title: Thermoreversible hydrogels based on triblock copolymers of poly(ethylene glycol) and carboxyl functionalized poly(ε-caprolactone): The effect of carboxyl group substitution on the transition temperature and biocompatibility in plasma.
abstract: In this study we report on the development, characterization and plasma protein interaction of novel thermoresponsive in situ hydrogels based on triblock copolymers of poly(ethylene glycol) (PEG) and poly(α-carboxyl-co-benzyl carboxylate)-ε-caprolactone (PCBCL) having two different degrees of carboxyl group substitution on the PCBCL block. Block copolymers were synthesized through ring-opening polymerization of α-benzyl carboxylate-ε-caprolactone by dihydroxy PEG, leading to the production of poly(α-benzyl carboxylate-ε-caprolactone)-PEG-poly(α-benzyl carboxylate-ε-caprolactone) (PBCL-PEG-PBCL). This was followed by partial debenzylation of PBCL blocks under controlled conditions, leading to the preparation of PCBCL-PEG-PCBCL triblock copolymers with 30 and 54mol.% carboxyl group substitution. Prepared PCBCL-PEG-PCBCL block copolymers have been shown to have a concentration-dependent sol to gel transition as a result of an increase in temperature above ∼29°C, as evidenced by the inverse flow method, differential scanning calorimetry and dynamic mechanical analysis. The sol-gel transition temperature/concentration and dynamic mechanical properties of the gel were found to be dependent on the level of carboxyl group substitution. Both hydrogels (30 and 54mol.% carboxyl group substitution) showed similar amounts of protein adsorption but striking differences in the profiles of the adsorbed proteome. Additionally, the two systems showed similarities in their clot formation kinetics but substantial differences in clot endpoints. The results show great promise for the above-mentioned thermoreversible in situ hydrogels as biocompatible materials for biomedical applications.
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2E1, Canada.
authors.forename: Nazila
authors.initials: N
authors.lastname: Safaei Nikouei
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2E1, Canada.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Vakili
authors.affiliation: Department of Biomedical Engineering, University of Alberta, Edmonton, Alberta T6G 2V4, Canada; National Research Council, National Institute for Nanotechnology, Edmonton, Alberta T6G 2M9, Canada.
authors.forename: Markian S
authors.initials: MS
authors.lastname: Bahniuk
authors.affiliation: Department of Biomedical Engineering, University of Alberta, Edmonton, Alberta T6G 2V4, Canada; National Research Council, National Institute for Nanotechnology, Edmonton, Alberta T6G 2M9, Canada; Department of Chemical and Materials Engineering, University of Alberta, Edmonton, Alberta T6G 2V4, Canada.
authors.forename: Larry
authors.initials: L
authors.lastname: Unsworth
authors.affiliation: Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta T6G 2P5, Canada.
authors.forename: Ali
authors.initials: A
authors.lastname: Akbari
authors.affiliation: Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta T6G 2P5, Canada.
authors.forename: Jianping
authors.initials: J
authors.lastname: Wu
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2E1, Canada; Department of Chemical and Materials Engineering, University of Alberta, Edmonton, Alberta T6G 2V4, Canada. Electronic address: afsaneh@ualberta.ca.
authors.forename: Afsaneh
authors.initials: A
authors.lastname: Lavasanifar
mesh_terms: D001672:Biocompatible Materials; D001777:Blood Coagulation; D002152:Calorimetry, Differential Scanning; D006801:Humans; D020100:Hydrogels; D010949:Plasma; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D013696:Temperature
chemical_list: D001672:Biocompatible Materials; D020100:Hydrogels; D011091:Polyesters; C016240:polycaprolactone; D011092:Polyethylene Glycols
keywords: Biocompatibility; Biodegradable gel; In situ hydrogel; Protein adsorption; Thermoresponsive