Thermoresponsive and Biodegradable Amphiphilic Block Copolymers with Pendant Functional Groups

Abstract

BACKGROUND: To develop the biodegradability and thermoresponsive hydrogel, in this work we designed a pendantfunctionalized, thermoresponsive, amphiphilic block copolymer. METHODS: Methoxy poly(ethylene glycol) (MPEG)-b-[poly(e-caprolactone)-ran-poly(e-caprolactone-3-one)-ran-polylactic acid] (MCL) and (MPEG-b-[PCL-ran-POD-ran-PLA]) [MCL-(CO)] block copolymers were prepared by ringopening polymerization of e-caprolactone, OD and lactide monomers. The subsequent derivatization of MCL-(CO) provided MPEG-b-[PCL-ran-poly(e-caprolactone-3-COOH)-ran-PLA] [MCL-(COOH)] with COOH pendant groups and MPEG-b-[PCL-ran-poly(e-caprolactone-3-NH 2 )-ran-PLA] [MCL-(NH 2 )] with NH 2 pendant groups. RESULTS: The measured segment ratios of MCL-(CO), MCL-(COOH), and MCL-(NH 2 ) agreed well with the target ratios. The abundances of the COOH and NH 2 groups in the MCL-(COOH) and MCL-(NH 2 ) copolymers were determined by 1 H-and 13 C-nuclear magnetic resonance spectroscopy, and agreed well with the target abundances. MCL-(CO), MCL-(COOH), and MCL-(NH 2 ) formed homogeneous, white, opaque emulsions at room temperature. Rheological analysis of the block copolymer suspensions indicated a solution-to-hydrogel phase transition as a function of temperature. The solution-to-hydrogel phase transitions and the biodegradation of MCL-(CO), MCL-(COOH), and MCL-(NH 2 ) were affected by varying the type (ketone, COOH, or NH 2 ) and abundance of the pendant groups. CONCLUSION: MCL-(CO), MCL-(COOH), and MCL-(NH 2 ) with ketone, COOH, and NH 2 pendant groups showed solution-to-hydrogel phase transitions and biodegradation behaviors that depended on both the type and number of pendant groups.

Click Chemistry-Based Injectable Hydrogels and Bioprinting Inks for Tissue Engineering Applications

“…Notable first click chemistry-based hydrogel was reported by Ossipov et al [6] which was formed using poly(vinyl alcohol) (PVA) polymer. These kinds of hydrogel preparation methods have improved in the recent decade and provide the scientists a valuable tool to modify or synthesize novel polymers with multifunctional properties for numerous applications such as tissue engineering, drug delivery, regenerative medicine and other biomedical applications [7][8][9][10]. As explained by Sharpless' research group, click chemistry reactions needs to be modular, should have wide scope, very high yields, stable at physiological conditions, highly stereo-specific, non-toxic end products, under the simple reaction conditions being started with easily available materials and reagents.…”

Biological responses to physicochemical properties of biomaterial surface

“…376 Using these approaches, researchers can synthesize novel polymers and multifunctional hydrogels for biomedical applications. 377,378 ''Click'' chemistry synthesis occurs under stable physiological conditions, with highly stereo-specific and simple product separation. It does not produce any toxic end products.…”

Thermo-responsive block copolymers: assembly and application

“…In order to obtain desired block copolymers, researchers can purposefully select monomers and design block copolymers to better exploit their often-high inherent functionalities. Not only can monomers used to build block copolymers be functionalized, 9,83 but the phase transition temperature of thermo-responsive block copolymers can also be adjusted by copolymerizing with either hydrophilic or hydrophobic monomers, 84 modifying hydrophilic/hydrophobic end groups, 85 adjusting the molecular weight of block copolymers, the ratio of hydrophilic/hydrophobic monomers, the ionic strength of aqueous solution 86 and the polymer concentration. 57,59–61,87 The increase in molecular weight of hydrophobic blocks and copolymerization with hydrophobic monomers will result in a lower phase transition temperature of LCST-type block copolymers.…”