Hydrophilization of Poly(Caprolactone) Copolymers through Introduction of Oligo(Ethylene Glycol) Moieties

Abstract

In this study, a new family of poly(ε-caprolactone) (PCL) copolymers that bear oligo(ethylene glycol) (OEG) moieties is described. The synthesis of three different oligo(ethylene glycol) functionalized epoxide monomers derived from 2-methyl-4-pentenoic acid, and their copolymerization with ε-caprolactone (CL) to poly(CL-co-OEG-MPO) copolymers is presented. The statistical copolymerization initiated with SnOct2/BnOH yielded the copolymers with varying OEG content and composition. The linear relationship between feed ratio and incorporation of the OEG co-monomer enables control over backbone functional group density. The introduction of OEG moieties influenced both the thermal and the hydrophilic characteristics of the copolymers. Both increasing OEG length and backbone content resulted in a decrease in static water contact angle. The introduction of OEG side chains in the PCL copolymers had no adverse influence on MC-3TE3-E1 cell interaction. However, changes to cell form factor (Φ) were observed. While unmodified PCL promoted elongated (anisotropic) morphologies (Φ = 0.094), PCL copolymer with tri-ethylene glycol side chains at or above seven percent backbone incorporation induced more isotropic cell morphologies (Φ = 0.184) similar to those observed on glass controls (Φ = 0.151).

Biodegradable PEG-Based Amphiphilic Block Copolymers for Tissue Engineering Applications

“…42 Similarly, Wurth et al recently showed that the incorporation of oligo(ethylene glycol) side chains into PCL can reduce the water contact angle of films from ~90º to ~35º. 43,44 Dramatic increases in surface aqueous wettability have also been observed for electrospun amphiphilic scaffolds. Electrospun hydrophobic PLA and PLGA scaffolds have been characterized with water contact angles as high as 120º.…”

“…32 The tunable degradation rates, ease of processing and established medical uses of PLA and PLGA have made them attractive choices for integration with PEG to form amphiphilic di-block, 17,33–37 tri-block, 38–42 or multi-block copolymers. 43–47 …”

Enhanced cellular uptake of nanoparticles by increasing the hydrophobicity of poly(lactic acid) through copolymerization with cell-membrane-lipid components

“…We have previously reported a simple and versatile approach to introduce functional elements along the aliphatic polyester backbone by copolymerizing lactones with α-ω-epoxy esters. 11 This copolymerization approach has been successfully exploited to introduce along PLA and poly(caprolactone) backbone many moieties such as hydrophilic polyethylene glycol (PEG) chains, 12 side groups with negative and positive charge, 13 and more recently chemical groups amenable to conjugation of biomolecules and dyes via click chemistry. 14 Building on these successes, in this study we synthesized epoxy esters of two of the most common lipid components of cells, namely octadecanol and cholesterol, with 2-methyl-4-pentenoic acid (MPA) (Figure S1 and Figure S2 in ESI), and copolymerized them with L-lactide using the tin-catalyzed ring opening copolymerization (ROP) to yield amorphous to semi-crystalline polymers with enhanced hydrophobicity (Figure 1).…”

“…23 Adjusting the hydrophilic lipophilic balance (HLB) is one means to influence the material-cell interaction profile of polymers. 12 In this study we had theorized that the incorporation of cell lipid components into the PLA backbone would confer hydrophobic characteristics to the copolymers. The presence of a lipid rich surface was verified using attenuated total reflection-IR (ATR-IR) as discussed later (Figure 3B).…”

Biocatalytic Route for the Synthesis of Oligoesters of Hydroxy-Fatty acids and ϵ-Caprolactone

“…Although PCL is a valuable biomaterial with important applications for drug‐delivery systems and bioresorbable scaffolds, several drawbacks such as low hydrophilicity, low melting point (≈60 °C), and relatively slow biodegradability impeded its extensive development . To overcome these drawbacks, basically two solutions are available: blending with other biomaterials, like hydrophilic polymers or synthesis of copolymers with improved properties . In the same time, melting point in the physiological range can be advantageous for specific biomedical applications, while slow degradation rate results in longer stability of the implants .…”