June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Optimization of an in situ-forming interpenetrating polymer network of collagen and hyaluronic acid hydrogel independently and simultaneously crosslinked by click chemistries
Author Affiliations & Notes
  • Peter Le
    Ophthalmology, Stanford University School of Medicine, Palo Alto, California, United States
  • Fang Chen
    Ophthalmology, Stanford University School of Medicine, Palo Alto, California, United States
  • Gabriella Maria Fernandes Cunha
    Ophthalmology, Stanford University School of Medicine, Palo Alto, California, United States
  • Krystal Lai
    Ophthalmology, Stanford University School of Medicine, Palo Alto, California, United States
  • David Myung
    Ophthalmology, Stanford University School of Medicine, Palo Alto, California, United States
    Chemical Engineering, Stanford University, Palo Alto, California, United States
  • Footnotes
    Commercial Relationships   Peter Le, None; Fang Chen, None; Gabriella Cunha, None; Krystal Lai, None; David Myung, Stanford (P)
  • Footnotes
    Support  National Institutes of Health (National Eye Institute K08EY028176 and a Departmental P30-EY026877 core grant), the Stanford SPARK Translational Research Program, a core grant and Career Development Award from the Research to Prevent Blindness (RPB) Foundation, the Matilda Ziegler Foundation (D.M.), and the VA Small Projects in Rehabilitation Research & Development Program.
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 171. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Peter Le, Fang Chen, Gabriella Maria Fernandes Cunha, Krystal Lai, David Myung; Optimization of an in situ-forming interpenetrating polymer network of collagen and hyaluronic acid hydrogel independently and simultaneously crosslinked by click chemistries. Invest. Ophthalmol. Vis. Sci. 2020;61(7):171.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : Collagen type I is the major extracellular matrix protein of the corneal stroma. Hyaluronic acid is a ubiquitous glycosaminoglycan known to promote wound healing in the cornea. Both are promising biomaterial building blocks for engineered corneal tissue. This study optimizes and characterizes a novel, in situ-forming, simultaneous interpenetrating polymer network (IPN) hydrogel that can potentially serve as a stroma tissue substitute to fill deep corneal defects and promote epithelialization.

Methods : The IPN was formed by mixing azide- and alkyne-conjugated collagen type I that react via strain-promoted azide-alkyne cycloaddition (SPAAC) with both methacrylated and thiolated hyaluronic acid (HA-MA, HA-SH) that react via thiol-ene reaction. The components were mixed at a 1:1 ratio and pH was increased to mildly alkaline conditions. Mechanical properties were measured by the storage modulus of the material to determine the stiffness of the gels. Light transmittance of the material after gelation was used to measure transparency. Cytocompatibility was assessed by live/dead assay and cell morphology to determine the ability of corneal epithelial cells to adhere and grow on the IPN.

Results : Increasing the pH to mild alkaline conditions (pH 8.0) and concentration of HA-MA and HA-SH decreased gelation time in the absence of light, heat, or other molecules. The mild alkalinity of the gel resulted in no visible damage to the cornea in ex vivo and in vivo rabbit eyes. The IPN displayed a higher storage modulus than non-crosslinked collagen and the SPAAC gel. Transparency of the gel reached over 95% within the spectrum of 380nm to 700nm, compared to the previously studied gel which exhibited 85% transparency. Corneal epithelial cells plated on top of the IPN gel exhibited improved morphology compared to the HA-only gels, which can be attributed to the addition of cell adhesion-promoting ligands inherent to the collagen in the IPN matrix.

Conclusions : The in situ-forming collagen/HA IPN hydrogel was optimized for faster gelation time while maintaining mechanical properties and increasing transparency. The IPN remains able to support epithelial cell growth while not damaging the corneal surface. These results support the potential use of the material as a scaffold for the reconstruction and regeneration of deep corneal defects.

This is a 2020 ARVO Annual Meeting abstract.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×