Enzyme-Mediated Ring-Opening Polymerization of Pentadecalactone to Obtain Biodegradable Polymer for Fabrication of Scaffolds for Bone Tissue Engineering

Abstract

The optimization of enzyme-mediated polymerization of pentadecalactone (PDL) was performed to obtain macromolecular products suitable for generation of 3D cell supports (scaffolds) for bone tissue engineering. Such parameters as temperature, monomer/enzyme ratio, and monomer concentration were studied. The maximum molecular weight of synthesized polymers was about 90,000. Methods allowing the introduction of reactive double bonds into polypentadecalactone (polyPDL) structure were developed. The macroporous matrices were obtained by modification of thermoinduced phase separation method.

Enzymatic ring opening polymerization of ω‐Pentadecalactone in different solvents in a variable‐volume view reactor

“…These molecular weight values are in agreement with literature results, where authors obtained poly(PDL) with molecular weights in the same range using Novozym 435 as catalyst and toluene as solvent in a ratio 2:1 (solvent:monomer) …”

“…During the last years, several studies evaluated the potential of poly(pentadecalactone) as a biomaterial for tissue engineering, prosthetic implants as scaffolds,and controlled drug release, since poly(pentadecalactone) is biocompatible, non‐toxic, and can be hydrolyzed under body conditions and excreted without causing collateral damage …”

“…Enzymatic ring opening polymerization (e‐ROP) of ω‐pentadecalactone (ω‐PDL) is promising because it presents high yield and very fast reaction kinetics being more efficient than the metal or acid‐catalyzed polymerization . However, in all works found to date, e‐ROP of ω‐PDL that takes place in solution uses toluene as solvent . No work reports the synthesis of poly(PDL) using solvents with a lower boiling point that can be more easily removed without leaving solvent traces, and this goes against the use of enzymes as catalysts since enzymes are classified as “green” catalysts, that do not leave any toxic traces on the final polymer and neither form toxic by‐products …”

Candida antarctica Lipase B as Catalyst for Cyclic Esters Synthesis, Their Polymerization and Degradation of Aliphatic Polyesters

“…They proved, that the reduction of the polymerization temperature from 90 to 55 °C and toluene/ monomer molar ratio from 10:1 to 1:1 gave PPDL with increased M n (66 to 81 and 49 to 86 kg mol −1 , respectively) and monomer conversion. The similar conclusion was presented by Korzhikov [86], although he found second optimum (between 100 and 110 °C) were the PPDL with high molar mass could be formed. The final product was characterized by M w about 88 kg mol −1 and Đ = 1.65.…”

“…Recently, oligomers of PPDL were obtained at 70 and 90 °C for 24 h [84]. PPDL can be also synthesized in the presence of HEMA initiator [85], in order to obtain methacrylated aliphatic polyester, which in further studies can be used for formation of macroporous matrices for tissue scaffolds [86]. Another difunctional poly(ω-PDL) designed for biomedical application was prepared by solvent free ROP of PDL in the presence of 4 wt% of N-435 and initiated by 6-mercapto-1-hexanol and terminated by γ-thiobutyrolactone or vinyl acrylate (Scheme 4e) [87].…”