Corneal Scar Repair through SPAACKL: Sutureless, Pro-regenerative Anterior Additive Collagen gel KeratopLasty

通过 SPAACKL 修复角膜疤痕:无缝线、促再生前部添加剂胶原蛋白凝胶 KeratopLasty

基本信息

  • 批准号:
    10570965
  • 负责人:
  • 金额:
    $ 50.69万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-03-01 至 2026-12-31
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY/ABSTRACT As the dome-shaped, transparent outermost part of the eye, the cornea provides the majority of the focusing power for the visual pathway. When it is damaged due to severe injury or disease, scarring often ensues, resulting in reduced vision and, in many cases, blindness. In spite of the various types of corneal transplants that are available, there remains a major clinical need for new modalities to restore transparency to scarred corneas without donor tissue, which is in short supply worldwide. Corneal mesenchymal stromal cells (c- MSCs) have known therapeutic effects on corneal scarring and wound healing, but the optimal way to deliver their benefits to the eye have yet to be determined. We are developing Sutureless, Pro-regenerative, Anterior Additive Collagen gel KeratopLasty (SPAACKL), a procedure that removes and replaces blinding corneal scars with a transparent, stroma-like gel matrix containing c-MSCs. After removal of corneal scar tissue, the material is applied to the defect as a viscous liquid suspension of c-MSCs, forming a crosslinked, transparent cellularized stromal substitute within minutes that not only recreates the smooth surface necessary for clear vision but also promotes rapid re-epithelialization. This technology leverages a crosslinking technology known as copper-free click chemistry that is bio-orthogonal: it does not react with proteins, cells, or biologic systems of any kind. As such, it can be safely applied to a corneal wound and around c-MSCs without producing toxic side products, and without the need for light energy, catalysts or accelerators. Our central hypothesis is that bio-orthogonal crosslinking can improve the regenerative benefits of c-MSCs by preserving the bioactivity of its encapsulated cargo compared to less specific crosslinking chemistries that are used currently in corneal surgery. In preliminary work, we have demonstrated that bio-orthogonally crosslinked gels support the growth of encapsulated stromal cells and have demonstrated the regenerative capacity of these cell-matrix composites to support rapid, multi-layered epithelialization both ex vivo and in vivo. Motivated by this data, our first aim is to test the hypothesis that matrix stiffness, composition, and crosslinking chemistry influence c-MSCs’ viability and secretion of pro- regenerative factors. Our second aim is to test the hypothesis that encapsulated c-MSCs exert their pro- regenerative influence on the corneal epithelium primarily through paracrine signaling. Our third aim is to evaluate the ability of bio-orthogonally crosslinked hydrogels to deliver therapeutic cargo that enhances epithelial and stromal regeneration through an in vivo keratectomy model. This research will build the foundational data for eventual clinical translation of a new way to treat corneal blindness without the need for sutures, light energy, or cadaveric donor tissue, and has the potential to one day help patients avoid the need for a traditional corneal transplant.
项目总结/文摘

项目成果

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David Myung其他文献

David Myung的其他文献

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{{ truncateString('David Myung', 18)}}的其他基金

Corneal Scar Repair through SPAACKL: Sutureless, Pro-regenerative Anterior Additive Collagen gel KeratopLasty
通过 SPAACKL 修复角膜疤痕:无缝线、促再生前部添加剂胶原蛋白凝胶 KeratopLasty
  • 批准号:
    10343517
  • 财政年份:
    2022
  • 资助金额:
    $ 50.69万
  • 项目类别:
Corneal Reconstruction through an In Situ-Forming Collagen Gel
通过原位形成胶原凝胶进行角膜重建
  • 批准号:
    10249065
  • 财政年份:
    2019
  • 资助金额:
    $ 50.69万
  • 项目类别:
In Situ Bioconjugation as a Therapeutic Delivery Modality to Enhance Ocular Wound Healing
原位生物共轭作为增强眼部伤口愈合的治疗传递方式
  • 批准号:
    10171858
  • 财政年份:
    2017
  • 资助金额:
    $ 50.69万
  • 项目类别:

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