Solvent-Free Processing of Drug-Loaded Poly(ε-Caprolactone) Scaffolds with Tunable Macroporosity by Combination of Supercritical Foaming and Thermal Porogen Leaching

Abstract

Demand of scaffolds for hard tissue repair increases due to a higher incidence of fractures related to accidents and bone-diseases that are linked to the ageing of the population. Namely, scaffolds loaded with bioactive agents can facilitate the bone repair by favoring the bone integration and avoiding post-grafting complications. Supercritical (sc-)foaming technology emerges as a unique solvent-free approach for the processing of drug-loadenu7d scaffolds at high incorporation yields. In this work, medicated poly(ε-caprolactone) (PCL) scaffolds were prepared by sc-foaming coupled with a leaching process to overcome problems of pore size tuning of the sc-foaming technique. The removal of the solid porogen (BA, ammonium bicarbonate) was carried out by a thermal leaching taking place at 37 °C and in the absence of solvents for the first time. Macroporous scaffolds with dual porosity (50–100 µm and 200–400 µm ranges) were obtained and with a porous structure directly dependent on the porogen content used. The processing of ketoprofen-loaded scaffolds using BA porogen resulted in drug loading yields close to 100% and influenced its release profile from the PCL matrix to a relevant clinical scenario. A novel solvent-free strategy has been set to integrate the incorporation of solid porogens in the sc-foaming of medicated scaffolds.

Recent advances in melt electro writing for tissue engineering for 3D printing of microporous scaffolds for tissue engineering

“…While there are many scaffold fabrication techniques like emulsion freeze drying ( Sultana and Wang, 2008 ; Qian and Zhang, 2011 ; Sultana and Wang, 2012 ), gas foaming ( Manavitehrani et al, 2019 ; Luo et al, 2021 ; Chen Y et al, 2021 ), porogen leaching ( Bhaskar et al, 2018 ; Poddar et al, 2021 ; Santos-Rosales et al, 2021 ) or phase separation ( Ferrolino et al, 2018 ; Abzan et al, 2019 ; Zeinali et al, 2021 ), more recently additive manufacturing (AM) gained an increased interest for scaffold fabrication ( Shick et al, 2019 ; Szymczyk-Ziółkowska et al, 2020 ; Veeman et al, 2021 ). Generally, the term AM refers to a group of additive manufacturing techniques used to produce a scale model of a physical part or assembly as a three-dimensional model as quickly and inexpensively as possible.…”

Applications and Challenges of Supercritical Foaming Technology

“…(e) ScCO 2 -assisted foaming offers significant advantages in terms of solvent-free processability of the material and loading of bioactive compounds in high yields during integration. (f) Low residual CO 2 in the polymer matrix after foaming [ 12 , 14 , 16 , 17 ].…”

“…However, according to the present research, the control of bubble hole size has been achieved and applied to some extent, e.g., by increasing the affinity between the organic solvent and ScCO 2 to obtain low density and small pore size foam [ 13 ]; supercritical foaming technology was coupled with a leaching process to overcome problems of pore size tuning of the supercritical foaming technique [ 14 ]. This shows that this foaming technique is still feasible, although the finished size is difficult to control.…”

Biodegradable PCL-b-PLA Microspheres with Nanopores Prepared via RAFT Polymerization and UV Photodegradation of Poly(Methyl Vinyl Ketone) Blocks

“…Although phase separation is generated by self-assembly because of incompatibility between these segments, minimizing surface energy, the separation is restricted owing to segment chain connectivity [12,32]. Among the aforementioned technologies that allow for the controlled fabrication of porous polymers, direct templating is a useful method, because of the diverse templates and well-defined porous structures created by the removal of pore templates through the use of solvents, enzymes, or inorganic acids [12,14,33,34]. However, to the best of our knowledge, our previous report is the only one focusing on the fabrication of porous microsphere polymers using UV light [35], which is potentially a more advantageous method, as the porous microspheres could be formed without using additional templates.…”