Synthesis of pendent carboxyl-containing poly(ε-caprolactone-co- β-malic acid)-block-poly(l-lactide) copolymers for fabrication of nano-fibrous scaffolds

Nano-fibrous scaffolds modified with biological peptides, which can mimic the physical and chemical characteristics of an extracellular matrix (ECM), have been considered good candidate matrices for cell culture in tissue engineering application. In this study, a series of semicrystalline block copolymers, specifically pendent carboxyl-containing poly(ε-caprolactone-co-β-malic acid)-block-poly(l-lactide), were synthesized to fabricate nano-fibrous scaffolds via thermal induced liquid–liquid phase separation process. Random prepolymers P(CL-co-BMD) were first synthesized through ring-opening copolymerization of ε-CL and 3(S)-[(benzyloxycarbony)methyl]-1,4-dioxane-2,5-dione (BMD) in the presence of dodecanol as initiator and stannous octoate(Sn(Oct)2) as catalyst. The terminal hydroxyl of P(CL-co-BMD)-OH was subsequently added to initiate the ring-opening of l-LA catalyzed by Sn(Oct)2. After deprotection, a series of block copolymers, poly(ε-caprolactone-co-β-malic acid)-block-poly(l-lactide)(PCM-b-PLLA), were obtained and fabricated into nanofibrous scaffolds through thermally induced phase separation (TIPS) technique using tetrahydrofuran (THF) as solvent at a gelation temperature of −40 °C. The structure of the copolymers was characterized Nuclear Magnetic Resonance (1H NMR, 13C NMR), Gel Permeation Chromatography (GPC), and Differential Scanning Calorimetry (DSC). The crystallinity of the PCL segment generally decreased when the amount of BMD segment in P(CL-co-BMD) was increased. However, for PCM-b-PLLA, aside from the crystal melting peak of PLLA at 170 °C–180 °C, no indication of PCL section crystallization occurred because the crystallization of the PCL segment was interrupted by PLLA segment. The nanofiber size of the matrices was in the range of 180 nm–650 nm, similar to the architecture of ECM at the nanometer scale. These nanofibrous matrices have design potential to conjugate covalently to bioactive molecules for tissue engineering.