Design and synthesis of nonionic copolypeptide hydrogels with reversible thermoresponsive and tunable physical properties.
Polypeptide-based formulations that undergo liquid to hydrogel transitions upon change in temperature have become desirable targets since they can be mixed with cells or injected into tissues as liquids, and subsequently transform into rigid scaffolds or depots. Such materials have been challenging to prepare using synthetic polypeptides, especially when reversible gelation and tunable physical properties are desired. Here, we designed and prepared new nonionic diblock copolypeptide hydrogels (DCH) containing hydrophilic poly(γ-[2-(2-methoxyethoxy)ethyl]-rac-glutamate) and hydrophobic poly(l-leucine) segments, named DCHEO, and also further incorporated copolypeptide domains into DCHEO to yield unprecedented thermoresponsive DCH, named DCHT. Although previous attempts to prepare nonionic hydrogels composed solely of synthetic polypeptides have been unsuccessful, our designs yielded materials with highly reversible thermal transitions and tunable properties. Nonionic, thermoresponsive DCHT were found to support the viability of suspended mesenchymal stem cells in vitro and were able to dissolve and provide prolonged release of both hydrophilic and hydrophobic molecules. The versatility of these materials was further demonstrated by the independent molecular tuning of DCHT liquid viscosity at room temperature and DCHT hydrogel stiffness at elevated temperature, as well as the DCHT liquid to hydrogel transition temperature itself.
†Department of Chemistry and Biochemistry, University of California-Los Angeles, Los Angeles, California 90095-1569, United States.
Shanshan
S
Zhang
†Department of Chemistry and Biochemistry, University of California-Los Angeles, Los Angeles, California 90095-1569, United States.
Daniel J
DJ
Alvarez
‡Department of Neurobiology, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California 90095-1763, United States.
Michael V
MV
Sofroniew
†Department of Chemistry and Biochemistry, University of California-Los Angeles, Los Angeles, California 90095-1569, United States.|§Department of Bioengineering, University of California-Los Angeles, Los Angeles, California 90095-1600, United States.
Timothy J
TJ
Deming
D000818:Animals; D002478:Cells, Cultured; D006367:HeLa Cells; D006358:Hot Temperature; D006801:Humans; D020100:Hydrogels / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000187:drug effects; D051379:Mice; D010455:Peptides / Q000737:chemistry; D011099:Polyglutamic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D014783:Viscosity
D020100:Hydrogels; D010455:Peptides; C027819:polyleucine; D011099:Polyglutamic Acid