title: A shear-thinning hydrogel that extends in vivo bioactivity of FGF2.
abstract: We designed and tested a versatile hydrogel for tissue regeneration by preserving the bioactivity of growth factors. The shear-thinning gel self-assembles within 1 min from heparin and Laponite-a silicate nanoparticle, thus the name HELP gel. By not covalently modifying heparin, it should retain its natural affinity towards many proteins anchored in the extracellular matrix. In principle, HELP gel can bind any heparin-binding growth factor; we use fibroblast growth factor-2 (FGF2) in this study to demonstrate its utility. Heparin in the gel protects FGF2 from proteolytic degradation and allows it to be released over time with preserved bioactivity. FGF2 released from subcutaneously injected gel induces strong angiogenesis in a mouse model. The hydrogel degrades completely in vivo in 8 weeks with or without growth factors, eliciting mild inflammatory response but having little impacts on the surrounding tissue. The ease of preparation and scale-up makes this protein delivery platform attractive for clinical translation.
authors.affiliation: Department of Bioengineering and the McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Xiaochu
authors.initials: X
authors.lastname: Ding
authors.affiliation: Department of Bioengineering and the McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Bioengineering and the McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Zhouguang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Bioengineering and the McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Hassan
authors.initials: H
authors.lastname: Awada
authors.affiliation: Department of Bioengineering and the McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15260, USA; Department of Chemical and Petroleum Engineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Mechanical Engineering and Materials Science, University of Pittsburgh, Pittsburgh, PA 15261, USA; Clinical Translational Science Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. Electronic address: yaw20@pitt.edu.
authors.forename: Yadong
authors.initials: Y
authors.lastname: Wang
mesh_terms: D004058:Diffusion; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000737:chemistry*; D006493:Heparin / Q000378:metabolism*; D008422:Materials Testing; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D033081:Shear Strength; D017640:Silicates / Q000737:chemistry*; D013314:Stress, Mechanical; D014783:Viscosity
chemical_list: D053769:Nanocapsules; D017640:Silicates; D016222:Fibroblast Growth Factor 2; D006493:Heparin; C524813:laponite
keywords: Angiogenesis; Controlled release; Heparin-binding protein; Injectable hydrogel; Nanoparticle; Regenerative medicine