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  3. Mussel inspired sequential protein delivery based on self-healing injectable nanocomposite hydrogel

Mussel inspired sequential protein delivery based on self-healing injectable nanocomposite hydrogel

  • Int J Biol Macromol. 2024 Mar 4:130568. doi: 10.1016/j.ijbiomac.2024.130568.
Xiao Shuai Han 1,  Peng Cheng Li 1,  Heng Tao Song 2,  Yong Mei Chen 3,  Jian Hui Li 4,  Yang Yang 1,  Hao Peng Li 5,  Hideyuki Miyatake 6,  Yoshihiro Ito 6
Affiliations

Affiliations

  • 1 College of Bioresources Chemical and Materials Engineering, National Demonstration Center for Experimental Light Chemistry Engineering Education, Shaanxi University of Science and Technology, Xi'an 710021, PR China.
  • 2 Department of Surgical Oncology, Shaanxi Provincial People's Hospital, Xi'an 710068, PR China.
  • 3 College of Bioresources Chemical and Materials Engineering, National Demonstration Center for Experimental Light Chemistry Engineering Education, Shaanxi University of Science and Technology, Xi'an 710021, PR China. Electronic address: [email protected].
  • 4 Department of Surgical Oncology, Shaanxi Provincial People's Hospital, Xi'an 710068, PR China. Electronic address: [email protected].
  • 5 Second Affiliated Hospital of Xi'an Jiaotong University, College of Chemistry, Xi'an Jiaotong University, Xi'an 710049, PR China.
  • 6 Nano Medical Engineering Laboratory, RIKEN Cluster for Pioneering Research, Emergent Bioengineering Materials Research Team, RIKEN Center formergent Matter Science, 2-1 Hirosawa, Wako, Saitama 3510198, Japan.
PMID: 38447822 DOI: 10.1016/j.ijbiomac.2024.130568
Abstract

Polysaccharide based self-healing and injectable hydrogels with reversible characteristics have widespread potential in protein drug delivery. However, it is a challenge to design the dynamic hydrogel for sequential release of protein drugs. Herein, we developed a novel mussel inspired sequential protein delivery dynamic polysaccharide hydrogel. The nanocomposite hydrogel can be fabricated through doping polydopamine nanoparticles (PDA NPs) into reversible covalent bond (imine bonds) crosslinked polymer networks of oxidized hyaluronic acid (OHA) and carboxymethyl chitosan (CEC), named PDA NPs@OHA-l-CEC. Besides multiple capabilities (i.e., injection, self-healing, and biodegradability), the nanocomposite hydrogel can achieve sustained and sequential protein delivery of vascular endothelial growth factor (VEGF) and bovine serum albumin (BSA). PDA NPs doped in hydrogel matrix serve dual roles, acting as secondary protein release structures and form dynamic non-covalent interactions (i.e., hydrogen bonds) with Polysaccharides. Moreover, by adjusting the oxidation degree of OHA, the hydrogels with different crosslinking density could control overall protein release rate. Analysis of different release kinetic models revealed that Fickian diffusion drove rapid VEGF release, while the slower BSA release followed a Super Case II transport mechanism. The novel biocompatible system achieved sequential release of protein drugs has potentials in multi-stage synergistic drug deliver based on dynamic hydrogel.

Keywords

Mussel inspired; Self-healing injectable hydrogel; Sequential delivery.

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