Nanofiber-reinforced decellularized amniotic membrane improves limbal stem cell transplantation in a rabbit model of corneal epithelial defect

Zhengbing Zhou, Da Long, Chih Chien Hsu, Huanhuan Liu, Long Chen, Benjamin Slavin, Hui Lin, Xiaowei Li, Juyu Tang, Samuel Chi-Hung Yiu, Sami Tuffaha, Hai Quan Mao

Research output: Contribution to journalArticle

Abstract

Human amniotic membrane (AM) offers unique advantages as a matrix to support the transplantation of limbal stem cells (LSCs) due to its inherent pro-regenerative and anti-inflammatory properties. However, the widespread use of AM in clinical treatments of ocular surface disorders is limited by its weak mechanical strength and fast degradation, and high cost associated with preserving freshly isolated AM. Here we constructed a composite membrane consisting of an electrospun bioabsorbable poly(ε-caprolactone) (PCL) nanofiber mesh to significantly improve the ultimate tensile strength, toughness, and suture retention strength by 4–10-fold in comparison with decellularized AM sheet. The composite membrane showed extended stability and conferred longer-lasting coverage on wounded cornea surface compared with dAM. The composite membrane maintained the pro-regenerative and immunomodulatory properties of dAM, promoted LSC survival, retention, and organization, improved re-epithelialization of the defect area, and reduced inflammation and neovascularization. This study demonstrates the translational potential of our composite membrane for stem cell-based treatment of ocular surface damage. Statement of Significance: Human decellularized amniotic membrane (dAM) has been widely shown as a biodegradable and bioactive matrix for regenerative tissue repair. However, the weak mechanical property has limited its widespread use in the clinic. Here we constructed a composite membrane using a layer of electrospun poly(ε-caprolactone) (PCL) nanofiber mesh to reinforce the dAM sheet through covalent interfacial bonding, while retaining the unique bioactivity of dAM. In a rabbit model of limbal stem cell (LSC) deficiency induced by alkaline burn, we demonstrated the superior property of this PCL-dAM composite membrane for repairing damaged cornea through promoting LSC transplantation, improving re-epithelialization, and reducing inflammation and neovascularization. This new composite membrane offers great translational potential in supporting stem cell-based treatment of ocular surface damage.

Original languageEnglish (US)
JournalActa Biomaterialia
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Nanofibers
Amnion
Stem Cell Transplantation
Stem cells
Composite membranes
Rabbits
Membranes
Defects
Stem Cells
Re-Epithelialization
Cornea
Inflammation
Tensile Strength
Bioactivity
Toughness
Strength of materials
Sutures
Repair
Anti-Inflammatory Agents
Tensile strength

Keywords

  • Amniotic membrane
  • Composite membrane
  • Electrospinning
  • Limbal stem cell deficiency
  • Nanofibers
  • Transplantation

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Biochemistry
  • Biomedical Engineering
  • Molecular Biology

Cite this

Nanofiber-reinforced decellularized amniotic membrane improves limbal stem cell transplantation in a rabbit model of corneal epithelial defect. / Zhou, Zhengbing; Long, Da; Hsu, Chih Chien; Liu, Huanhuan; Chen, Long; Slavin, Benjamin; Lin, Hui; Li, Xiaowei; Tang, Juyu; Yiu, Samuel Chi-Hung; Tuffaha, Sami; Mao, Hai Quan.

In: Acta Biomaterialia, 01.01.2019.

Research output: Contribution to journalArticle

Zhou, Zhengbing ; Long, Da ; Hsu, Chih Chien ; Liu, Huanhuan ; Chen, Long ; Slavin, Benjamin ; Lin, Hui ; Li, Xiaowei ; Tang, Juyu ; Yiu, Samuel Chi-Hung ; Tuffaha, Sami ; Mao, Hai Quan. / Nanofiber-reinforced decellularized amniotic membrane improves limbal stem cell transplantation in a rabbit model of corneal epithelial defect. In: Acta Biomaterialia. 2019.
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abstract = "Human amniotic membrane (AM) offers unique advantages as a matrix to support the transplantation of limbal stem cells (LSCs) due to its inherent pro-regenerative and anti-inflammatory properties. However, the widespread use of AM in clinical treatments of ocular surface disorders is limited by its weak mechanical strength and fast degradation, and high cost associated with preserving freshly isolated AM. Here we constructed a composite membrane consisting of an electrospun bioabsorbable poly(ε-caprolactone) (PCL) nanofiber mesh to significantly improve the ultimate tensile strength, toughness, and suture retention strength by 4–10-fold in comparison with decellularized AM sheet. The composite membrane showed extended stability and conferred longer-lasting coverage on wounded cornea surface compared with dAM. The composite membrane maintained the pro-regenerative and immunomodulatory properties of dAM, promoted LSC survival, retention, and organization, improved re-epithelialization of the defect area, and reduced inflammation and neovascularization. This study demonstrates the translational potential of our composite membrane for stem cell-based treatment of ocular surface damage. Statement of Significance: Human decellularized amniotic membrane (dAM) has been widely shown as a biodegradable and bioactive matrix for regenerative tissue repair. However, the weak mechanical property has limited its widespread use in the clinic. Here we constructed a composite membrane using a layer of electrospun poly(ε-caprolactone) (PCL) nanofiber mesh to reinforce the dAM sheet through covalent interfacial bonding, while retaining the unique bioactivity of dAM. In a rabbit model of limbal stem cell (LSC) deficiency induced by alkaline burn, we demonstrated the superior property of this PCL-dAM composite membrane for repairing damaged cornea through promoting LSC transplantation, improving re-epithelialization, and reducing inflammation and neovascularization. This new composite membrane offers great translational potential in supporting stem cell-based treatment of ocular surface damage.",
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AU - Hsu, Chih Chien

AU - Liu, Huanhuan

AU - Chen, Long

AU - Slavin, Benjamin

AU - Lin, Hui

AU - Li, Xiaowei

AU - Tang, Juyu

AU - Yiu, Samuel Chi-Hung

AU - Tuffaha, Sami

AU - Mao, Hai Quan

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AB - Human amniotic membrane (AM) offers unique advantages as a matrix to support the transplantation of limbal stem cells (LSCs) due to its inherent pro-regenerative and anti-inflammatory properties. However, the widespread use of AM in clinical treatments of ocular surface disorders is limited by its weak mechanical strength and fast degradation, and high cost associated with preserving freshly isolated AM. Here we constructed a composite membrane consisting of an electrospun bioabsorbable poly(ε-caprolactone) (PCL) nanofiber mesh to significantly improve the ultimate tensile strength, toughness, and suture retention strength by 4–10-fold in comparison with decellularized AM sheet. The composite membrane showed extended stability and conferred longer-lasting coverage on wounded cornea surface compared with dAM. The composite membrane maintained the pro-regenerative and immunomodulatory properties of dAM, promoted LSC survival, retention, and organization, improved re-epithelialization of the defect area, and reduced inflammation and neovascularization. This study demonstrates the translational potential of our composite membrane for stem cell-based treatment of ocular surface damage. Statement of Significance: Human decellularized amniotic membrane (dAM) has been widely shown as a biodegradable and bioactive matrix for regenerative tissue repair. However, the weak mechanical property has limited its widespread use in the clinic. Here we constructed a composite membrane using a layer of electrospun poly(ε-caprolactone) (PCL) nanofiber mesh to reinforce the dAM sheet through covalent interfacial bonding, while retaining the unique bioactivity of dAM. In a rabbit model of limbal stem cell (LSC) deficiency induced by alkaline burn, we demonstrated the superior property of this PCL-dAM composite membrane for repairing damaged cornea through promoting LSC transplantation, improving re-epithelialization, and reducing inflammation and neovascularization. This new composite membrane offers great translational potential in supporting stem cell-based treatment of ocular surface damage.

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