Design of functional decellularized matrix for conjunctival epithelial stem cell maintenance and ocular surface reconstruction. (December 2022)

• Record Type: Journal Article
• Authors: Wu, Nianxuan; Gong, Danni; Chen, Jin; Chen, Junzhao; Chen, Liangbo; Sun, Hao; Fu, Yao
• Is Part Of: Materials & design. Volume 224(2022)
• Publication Date: 2022-12
• Subjects: Decellularized matrix -- Subconjunctival fibroblasts -- CONJUNCTIVAL epithelial stem cell -- Stem cell maintenance -- Ocular surface reconstruction; Materials -- Periodicals; Engineering design -- Periodicals; Matériaux -- Périodiques; Conception technique -- Périodiques; Electronic journals; 620.11
• DOI: 10.1016/j.matdes.2022.111278
• Languages: English
• ISSNs: 0264-1275

Abstract

Graphical abstract: Highlights: Decellularized matrix derived from subconjunctival fibroblasts (DM-SCF) obtained in situ from conjunctiva was prepared as a stem-cell-friendly scaffold. The functional niche provided by DM-SCF facilitates stem cell maintenance through Wnt/β-catenin and Notch pathways. DM-SCF can achieve long-term and superior functional repair of the ocular surface. Abstract: 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.