S-Protected Thiolated Chitosan versus Thiolated Chitosan as Cell Adhesive Biomaterials for Tissue Engineering

Chitosan (Ch) and different Ch derivatives have beenapplied intissue engineering (TE) because of their biocompatibility, favoredmechanical properties, and cost-effectiveness. Most of them, however,lack cell adhesive properties that are crucial for TE. In this study,we aimed to design an S-protected thiolated Ch derivative exhibitinghigh cell adhesive properties serving as a scaffold for TE. 3-((2-Acetamido-3-methoxy-3-oxopropyl)dithio)propanoic acid was covalently attached to Ch via a carbodiimide-mediatedreaction. Low-, medium-, and high-modified Chs (Ch-SS-1, Ch-SS-2,and Ch-SS-3) with 54, 107 and 140 & mu;mol of ligand per gram ofpolymer, respectively, were tested. In parallel, three thiolated Chs,namely Ch-SH-1, Ch-SH-2, and Ch-SH-3, were prepared by conjugating N-acetyl cysteine to Ch at the same degree of modificationto compare the effectiveness of disulfide versus thiol modificationon cell adhesion. Ch-SS-1 showed better cell adhesion capability thanCh-SS-2 and Ch-SS-3. This can be explained by the more lipophilicsurfaces of Ch-SS as a higher modification was made. Although Ch-SH-1,Ch-SH-2, and Ch-SH-3 were shown to be good substrates for cell adhesion,growth, and proliferation, Ch-SS polymers were superior to Ch-SH polymersin the formation of 3D cell cultures. Cryogels structured by Ch-SS-1(SSg) resulted in homogeneous scaffolds with tunable pore size andmechanical properties by changing the mass ratio between Ch-SS-1 andheparin used as a cross-linker. SSg scaffolds possessing interconnectedmicroporous structures showed good cell migration, adhesion, and proliferation.Therefore, Ch-SS can be used to construct tunable cryogel scaffoldsthat are suitable for 3D cell culture and TE.

Automated summary

Chitosan and its derivatives with high cell adhesion properties were designed and tested for their suitability as scaffold materials in tissue engineering. The attachment of a thiol group to chitosan significantly improved cell adhesion, with higher modification levels leading to better results. The resulting chitosan-based cryogels showed promise for 3D cell culture and tissue engineering.