Fibrillized peptide hydrogels and microgels for 3D cell culture and tissue engineering.

摘要

Self-assembling peptide-based nanofibers and hydrogels have been widely applied as cell delivery vehicles, vaccine adjuvants, and scaffolds for tissue engineering and 3D cell culture. Self-assembling peptides, owing to their specific sequences, self-associate into nanofibers when dissolved in aqueous buffers. Highly concentrated peptide solutions can form hydrogels, when triggered by increased ionic strength, pH adjustment, and/or change in temperature. The advantages of these peptide materials are that 1) they are chemically defined, which minimizes their batch-to-batch variances, 2) they are modular, which allows for easy synthesis and the inclusion of multiple different functional ligand-conjugated peptides, 3) they are controllably immunogenic.;Although the general feasibility of self-assembling peptide hydrogels for 3D cell encapsulation has been demonstrated by commercial products and several research groups including our own, these materials are not without their shortcomings. Their application as artificial matrices is hindered by 1) their relatively low mechanical strength and vulnerability to fracture, 2) their extreme thermodynamic stability and lack of mechanisms for degradation, and 3) their temporary cytotoxicity during the cell encapsulation processes. In this thesis, I have designed new peptide/depsipeptide sequences, as well as encapsulation processes, to address the above-mentioned problems. Briefly, I have designed microgels for cell encapsulation as an alternative to bulk encapsulation, which partly solved the fracture-in-gel problem. I have designed ester bond-containing depsipeptides to impart highly controllable biodegradation properties to the materials. I have also designed peptides whose gelation can be triggered by minor pH adjustment, to achieve high degrees of cell survival in the early steps of cell encapsulation.