Bioactive proteins delivery through core-shell nanofibers for meniscal tissue regeneration

Mimicking the ultrastructural morphology of the meniscus with nanofiber scaffolds, coupled with controlled growth-factor delivery to the appropriate cells, can help engineer tissue with the potential to grow, mature, and regenerate after in vivo implantation. We electrospun nanofibers encapsulating...

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Published in:	Nanomedicine Vol. 23; p. 102090
Main Authors:	Baek, Jihye, Lee, Emily, Lotz, Martin K, D'Lima, Darryl D
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-01-2020
Subjects:	Adolescent Adult Becaplermin - chemistry Becaplermin - pharmacology Co-axial electrospinning Core-shell structure Delayed-Action Preparations - chemistry Delayed-Action Preparations - pharmacology Female Humans Male Meniscus Meniscus - physiology Nanofibers Nanofibers - chemistry PDGF-BB Polyesters - chemistry Polyesters - pharmacology Regeneration - drug effects Tissue Engineering Tissue Scaffolds - chemistry Core-shell structure Meniscus Co-axial electrospinning Nanofibers Tissue engineering PDGF-BB
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Abstract	Mimicking the ultrastructural morphology of the meniscus with nanofiber scaffolds, coupled with controlled growth-factor delivery to the appropriate cells, can help engineer tissue with the potential to grow, mature, and regenerate after in vivo implantation. We electrospun nanofibers encapsulating platelet-derived growth factor (PDGF-BB), which is a potent mitogen and chemoattractant in a core of serum albumin contained within a shell of polylactic acid. We controlled the local PDGF-BB release by adding water-soluble polyethylene glycol to the polylactic acid shell to serve as a porogen. The novel core-shell nanofibers generated 3D scaffolds with an interconnected macroporous structure, with appropriate mechanical properties and with high cell compatibility. Incorporating PDGF-BB increased cell viability, proliferation, and infiltration, and upregulated key genes involved in meniscal extracellular matrix synthesis in human meniscal and synovial cells. Our results support proof of concept that these core-shell nanofibers can create a cell-favorable nanoenvironment and can serve as a system for sustained release of bioactive factors. We electrospun core-shell nanofibers encapsulating platelet-derived growth factor (PDGF-bb) in a core of serum albumin contained within a shell of polylactic acid. Transmission electron microscopy revealed the core of serum albumin containing PDGF-bb. Incorporating PDGF-bb increased cell viability, proliferation, and migration. Core-shell nanofibers can create a cell-favorable nanoenvironment and serve as a model system for sustained release of bioactive factors. [Display omitted]
AbstractList	Mimicking the ultrastructural morphology of the meniscus with nanofiber scaffolds, coupled with controlled growth-factor delivery to the appropriate cells, can help engineer tissue with the potential to grow, mature, and regenerate after in vivo implantation. We electrospun nanofibers encapsulating platelet-derived growth factor (PDGF-BB), which is a potent mitogen and chemoattractant in a core of serum albumin contained within a shell of polylactic acid. We controlled the local PDGF-BB release by adding water-soluble polyethylene glycol to the polylactic acid shell to serve as a porogen. The novel core-shell nanofibers generated 3D scaffolds with an interconnected macroporous structure, with appropriate mechanical properties and with high cell compatibility. Incorporating PDGF-BB increased cell viability, proliferation, and infiltration, and upregulated key genes involved in meniscal extracellular matrix synthesis in human meniscal and synovial cells. Our results support proof of concept that these core-shell nanofibers can create a cell-favorable nanoenvironment and can serve as a system for sustained release of bioactive factors. We electrospun core-shell nanofibers encapsulating platelet-derived growth factor (PDGF-bb) in a core of serum albumin contained within a shell of polylactic acid. Transmission electron microscopy revealed the core of serum albumin containing PDGF-bb. Incorporating PDGF-bb increased cell viability, proliferation, and migration. Core-shell nanofibers can create a cell-favorable nanoenvironment and serve as a model system for sustained release of bioactive factors. [Display omitted] Mimicking the ultrastructural morphology of the meniscus with nanofiber scaffolds, coupled with controlled growth-factor delivery to the appropriate cells, can help engineer tissue with the potential to grow, mature, and regenerate after in vivo implantation. We electrospun nanofibers encapsulating platelet-derived growth factor (PDGF-BB), which is a potent mitogen and chemoattractant in a core of serum albumin contained within a shell of polylactic acid. We controlled the local PDGF-BB release by adding water-soluble polyethylene glycol to the polylactic acid shell to serve as a porogen. The novel core-shell nanofibers generated 3D scaffolds with an interconnected macroporous structure, with appropriate mechanical properties and with high cell compatibility. Incorporating PDGF-BB increased cell viability, proliferation, and infiltration, and upregulated key genes involved in meniscal extracellular matrix synthesis in human meniscal and synovial cells. Our results support proof of concept that these core-shell nanofibers can create a cell-favorable nanoenvironment and can serve as a system for sustained release of bioactive factors. We electrospun core-shell nanofibers encapsulating platelet-derived growth factor (PDGF-bb) in a core of serum albumin contained within a shell of polylactic acid. Transmission electron microscopy revealed the core of serum albumin containing PDGF-bb. Incorporating PDGF-bb increased cell viability, proliferation, and migration. Core-shell nanofibers can create a cell-favorable nanoenvironment and serve as a model system for sustained release of bioactive factors. Mimicking the ultrastructural morphology of the meniscus with nanofiber scaffolds, coupled with controlled growth-factor delivery to the appropriate cells, can help engineer tissue with the potential to grow, mature, and regenerate after in vivo implantation. We electrospun nanofibers encapsulating platelet-derived growth factor (PDGF-BB), which is a potent mitogen and chemoattractant in a core of serum albumin contained within a shell of polylactic acid. We controlled the local PDGF-BB release by adding water-soluble polyethylene glycol to the polylactic acid shell to serve as a porogen. The novel core-shell nanofibers generated 3D scaffolds with an interconnected macroporous structure, with appropriate mechanical properties and with high cell compatibility. Incorporating PDGF-BB increased cell viability, proliferation, and infiltration, and upregulated key genes involved in meniscal extracellular matrix synthesis in human meniscal and synovial cells. Our results support proof of concept that these core-shell nanofibers can create a cell-favorable nanoenvironment and can serve as a system for sustained release of bioactive factors.
ArticleNumber	102090
Author	D'Lima, Darryl D Baek, Jihye Lee, Emily Lotz, Martin K
AuthorAffiliation	a Shiley Center for Orthopaedic Research and Education at Scripps Clinic, 10666 North Torrey Pines Road, MS126, La Jolla, CA 92037 b Department of Molecular Medicine, Scripps Research, 10550 North Torrey Pines Road, MB-102A, La Jolla, CA 92037
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Author_xml	– sequence: 1 givenname: Jihye surname: Baek fullname: Baek, Jihye email: jbaek@scripps.edu organization: Shiley Center for Orthopaedic Research and Education at Scripps Clinic, La Jolla, CA – sequence: 2 givenname: Emily surname: Lee fullname: Lee, Emily email: emilyelizabethlee@gmail.com organization: Shiley Center for Orthopaedic Research and Education at Scripps Clinic, La Jolla, CA – sequence: 3 givenname: Martin K surname: Lotz fullname: Lotz, Martin K email: mlotz@scripps.edu organization: Department of Molecular Medicine, Scripps Research, La Jolla, CA – sequence: 4 givenname: Darryl D surname: D'Lima fullname: D'Lima, Darryl D email: ddlima@scripps.edu organization: Shiley Center for Orthopaedic Research and Education at Scripps Clinic, La Jolla, CA
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Keywords	Core-shell structure Meniscus Co-axial electrospinning Nanofibers Tissue engineering PDGF-BB
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Notes	J.B., M.K.L., and D.D.D. designed the study and wrote the manuscript in close collaboration with the other authors. J.B. and E. L. conducted cell culture studies and conducted histology and qPCR analyses. J.B conducted and interpreted the SEM analysis. J.B. conducted the ex vivo repair model. All authors discussed the results and approved the final version of the article. Author Contributions
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Snippet	Mimicking the ultrastructural morphology of the meniscus with nanofiber scaffolds, coupled with controlled growth-factor delivery to the appropriate cells, can...
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SubjectTerms	Adolescent Adult Becaplermin - chemistry Becaplermin - pharmacology Co-axial electrospinning Core-shell structure Delayed-Action Preparations - chemistry Delayed-Action Preparations - pharmacology Female Humans Male Meniscus Meniscus - physiology Nanofibers Nanofibers - chemistry PDGF-BB Polyesters - chemistry Polyesters - pharmacology Regeneration - drug effects Tissue Engineering Tissue Scaffolds - chemistry
Title	Bioactive proteins delivery through core-shell nanofibers for meniscal tissue regeneration
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