRACT: Effective therapy of wounds is difficult, especially for chronic, non-healing wounds, and novel therapeutics are urgently needed. This challenge can be addressed with bioactive wound dressings providing a microenvironment and facilitating cell proliferation and migration, ideally incorporating actives which initiate and/or progress effective healing upon release. In this context, electrospun scaffolds loaded with growth factors emerged as promising wound dressings due to their biocompatibility, similarity to the extracellular matrix and potential for controlled drug release. In this study, electrospun core-shell fibers were designed composed of a combination of polycaprolactone and polyethylene oxide. Insulin, a proteohormon with growth factor characteristics, was successfully incorporated into the core and was released in a controlled manner. The fibers exhibited favorable mechanical properties and a surface guiding cell migration for wound closure in combination with a high uptake capacity for wound exudate. Biocompatibility and significant wound healing effects were shown in interaction studies with human skin cells. As a new approach, analysis of the wound proteome in treated ex vivo human skin wounds clearly demonstrated a remarkable increase in wound healing biomarkers. Based on these findings, insulin-loaded electrospun wound dressings bear a high potential as effective wound healing therapeutics overcoming current challenges in the clinics.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Skin

DISEASE(S): Wounds And Injuries

SUBMITTER: Jasmin Schäfer

LAB HEAD: Christian Münch

PROVIDER: PXD034076 | Pride | 2022-12-19

REPOSITORIES: Pride

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Project description:Bacterial infections of wounds are associated with poor healing and worse scarring. We sought to identify transcriptomic patterns associated with impaired healing of wounds infected with Klebsiella pneumoniae (K.p.) or Pseudomonas aeruginosa (P.a.) using a rabbit ear wound model. Wounds created on post-operative day (POD) 0 were infected on POD3, within the inflammatory phase of healing. On POD4 the infected wounds were harvested for microarray/transcriptome analysis. Other wounds with 24-hour infections were treated with topical antibiotic to promote biofilm formation and harvested on POD6 or POD12. On POD4 before antibiotic treatment, both wounds contained elevated transcripts that enriched predominantly into inflammation/infection-response pathways and functions characteristic of infiltrating leukocytes. But there were 5-fold more elevated transcripts in P.a.- than K.p.-infected wounds. Additionally, unique to P.a.-infected wounds, was a minor network of inflammation/infection-response molecules with predicted upstream regulation predominated by type I interferons. Also on POD4, Dnr-transcripts of both wounds were enriched into stress-response pathways such as EIF2 signaling. But there were 8-fold more Dnr-transcripts in P.a.- than K.p.-infected wounds, and many more of them enriched in the function, cell death, suggesting that resident dermal cells of P.a.-infected wounds failed to survive a more destructive P.a. infection. On POD6, following two days of antibiotic treatment, the biofilm-colonized wounds expressed magnitudes fewer inflammation and stress-response transcripts. However, a single regulatory network of P.a.-infected wounds was found to consist of Upr-transcripts enriching immune/infection-response functions predicted to be regulated by type I interferons, which was similar to the network unique to P.a.-infected wounds on POD4. On POD12, genes expressed by K.p.-infected wounds suggesting healing, while for P.a.-infected wounds they suggested stalled healing. The similarities and differences between the wound responses to these infections further define the molecular foundations of healing impaired by infections. Rabbit ear Wounds created on post-operative day (POD) 0 were infected with Klebsiella pneumoniae (K.p.) or Pseudomonas aeruginosa (P.a.) on POD3 and harvested on POD4 for RNA extraction. Other wounds with 24-hour infections were treated with topical antibiotic to promote biofilm formation and harvested on POD6 or POD12.

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Bioactive insulin-loaded electrospun wound dressings for localized drug delivery and stimulation of protein expression associated with wound healing

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