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A functional corona around extracellular vesicles enhances angiogenesis, skin regeneration and immunomodulation.

ABSTRACT: Nanoparticles can acquire a plasma protein corona defining their biological identity. Corona functions were previously considered for cell-derived extracellular vesicles (EVs). Here we demonstrate that nano-sized EVs from therapy-grade human placental-expanded (PLX) stromal cells are surrounded by an imageable and functional protein corona when enriched with permissive technology. Scalable EV separation from cell-secreted soluble factors via tangential flow-filtration (TFF) and subtractive tandem mass-tag (TMT) proteomics revealed significant enrichment of predominantly immunomodulatory and proangiogenic proteins. Western blot, calcein-based flow cytometry, super-resolution and electron microscopy verified EV identity. PLX-EVs partly protected corona proteins from protease digestion. EVs significantly ameliorated human skin regeneration and angiogenesis in vivo, induced differential signalling in immune cells, and dose-dependently inhibited T cell proliferation in vitro. Corona removal by size-exclusion or ultracentrifugation abrogated angiogenesis. Re-establishing an artificial corona by cloaking EVs with fluorescent albumin as a model protein or defined proangiogenic factors was depicted by super-resolution microscopy, electron microscopy and zeta-potential shift, and served as a proof-of-concept. Understanding EV corona formation will improve rational EV-inspired nano-therapy design.

SUBMITTER: Wolf M

PROVIDER: S-EPMC8994701 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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A functional corona around extracellular vesicles enhances angiogenesis, skin regeneration and immunomodulation.

Wolf Martin M Poupardin Rodolphe W RW Ebner-Peking Patricia P Andrade André Cronemberger AC Blöchl Constantin C Obermayer Astrid A Gomes Fausto Gueths FG Vari Balazs B Maeding Nicole N Eminger Essi E Binder Heide-Marie HM Raninger Anna M AM Hochmann Sarah S Brachtl Gabriele G Spittler Andreas A Heuser Thomas T Ofir Racheli R Huber Christian G CG Aberman Zami Z Schallmoser Katharina K Volk Hans-Dieter HD Strunk Dirk D

Journal of extracellular vesicles 20220401 4

Nanoparticles can acquire a plasma protein corona defining their biological identity. Corona functions were previously considered for cell-derived extracellular vesicles (EVs). Here we demonstrate that nano-sized EVs from therapy-grade human placental-expanded (PLX) stromal cells are surrounded by an imageable and functional protein corona when enriched with permissive technology. Scalable EV separation from cell-secreted soluble factors via tangential flow-filtration (TFF) and subtractive tande ...[more]

PMID: 35398993

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Project description:BackgroundDental implants are an important option for replacement of missing teeth. A major clinical challenge is how best to accelerate bone regeneration and reduce the healing time for functional restoration after implant placement. A sclerostin-neutralizing antibody (Scl-Ab) has been shown to enhance alveolar bone formation and fracture repair. The aim of this study was to investigate the effects of systemic administration of Scl-Ab on dental implant osseointegration and bone regeneration in an experimental alveolar ridge tooth extraction model.Materials and methodsTo investigate the effects of Scl-Ab on bone regeneration and dental implant osseointegration, an experimental alveolar bone osteotomy rat model was adopted. One month after extraction of maxillary right first molars, osteotomy defects were created at the coronal aspect of each of the extraction sites, and 1 × 2-mm custom titanium implants were installed into the osteotomies. Coincident with implant placement, Scl-Ab was administered subcutaneously at a dose of 25 mg/kg twice weekly for 10-28 days and compared with a vehicle control. Animals were sacrificed 10, 14, and 28 days after surgery, and maxillae were harvested and analyzed by microcomputed tomography (microCT), histology, and histomorphometry.ResultsmicroCT analysis demonstrated that the maxillary bone volume fraction was approximately 2- to 2.5-fold greater in Scl-Ab-treated animals compared with vehicle alone at days 14 and 28. Consistent with those findings, two-dimensional bone fill percentages within the coronal osteotomy sites were highest in Scl-Ab treatment groups at 28 days. In addition, bone-implant contact at 28 days was approximately twofold greater in the Scl-Ab group compared with the vehicle control.ConclusionsThese results indicate that systemic Scl-Ab administration enhances osseointegration and bone regeneration around dental implants. This approach offers potential as a treatment modality for patients with low bone mass or bone defects to achieve more predictable bone regeneration at alveolar bone defects and to enhance dental implant osseointegration.

Dataset Information

A functional corona around extracellular vesicles enhances angiogenesis, skin regeneration and immunomodulation.

Publications

A functional corona around extracellular vesicles enhances angiogenesis, skin regeneration and immunomodulation.

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