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Title

Crosslinking of Dermis-Derived Hydrogels Increases Stiffness and Alters Resistance to Degradation

Creator

Pilipchuk, Sophia

Date

2011-09-13, 2011

Description

Hydrogels have been investigated extensively as biomaterials for three-dimensional tissue reconstruction and regeneration. Incorporation of...
Show moreHydrogels have been investigated extensively as biomaterials for three-dimensional tissue reconstruction and regeneration. Incorporation of tissue-specific features into synthetic materials is difficult, due to limited ability to recreate the complex multi-component nature of extracellular matrices (ECM). ECM-rich hydrogels extracted and assembled from soft tissues have been shown to stimulate the formation of vascularized tissue in vitro and in vivo.1,2,3 Hydrogels derived from dermal tissue using this technique contain basement membrane proteins, including laminin 3, collagen IV, and collagen VII, all of which are essential for proper skin function.2 While these materials have significant biological activity, their poor mechanical properties and rapid degradation in vivo hinder their performance in wound healing applications. This study investigates the effect of covalent crosslinking on the mechanical properties, biological activity, and degradation (in vitro and in vivo) of dermal-derived hydrogels. Glutaraldehyde (GA) is a well-known crosslinking agent used in clinically approved products to prolong lifetime and increase strength of materials. Compression tests indicated increasing elastic modulus and yield stress of crosslinked hydrogels with crosslinking time (p<0.05). The crosslinked ECM were resistant to pepsin degradation in vitro. Gels and gel extracts were non toxic, and fibroblasts adhered and spread on gels at all crosslink densities. Crosslinking drastically slowed degradation relative to controls (non-crosslinked gels) in vivo in a subcutaneous implant model relative to control. While degradation was slowed, inflammation was low and mature vascularized tissue formed in the gels, suggesting that the materials retained the ability to induce tissue invasion. These results support the potential use of dermis-derived hydrogels as promising constructs for applications in tissue engineering and suggest that covalent crosslinking can be used to enhance mechanical properties and prolong hydrogel lifetime while inducing vascularized tissue formation.
Based on this research, IIT biomedical engineering undergraduate senior Sophia Pilipchuk was named one of five recipients of the Biomedical Engineering Society (BMES) Undergraduate Student Award, to be presented in October 2011 at the BMES Annual Business Meeting in Hartford, Connecticut. Up to eight undergraduate students are selected from around the country on the basis of originality, significance, thoroughness of design analysis, and performance evaluation.
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