title: Compression-induced structural and mechanical changes of fibrin-collagen composites.
abstract: Fibrin and collagen as well as their combinations play an important biological role in tissue regeneration and are widely employed in surgery as fleeces or sealants and in bioengineering as tissue scaffolds. Earlier studies demonstrated that fibrin-collagen composite networks displayed improved tensile mechanical properties compared to the isolated protein matrices. Unlike previous studies, here unconfined compression was applied to a fibrin-collagen filamentous polymer composite matrix to study its structural and mechanical responses to compressive deformation. Combining collagen with fibrin resulted in formation of a composite hydrogel exhibiting synergistic mechanical properties compared to the isolated fibrin and collagen matrices. Specifically, the composite matrix revealed a one order of magnitude increase in the shear storage modulus at compressive strains>0.8 in response to compression compared to the mechanical features of individual components. These material enhancements were attributed to the observed structural alterations, such as network density changes, an increase in connectivity along with criss-crossing, and bundling of fibers. In addition, the compressed composite collagen/fibrin networks revealed a non-linear transformation of their viscoelastic properties with softening and stiffening regimes. These transitions were shown to depend on protein concentrations. Namely, a decrease in protein content drastically affected the mechanical response of the networks to compression by shifting the onset of stiffening to higher degrees of compression. Since both natural and artificially composed extracellular matrices experience compression in various (patho)physiological conditions, our results provide new insights into the structural biomechanics of the polymeric composite matrix that can help to create fibrin-collagen sealants, sponges, and tissue scaffolds with tunable and predictable mechanical properties.
authors.affiliation: Department of Cell and Developmental Biology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, United States; Department of Applied and Computational Mathematics and Statistics, University of Notre Dame, Notre Dame, IN 46556, United States; Department of Applied and Computational Mathematics and Statistics, University of Notre Dame, Notre Dame, IN 46556, United States.
authors.forename: O V
authors.initials: OV
authors.lastname: Kim
authors.affiliation: Department of Cell and Developmental Biology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, United States.
authors.forename: R I
authors.initials: RI
authors.lastname: Litvinov
authors.affiliation: Department of Computer Science and Engineering, University of Notre Dame, Notre Dame, IN 46556, United States.
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Computer Science and Engineering, University of Notre Dame, Notre Dame, IN 46556, United States.
authors.forename: D Z
authors.initials: DZ
authors.lastname: Chen
authors.affiliation: Department of Cell and Developmental Biology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, United States. Electronic address: weisel@mail.med.upenn.edu.
authors.forename: J W
authors.initials: JW
authors.lastname: Weisel
authors.affiliation: Department of Applied and Computational Mathematics and Statistics, University of Notre Dame, Notre Dame, IN 46556, United States; Department of Mathematics, University of California Riverside, CA 92521, United States; Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, United States. Electronic address: malber@nd.edu.
authors.forename: M S
authors.initials: MS
authors.lastname: Alber
mesh_terms: D000818:Animals; D040761:Biomimetic Materials / Q000737:chemistry*; D003094:Collagen / Q000737:chemistry* / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000737:chemistry / Q000648:ultrastructure; D005337:Fibrin / Q000737:chemistry* / Q000648:ultrastructure; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D008422:Materials Testing; D011312:Pressure; D051381:Rats; D013314:Stress, Mechanical; D013718:Tensile Strength; D023822:Tissue Engineering; D054457:Tissue Scaffolds
chemical_list: D020100:Hydrogels; D005337:Fibrin; D003094:Collagen
keywords: Collagen; Compression; Fibrin; Fibrin-collagen composites; Structural properties; Viscoelasticity