Strong and Injectable Hydrogels Based on Multivalent Metal Ion-Peptide Cross-linking

  • PDF / 1,081,525 Bytes
  • 8 Pages / 595.32 x 841.92 pts (A4) Page_size
  • 1 Downloads / 159 Views

DOWNLOAD

REPORT


doi: 10.1007/s40242-020-9100-y

Article

Strong and Injectable Hydrogels Based on Multivalent Metal Ion-Peptide Cross-linking YU Wenting1,2#, XUE Bin1,2#*, ZHU Zhenshu1, SHEN Ziqin3, QIN Meng1, WANG Wei1* and CAO Yi1,2 1. Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, Department of Physics, Nanjing University, Nanjing 210093, P. R. China; 2. Shenzhen Research Institute of Nanjing University, Shenzhen 518057, P. R. China; 3. International Center, Nanjing Foreign Language School, Nanjing 210000, P. R. China Abstract Injectable hydrogels are ideal biomaterials for delivering cells, growth factors and drugs specifically to localized lesions and subsequent controlled release. Many factors can affect the efficacy of injectable hydrogels. To avoid potential damage to encapsulated cells or drugs, injectable hydrogels should be highly dynamic so that they can undergo shear-thinning at low strain rates and rapidly reform after injection. However, dynamic hydrogels are often mechanically weak, leading to the leakage of encapsulated cells or drugs. Here we demonstrated a convenient method to improve the mechanical strength without jeopardizing the dynamic properties of hydrogels by using metal ion-peptide crosslinkers containing multiple metal ion-ligand bonds. We showed that the dynamic properties of the hydrogels correlated with the intrinsic dynamics of the metal-ligand bonds and were not affected by the formation of multivalent binding. Yet, the mechanical stability of the hydrogels was significantly improved due to the increa sed thermodynamic stability of the crosslinkers. We further showed that the drug release rates were slowed down by the formation of multivalent crosslinkers. Our results highlight the importance of ligand valency to the mechanical response of hydrogels and provide a universal route to rationally tune the dynamic and mechanical properties of injectable hydrogels. Keywords Peptide-ion coordination; Ligand cooperativity; Injectable hydrogel; Mechanical response

1

Introduction

Hydrogels have been widely used in many biomedical fields, including drug delivery and tissue engineering, due to their outstanding biocompatibility, tunable mechanical properties, and convenient synthesis and functionalization[1—13]. Particularly, injectable hydrogels are promising candidates as cell/drug delivery carriers and tissue engineering scaffolds, and can be used with minimal invasion[14—19]. The injectable hydrogels can be formulated through either in situ gelation or shear-thinning mechanism. The former ones are typically based on various chemical cross-linking reactions, such as Michael-type addition reaction[20—22], disulfide bond formation[23,24] and aldehyde-mediated crosslinking[25,26]. The latter ones rely on reversible noncovalent interactions, including coordination interactions[27—42], host-guest interactions[43—48], ionic paring[49,50], hydrogen bonding[51—59], hydrophobic effects[60—64] and specific protein-protein interactions[3,65,66]. The