Multi-Functional Gelatin-Dithiolane Hydrogels for Tissue Engineering

Asim S., Tuftee C., Qureshi A. T., Callaghan R., Geary M. L., Santra M., ...More

Advanced Functional Materials, 2024 (SCI-Expanded) identifier

  • Publication Type: Article / Article
  • Publication Date: 2024
  • Doi Number: 10.1002/adfm.202407522
  • Journal Name: Advanced Functional Materials
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, Applied Science & Technology Source, Chemical Abstracts Core, Chimica, Communication Abstracts, Compendex, INSPEC, MEDLINE, Metadex, Civil Engineering Abstracts
  • Keywords: bioadhesion, bioprinting, dithiolane cross-linking, gelatin hydrogels, stress relaxation
  • Çukurova University Affiliated: No

Abstract

Biomaterials that integrate multiple functionalities, mimic the extracellular matrix (ECM) microenvironment to support cellular growth, and adhere robustly to damaged tissues are highly needed to advance tissue engineering. Protein-based biomaterials are promising due to their inherent biocompatibility, biomimicry, biodegradation, and cell-supportive properties. Herein, by leveraging the unique ability of dithiolanes to generate on-demand in situ thiols, a new class of dithiolane-modified, protein-based biomaterial that combines unique, seemingly opposing functions for tissue engineering is developed. Dithiolane-modified gelatin, a model protein used herein, enabled photoinitiator-free photo-crosslinking to form multi-functional gelatin-dithiolane (GelDT) hydrogels, which displayed exceptional long-term stability in cell culture media (>28 days) to support the growth of both surface-seeded and encapsulated cells. GelDT hydrogels allowed pre-gelation tuning of biomechanical properties and biodegradation via introducing physical crosslinks, and post-gelation tuning of matrix stress-relaxation rate, via responding to exogenous thiols, independently of other parameters. Furthermore, GelDT enabled covalent immobilization of bio-active molecules, glutathione-responsive drug release, supported efficient 3D bioprinting due to its shear-thinning ability, and demonstrated robust tissue adhesion in various contexts (bare skin, ex-vivo, in-vivo) due to covalent disulfide coupling with endogenous tissue thiols. Together, this study presents a novel multi-responsive and multi-functional protein-based biomaterial, anticipated to advance tissue engineering and regeneration.