A functionalizable reverse thermal gel based on a polyurethane/PEG block copolymer

Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15219, USA.
Biomaterials (Impact Factor: 8.56). 10/2010; 32(3):777-86. DOI: 10.1016/j.biomaterials.2010.09.044
Source: PubMed


Injectable reverse thermal gels have great potentials as biomaterials for tissue engineering and drug delivery. However, most existing gels lack functional groups that can be modified with biomolecules that can guide cell/material interactions. We created an amine-functionalized ABA block copolymer, poly(ethylene glycol)-poly(serinol hexamethylene urethane), or ESHU. This reverse thermal gel consists of a hydrophobic block (B): poly(serinol hexamethylene urethane) and a hydrophilic block (A): poly(ethylene glycol). The polymer was characterized by GPC, FTIR and (1)H FTNMR. Rheological study demonstrated that ESHU solution in phosphate-buffered saline initiated phase transition at 32 °C and reached maximum elastic modulus at 37 °C. The in vitro degradation tests performed in PBS and cholesterol esterase solutions revealed that the polymer was hydrolyzable and the presence of cholesterol esterase greatly accelerated the hydrolysis. The in vitro cytotoxicity tests carried out using baboon smooth muscle cells demonstrated that ESHU had good cytocompatibility with cell viability indistinguishable from tissue culture treated polystyrene. Subcutaneous implantation in rats revealed well tolerated accurate inflammatory response with moderate ED-1 positive macrophages in the early stages, which largely resolved 4 weeks post-implantation. We functionalized ESHU with a hexapeptide, Ile-Lys-Val-Ala-Val-Ser (IKVAVS), which gelled rapidly at body temperature. We expect this new platform of functionalizable reverse thermal gels to provide versatile biomaterials in tissue engineering and regenerative medicine.

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    • "Serinol is a rather new building-block for the preparation of PUs. This serine derivative has two–OH groups for reaction with a suitable diisocyanate, and one–BOC protected NH 2 group that, after polymerization and deprotection, is available for further chemical functionalization (Park et al., 2011). "
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    • "Temperaturesensitive hydrogels, which exist in the sol state at low temperatures but turn into a gel state at physiological temperature (37 °C), have attracted considerable attention. Typical examples of temperature-sensitive hydrogels are as listed: poly(N-isopropylacrylamide ) [26], Pluronic and its derivative [27] [28], triblock copolymers consisting of hydrophilic poly(ethylene glycol) (PEG) and hydrophobic block including poly(caprolactone-co-lactide) (PCLA–PEG–PCLA), poly(caprolactone) (PCL–PEG–PCL), poly(lactide-co-glycolide ) (PLGA–PEG–PLGA), poly(phosphazene) [29] [30] [31] [32] [33] [34] and natural polymers [8]. However, temperature-sensitive hydrogels are normally neutral, which limits their application to the delivery of ionic drugs/proteins. "
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