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Title: Sequentially-crosslinked bioactive hydrogels as nano-patterned substrates with customizable stiffness and degradation for corneal tissue engineering applications
Authors: Rizwan M.
Peh G.S.L.
Ang H.-P.
Lwin N.C.
Adnan K.
Mehta J.S.
Tan W.S.
Yim E.K.F. 
Keywords: GelMA
Human corneal endothelium
Hydrogel membrane
Issue Date: 1-Mar-2017
Publisher: Elsevier Ltd
Citation: Rizwan M., Peh G.S.L., Ang H.-P., Lwin N.C., Adnan K., Mehta J.S., Tan W.S., Yim E.K.F. (2017-03-01). Sequentially-crosslinked bioactive hydrogels as nano-patterned substrates with customizable stiffness and degradation for corneal tissue engineering applications. Biomaterials 120 : 139-154. ScholarBank@NUS Repository.
Abstract: Naturally-bioactive hydrogels like gelatin provide favorable properties for tissue-engineering but lack sufficient mechanical strength for use as implantable tissue engineering substrates. Complex fabrication or multi-component additives can improve material strength, but often compromises other properties. Studies have shown gelatin methacrylate (GelMA) as a bioactive hydrogel with diverse tissue growth applications. We hypothesize that, with suitable material modifications, GelMA could be employed for growth and implantation of tissue-engineered human corneal endothelial cell (HCEC) monolayer. Tissue-engineered HCEC monolayer could potentially be used to treat corneal blindness due to corneal endothelium dysfunction. Here, we exploited a sequential hybrid (physical followed by UV) crosslinking to create an improved material, named as GelMA+, with over 8-fold increase in mechanical strength as compared to regular GelMA. The presence of physical associations increased the subsequent UV-crosslinking efficiency resulting in robust materials able to withstand standard endothelium insertion surgical device loading. Favorable biodegradation kinetics were also measured in�vitro and in�vivo. We achieved hydrogels patterning with nano-scale resolution by use of oxygen impermeable stamps that overcome the limitations of PDMS based molding processes. Primary HCEC monolayers grown on GelMA+�carrier patterned with pillars of optimal dimension demonstrated improved zona-occludin-1 expression, higher cell density and cell size homogeneity, which are indications of functionally-superior transplantable monolayers. The hybrid crosslinking and fabrication approach offers potential utility for development of implantable tissue-engineered cell-carrier constructs with enhanced bio-functional properties. � 2017 Elsevier Ltd
Source Title: Biomaterials
ISSN: 01429612
DOI: 10.1016/j.biomaterials.2016.12.026
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