Synthesis and Characterization of RGD Peptide Grafted Poly(ethylene glycol)-b-Poly(l-lactide)-b-Poly(l-glutamic acid) Triblock Copolymer

Abstract

Advances in tissue engineering require biofunctional scaffolds that can provide not only physical support for cells but also chemical and biological cues needed in forming functional tissues. To achieve this goal, a novel RGD peptide grafted poly(ethylene glycol)-b-poly(L-lactide)-b-poly(L-glutamic acid) (PEG-PLA-PGL/RGD) was synthesized in four steps (1) to prepare diblock copolymer PEG-PLA-OH and to convert its -OH end group into -NH(2) (to obtain PEG-PLA-NH(2)), (2) to prepare triblock copolymer PEG-PLA-PBGL by ring-opening polymerization of NCA (N-carboxyanhydride) derived from benzyl glutamate with diblock copolymer PEG-PLA-NH(2) as macroinitiator, (3) to remove the protective benzyl groups by catalytic hydrogenation of PEG-PLA-PBGL to obtain PEG-PLA-PGL, and (4) to react RGD (arginine-glycine-(aspartic amide)) with the carboxyl groups of the PEG-PLA-PGL. The structures of PEG-PLA-PGL/RGD and its precursors were confirmed by (1)H NMR, FT-IR, amino acid analysis, and XPS analysis. Addition of 5 wt % PEG-PLA-PGL/RGD into a PLGA matrix significantly improved the surface wettability of the blend films and the adhesion and proliferation behavior of human chondrocytes and 3T3 cells on the blend films. Therefore, the novel RGD-grafted triblock copolymer is expected to find application in cell or tissue engineering.

Synthesis and characterization of the biomaterial poly(lactic acid‐co‐Nε‐carbobenzoyloxy‐L‐lysine) via direct melt copolymerization

“…Because these amphiphilic polymers contain both biodegradable esters and amide groups in the chain, their biodegradation behaviors are different from those of the corresponding homopolymers and some copolyesters, and they exhibit a better hydrophilicity and biocompatibility than unmodified PLA; this makes PLAA very useful for biodegradable biomedical materials, including drugdelivery vehicles. [9][10][11][12][13][14][15][16][17] Particularly, because of the physiological and biochemical effects of lysine (Lys) for the human body, 18,19 great importance has been directed toward the application of Lys in medical and material fields recently. [12][13][14][15][16][17] To avoid unfavorable side reactions before use, the terminal amino group of Lys with multifunctional groups must be protected, and this is usually done by the use of N e -carbobenzoyloxy-Llysine [Lys(Z)] as a starting material during the synthesis of polymers based on Lys.…”

Smart polymeric gels: Redefining the limits of biomedical devices

“…The integrin-binding activity of natural adhesion proteins can be partially mimicked by oligopepetide sequences [95,96], such as the ubiquitous RGD (i.e., arginineglycine-aspartic acid) [97][98][99][100], RGD and PHSRN (i.e., proline-histidine-serine-arginineasparagine) (in synergy) [101,102], IKVAV (i.e., isoleucine-lysine-valine-alanine-valine) [103][104][105], YIGSR (tyrosine-isoleucine-glycine-serine-arginine) [106,107], PHSRN , and so on. Harden et al went a step further from the triblock architecture initially proposed by Tirrell et al by conjugating RGD to the central block of the modular triblock protein architecture.…”

Impact of nanotechnology in cancer: emphasis on nanochemoprevention

“…76 PEGylated polylactic acid/PLGA nanoparticles have been demonstrated to exhibit significantly increased blood circulation time and relatively lowered accumulation in different organs compared with their non-PEGylated counterparts. [77][78][79] In vivo experiments also show significantly high accumulation of the PEGylated nanoformulation in tumor tissues due to the enhanced permeation and retention effect. This enhanced permeability and retention is mainly due to the difference in vasculature between tumor tissue and normal tissue.…”