title: The incorporation of extracellular matrix proteins in protein polymer hydrogels to improve encapsulated beta-cell function.
abstract: Biomaterial encapsulation of islets has been proposed to improve the long-term success of islet transplantation by recreating a suitable microenvironment and enhancing cell-matrix interactions that affect cellular function. Protein polymer hydrogels previously showed promise as a biocompatible scaffold by maintaining high cell viability. Here, enzymatically-crosslinked protein polymers were used to investigate the effects of varying scaffold properties and of introducing ECM proteins on the viability and function of encapsulated MIN6 β-cells. Chemical and mechanical properties of the hydrogel were modified by altering the protein concentrations while collagen IV, fibronectin, and laminin were incorporated to reestablish cell-matrix interactions lost during cell isolation. Rheology indicated all hydrogels formed quickly, resulting in robust, elastic hydrogels with Young's moduli similar to soft tissue. All hydrogels tested supported both high MIN6 β-cell viability and function and have the potential to serve as an encapsulation platform for islet cell delivery in vivo.
authors.affiliation: Northwestern University, Department of Chemical and Biological Engineering, Evanston, IL, USA.
authors.forename: Liese N
authors.initials: LN
authors.lastname: Beenken-Rothkopf
authors.forename: Lindsay S
authors.initials: LS
authors.lastname: Karfeld-Sulzer
authors.forename: Nicolynn E
authors.initials: NE
authors.lastname: Davis
authors.forename: Ryan
authors.initials: R
authors.lastname: Forster
authors.forename: Annelise E
authors.initials: AE
authors.lastname: Barron
authors.forename: Magali J
authors.initials: MJ
authors.lastname: Fontaine
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001672:Biocompatible Materials / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D060833:Cellular Microenvironment / Q000502:physiology*; D002846:Chromatography, Affinity; D003094:Collagen; D016326:Extracellular Matrix Proteins / Q000494:pharmacology*; D005353:Fibronectins; D020100:Hydrogels / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000502:physiology*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D007797:Laminin; D051379:Mice; D008969:Molecular Sequence Data; D011108:Polymers / Q000494:pharmacology*; D012212:Rheology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D001672:Biocompatible Materials; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D020100:Hydrogels; D007797:Laminin; D011108:Polymers; D000255:Adenosine Triphosphate; D003094:Collagen
keywords: extracellular matrix proteins; hydrogel; islet transplantation