A Caltech Library Service

Mitigating Scarring and Inflammation during Corneal Wound Healing using Nanofiber-Hydrogel Scaffolds


Fu, Amy Hau Yu (2015) Mitigating Scarring and Inflammation during Corneal Wound Healing using Nanofiber-Hydrogel Scaffolds. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/Z9Q81B00.


Due to the universal lack of donor tissue, there has been emerging interest in engineering materials to stimulate living cells to restore the features and functions of injured organs. We are particularly interested in developing materials for corneal use, where the necessity to maintain the tissue’s transparency presents an additional challenge. Every year, there are 1.5 – 2 million new cases of monocular blindness due to irregular healing of corneal injuries, dwarfing the approximately 150,000 corneal transplants performed. The large gap between the need and availability of cornea transplantation motivates us to develop a wound-healing scaffold that can prevent corneal blindness.

To develop such a scaffold, it is necessary to regulate the cells responsible for repairing the damaged cornea, namely myofibroblasts, which are responsible for the disordered and non-refractive index matched scar that leads to corneal blindness. Using in vitro assays, we identified that protein nanofibers of certain orientation can promote cell migration and modulate the myofibroblast phenotype. The nanofibers are also transparent, easy to handle and non-cytotoxic. To adhere the nanofibers to a wound bed, we examined the use of two different in situ forming hydrogels: an artificial extracellular matrix protein (aECM)-based gel and a photo-crosslinkable heparin-based gel. Both hydrogels can be formed within minutes, are transparent upon gelation and are easily tunable.

Using an in vivo mouse model for epithelial defects, we show that our corneal scaffolds (nanofibers together with hydrogel) are well-tolerated (no inflammatory response or turbidity) and support epithelium regrowth. We developed an ex vivo corneal tissue culture model where corneas that are wounded and treated with our scaffold can be cultured while retaining their ability to repair wounds for up to 21 days. Using this technique, we found that the aECM-based treatment induced a more favorable wound response than the heparin-based treatment, prompting us to further examine the efficacy of the aECM-based treatment in vivo using a rabbit model for stromal wounds. Results show that treated corneas have fewer myofibroblasts and immune cells than untreated ones, indicating that our corneal scaffold shows promise in promoting a calmer wound response and preventing corneal haze formation.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:cornea; wound healing; scaffolds
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Chemical Engineering
Awards:Constantin G. Economou Memorial Prize, 2011
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Kornfield, Julia A.
Thesis Committee:
  • Kornfield, Julia A. (chair)
  • Tirrell, David A.
  • Davis, Mark E.
  • Shapiro, Mikhail G.
Defense Date:19 May 2015
Non-Caltech Author Email:amyfu.hy (AT)
Record Number:CaltechTHESIS:05272015-172038281
Persistent URL:
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:8893
Deposited By: Amy Fu
Deposited On:28 May 2015 19:27
Last Modified:04 Oct 2019 00:08

Thesis Files

PDF - Final Version
See Usage Policy.


Repository Staff Only: item control page