Biodegradable poly(ethylene glycol)–peptide hydrogels with well-defined structure and properties for cell delivery

• Published in: Biomaterials 2009-03, Vol.30 (8), p.1453-1461
• Main Authors: Liu, Shao Qiong, Rachel Ee, Pui Lai, Ke, Chyan Ying, Hedrick, James L, Yang, Yi Yan
• Format: Article
• Language: English
• Subjects: Acetylene - chemistry; Advanced Basic Science; Amino Acid Sequence; Azides - chemistry; Azides - pharmacology; Biocompatible Materials - metabolism; Catalysis - drug effects; Cell Adhesion - drug effects; Cell attachment; Cell Proliferation - drug effects; Cells, Cultured; Click chemistry; Dentistry; Fibroblasts - cytology; Fibroblasts - drug effects; Humans; Hydrogels - chemistry; Magnetic Resonance Spectroscopy; Microscopy, Electron, Scanning; Molecular Sequence Data; PEG; Peptide hydrogel; Peptides - chemistry; Peptides - pharmacology; Polyethylene Glycols - metabolism; RGD; Rheology; Temperature; Time Factors
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2008.11.023

Abstract In this study, biodegradable PEG–peptide hydrogels have been synthesized using Click chemistry. A series of Arg-Gly-Asp (RGD) containing peptides were prepared via a solid phase synthesis approach, which were further functionalized with azide to yield peptide azide or peptide diazide. A tetra-hydroxy terminated 4-arm PEG was functionalized with acetylene and was reacted with peptide azide/diazide and/or PEG diazide to produce hydrogels via a copper mediated 1,3-cycloaddition (Click chemistry) generating a triazole linkage as the networking forming reaction. The gelation time ranged from 2 to 30 min, depending on temperature, catalyst and precursor concentration, as well as peptide structure. The resulting hydrogels were characterized by swelling, viscoelastic properties and morphology as well as their ability for cell attachment and proliferation. Hydrogels cross-linked by peptide diazide yielded higher storage modulus ( G ′) with shorter spacers between azide groups. As expected, the swelling degree decreased while the G ′ increased with increasing the concentration of the precursors as a result of increased cross-linking density. Primary human dermal fibroblasts were used as model cells to explore the possibility of using the RGD peptide hydrogels for cell-based wound healing. The attachment and proliferation of the cells on the hydrogels were evaluated. The RGD peptide hydrogels synthesized with a peptide concentration of 2.7–5.4 m m achieved significantly improved cell attachment and greater cell proliferation rate when compared to the hydrogels without RGD peptides. These hydrogels may provide a platform technology to deliver cells for tissue repair.