title: Recombinant Resilin-Based Bioelastomers for Regenerative Medicine Applications.
abstract: The outstanding elasticity, excellent resilience at high-frequency, and hydrophilic capacity of natural resilin have motivated investigations of recombinant resilin-based biomaterials as a new class of bio-elastomers in the engineering of mechanically active tissues. Accordingly, here the comprehensive characterization of modular resilin-like polypeptide (RLP) hydrogels is presented and their suitability as a novel biomaterial for in vivo applications is introduced. Oscillatory rheology confirmed that a full suite of the RLPs can be rapidly cross-linked upon addition of the tris(hydroxymethyl phosphine) cross-linker, achieving similar in situ shear storage moduli (20 k ± 3.5 Pa) across various material compositions. Uniaxial stress relaxation tensile testing of hydrated RLP hydrogels under cyclic loading and unloading showed negligible stress reduction and hysteresis, superior reversible extensibility, and high resilience with Young's moduli of 30 ± 7.4 kPa. RLP hydrogels containing MMP-sensitive domains are susceptible to enzymatic degradation by matrix metalloproteinase-1 (MMP-1). Cell culture studies revealed that RLP-based hydrogels supported the attachment and spreading (2D) of human mesenchymal stem cells and did not activate cultured macrophages. Subcutaneous transplantation of RLP hydrogels in a rat model, which to our knowledge is the first such reported in vivo analysis of RLP-based hydrogels, illustrated that these materials do not elicit a significant inflammatory response, suggesting their potential as materials for tissue engineering applications with targets of mechanically demanding tissues such as vocal fold and cardiovascular tissues.
authors.affiliation: Department of Materials Science and Engineering, University of Delaware, Newark, DE, 19716, USA.
authors.forename: Linqing
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Biomedical Engineering, National Cerebral and Cardiovascular Center Research Institute, Fujishiro-dai Suita, Osaka, 565-8565, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mahara
authors.affiliation: Department of Materials Science and Engineering, University of Delaware, Newark, DE, 19716, USA.
authors.forename: Zhixiang
authors.initials: Z
authors.lastname: Tong
authors.affiliation: Department of Materials Science and Engineering, University of Delaware, Newark, DE, 19716, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Levenson
authors.affiliation: Department of Materials Science and Engineering, University of Delaware, Newark, DE, 19716, USA.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: McGann
authors.affiliation: Department of Materials Science and Engineering, Department of Biomedical Engineering, University of Delaware, Newark, DE, 19716, USA.
authors.forename: Xinqiao
authors.initials: X
authors.lastname: Jia
authors.affiliation: Department of Biomedical Engineering, National Cerebral and Cardiovascular Center Research Institute, Fujishiro-dai Suita, Osaka, 565-8565, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Yamaoka
authors.affiliation: Department of Materials Science and Engineering, Department of Biomedical Engineering, University of Delaware, Newark, DE, 19716, USA.
authors.forename: Kristi L
authors.initials: KL
authors.lastname: Kiick
mesh_terms: D000818:Animals; D004330:Drosophila; D020724:Elastomers / Q000494:pharmacology*; D006801:Humans; D020100:Hydrogels / Q000494:pharmacology; D007150:Immunohistochemistry; D019476:Insect Proteins / Q000494:pharmacology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects; D051379:Mice; D000067996:RAW 264.7 Cells; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology*; D044968:Regenerative Medicine / Q000379:methods*; D040521:Subcutaneous Tissue / Q000187:drug effects; D013718:Tensile Strength / Q000187:drug effects
chemical_list: D020724:Elastomers; D020100:Hydrogels; D019476:Insect Proteins; D011994:Recombinant Proteins; C030951:resilin
keywords: bio-elastomer; hydrogel; resilin-like polypeptide; tissue engineering; vocal fold