Introduction: Synthetic polypeptides are a class of unique biodegradable polymers with excellent biocompatibility and structures mimicking natural proteins. In our recent studies, a series of injectable hydrogels based on polypeptides, especially poly(L-glutamic acid), were developed. Their potential applications as biomimetic scaffolds for 3D cell culture or as drug depots for localized drug delivery were investigated. Methods: Polypeptides were synthesized by ring-opening polymerization of α-amino acid-N-carboxyanhydrides. The polypeptide hydrogels were formed through different mechanisms, including thermo-induced formation of micellar network, Schiff-based reaction and enzyme-catalyzed crosslinking. Results: It was found that the mechanical property and degradation rate of the hydrogels could be adjusted by tailoring the polymer composition, polymer content and crosslinking method. The MTT assay in vitro and histological analysis indicated that the polypeptide hydrogels showed good cytocompatibility in vitro and good histocompatibility in vivo. A series of injectable hydrogels based on poly(L-glutamic acid) or glycopolypeptide were designed and prepared via enzymatic crosslinking as platforms for regulating cell behavior. It was found that the morphology and proliferation rate of BMSCs within the hydrogels were influenced by polymer content. The bio-functionalization of the hydrogels with monosaccharides or RGD peptides promoted 3D cell proliferation and cell adhesion. Moreover, the dynamic adjustment of hydrogel degradation and cell adhesion were achieved through the incorporation of a glutathione-responsive linkage. Additionally, polypeptide hydrogels were also studied for localized delivering single or multiple drugs for anticancer treatments. After peritumoral injection into tumor-bearing mice, the drug-incorporated hydrogels exhibited prolonged tumor inhibition efficacies, as well as reduced systemic toxic side-effects, compared to treatments with drug solutions. Conclusions: Injectable polypeptide hydrogels were designed and investigated for different biomedical applications, including acting as biomimetic scaffolds for 3D cell culture and regulating cell behavior, as well as serving as depots for localized delivering single or multiple anticancer drugs for tumor treatments.

Injectable polypeptide hydrogels for biomedical applications

254th National Meeting (2017)

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