Design of functional decellularized matrix for conjunctival epithelial stem cell maintenance and ocular surface reconstruction

Conjunctival defects severely impair ocular surface homeostasis and vision. However, the existing conjunctival reconstruction methods are still unable to achieve satisfactory functional replacement of conjunctiva. Scaffold materials that provide a more stem-cell-friendly microenvironment are in urge...

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Main Authors: Nianxuan Wu, Danni Gong, Jin Chen, Junzhao Chen, Liangbo Chen, Hao Sun, Yao Fu
Format: Article
Language:English
Published: Elsevier 2022-12-01
Series:Materials & Design
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0264127522009005
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author Nianxuan Wu
Danni Gong
Jin Chen
Junzhao Chen
Liangbo Chen
Hao Sun
Yao Fu
author_facet Nianxuan Wu
Danni Gong
Jin Chen
Junzhao Chen
Liangbo Chen
Hao Sun
Yao Fu
author_sort Nianxuan Wu
collection DOAJ
description Conjunctival defects severely impair ocular surface homeostasis and vision. However, the existing conjunctival reconstruction methods are still unable to achieve satisfactory functional replacement of conjunctiva. Scaffold materials that provide a more stem-cell-friendly microenvironment are in urgent need of improvement. Herein we reported a functional conjunctival reconstruction scaffold constructed from decellularized matrix derived from rabbit subconjunctival fibroblasts (DM-SCF) loaded with conjunctival epithelial stem cells (CjESCs) for ocular surface repair. The DM-SCF had a thickness and mechanical strength close to that of normal conjunctiva and showed excellent biocompatibility. CjESCs inoculated on DM-SCF maintained good stem cell properties, which showed long-term maintenance of low differentiation and good proliferation activity. DM-SCF transplantation with CjESCs showed satisfactory results in rabbit models of a large conjunctival defect. The conjunctiva was reconstructed with abundant goblet cell expression and regular fiber arrangement. Protein mass spectrometry revealed the active extracellular matrix components of DM-SCF, regulating the activation of Wnt/β-catenin and Notch pathways for stem cell maintenance. Overall, our study developed a promising new strategy for ocular surface reconstruction by optimizing bioactive scaffold and providing functional stem cell niche, so as to achieve long-standing and superior functional repair.
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spelling doaj.art-d6d1ca6296604ff9927dd0fc69dcffc52022-12-22T04:42:04ZengElsevierMaterials & Design0264-12752022-12-01224111278Design of functional decellularized matrix for conjunctival epithelial stem cell maintenance and ocular surface reconstructionNianxuan Wu0Danni Gong1Jin Chen2Junzhao Chen3Liangbo Chen4Hao Sun5Yao Fu6Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, ChinaDepartment of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, ChinaDepartment of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, ChinaDepartment of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, ChinaDepartment of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, ChinaCorresponding authors at: Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, ChinaCorresponding authors at: Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, ChinaConjunctival defects severely impair ocular surface homeostasis and vision. However, the existing conjunctival reconstruction methods are still unable to achieve satisfactory functional replacement of conjunctiva. Scaffold materials that provide a more stem-cell-friendly microenvironment are in urgent need of improvement. Herein we reported a functional conjunctival reconstruction scaffold constructed from decellularized matrix derived from rabbit subconjunctival fibroblasts (DM-SCF) loaded with conjunctival epithelial stem cells (CjESCs) for ocular surface repair. The DM-SCF had a thickness and mechanical strength close to that of normal conjunctiva and showed excellent biocompatibility. CjESCs inoculated on DM-SCF maintained good stem cell properties, which showed long-term maintenance of low differentiation and good proliferation activity. DM-SCF transplantation with CjESCs showed satisfactory results in rabbit models of a large conjunctival defect. The conjunctiva was reconstructed with abundant goblet cell expression and regular fiber arrangement. Protein mass spectrometry revealed the active extracellular matrix components of DM-SCF, regulating the activation of Wnt/β-catenin and Notch pathways for stem cell maintenance. Overall, our study developed a promising new strategy for ocular surface reconstruction by optimizing bioactive scaffold and providing functional stem cell niche, so as to achieve long-standing and superior functional repair.http://www.sciencedirect.com/science/article/pii/S0264127522009005Decellularized matrixSubconjunctival fibroblastsCONJUNCTIVAL epithelial stem cellStem cell maintenanceOcular surface reconstruction
spellingShingle Nianxuan Wu
Danni Gong
Jin Chen
Junzhao Chen
Liangbo Chen
Hao Sun
Yao Fu
Design of functional decellularized matrix for conjunctival epithelial stem cell maintenance and ocular surface reconstruction
Materials & Design
Decellularized matrix
Subconjunctival fibroblasts
CONJUNCTIVAL epithelial stem cell
Stem cell maintenance
Ocular surface reconstruction
title Design of functional decellularized matrix for conjunctival epithelial stem cell maintenance and ocular surface reconstruction
title_full Design of functional decellularized matrix for conjunctival epithelial stem cell maintenance and ocular surface reconstruction
title_fullStr Design of functional decellularized matrix for conjunctival epithelial stem cell maintenance and ocular surface reconstruction
title_full_unstemmed Design of functional decellularized matrix for conjunctival epithelial stem cell maintenance and ocular surface reconstruction
title_short Design of functional decellularized matrix for conjunctival epithelial stem cell maintenance and ocular surface reconstruction
title_sort design of functional decellularized matrix for conjunctival epithelial stem cell maintenance and ocular surface reconstruction
topic Decellularized matrix
Subconjunctival fibroblasts
CONJUNCTIVAL epithelial stem cell
Stem cell maintenance
Ocular surface reconstruction
url http://www.sciencedirect.com/science/article/pii/S0264127522009005
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