Dehydrated silk fibroin matrices as versatile delivery systems for extracellular vesicles

Frontiers in Bioengineering and Biotechnology, vol. 14, pp. 1873981

Abstract

Extracellular vesicles (EVs) have emerged as promising alternatives to cell-based therapies due to their low immunogenicity, ability to carry therapeutic cargo, and enhanced stability. However, rapid clearance from the bloodstream and phagocytic uptake by macrophages after systemic or local administration limit their therapeutic efficacy, highlighting the need for delivery systems that enable sustained and localized EV release. In this study, a natural protein silk fibroin (SF) was selected as a biomaterial carrier due to its tunable degradation kinetics and biocompatibility. SF was produced into nonwovens and films to investigate the effect of material structure on EV delivery in dehydrated SF matrices. A mild water vapor annealing approach was applied to tune structural stability and β-sheet formation while preserving EV integrity. Gingival fibroblast (GF)-derived EVs were successfully incorporated into nonwovens and films. EV-loaded nonwovens and films demonstrated distinct release characteristics over 14 days, with nonwovens providing a more controlled release and films showing delayed but accelerated release at later time points. EV morphology was preserved after release, and the EVs were notably internalized by human umbilical vein endothelial cells (HUVECs). Both EV-loaded materials enhanced the migration in a wound healing assay. These findings highlight the potential of dehydrated SF matrices as promising EV delivery systems for future regenerative medicine applications.

Authors 9

1. Alp Sarisoy Aachen Department of Biohybrid & Medical Textiles (BioTex) Institute of Applied Medical Engineering

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Biohybrid & Medical Textiles (BioTex), Institute of Applied Medical Engineering, Uniklinik RWTH Aachen

2. Yong Xu Aachen Department of Biohybrid & Medical Textiles (BioTex) Institute of Applied Medical Engineering

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Biohybrid & Medical Textiles (BioTex), Institute of Applied Medical Engineering, Uniklinik RWTH Aachen

3. Stephan Rütten Aachen Electron Microscopy Facility Institute of Pathology

   Universitätsklinikum Aachen

   Affiliation as printed

   Electron Microscopy Facility, Institute of Pathology, Uniklinik RWTH Aachen

4. Eva Miriam Buhl Aachen Electron Microscopy Facility Institute of Pathology

   Universitätsklinikum Aachen

   Affiliation as printed

   Electron Microscopy Facility, Institute of Pathology, Uniklinik RWTH Aachen

5. Cécile L. Maire

   University Medical Center Hamburg-Eppendorf

   Affiliation as printed

   Department of Neurosurgery, University Medical Center Hamburg-Eppendorf

6. Sandra Fuest

   University Medical Center Hamburg-Eppendorf

   Affiliation as printed

   Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf

7. Ralf Smeets

   University Medical Center Hamburg-Eppendorf

   Affiliation as printed

   Department of Oral and Maxillofacial Surgery, Division of Regenerative Orofacial Medicine, University Medical Center Hamburg-Eppendorf

   Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf

8. Franz Lennard Ricklefs

   University Medical Center Hamburg-Eppendorf

   Affiliation as printed

   Department of Neurosurgery, University Medical Center Hamburg-Eppendorf

9. Christian Apel corresponding Aachen Department of Biohybrid & Medical Textiles (BioTex) Institute of Applied Medical Engineering

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Biohybrid & Medical Textiles (BioTex), Institute of Applied Medical Engineering, Uniklinik RWTH Aachen