Abstract
The development of porous hyaluronic acid (HA) hydrogels for corneal endothelial tissue engineering is attractive because they can be used as functional cell delivery carriers to help in the reconstruction of damaged areas. The purpose of this study was to investigate the corneal endothelial cytocompatibility and cell delivery performance of porous HA hydrogel biomaterials fabricated at different pre-freezing temperatures. As compared to their counterparts prepared at −80 °C, the HA samples fabricated at higher pre-freezing temperature (i.e., 0 °C) exhibited a larger pore size and higher porosity, thereby leading to lower resistance to glucose permeation. Live/dead assays and gene expression analyses showed that the restricted porous structure of HA carriers decreases the viability and ionic pump function of cultured corneal endothelial cells (CECs). The results also indicated that the porous hydrogel biomaterials fabricated at high pre-freezing temperature seem to be more compatible with rabbit CECs. In an animal model of corneal endothelial dysfunction, the wounded rabbit corneas receiving bioengineered CEC sheets and restricted porous-structured HA carriers demonstrated poor tissue reconstruction. The therapeutic efficacy of cell sheet transplants can be improved by using carrier materials prepared at high pre-freezing temperature. Our findings suggest that the cryogenic operation temperature-mediated pore microstructure of HA carriers plays an important role in corneal endothelial cytocompatibility and cell delivery performance.
Highlights
Biomaterial hydrogels can provide a favorable microenvironment for cell organization and tissue regeneration [1]
It has been documented that the variations in the pore microstructure of biomaterial hydrogels reflect the importance of heat transfer rates during the cryogenic treatment [24]
While a few small pores were present on the surface of hyaluronic acid (HA) carriers prepared by freezing at 0 °C, the samples frozen at −80 °C showed fine-grained microstructures with almost no pores
Summary
Biomaterial hydrogels can provide a favorable microenvironment for cell organization and tissue regeneration [1]. The tissue-compatible hydrogel carriers are widespread in current cell delivery applications. Liu et al have demonstrated that the constructs fabricated by culturing human umbilical cord mesenchymal stem cells in a fibrin hydrogel containing degradable microbeads display enhanced cell viability and successful myogenic differentiation with the formation of multinucleated myotubes [4]. These studies reflect the importance of using natural or synthetic biomaterials as functional cell delivery carriers
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