title: Synthesis and in vitro evaluation of enzymatically cross-linked elastin-like polypeptide gels for cartilaginous tissue repair.
abstract: Genetically engineered elastin-like polypeptide (ELP) hydrogels offer unique promise as scaffolds for cartilage tissue engineering because of the potential to promote chondrogenesis and to control mechanical properties. In this study, we designed and synthesized ELPs capable of undergoing enzyme-initiated gelation via tissue transglutaminase, with the ultimate goal of creating an injectable, in situ cross-linking scaffold to promote functional cartilage repair. Addition of the enzyme promoted ELP gel formation and chondrocyte encapsulation in a biocompatible process, which resulted in cartilage matrix synthesis in vitro and the potential to contribute to cartilage mechanical function in vivo. A significant increase in the accumulation of sulfated glycosaminoglycans was observed, and histological sections revealed the accumulation of a cartilaginous matrix rich in type II collagen and lacking in type I collagen, indicative of hyaline cartilage formation. These results provide evidence of chondrocytic phenotype maintenance for cells in the ELP hydrogels in vitro. In addition, the dynamic shear moduli of ELP hydrogels seeded with chondrocytes increased from 0.28 to 1.7 kPa during a 4-week culture period. This increase in the mechanical integrity of cross-linked ELP hydrogels suggests restructuring of the ELP matrix by deposition of functional cartilage extracellular matrix components.
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708, USA.
authors.forename: Melissa K
authors.initials: MK
authors.lastname: McHale
authors.forename: Lori A
authors.initials: LA
authors.lastname: Setton
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Chilkoti
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D002356:Cartilage / Q000166:cytology / Q000502:physiology*; D018929:Cell Culture Techniques / Q000379:methods; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000502:physiology*; D024042:Collagen Type I / Q000096:biosynthesis; D004549:Elastin / Q000737:chemistry; D005069:Evaluation Studies as Topic; D006801:Humans; D020100:Hydrogels; D011994:Recombinant Proteins / Q000737:chemistry; D013552:Swine; D023822:Tissue Engineering / Q000379:methods; D011503:Transglutaminases / Q000737:chemistry
chemical_list: D001672:Biocompatible Materials; D024042:Collagen Type I; D020100:Hydrogels; D011994:Recombinant Proteins; D004549:Elastin; D011503:Transglutaminases