3D bioprinting of gellan gum-based hydrogels tethered with laminin-derived peptides for improved cellular behavior

Omar Alheib, Lucilia P. da Silva, Yun Hee Youn, Il Keun Kwon, Rui L. Reis, Vitor M. Correlo

Research output: Contribution to journalArticlepeer-review

Abstract

The treatment of skeletal muscle defects is still a topic of noteworthy concern since surgical intervention is not capable of recovering muscle function. Herein, we propose myoblasts laden in laminin-inspired biofunctionalized gellan gum hydrogels as promising tissue-engineered skeletal muscle surrogates. Gellan gum-based hydrogels were developed by combining native gellan gum (GG) and GG tethered with laminin-derived peptides (CIKVAVS (V), KNRLTIELEVRTC (T) or RKRLQVQLSIRTC (Q)), using different polymer content (0.75%–1.875%). Hydrogels were characterized in terms of compressive modulus, molecules trafficking, and C2C12 adhesion. Hydrogels with higher polymeric content (1.125%–1.875%) showed higher stiffness whereas hydrogels with lower polymer content (0.75%–1.125%) showed higher fluorescein isothiocyanate-dextran molecules diffusion. Cell spreading was achieved regardless of the laminin-derived peptide but preferred in hydrogels with higher polymer content (1.125%–1.875%). Taken together, hydrogels with 1.125% of polymer content were selected for printability analysis. GG-based inks showed a non-newtonian, shear-thinning, and thixotropic behavior suitable for printing. Accordingly, all inks were printable, but inks tethered with T and Q peptides presented some signs of clogging. Cell viability was affected after printing but increased after 7 days of culture. After 7 days, cells were spreading but not showing significant signs of cell–cell communications. Therefore, cell density was increased, thus, myocytes loaded in V-tethered GG-based inks showed higher cell–cell communication, spreading morphology, and alignment 7, 14 days post-printing. Overall, myoblasts laden in laminin-inspired biofunctionalized GG-based hydrogels are a promising skeletal muscle surrogate with the potential to be used as in vitro model or explored for further in vivo applications.

Original languageEnglish
Pages (from-to)1655-1668
Number of pages14
JournalJournal of Biomedical Materials Research - Part A
Volume110
Issue number10
DOIs
Publication statusAccepted/In press - 2022

Keywords

  • cell encapsulation
  • gellan gum
  • laminin
  • tissue engineering

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