Supercritical CO2 technology for one-pot foaming and sterilization of polymeric scaffolds for bone regeneration

• Published in: International journal of pharmaceutics 2021-08, Vol.605, p.120801-120801, Article 120801
• Main Authors: Santos-Rosales, Víctor, Magariños, Beatriz, Starbird, Ricardo, Suárez-González, Javier, Fariña, José B., Alvarez-Lorenzo, Carmen, García-González, Carlos A.
• Format: Article
• Language: English
• Subjects: Bone scaffold; Hydrogen peroxide; Spores; Sterilization; Supercritical CO2
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2021.120801

[Display omitted] •An integrated scCO2 sterilization/foaming procedure was implemented.•Sterile PCL/PLGA bone scaffolds were successfully manufactured with this method.•No cytotoxic H2O2 residues were found in scaffolds once cultured with fibroblasts.•scCO2 sterilization preserved the physicochemical properties of the scaffolds.•Differently, gamma-ray sterilization (15 kGy) induced significant changes.•B. pumilus is proposed as biological indicator to evaluate scCO2 sterilization. Sterilization is a quite challenging step in the development of novel polymeric scaffolds for regenerative medicine since conventional sterilization techniques may significantly alter their morphological and physicochemical properties. Supercritical (sc) sterilization, i.e. the use of scCO2 as a sterilizing agent, emerges as a promising sterilization method due to the mild operational conditions and excellent penetration capability. In this work, a scCO2 protocol was implemented for the one-pot preparation and sterilization of poly(ε-caprolactone) (PCL)/poly(lactic-co-glycolic acid) (PLGA) scaffolds. The sterilization conditions were established after screening against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) vegetative bacteria and spores of Bacillus stearothermophilus, Bacillus pumilus and Bacillus atrophaeus. The transition from the sterilization conditions (140 bar, 39 °C) to the compressed foaming (60 bar, 26 °C) was performed through controlled depressurization (3.2 bar/min) and CO2 liquid flow. Controlled depressurization/pressurization cycles were subsequently applied. Using this scCO2 technology toolbox, sterile scaffolds of well-controlled pore architecture were obtained. This sterilization procedure successfully achieved not only SAL-6 against well-known resistant bacteria endospores but also improved the scaffold morphologies compared to standard gamma radiation sterilization procedures.