Displaying Lipid Chains in a Peptide–Polysaccharide-Based Self-Assembled Hydrogel Network

Abstract

Reducing the complex extracellular matrices (ECM) to chemically defined polymer networks represents an attractive avenue for understanding and recapitulating the biology of the ECM. However, while lipids are also important components of ECM, it remains challenging to investigate lipids as a modular functionality in synthetic biomaterials, especially in a self-assembled network. In this study, in order to establish a modular amphiphilic system, lipid-modifications are introduced into a noncovalent hydrogel system cross-linked by peptide–polysaccharide interaction through conjugating fatty acids of different lengths to a peptide. The amphiphilic matrices can interact with hydrophobic drugs, thus enhance their loading efficiency and result in sustainable release. The physical hydrogel system can be used for encapsulating cells, while embedded mesenchymal stromal cells exhibit high viability and retain immunoregulatory activity. In addition, the material can also be used for gel-in-gel injection to model drug partitioning in 3D, as well as controlled fast gel degradation under an extremely mild condition using human serum albumin (HSA). This self-assembling modular system can provide a versatile toolbox to tailor synthetic polymers for engineering 3D models to study bioactive molecules, such as hydrophobic hormones and drugs as well as to develop injectable therapeutic materials.

Thermophoresis of Molecules and Structures of different Sizes in Self-assembled Biomatrices

“…Although the introduction of lipid group into matrix has little effect on the thermodiffusion of the network, the lipid moieties can interact with the hydrophobic compound, thus limiting its thermodiffusion as a free molecule. We have previously shown that Cy5-CsA can bind to KA7-C 16 -starPEG and KA7-C 8 -starPEG with K d values of 30 µ M and 608 µ M, respectively 11 . Eventually, in an amphiphilic matrix, the A T value of Cy5-CsA can be smaller than that in solution, especially in the KA7-C 16 -starPEG/DS and KA7-C 16 -starPEG/SCD hydrogels.…”

“…Although the introduction of lipid group into matrix has little effect on the thermodiffusion of the network, the lipid moieties can interact with the hydrophobic compound, thus limiting its thermodiffusion as a free molecule. We have previously shown that Cy5-CsA can bind to KA7-C16-starPEG and KA7-C8-starPEG with Kd values of 30 µM and 608 µM, respectively 11 .…”

“…The gelation of KA7-starPEG/DS and KA7-starPEG/heparin hydrogels is largely driven by the electrostatic interaction between the positively charged peptides and the negatively charge polysaccharides. While the KA7-lipid-starPEG/DS system introduces a lipophilic component into the zwitterionic matrix, the KA7-starPEG/SCD hydrogel possesses a relatively hydrophobic interior in the network 11 . Matrix thermophoresis has been detected in these materials of different compositions and solid contents.…”

“…The synthetic system can mimic many chemical features of ECM by presenting polypeptide, oligosaccharide, and lipophilic moieties. It is important to note that different from covalently crosslinked polymers, these self-assembled matrices possess heterogeneous and large pores (in µ m scale) 11 , thus allowing for the diffusion of molecules and nanostructures. Owing to the high-throughput of the MST assay, we investigated the thermophoretic behaviors of a large variety of biomolecules of different natures and sizes (e.g.…”

A Three‐In‐One Assembled Nanoparticle Containing Peptide–Radio‐Sensitizer Conjugate and TLR7/8 Agonist Can Initiate the Cancer‐Immunity Cycle to Trigger Antitumor Immune Response

“…[ 21 ] However, the low solubility of these nontherapeutic alkyl chain may lead to a poor bioavailability such as stearic acid and arachidic acid. [ 22 ] In this study, we introduced RT sensitizer NIA as a hydrophobic core into a system and synthesized an amphipathic peptide, while the decrease in solubility is unobserved.…”