title: Mechanically Stiff Nanocomposite Hydrogels at Ultralow Nanoparticle Content.
abstract: Although hydrogels are able to mimic native tissue microenvironments, their utility for biomedical applications is severely hampered due to limited mechanical stiffness and low toughness. Despite recent progress in designing stiff and tough hydrogels, it is still challenging to achieve a cell-friendly, high modulus construct. Here, we report a highly efficient method to reinforce collagen-based hydrogels using extremely low concentrations of a nanoparticulate-reinforcing agent that acts as a cross-link epicenter. Extraordinarily, the addition of these nanoparticles at a 10 000-fold lower concentration relative to polymer resulted in a more than 10-fold increase in mechanical stiffness and a 20-fold increase in toughness. We attribute the high stiffness of the nanocomposite network to the chemical functionality of the nanoparticles, which enabled the cross-linking of multiple polymeric chains to the nanoparticle surface. The mechanical stiffness of the nanoengineered hydrogel can be tailored between 0.2 and 200 kPa simply by manipulating the size of the nanoparticles (4, 8, and 12 nm), as well as the concentrations of the nanoparticles and polymer. Moreover, cells can be easily encapsulated within the nanoparticulate-reinforced hydrogel network, showing high viability. In addition, encapsulated cells were able to sense and respond to matrix stiffness. Overall, these results demonstrate a facile approach to modulate the mechanical stiffness of collagen-based hydrogels and may have broad utility for various biomedical applications, including use as tissue-engineered scaffolds and cell/protein delivery vehicles.
authors.affiliation: Department of Biomedical Engineering, Texas A&M University , College Station, Texas 77843, United States.
authors.forename: Manish K
authors.initials: MK
authors.lastname: Jaiswal
authors.affiliation: Department of Biomedical Engineering, Texas A&M University , College Station, Texas 77843, United States.
authors.forename: Janet R
authors.initials: JR
authors.lastname: Xavier
authors.affiliation: Department of Biomedical Engineering, Texas A&M University , College Station, Texas 77843, United States.
authors.forename: James K
authors.initials: JK
authors.lastname: Carrow
authors.affiliation: Department of Biomedical Engineering, Texas A&M University , College Station, Texas 77843, United States.
authors.forename: Prachi
authors.initials: P
authors.lastname: Desai
authors.affiliation: Department of Biomedical Engineering, Texas A&M University , College Station, Texas 77843, United States.|Department of Materials Science and Engineering, Texas A&M University , College Station, Texas 77843, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Alge
authors.affiliation: Department of Biomedical Engineering, Texas A&M University , College Station, Texas 77843, United States.|Department of Materials Science and Engineering, Texas A&M University , College Station, Texas 77843, United States.|Center for Remote Health Technologies and Systems, Texas A&M University , College Station, Texas 77843, United States.
authors.forename: Akhilesh K
authors.initials: AK
authors.lastname: Gaharwar
mesh_terms: D000818:Animals; D018914:Cells, Immobilized / Q000166:cytology / Q000502:physiology; D003094:Collagen / Q000737:chemistry; D004298:Dopamine / Q000737:chemistry; D052203:Ferrosoferric Oxide / Q000737:chemistry; D005780:Gelatin / Q000737:chemistry; D006244:Hardness; D006245:Hardness Tests; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D008422:Materials Testing; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology; D008689:Methacrylates / Q000737:chemistry; D051379:Mice; D041681:NIH 3T3 Cells; D053761:Nanocomposites / Q000737:chemistry* / Q000648:ultrastructure; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry
chemical_list: D020100:Hydrogels; D008689:Methacrylates; D011092:Polyethylene Glycols; D005780:Gelatin; D003094:Collagen; D004298:Dopamine; D052203:Ferrosoferric Oxide
keywords: hydrogels; mechanical stiffness; nanocomposites; nanoparticles; tissue engineering